NRG-BR007, A Phase III Clinical Trial Evaluating De-Escalation of Breast Radiation for Conservative Treatment of Stage I, Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)
De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
- The patient must have an ECOG performance status of 0 or 1.
- The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection).
- The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
- Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
- The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
- By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm);
- By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible);
- Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen;
- ** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.
- The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive;
- The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
- Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or documented bilateral oophorectomy.
- The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.
- The patient must have recovered from surgery with the incision completely healed and no signs of infection.
- Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.
- Definitive clinical or radiologic evidence of metastatic disease. -pT2
•pT4 tumors including inflammatory breast cancer. - Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
- Patient had a mastectomy.
- Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
- Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
- Non-epithelial breast malignancies such as sarcoma or lymphoma.
- Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible).
- Paget's disease of the nipple.
- Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible).
- Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible).
- Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible).
- Treatment plan that includes regional nodal irradiation.
- Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry. (Short course endocrine therapy of less than 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
- History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.
- Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
- Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible.
- Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
- Prior breast or thoracic RT for any condition.
- Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
- Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment.
- Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
- Use of any investigational product within 30 days prior to study entry.
Eligibility last updated 9/20/21. Questions regarding updates should be directed to the study team contact.
Bladder Bank (Bladder Bank)
Bladder Bank
- Age ≥ 18 years.
- Patient has undergone office-based evaluation for hematuria (CT, ultrasound, cystoscopy).
- Patient has known cancer outside of the target cancer 5 years prior to current collection (not including basal cell or squamous cell skin cancers; if patient has not been seen or if information is not available, the patient is eligible).
- Patient has recurrent bladder cancer.
- Patient has ever been previously diagnosed with UTUC (Upper Tract Urothelial Carcinoma) prior to bladder resection.
- Patient has prior diagnosis of bladder cancer for which intravesical immunotherapy (BCG) or chemotherapy (Mitomycin, Valrubicin) was provided.
- Patient has received chemotherapy class drugs for the treatment of cancer in the 5 years prior to current collection.
- Patient has had any prior radiation therapy to the target lesion prior to current collection.
- Patient has had a biopsy to the target organ and/or lesion within 3 days before collection.
- Patient has undergone cystectomy.
- Patient has transurethral instrumentation (placement of urinary catheter) within 7 days prior to urine collection.
- Patient has had a urinary tract infection within 14 days prior to urine collection.
- Patient has chronic indwelling urinary catheter
- Patient has prior diagnosis of bladder cancer for which prior resection of tumor was performed.
Eligibility last updated 6/29/22. Questions regarding updates should be directed to the study team contact.
Immune Checkpoint Inhibition and Humoral Immune Response in Systemic Autoimmunity (ICIRA)
ICI and Response in Autoimmunity
- Adults, age ≥ 18 years.
- Any concomitant malignancy being treated with any PD-1 inhibitor (pembrolizumab, nivolumab or cemiplimab) as monotherapy and the presence of inflammatory arthritis defined by:
- provider documented inflammatory arthritis (meet 2010 EULAR/ACR classification criteria of RA) in one or more large or small joints; and at least one or more of the following:
- elevated inflammatory markers;
- supportive imaging and/or supportive synovial fluid analysis.
- Active infection.
- Prior history of the rheumatic disease.
- Any B cell depletion therapy.
- PActive use of high (≥ 30 mg daily) of prednisone or steroid equivalent.
- Clinical features suggestive of non-RA autoimmune rheumatic disease (e.g., lupus, Sjogren’s, psoriatic arthritis, etc.) or axial spondyloarthropathy.
Eligibility last updated 9/21/21. Questions regarding updates should be directed to the study team contact.
A Real-world Comparative Effectiveness Trial of Treatment Strategies in Patients with Rheumatoid Arthritis: The RA-PRO (Patient Reported Outcomes) Pragmatic Trial (RA-PROPR) (RA-PROPR)
RA-PRO PRAGMATIC TRIAL
- Prior TNFi biologic treatment – Patient has active, moderate-high disease activity RA (CDAI ≥ 10 and HAQ ≥ 0.5) despite the use/experience for ≥ 3 months of a TNFi-biologic OR discontinued the medication(s) due to intolerability or toxicity irrespective of treatment duration prior to the first dose of study drug; AND
- Glucocorticoid and NSAID treatment
•If receiving glucocorticoids (≤ 10 mg/day of prednisone of equivalent) or NSAIDs, on stable doses for ≥ 2 weeks prior to randomization; AND - Insurance
•Insurance plan or patient assistance program allows access to at least 1 drug in each of the two treatment strategies for 1 year trial duration. Participants will be allowed to continue their conventional synthetic DMARD (csDMARD) therapy if they had been using it for ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, and leflunomide (TNFi-biologic and tsDMARD) through insurance plan or a patient assistance program/plan.
- Prior treatment with more than three biologics, defined as TNFi-biologic or non-TNFi biologic.
- Prior treatment with targeted synthetic DMARD.
- Concomitant use of cyclosporine, or azathioprine within 2-months before randomization.
- History of sensitivity to all 4 non-TNF-biologic or a targeted synthetic DMARD.
- Glucocorticoid injection (intravenous, intramuscular, or intraarticular) within 1 month of study entry.
- Live vaccine within 90 days of study entry.
- Acute infection treated with parenteral antibiotics or hospitalization within 1 month or with oral antibiotics within 2 weeks of study entry; or chronic infections requiring long-term antibiotic suppressive therapy.
- History of HIV or opportunistic infections.
- New York Heart Association Class III or IV heart failure.
- Latent TB not treated with anti-mycobacterial medication.
- Untreated Hepatitis B or C infection.
- History of deep venous thrombosis or pulmonary embolism.
- Pregnant or nursing women.
- History of herpes zoster or shingles.
Eligibility last updated 6/1/22. Questions regarding updates should be directed to the study team contact.
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy of Tadalafil Versus Placebo in Improving Hemodynamics and End-Organ Dysfunction in Fontan Physiology (TRIUMPH Trial) (TRIUMPH)
Tadalafil vs. Placebo to Improve Hemodynamics and End-Organ Dysfunction in Fontan Physiology
- Patients ≥ 18 years old.
- Have previously undergone a Fontan Palliation.
- Able to exercise using a supine bike.
- Able to undergo an MRI.
- Ability and willingness to provide written consent.
- Undergoing a clinically indicated Cardiac Catheterization
- Patients < 18 years old.
- Current intravenous inotropic drugs.
- Current use of alpha-blockers, pulmonary vasodilators, or nitrates.
- Unable to exercise.
- Pregnancy or lactating.
- Unable or unwilling to consent.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 7/26/22. Questions regarding updates should be directed to the study team contact.
ORIC-533-01, An Open-label Phase 1b Study of ORIC-533 in Patients With Relapsed or Refractory Multiple Myeloma
Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma
- Diagnosis of multiple myeloma (MM) with relapsed or refractory disease according to IMWG Criteria
- Refractory to or not eligible for MM treatment regimens known to provide clinical benefit, including but not limited to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, with documented disease progression
- Measurable disease at screening, including at least 1 of the criteria below:
- Serum M-protein >0.5 g/dL (Patients with IgA myeloma in whom serum M protein is unreliable due to comigration of normal serum proteins may be considered eligible if total IgA >400 mg/dL)
- Urine M-protein >200 mg/24 hours
- Serum free light chains (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
- Measurable bone or extramedullary plasmacytoma
- ECOG performance status ≤2
- Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
- Estimated glomerular filtration rate ≥40 mL/min/1.73 m2.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both ≤3 times of upper limit of normal, unless there is suspected disease in the
liver, in which case, no limit is set provided serum bilirubin is within eligibility criterion
- Total bilirubin <1.5 × upper limit of normal (ULN), except in study participants with Gilbert's syndrome
- Platelet count >40,000/?L
- Absolute neutrophil count (ANC) >1000/?L
- Left ventricular ejection fraction (LVEF) >45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA)
- Baseline oxygen saturation >92% on room air
- Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy
- Previous or concurrent plasma cell leukemia, AL amyloidosis, or POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome
- Known central nervous system (CNS) involvement
- Evidence of hyperviscosity syndrome
- Receiving any investigational treatment with a novel investigational agent (i.e., no approved indication) within 28 days prior to the first dose of study drug
- Not recovered or stabilized from all toxicities from prior anticancer therapies and/or radiotherapy to Grade <2 with the exception of peripheral neuropathy
- Major surgery or radiation therapy within 14 days prior to first dose of study drug or incomplete recovery from adverse effects resulting from such procedure
- Those who require limited course of radiation for management of bone pain for ≤14 days from initiation of therapy are not excluded
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days of starting therapy
- Those who are on prophylactic antibiotics only, or on antibiotics and have confirmation of resolution of active infection, are eligible
- Daily requirement for corticosteroids (equivalent to >10 mg/day prednisone). Inhalation corticosteroids are exempt from this criterion
- Exception: Corticosteroid dose equivalent >10 mg/day prednisone is acceptable if physiological levels require, so long as the dose is stable for at least 7 days prior to initiation of therapy
- Lower amounts of corticosteroids that are not part of a daily requirement within 14 days prior to initiating therapy are also acceptable
- Known seropositive for active viral infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C virus (HCV). Those who are seropositive because of
hepatitis B vaccine are eligible. Patients who are positive for HBV core antibody or HBV surface antigen must have a negative polymerase chain reaction (PCR) result prior
to enrollment. Those who are PCR positive will be excluded.
- History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months of first dose of study drug
- QTcF >470 msec
- Other concurrent serious uncontrolled medical, psychological, or addictive conditions that, in the opinion of the investigator, may interfere with protocol compliance or
contraindicates participation in the study
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/18/23. Questions regarding updates should be directed to the study team contact.
Detection of Colorectal Cancer or Advanced Neoplasia by Stool DNA in Lynch Syndrome: CORAL Study (CORAL)
Collecting Blood and Stool Samples to Detect Colorectal Cancer or Advanced Neoplasia in Lynch Syndrome Patients, CORAL Study
- Patients at least 18 years of age
- Individuals diagnosed with Lynch syndrome (mutation in MLH1, MSH2, MSH6, PMS2, EPCAM)
or suspected Lynch syndrome or individuals diagnosed with early onset colorectal
cancer (CRC) (< 50 years old [yo])
- Colonoscopy/flexible sigmoidoscopy (flex sig) scheduled +/- 90 days from sample
collection
- Patient has agreed to participate and has signed the study consent form
- Patient has known cancer (stage I-IV) 5 years prior to current sample collection (not
including basal cell or squamous cell skin cancers; if patient has not been seen or if
information is not available, the patient is eligible)
- Patient has received chemotherapy class drugs for the treatment of cancer in the 5
years prior to current sample collection
- Patient has had any abdominal radiation therapy prior to current sample collection
- Patient had therapy to the target lesion with intent to completely remove or debulk
the lesion prior to sample collection (examples include snare polypectomy, endoscopic
mucosal resection [EMR], endoscopic submucosal dissection [ESD], surgical resection,
trans anal excision)
- Patient has prior diagnosis of non-lynch hereditary colon cancer syndrome (familial
adenomatous polyposis [FAP], MUTYH-associated polyposis [MAP], Peutz-Jeghers syndrome
[PJS], juvenile polyposis syndrome [JPS], PTEN, POL)
- ADDITIONAL STOOL EXCLUSIONS:
- Bowel prep < 7 days prior to stool collection
- Oral or rectal contrast given within 7 days prior to stool collection
- Removal of more than 50% of colon or presence of ileostomy
- Enteral feeds or total parenteral nutrition (TPN)
- Diagnosis of inflammatory bowel disease
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 1/13/23. Questions regarding updates should be directed to the study team contact.
A Randomized Phase 2 Trial With a Safety Lead-In to Evaluate Palbociclib Versus Palbociclib and Cemiplimab for the Treatment of Advanced Dedifferentiated Liposarcoma
Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma
- ELIGIBILITY CRITERIA (STEP 1): Patients must have histologically documented
dedifferentiated liposarcoma (DDLPS). Patients with mixed
well-differentiated/ dedifferentiated liposarcoma (WD/DD LPS) tumors are eligible
provided there is a histologically confirmed DDLPS component at some point during the
treatment course
- Disease must be metastatic or locally advanced and surgically unresectable, in
the opinion of the treating investigator
- Note: Intact retinoblastoma protein (RB) can be assumed in DDLPS. In a query of
project Genomics Evidence Neoplasia Information Exchange (GENIE) (American
Association for Cancer Research [AACR]), including 286 DDLPS tumors, the rate of
RB1 mutation in DDLPS was 1.37%. Therefore, molecular testing to determine intact
Rb is not required
- ELIGIBILITY CRITERIA (STEP 1): Patients must have at least one lesion that is
measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
criteria to be eligible for this study. Previously radiated lesions should not be used
as target lesions unless there is documented evidence of disease progression of that
lesion after radiation
- ELIGIBILITY CRITERIA (STEP 1): Patients may have received any number of prior systemic
treatment lines for DDLPS, including none
- ELIGIBILITY CRITERIA (STEP 1): Patients must have recovered to baseline or =< grade 1
per CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse
events are clinically nonsignificant and/or stable on supportive therapy, and with the
exceptions of fatigue (which must be =< grade 2), alopecia and/or endocrinopathies
related to prior immunotherapy which are controlled with hormone replacement
- ELIGIBILITY CRITERIA (STEP 1): Patients must have completed all prior anti-cancer
treatment, including radiation, >= 14 days prior to registration
- ELIGIBILITY CRITERIA (STEP 1): Age >= 18 years
- ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) Performance
Status 0-2
- ELIGIBILITY CRITERIA (STEP 1): Absolute neutrophil count (ANC) >= 1000/mm^3
- ELIGIBILITY CRITERIA (STEP 1): Platelet count >= 100,000/mm^3
- ELIGIBILITY CRITERIA (STEP 1): Hemoglobin >= 9 g/dL
- ELIGIBILITY CRITERIA (STEP 1): Creatinine clearance (CrCl) >= 30 mL/min
- ELIGIBILITY CRITERIA (STEP 1): Total bilirubin =< 1.5 x upper limit of normal (ULN)
- ELIGIBILITY CRITERIA (STEP 1): Aspartate aminotransferase (AST)/alanine
aminotransferase (ALT) =< 3.0 x ULN
- ELIGIBILITY CRITERIA (STEP 1): Patients with known history or current symptoms of
cardiac disease, or history of treatment with cardiotoxic agents, should have a
clinical assessment of cardiac function using the New York Heart Association
Functional Classification. To be eligible, patients should be class IIB or better.
Furthermore, patients may not have an uncontrolled ventricular arrhythmia or recent
(within 3 months) myocardial infarction
- ELIGIBILITY CRITERIA (STEP 1): For patients with evidence of chronic hepatitis B (HBV)
infection, the HBV viral load must be undetectable on suppressive therapy, if
indicated
- ELIGIBILITY CRITERIA (STEP 1): Patients with a history of hepatitis C virus (HCV)
infection must have been treated and cured. For patients with HCV infection who are
currently receiving treatment, they are eligible if they have an undetectable HCV
viral load
- ELIGIBILITY CRITERIA (STEP 1): Human immunodeficiency virus (HIV)-infected patients on
effective anti-retroviral therapy with undetectable viral load within 6 months are
eligible for this trial
- ELIGIBILITY CRITERIA (STEP 1): Patients with a prior or concurrent malignancy whose
natural history or treatment does not have the potential to interfere with the safety
or efficacy assessment of the investigational regimen are eligible for this trial.
Patients participating on this trial may not be receiving other anti-neoplastic
therapies and there should be no anticipated need for such therapy
- ELIGIBILITY CRITERIA (STEP 1): Patients with treated brain metastases that are
non-progressing are eligible if follow-up brain imaging performed at least 4 weeks
after central nervous system (CNS)-directed therapy shows no evidence of progression.
Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are not eligible
- ELIGIBILITY CRITERIA (STEP 1): Patients must be able to swallow oral medications
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): In
order to cross over to Arm 2, patients must meet the same eligibility criteria as
described above
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2):
Patients must have demonstrated progression of disease on palbociclib monotherapy (Arm
1) per RECIST version 1.1 criteria
- ELIGIBILITY CRITERIA (STEP 1): Patients may not have received prior treatment with
CDK4/6 inhibitors (including, but not limited to: palbociclib, ribociclib or
abemaciclib) or anti-PD-1/anti-PD-L1 antibodies
- ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because this study
involves an agent that has known genotoxic, mutagenic and teratogenic effects
* Therefore, for women of childbearing potential only, a negative serum pregnancy test
done =< 7 days prior to registration is required
- ELIGIBILITY CRITERIA (STEP 1): Patients must not have an active autoimmune disease
with the exception of vitiligo, well-controlled asthma or allergic rhinitis, type 1
diabetes, psoriasis or hypothyroidism. Patients with a history of adrenal
insufficiency are eligible if on a stable dose of prednisone =< 10 mg or equivalent
- ELIGIBILITY CRITERIA (STEP 1): Patients must not have an uncontrolled intercurrent
illness including, but not limited to, ongoing or active infection, uncontrolled major
seizure disorder, unstable spinal cord compression, superior vena cava syndrome,
extensive interstitial bilateral lung disease on high resolution computed tomography
(HRCT) scan or any other condition that would limit compliance with study requirements
- ELIGIBILITY CRITERIA (STEP 1): Patients may not require the use of chronic steroids in
excess of 10 mg prednisone daily or equivalent
- ELIGIBILITY CRITERIA (STEP 1): Patients may not require concomitant use of known
strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease
inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir,
boceprevir, telaprevir). The required washout period prior to re-registration 2 weeks
- ELIGIBILITY CRITERIA (STEP 1): Patients may not require concomitant use of known
strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin,
rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort). The required
washout period prior to re-registration is 5 weeks for enzalutamide or phenobarbital
and 3 weeks for other agents
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2):
Patients may not have experienced a grade 3 or higher non-hematologic adverse event
deemed clinically significant in the opinion of the treating investigator, or have
discontinued palbociclib due to toxicity, while participating on Arm 1
- Patients must also have recovered to baseline or =< grade 1 per CTCAE version 5.0
from toxicity related to Arm 1 treatment, unless adverse events are clinically
nonsignificant and/or stable on supportive therapy, and with the exceptions of
fatigue (which must be =< grade 2), alopecia and/or endocrinopathies related to
prior immunotherapy which are controlled with hormone replacement
- Note: Patients who underwent dose reduction of palbociclib during treatment on
Arm 1 will begin treatment on Arm 2 at the same dose (i.e. dose re-escalation is
not allowed)
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2):
Patients may not have received prior treatment with anti-PD-1/anti-PD-L1 antibodies
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): Not
pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects * Therefore, for women of childbearing
potential only, a negative serum pregnancy test done =< 7 days prior to
re-registration is required
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 2/17/23. Questions regarding updates should be directed to the study team contact.
ALKS 4230-006, A Phase 2, Open-Label, Multicenter, Cohort Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma Who Have Previously Received Anti-PD-[L]-1 Therapy - ARTISTRY-6 (ARTISTRY-6)
Nemvaleukin Alfa (ALKS 4230) Monotherapy in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma
- The patient must have the following tumor types:
Cohort 1: Patient has unresectable and/or metastatic cutaneous melanoma. No more than 5
patients with acral melanoma may enroll in this cohort.
Cohort 2: Patient has unresectable and/or metastatic mucosal melanoma.
Cohort 3: Patient has unresectable and/or metastatic cutaneous melanoma. Patients with
acral melanoma may not enroll in this cohort.
- The patient must have received previous treatment as follows:
1. Patient has received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy,
and no more than one other prior regimen of systemic anti-neoplastic therapy (eg,
targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy
counts as one prior regimen.
2. Patients have experienced objective response (partial response [PR] or CR; by
RECIST 1.1 or iRECIST) or stable disease (SD; by RECIST 1.1 or iRECIST) as best
overall response (BOR) to anti-PD-[L]1 therapy. Patients with confirmed
progressive disease (by RECIST 1.1 or iRECIST) as best response may be included,
if they received anti-PD-[L]1 therapy for a minimum of 12 weeks (eg, from first
dose to last dose).
3. Patients with BRAF mutations may or may not have received prior targeted therapy.
- Patients must have disease that is measurable based on RECIST 1.1., that has not
recently been irradiated or used to collect a biopsy.
- Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying
archival tumor tissue.
- Patient has an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 and an
estimated life expectancy of ≥3 months.
- Additional criteria may apply.
- Patient has uveal melanoma (all cohorts) or acral melanoma (Cohort 2 and Cohort 3).
- Patient has received prior interleukin (IL)-2-based or IL-15-based cytokine therapy;
patient has had exposure, including intralesional, to IL-12 or analogs thereof.
- Patient requires systemic corticosteroids (>10 mg of prednisone daily, or equivalent)
however, replacement doses, topical, ophthalmologic, and inhalational steroids are
permitted.
- Patient has undergone prior solid organ and/or non-autologous hematopoietic stem cell
or bone marrow transplant.
- Patient is currently pregnant, breastfeeding, or is planning to become pregnant or to
begin breastfeeding during the study period or within 30 days after last study drug
administration.
- Patients with active or symptomatic central nervous system metastases unless the
metastases have been treated by surgery and/or radiation therapy and/or gamma knife,
the subject has been tapered to a dose of 10 mg of prednisone (or equivalent) or less
of corticosteroids for at least 2 weeks before the first dose, and the subject is
neurologically stable. Patients with leptomeningeal disease are excluded.
- Patient has known or suspected hypersensitivity to any components of nemvaleukin.
- Patients with an uncontrollable bleeding disorder.
- Patient has QT interval corrected by the Fridericia Correction Formula values of >470
msec (in females) or >450 msec (in males); patient who is known to have congenital
prolonged QT syndromes; or patient who is on medications known to cause prolonged QT
interval on ECG.
- Patient has developed Grade ≥3 immune-related AEs (irAEs) while on prior
immunotherapy, (eg, pneumonitis and nephritis) and has not recovered to ≤Grade 1
and/or are on systemic steroids within 14 days of first dose of study drug.
- Patients who have previously discontinued immunotherapy due to immune-related adverse
event (irAEs) will be excluded.
- Additional criteria may apply.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 4/17/23. Questions regarding updates should be directed to the study team contact.
A Phase I Study With an Expansion Cohort of Duvelisib and Nivolumab in Mycosis Fungoides (MF) and Sezary Syndrome (SS)
Duvelisib and Nivolumab for the Treatment of Stage IIB-IVB Mycosis Fungoides and Sezary Syndrome
- Patients must have histologically or cytologically confirmed MF or SS, stages IIB to
IVB with measurable disease and/or detectable blood involvement based on the Global
Cutaneous Lymphoma Response Criteria
- Patients must have had at least one line of prior systemic therapy
- Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of duvelisib in combination with nivolumab in patients < 18 years of age,
children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
- Absolute neutrophil count >= 1000/mcL
- Platelets > 75,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) or =< 5 x
institutional ULN if with history of Gilbert's syndrome
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x institutional ULN
- Creatinine =< 2.0 x institutional ULN
- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
- The effects of nivolumab and duvelisib on the developing human fetus are unknown. For
this reason and because other therapeutic agents used in this trial are known to be
teratogenic, women of child-bearing potential (WOCBP) and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence) prior
to study entry and for the duration of study participation. WOCBP should use an
adequate method to avoid pregnancy for 5 months after the last dose of investigational
drug. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25
IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 7 days prior to
the start of nivolumab. Women must not be breastfeeding. Men who are sexually active
with WOCBP must use any contraceptive method with a failure rate of less than 1% per
year. Men receiving nivolumab and duvelisib and who are sexually active with WOCBP
will be instructed to adhere to contraception for a period of 7 months after the last
dose of investigational product. Women who are not of childbearing potential (i.e.,
who are postmenopausal or surgically sterile as well as azoospermic men) do not
require contraception. WOCBP is defined as any female who has experienced menarche and
who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy)
or who is not postmenopausal. Menopause is defined clinically as 12 months of
amenorrhea in a woman over 45 in the absence of other biological or physiological
causes. In addition, women under the age of 55 must have a documented serum follicle
stimulating hormone (FSH) level less than 40 mIU/mL
- Should a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately. Men
treated or enrolled on this protocol must also agree to use adequate contraception
prior to the study, for the duration of study participation, and 7 months after
completion of administration of investigational agents on this study
- Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- Prior therapy with a PI3K inhibitor
- Prior therapy with nivolumab or other agents targeting T-cell co-stimulation or
checkpoint pathways
- Patients with active autoimmune disease or history of autoimmune disease that might
recur, which may affect vital organ function or require immune suppressive treatment
including systemic corticosteroids, should be excluded. These include but are not
limited to patients with a history of immune related neurologic disease, multiple
sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia
gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE),
connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's,
ulcerative colitis, hepatitis; and patients with a history of toxic epidermal
necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be
excluded because of the risk of recurrence or exacerbation of disease. Patients with
vitiligo, endocrine deficiencies including thyroiditis managed with replacement
hormones including physiologic corticosteroids are eligible. Patients with rheumatoid
arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with
topical medication and patients with positive serology, such as antinuclear antibodies
(ANA), anti-thyroid antibodies should be evaluated for the presence of target organ
involvement and potential need for systemic treatment but should otherwise be eligible
- Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,
residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger (precipitating event)
- Patients should be excluded if they have a condition requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 7 days of study drug administration. Inhaled or
topical steroids, steroids for physiologic or adrenal replacement doses =< 10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune disease.
Patients are permitted to use topical, ocular, intra-articular, intranasal, and
inhalational corticosteroids (with minimal systemic absorption). A brief course of
corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of
non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by
contact allergen) is permitted
- History of tuberculosis treatment within the 2 years prior to enrollment
- Ongoing treatment with other immunosuppressive agent including, but not limited to,
methotrexate, azathioprine, anti-tumor necrosis factor (TNF) agents, etc. with the
exception of steroids
- Administration of a live or live attenuated vaccine within 6 weeks of initiation of
study therapy
- Ongoing treatment with systemic steroids at dose equivalent to greater than prednisone
10 mg daily or other immunosuppressive medication within 7 days of initiation of study
therapy
- Inhaled steroids will be permitted
- Topical steroids for cutaneous manifestations of MF/SS will be permitted below:
- Continued use of select concomitant topical steroids is permitted if the
patient has remained clinically stable for at least 4 weeks.
- Patients who are on low or moderate potency topical corticosteroids may
participate if they are on a stable dose for at least 4 weeks before
enrollment. Local injections of corticosteroids are acceptable; all
corticosteroids will be reported as concomitant medications.
- Patients prescribed prednisone 10 mg PO daily or less (or equivalent) will not be
excluded
- Concomitant use of another systemic therapy for MF/SS. Patients must have the
following minimum wash-out from previous treatments:
- At least 8 weeks for low-dose (12 Gy or less) total skin electron beam therapy
(TSEBT)
- At least 4 weeks for systemic cytotoxic anticancer agents or for tumor-targeting
monoclonal antibodies (mAbs), with the exception of alemtuzumab, for which the
washout is at least 16 weeks
- At least 2 weeks or 5 half-lives for systemic retinoids, interferons, vorinostat,
romidepsin, and denileukin diftitox, or anticancer investigational agents that
are not defined as immunotherapy
- At least 2 weeks for local radiation therapy
- At least 1 week for topical retinoids, nitrogen mustard, or imiquimod
- Concomitant malignancy requiring active systemic therapy, excluding adjuvant endocrine
therapy with the following exceptions:
- Patients with non-melanoma skin cancer or carcinoma in situ of the cervix will
not be excluded
- Adjuvant or maintenance therapy to reduce the risk of recurrence of another
malignancy (excluding cutaneous T-cell lymphoma) is permissible after discussion
with the Washington University principal investigator
- Subjects with previous malignancies are eligible if disease-free for > 2 years
- History of solid organ transplantation or allogeneic bone marrow transplantation
- Uncontrolled infection requiring systemic antimicrobials: Patients on antibacterial,
antifungal, and antiviral prophylaxis will not be excluded if all other exclusion /
inclusion criteria are met
- Patients with active cytomegalovirus (CMV) (positive serology for anti-CMV IgM
antibody and negative for anti-CMV IgG antibody or positive CMV PCR with clinical
manifestations consistent with active CMV infection) and requiring therapy will be
excluded from participation in the study. Carriers will be monitored per institutional
guidelines
- Patients should be excluded if they have known active hepatitis B (e.g. hepatitis B
virus [HBV] surface antigen [HBsAg] reactive) or hepatitis C (e.g. hepatitis C virus
[HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Patients with chronic HBV or HCV are defined as patients with positive hepatitis
B serology: Patients with a negative HBsAg and a positive hepatitis B core
antibody (HBcAb) require an undetectable/negative hepatitis B deoxyribonucleic
acid (DNA) test (e.g. polymerase chain reaction [PCR] test) to be enrolled, and
will require prophylactic antiviral treatment initiated prior to the first dose
of study drug, and continued until approximately 6 to 12 months after completion
of study drug(s)
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1), with the exception of alopecia and
neuropathy
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to duvelisib or nivolumab
- Patients receiving any medications or substances that are strong inhibitors or
inducers of CYP3A4 are ineligible to start study therapy. Patients who are on strong
inhibitors or inducers of CYP3A4 may start study therapy if discontinued 5 half lives
before start of study therapy. Because the lists of these agents are constantly
changing, it is important to regularly consult a frequently-updated medical reference.
As part of the enrollment/informed consent procedures, the patient will be counseled
on the risk of interactions with other agents, and what to do if new medications need
to be prescribed or if the patient is considering a new over-the-counter medicine or
herbal product
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
or active infection, interstitial lung disease or active, non-infectious pneumonitis,
congestive heart failure New York Heart Association (NYHA) grade >= 3, unstable angina
pectoris, and cardiac arrhythmia
- Patients with psychiatric illness/social situations that would limit compliance with
study requirements
- Baseline QT interval corrected with Fridericia's method (QTcF) > 500 ms
- Note: Criteria does not apply to subjects with a right or left bundle branch
block
- Pregnant women are excluded from this study because nivolumab has the potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
nivolumab, breastfeeding should be discontinued if the mother is treated with
nivolumab. These potential risks may also apply to other agents used in this study
- Patients who have had evidence of active or acute diverticulitis, intra-abdominal
abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are
known risk factors for bowel perforation should be evaluated for the potential need
for additional treatment before coming on study
Eligibility last updated 8/8/22. Questions regarding updates should be directed to the study team contact.
Periarticular Bupivacaine + Meloxicam ER Solution Versus Standard Practice During Total Knee Arthroplasty: A single institution, single-blinded, randomized clinical trial
Periarticular Bupivacaine + Meloxicam ER Solution Versus Standard Practice During Total Knee Arthroplasty
- ASA classification I to III, older than or equal to 18 years old.
- All genders.
- Presenting for primary total knee replacement for degenerative joint disease.
- Patient capable of providing their own informed consent.
- Vulnerable study populations including prisoners.
- Patients with a contralateral total knee arthroplasty < 2 years prior to the index procedure.
- Compromised health barring them from proceeding with surgery including acute or chronic kidney injury identified pre-operative.
- Patients unable to provide their own informed consent.
- Pregnancy.
- Patients with documented chronic pain syndromes.
- Patients with a history of prolonged daily opioids (more than 1 month) with an oral morphine equivalent of greater than 5mg/day.
- BMI > 45 kg/m^2.
- Allergies to any component of the study medications, including specific history of type 1 hypersensitivities to any NSAID.
- Patients with impaired cognitive function.
- Major systemic illnesses such as severe renal (estimated glomerular filtration rate less than 50ml/min), coronary artery disease requiring a bypass graft (CABG), other cardiac problems including congestive heart failure (CHF New York Heart Association class III to IV), or severe hepatic disorders defined as current or past diagnosis of acute/subacute liver necrosis, acute hepatic failure, chronic liver disease, liver abscess, hepatic coma, hepatorenal syndrome and other disorders of the liver.
Eligibility last updated 10/12/21. Questions regarding updates should be directed to the study team contact.
2020-0641, Pembrolizumab in Combination with Dabrafenib and Trametinib as a Neoadjuvant Strategy Prior to Surgery in BRAF-mutated Anaplastic Thyroid Cancer
Pembrolizumab, Dabrafenib, and Trametinib Before Surgery for the Treatment of BRAF-Mutated Anaplastic Thyroid Cancer
- Pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma. Diagnosis may include consistent with or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present.
- Must have a BRAFV600E mutation-positive tumor, as determined by BRAF V600E immunohistochemistry on tumor tissue, genetic/molecular testing of tumor, or cell free (cf)NDA liquid biopsy.
- Have measurable disease based on RECIST 1.1.
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Total bilirubin ≤ 3 x ULN for patients with Gilbert's syndrome.
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN, (5 x ULN for patients with concurrent liver metastases).
- Serum creatinine ≤ within 1.5 x ULN.
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L.
- Platelets ≥ 100 x 10^9/L.
- Hemoglobin ≥ 9.0 g/dL or 5.6 mmol/L.
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulant.
- Subjects must be willing to undergo tumor biopsy prior to and after the run-in with dabrafenib/trametinib (DT), unless in the opinion of the treating physician, a biopsy is not feasible or safe. Subjects must be willing to ultimately undergo surgery if their tumor becomes surgically resectable. Research subjects retain the right to refuse any research interventions.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- A male participant must agree to use a contraception of this protocol during the treatment period and for at least 8 months after the last dose of study treatment and refrain from donating sperm during this period.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP); OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after the last dose of study treatment.
- Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) class II.
- Untreated brain metastases.
- Prior chemotherapy within < 1 week prior to study day 1 or patients who have not recovered (i.e., ≤ grade 2) from adverse events due to a previously administered agent, except for patients who have been on dabrafenib/trametinib (DT) according to the standard run-in outlined in the trial schema.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- History of human immunodeficiency virus (HIV) or active hepatitis B (chronic or acute) or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. However, patients with past or resolved hepatitis B virus (HBV) should be monitored for reactivation by a specialist. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
- Note: no testing for HIV, hepatitis B and hepatitis C is required unless mandated by local heath authority.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Females who are breastfeeding or pregnant at screening or baseline (as documented by a positive beta-human chorionic gonadotropin [beta-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG [or hCG]). A women of childbirth potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to the first infusion will be excluded. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- More than 30 days of DT therapy prior to enrollment.
- A known history of retinal vein occlusion (RVO), central serous retinopathy (CSR), uncontrolled glaucoma or ocular hypertension.
Eligibility last updated 9/27/21. Questions regarding updates should be directed to the study team contact.
TBCRC056: A Phase II Study of Niraparib With Dostarlimab Therapy as Neoadjuvant Treatment for Patients With BRCA-mutated Breast Cancer
Niraparib + TSR042 In BRCA Mutated Breast Cancer
- Participants must meet the following criteria on screening examination to be eligible
to participate in the study. Laboratory assessments for eligibility must be completed
within 14 days prior to the date of registration. Diagnostic imaging, such as MRIs and
CT scans, must be performed within 28 days of the planned treatment start.
- Participants must have histologically or cytologically confirmed invasive breast
cancer Stage I to III with primary tumor size at least 1.5 cm defined by physical exam
or imaging (whichever is larger). In the case of a multifocal, multicentric, or
bilateral disease, the largest lesion must be ≥ 1.5 cm and designated as the "index"
lesion for tumor evaluations. Patients with inflammatory breast carcinoma are not
eligible.
- Participants must have documentation of estrogen receptor (ER) and progesterone
receptor (PR) testing by IHC according to local institutional guidelines in a
CLIA-approved setting. Central confirmation of ER/PR status is not required. All
tumors must be HER2 negative.
- Arms A and B: Target lesion must be ER and PR negative (<10% staining) by local
review.
- Arm C: Target lesion must be ER and/or PR positive (>10% staining) by local
review.
- Participants must have documented HER2-negative invasive tumor according to local
institutional guidelines in a CLIA-approved setting. Central confirmation of HER2
status is not required. HER2 negative is defined as:
- 0 or 1+ by IHC, OR
- Lack of gene amplification with HER2/CEP17 ratio < 2 by ISH, OR
- Copy number < 6 by ISH
- Participants must have documented germline mutation in BRCA1, BRCA2 or PALB2 that is
deleterious or suspected to be deleterious (known or predicted to be detrimental/lead
to loss of function). Mutation must be identified through a CLIA-approved laboratory.
Final determination of eligibility for any discordant results in pathogenicity will be
made by the sponsor-investigator. A formal eligibility exception will not be required
in these cases as long as approval by overall study PI is granted and documented.
- Participants with multifocal, multicentric or bilateral disease are eligible if at
least one lesion meets criteria for the study. In this circumstance, the investigator
must determine which will represent the target lesion to be assessed for response.
This should remain consistent throughout the study. The target lesion should be
selected on the basis of its size (lesion with the longest diameter) and suitability
for accurate repetitive measurements.
- Participants with an eligible target lesion, and another small HER2+ tumor (for
example, < 6 mm), may be eligible for enrollment following discussion and agreement
with the overall principal investigator. A formal eligibility exception will not be
required in these cases as long as approval by the sponsor-investigator is granted and
documented.
- Female or male ≥ 18 years of age
- Breast imaging should include imaging of the ipsilateral axilla. For subjects with a
clinically positive axilla by physical examination or imaging, axillary tissue
acquisition is not required. For patients with a clinically negative axilla by
examination and imaging, tissue acquisition is not required. For equivocal imaging
findings, tissue acquisition (a needle aspiration, core biopsy) is required. Sentinel
Lymph Node (SLN) biopsy before neoadjuvant therapy is not allowed.
- ECOG performance status of 0 or 1
- Adequate organ and bone marrow function as defined below:
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/dl
- Total serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), (≤2.0 in
patients with documented Gilbert's Syndrome)
- AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN
- Serum or plasma creatinine ≤ 1.5 × institutional ULN, OR calculated creatinine
clearance > 50 mL/min using the Cockcroft-Gault equation
- International normalized ratio (INR) OR prothrombin time (PT) ≤1.5× ULN.
Participants who are receiving anticoagulant therapy are eligible as long as PT
or partial thromboplastin (PTT) is within therapeutic range of intended use of
anticoagulants. Activated partial thromboplastin time (aPTT) must be ≤1.5× ULN
unless patient is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
- Premenopausal women must have a negative urine or serum pregnancy test within 7 days
of treatment start. Women are considered non-childbearing (by other than medical
reasons) if they:
- are ≥45 years of age and without menses for >1 year
- have been amenorrhoeic for <2 years without history of a hysterectomy and
oophorectomy with a follicle stimulating hormone value in the postmenopausal
range upon screening evaluation
- are post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.
Documented hysterectomy or oophorectomy must be confirmed with medical records of
the actual procedure or confirmed by an ultrasound. Tubal ligation must be
confirmed with medical records of the actual procedure, otherwise the patient
must be willing to use an adequate barrier method throughout the study, starting
with the screening visit through 180 days after the last dose of study treatment.
See list of acceptable birth control methods. Information must be captured
appropriately within the site's source documents. Note: Abstinence is acceptable
if this is the established and preferred contraception for the patient.
- Male and female participants of childbearing potential must agree to adhere to
adequate contraception as defined in the protocol for the duration of study
participation and for 150 days after the last dose of study treatment.
- Female participants must agree to not breastfeed during the study or for 150 days
after the last dose of study treatment.
- Participants must agree to not donate blood during the study or for 90 days after the
last dose of study treatment.
- Ability to understand and willingness to sign an informed consent document.
- Ability to swallow and retain oral medication.
- Patients undergoing breast conserving therapy (ie lumpectomy) should not have any
contraindications to radiation therapy.
- Participants must be willing to undergo the mandatory research biopsy at baseline and
after 3 weeks on study treatment. Participants who undergo an attempted research
biopsy procedure for the purpose of this protocol and in whom inadequate tissue is
obtained are not required to undergo a repeat biopsy in order to continue on the
protocol.
- Stage IV breast cancer.
- Concurrent therapy with any other investigational product
- Prior treatment for the current breast cancer, including prior chemotherapy, immune
therapy, hormonal therapy, radiation, or investigational therapy for this diagnosis.
- Excisional biopsy of the primary tumor and/or excision of axillary lymph nodes,
including SLNB, prior to study treatment.
- Participants with a history of malignancy are ineligible except in the following
circumstances:
- Individuals with a history of invasive breast cancer are not eligible unless they
have been disease-free for a minimum of three years.
- Individuals with a malignancy history other than invasive breast cancer are
eligible if they have no active malignancy and are deemed by the investigator to
be at low risk for recurrence of that malignancy.
- Individuals with the following cancer history are eligible: adequately treated
nonmelanoma skin cancers, curatively treated in situ cancer of the cervix, ductal
carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma.
- Other exceptions may exist following agreement with the sponsor-investigator
- Patients with a diagnosis of immunodeficiency, or currently receiving systemic steroid
therapy or any other form of immunosuppressive within 7 days prior to the first dose
of study treatment. Use of local corticosteroid injections (e.g. intraarticular
injections), inhaled, intranasal, ophthalmic, and topical corticosteroids, and
subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g.
CT scan pre-medication) are allowed.
- Patients with autoimmune disease that has required systemic treatment within the past
2 years (i.e. with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.
- Patients with a history of interstitial lung disease or pneumonitis.
- Patients who have received a live vaccine within 2 weeks prior to the start of study
treatment.
- Patients who have undergone any major surgery within 3 weeks prior to study entry:
patients must have recovered to baseline from any effects of any major surgery.
- Patients with concurrent HIV infection are eligible provided they meet the following
criteria:
- CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
- No history of AIDS-defining opportunistic infection within 12 months prior to
enrollment
- Any medication used in an antiretroviral therapy (ART) regimen must have no known
interaction with the study agents
- Patients with active or chronic Hepatitis B or C are eligible provided they meet the
liver function laboratory criteria described in 3.1.10 and cannot be on any medication
with a known interaction with the study agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure
disorder, unstable spinal cord compression, superior vena cava syndrome or psychiatric
illness/social situations that would limit compliance with study requirements.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to niraparib, dostarlimab, or their excipients.
- Transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol
therapy.
- Known history of myelodysplastic syndrome (MDS) or or acute myeloid leukemia (AML).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 5/16/23. Questions regarding updates should be directed to the study team contact.
A Phase 1b/2 Study of the PARP Inhibitor Niraparib in Combination With Trastuzumab in Patients With Metastatic HER2+ Breast Cancer
Niraparib in Combination With Trastuzumab in Metastatic HER2+ Breast Cancer
- Women age ≥ 18 years.
- Eastern Cooperative Oncology Group performance status 0-2 (Karnofsky >60%).
- Patients with metastatic breast cancer.
- HER2 (human epidermal growth factor receptor 2)-positive breast cancer prospectively determined on the primary tumor by a local pathology laboratory and defined as:
- Immunohistochemistry (IHC) score of 3+ and/or positive by ISH (defined by In Situ Hybridization ratio of ≥ 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies). Both IHC and ISH assays will be performed; however, only one positive result is required for eligibility.
- Estrogen/progesterone receptor positive OR negative disease allowed.
- Patients must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Patients that have failed at least one anti-HER2 therapy in the metastatic setting.
- Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count ≥ 1,500/mL;
- platelets ≥ 100,000/mL;
- total bilirubin ≤ institutional upper limit of normal (ULN);
- aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 5 ≤ X institutional ULN;
- creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
- Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram (preferred) or multigated acquisition (MUGA) scans.
- Willing and able to comply with the requirements of the protocol.
- Patient is able to take oral medication.
- Signed informed consent.
- Female patients of childbearing potential must be willing to use one highly effective form of hormonal contraception or two effective forms of nonhormonal contraception.
- Contraception must continue for the duration of study treatment and for 7 months after the last dose of study treatment. The above contraception is not a requirement in the case of any of the following:
- The patient, or partner of the patient, is surgically sterilized;
- The female patient is > 45 years of age and is postmenopausal (has not menstruated for at least 12 consecutive months;
- The patient truly abstains from sexual activity and when this is the preferred option to avoid conception and contraception and/or usual lifestyle of the patient.
- Metastatic breast cancer patients who are HER2 positive and have NOT progressed on at least one prior HER2-targeted therapies for metastatic disease -Patients who have not recovered from CTCAE, v. 4.03 grade 2 or higher toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment. Subjects receiving weekly therapy must have a washout period from prior chemotherapy of as least one week. Washout period for chemotherapy administered every 2, 3, or 4 weeks will be 2, 3, and 4 weeks respectively, provided subject has recovered from toxicities of prior therapy such that retreatment is appropriate.
- Patients must be at least two weeks from prior RT.
- Patients must have a one-week washout period from prior hormonal therapy (e.g., testosterone, estrogen, progestin, gonadotropin-releasing hormone antagonist).
- Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability. No concurrent anti-cancer treatment of any type.
- Patients with known germline BRCA 1 or BRCA 2 mutations.
- Patient has undergone prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor.
- Prior treatment of a total doxorubicin > 360 mg/m^2 (or equivalent).
- Patient has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected).
- Patient has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). -Chronic immunosuppressive therapies including systemic corticosteroids or concurrent short-term use of immunosuppressive therapies is not allowed. Short- term corticosteroid use must be discontinued at least 2 weeks prior to study treatment.
- Patients with known grade 2 or greater allergic reactions attributed to compounds of similar chemical or biological composition to niraparib are ineligible for study enrollment.
- Patients with known grade 2 or greater allergic reactions attributed to compounds of similar chemical or biological composition to herceptin are ineligible for study enrollment.
- Patient is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 7 months after the last dose of study treatment. -History of non-breast malignancies within the 5 years prior to study entry, except for the following:
- Carcinoma in situ (CIS) of the cervix;
- CIS of the colon;
- Melanoma in situ;
- Basal cell and squamous cell carcinomas of the skin.
- Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection that requires systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
- Cardiopulmonary dysfunction as defined by any of the following prior to randomization:
- History of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.0) Grade ≥3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class ≥ II;
- Angina pectoris requiring anti-angina medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease -High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third degree AV-block]);
- Significant symptoms (Grade ≥ 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia;
- Myocardial infarction within 12 months prior to randomization.
- Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg).
- Evidence of transmural infarction on ECG.
- Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening.
- Requirement for oxygen therapy.
Eligibility last updated 9/28/21. Questions regarding updates should be directed to the study team contact.
Voice Signal Analysis to Screen for Depression and Anxiety in Patients with Persistent Post-COVID symptoms (Voila)
Voice Signal PASC Study
- Aged 18 years of age or older.
- Patients who have had a recent episode of COVID-19 and who present to the Post COVID-19 Clinic at Mayo Clinic Rochester.
- Access to smartphone (iOS or Android operating systems).
- Ability to complete study questionnaires and provide voice samples using a smartphone application.
- Known history of voice disorder either primary or secondary to neuromuscular or other pathology.
- Cognitively impaired patients.
- Prisoners.
- Non-English speakers.
- Currently on another study assessing depression or quality of life.
Eligibility last updated 2/22/23. Questions regarding updates should be directed to the study team contact.
ARST2031, A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide (VINO-AC) Plus Maintenance Chemotherapy With Vinorelbine and Oral Cyclophosphamide (VINO-CPO) vs Vincristine, Dactinomycin and Cyclophosphamide (VAC) Plus VINO-CPO Maintenance in Patients With High Risk Rhabdomyosarcoma (HR-RMS) (ARST2031)
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
- Patients must be ≤ 50 years of age at the time of enrollment.
- Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification are eligible to enroll on the study based upon Stage, Group, and age, as below. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) Classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants.
- ERMS -Stage 4, group IV, ≥ 10 years of age.
- ARMS -Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age.
- Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study.
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) 7 ≥ 0 mL/min/1.73 m^2; or
- A serum creatinine based on age/gender as follows:
- Age | Maximum serum creatinine (mg/dL)
- 1 month to < 6 months | 0.4 mg/dL (male); 0.4 mg/dL (female);
- 6 months to < 1 year 0.5 mg/dL (male) | 0.5 mg/dL (female);
- 1 to < 2 years 0.6 mg/dL (male) | 0.6 mg/dL (female);
- 2 to < 6 years 0.8 mg/dL (male) | 0.8 mg/dL (female);
- 6 to < 10 years 1 mg/dL (male) | 1 mg/dL (female);
- 10 to < 13 years; 1.2 mg/dL (male) | 1.2 mg/dL (female);
- 13 to < 16 years; 1.5 mg/dL (male) | 1.4 mg/dL (female);
- ≥ 16 years; 1.7 mg/dL (male) | 1.4 mg/dL (female).
- The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR39 utilizing child length and stature data published by the CDC.
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
- If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age.
- All patients and/or their parents or legal guardians must sign a written informed consent.
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
- Patients with evidence of uncontrolled infection are not eligible.
- RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed.
- Patients with central nervous system involvement of RMS as defined below:
- Malignant cells detected in cerebrospinal fluid;
- Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed);
- Diffuse leptomeningeal disease;
- Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment;
- Note: the following exception:
- Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation.
- Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy.
- Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment.
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
Eligibility last updated 9/29/21. Questions regarding updates should be directed to the study team contact.
A051902: A Randomized Phase II Study of CHO(E)P vs CC-486-CHO(E)P vs Duvelisib-CHO(E)P in Previously Untreated CD30 Negative Peripheral T-Cell Lymphomas
Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma
- Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10% CD30 expression by immunohistochemistry in the following subtypes (by local review): nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma.
- Patients will be stratified by presence or absence of TFH phenotype (i.e., diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of pathology. Determination of TFH phenotype can be defined by expression of two or more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by immunohistochemistry.
- Measurable disease as defined by the Lugano criteria.
- No prior systemic therapy for lymphoma (excluding corticosteroids).
- Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to registration is required.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Platelet count ≥ 75,000/mm^3 (≥ 50,000/mm^3 if secondary to bone marrow involvement from lymphoma per investigator assessment; the first 12 patients on each arm of the study must have platelets ≥ 75,000/mm^3 regardless of bone marrow involvement).
- Absolute neutrophil count (ANC) ≥ 1,000/mm^3.
- Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN) * Except in subjects with documented liver involvement by lymphoma.
- Calculated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula.
- Total bilirubin ≤ 2.0 x ULN * Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement by lymphoma.
- Archival tissue must be available for submission.
- No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Those who are seropositive (e.g., hepatitis B core antibody [Ab] positive) are permitted if they are negative by polymerase chain reaction (PCR). Those who are seropositive for hepatitis B and are negative for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed antiviral therapy. Those who have hepatitis C Ab positivity who have completed curative therapy for hepatitis C with negative hepatitis C PCR are eligible.
- Patients with history of HIV are eligible if they have an undetectable viral load for at least 6 months.
- No active uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment).
- Patients with Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted.
- Patients must have documented left ventricular ejection fraction of ≥ 45%.
- No significant active cardiac disease within the previous 6 months including:
- New York Heart Association (NYHA) class III or IV congestive heart failure;
- Unstable angina or angina requiring surgical or medical intervention; and/or
- Myocardial infarction.
- Patients with expression of CD30 in ≥ 10% of the tumor (based on local immunohistochemistry review) regardless of histology will not be permitted.
- Patients with a diagnosis of other PTCL subtype histologies other than those specified in the inclusion criteria are excluded including large cell transformation of mycosis fungoides.
- Patients known to have HTLV 1/2.
- Patients with known central nervous system involvement.
- No concurrent malignancy requiring active therapy within the last 3 years with the exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer. Adjuvant hormonal therapy for cancer previously treated for curative intent is permitted.
- No contraindication to any drug in the chemotherapy regimen, including neuropathy ≥ grade 2.
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
Eligibility last updated 9/30/21. Questions regarding updates should be directed to the study team contact.
Analysis of Patients with Polyuria as a Manifestation of Paroxysmal Atrial Tachyarrhythmias (ATACHPOLY)
Analysis of Fast Atrial Rhythm Manifesting with Increased Urination
- Age 18 or older.
- Patients with paroxysmal atrial tachyarrhythmias with and without polyuria as a manifestation of their tachyarrhythmia episode.
- Documentation of their paroxysmal atrial tachyarrhythmia episode.
- Patients who are unable to manage the logistics of participating in the study (coming to Saint Mary’s Hospital ot have their blood drawn and urine sample collected during their atrial tachyarrhythmia episode).
- Chronic kidney disease stage 4 or higher.
- Clinical history of heart failure.
Eligibility last updated 10/1/21. Questions regarding updates should be directed to the study team contact.
A Phase 1/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies
Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies
Key
- Confirmed diagnosis of one of the following:
NHL Cohorts:
1. MZL i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after,
or was refractory to, at least one prior therapy ii. Active disease requiring
treatment
2. FL i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of
hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was
refractory to, at least 1 prior systemic therapy
3. DLBCL i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed
after, or was refractory to, at least two prior systemic therapies and has either
progressed following or is not a candidate for autologous stem cell transplant (due to
comorbidities or non-responsiveness to salvage chemotherapy)
4. Transformed indolent B-cell NHL i. Any lymphoma otherwise eligible for Part 1 that has
transformed into a more aggressive lymphoma. Patients with transformation from CLL or
SLL (Richter's transformation) are not eligible for Part 1
CLL/SLL Cohorts:
5. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic
Leukemia (IWCLL) criteria i. Disease characterized as Treatment Naive (TN) or R/R
disease defined as disease that relapsed after, or was refractory to, at least 1 prior
therapy ii. Requiring treatment as defined by history
MCL cohorts:
6. WHO-defined MCL I. R/R MCL defined as disease that relapsed after, or was refractory
to, at least 1 prior systemic therapy; ii. Requiring treatment in the opinion of the
investigatorr
WM cohorts:
g. WHO-defined WM (clinical and definitive histologic diagnosis) i. R/R disease defined as
disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. Meeting at
least 1 criterion for treatment according to consensus panel criteria from the Seventh
International Workshop on Waldenström's Macroglobulinemia (Dimopoulos et al 2014)
- Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI),
defined as:
1. CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2
perpendicular dimensions or clonal lymphocytes measured by flow cytometry
2. DLBCL, FL, MZL, SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1
extranodal lesion > 1.0 cm in the longest diameter, measurable in at least 2
perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable
for this study
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Adequate organ function
- Adequate pancreatic function indicated by:
1. Serum amylase ≤ 1.5 x upper limit of normal (ULN)
2. Serum lipase ≤ 1.5 x ULN
Key
- Known central nervous system involvement by lymphoma/leukemia
- Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected
Richter's syndrome
- Prior therapy ≥ 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 5/18/23. Questions regarding updates should be directed to the study team contact.
Veri-T: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of Oral Verdiperstat (BHV-3241) in Patients With Semantic Variant Primary Progressive Aphasia (svPPA) Due to Frontotemporal Lobar Degeneration With TDP-43 Pathology (FTLD-TDP) (Veri-T)
Veri-T: A Trial of Verdiperstat in Patients With svPPA Due to TDP-43 Pathology (Veri-T-001)
- Between 18 and 85 years of age (inclusive) at the initial screening visit.
- Meets 2011 consensus criteria for svPPA (Gorno-Tempini et al. 2011).
- MRI at screening is consistent with the underlying svPPA with no large strokes or severe white matter disease (Fazekas Grade ≤ 2; Fazekas et al. 1987);
- CDR® plus NACC FTLD (Miyagawa et al. 2020) global score at screening ≤1.
- The following medications are allowed, but must be stable for 2 months prior to the initial screening visit:
- Food and Drug Administration (FDA)-approved Alzheimer's disease (AD) medications;
- FDA-approved psychotropic medications;
- Other medications (except those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to the initial screening visit.
- Has a reliable study partner who agrees to accompany the participant to visits, and spends at least 5 hours per week with the participant.
- Agrees to 2 LPs.
- Signed and dated written informed consent obtained from the participant and the participant's study partner in accordance with local Institutional Review Board (IRB) regulations.
- WOCBP must agree to abstain from sex or use highly effective birth control that includes two methods of contraception (one of which must be a barrier method) for the duration of the screening period, the RDBPC treatment period, and for 30 days after the last dose of study drug (active or placebo).
- Males must agree to abstain from sex with WOCBP or use an adequate method of contraception for the duration of the RDBPC treatment period and for 90 days after the last dose of study drug (active or placebo).
- Able to swallow pills whole without crushing or chewing.
- A clinical diagnosis of probable AD (McKhann et al. 2011) or previous biomarker evidence of AD biology using amyloid positron emission tomography (PET) imaging, CSF amyloid beta (A?)/total tau (t-tau) ratio, CSF/plasma amyloid beta isoform with 40 amino acid residues (Aβ40)/amyloid beta isoform with 42 amino acid residues (Aβ42) ratio, or plasma phosphorylated tau [phosphorylated tau at residue 181 (p-tau181) and phosphorylated tau at residue 217 (p-tau217)] assessments.
- A clinical diagnosis of a comorbid FTLD-associated clinical syndrome other than svPPA, including:
- logopenic primary progressive aphasia (lvPPA; Gorno-Tempini et al. 2011);
- non-fluent/agrammatic variant primary progressive aphasia (nfvPPA; Gorno-Tempini et al. 2011);
- behavioral variant for frontotemporal dementia (bvFTD; Rascovsky et al. 2011). Patients who meet diagnostic criteria for svPPA (Gorno-Tempini et al. 2011) may still be included if they have a secondary diagnosis of bvFTD, so long as the PI can reasonably attribute their disinhibition, dietary changes, compulsions, and/or loss of empathy to anterior temporal lobe atrophy (Seeley et al. 2005) and MRI is consistent with right anterior atrophy (or left temporal atrophy in participants with suspected right hemispheric language dominance);
- progressive supranuclear palsy (PSP; Höglinger et al. 2017); e. corticobasal syndrome (CBS; Armstrong et al. 2013).
- Any other medical condition other than FTLD that is likely to account for cognitive or behavioral deficits (e.g., uncontrolled seizure disorder, stroke, vascular dementia, substance abuse or alcoholism, Lewy body disease).
- History of uncontrolled thyroid disease or evidence thereof [i.e., abnormal free thyroxine (T4) levels and thyroid stimulating hormone (TSH) > 10 milli-international units (mIU)/liter (L) at screening (confirmed by repeat)].
- Serious autoimmune disease, or ongoing immunocompromised state.
- History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof at screening).
- History or presence of gastrointestinal (GI) or other disease known to interfere with absorption, distribution, metabolism, or excretion of drugs, or a history of surgery known to interfere with absorption or excretion of drugs (i.e., gastric bypass).
- Within 1 year prior to initial screening visit or between screening and baseline (pre-dose Day 1), any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of, unstable angina; or syncope.
- History of major psychiatric illness or untreated depression that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data.
- Neutrophil count <1,500/cubic millimeter (mm3), platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin (TBL) >1.5 x ULN, alanine aminotransferase (ALT) >1.5 x ULN, aspartate aminotransferase (AST) >1.5 x ULN, or international normalized ratio (INR) >1.2 at screening (confirmed by repeat).
- Evidence of any clinically significant findings on screening or baseline evaluations which, in the opinion of the PI would pose a safety risk or interfere with appropriate interpretation of study data.
- Corrected QT interval by Fridericia (QTcF) ≥ 470 milliseconds (msec) or uncontrolled arrhythmia or frequent premature ventricular contractions (PVCs; >5/minute) or Mobitz Type II second or third degree atrioventricular (AV) block or left bundle branch block or right bundle branch block with a QRS duration ≥ 150 msec or intraventricular conduction defect with a QRS duration ≥ 150 msec or evidence of acute or sub-acute myocardial infarction or ischemia or other ECG findings at screening or baseline that, in the PI's opinion, would preclude participation in the study.
- Pathologic renal findings at screening as defined by the presence of either of the following criteria:
- Estimated glomerular filtration rate (eGFR) [determined by the Modification of Diet in Renal Disease (MDRD) Study equation] < 30 milliliter (mL)/minute/1.73 square meter (m^2). The MDRD Study equation is as follows: eGFR (mL/minute/1.73 m^2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American), where Scr = serum creatinine in mg/deciliter (dL) as measured by a method calibrated to an isotope dilution mass spectrometry (IDMS) reference method;
- Serum creatinine ≥ 2.5 mg/dL;
- Hemoglobin A1C > 7.5% at screening (confirmed by repeat);
- Current or recent history (within four weeks prior to initial screening visit) of a clinically significant bacterial, fungal, or mycobacterial infection.
- Current clinically significant viral infection, including "known" positive status for human immunodeficiency virus (HIV) (i.e., based on prior testing; HIV testing will not be performed as part of the screening evaluations for this trial).
- Major surgery within four weeks prior to initial screening visit.
- Blood transfusion within 4 weeks of initial screening visit.
- History of stem cell treatment.
- Any contraindication for MRI or unable to tolerate MRI at screening.
- Any contraindication to or unable to tolerate LP at screening, including the use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to the initial screening visit.
- Participants who, in the opinion of the PI, are unable or unlikely to comply with the dosing schedule or study evaluations.
- Prior treatment with verdiperstat.
- Treatment with another investigational drug within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with investigational drugs other than verdiperstat while on study will not be allowed.
- Treatment with systemic corticosteroids or steroid sparing systemic immunosuppressive agents within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with systemic corticosteroids or other systemic immunosuppressive therapy while on study will not be allowed.
- Treatment with strong inhibitors of CYP1A2 (i.e., ciprofloxacin, enoxacin, fluvoxamine) within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with strong inhibitors of CYP1A2 while on study will not be allowed.
- Known hypersensitivity to the inactive ingredients in the study drug products (active or placebo).
- Known to be pregnant or lactating, or positive pregnancy test at screening or baseline (pre-dose Day 1).
- Cancer within 5 years of initial screening visit, except for basal cell carcinoma.
- History or evidence at screening of known disease-associated mutations associated with FTLD without trans-activation response deoxyribonucleic acid-binding protein of 43 kilodaltons (TDP-43) inclusions [e.g., mutations in the genes encoding chromatin-modifying protein/charged multivesicular body protein B2 (CHMPB2), microtubule-associated protein tau (MAPT), or fused in sarcoma (FUS)].
Eligibility last updated 3/7/23. Questions regarding updates should be directed to the study team contact.
Phase 2 Clinical Trial of FIsetin to Treat CArpal Tunnel Syndrome (FITCATS) (FITCATS)
A Study of FIsetin to Treat CArpal Tunnel Syndrome
- Males and females between age 21 and 80 years of age.
- Symptoms of numbness or tingling for at least 4 weeks in at least two digits on one hand that include thumb, index, long, or radial border of ring finger.
- Classic or probable carpal tunnel syndrome on Katz-Stirrat hand diagram.
- A clinical diagnosis of carpal tunnel syndrome. Patients with bilateral CTS will have the more severe hand enrolled.
- Able to complete English-language questionnaires and clinical evaluations.
- Willingness to avoid pregnancy:
-
- Female participants of childbearing potential must have a negative pregnancy test at screening (serum) and before the first dose on Day 1 (urine), before the third dose on Day 29 (urine), and 60 days after the final dose on day 60 (urine);
- Sexually active female participants of childbearing potential must agree to take appropriate precautions to avoid pregnancy from screening until 30 days after the last dose of study drug (day 60). Permitted methods in preventing pregnancy will be communicated to the participants and their compliance confirmed;
- All female participants of childbearing potential will refrain from donating oocytes from screening-day 60 of the study;
- Women without child bearing potential (i.e.., surgically sterile with hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible to participate without the above precautions.
- Willing and able to comply with study procedures and requirements and attend all study visits as defined in this protocol.
- Unable or unwilling to give informed consent.
- Pregnant or breast feeding.
- Previous carpal tunnel release on the study hand.
- History of steroid injection into carpal tunnel or surgery on the affected wrist within the past 6 months.
- Prisoners, institutionalized individuals, or others who may be considered vulnerable populations, such as individuals with dementia.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/17/23. Questions regarding updates should be directed to the study team contact.
The In4M Study: Integrating 4 Methods to Assess Physical Function in Cancer Patients
The In4M Study: Integrating 4 Measures to Assess Physical Function in Cancer Patients
- Age 18 and over;
- English- or Spanish speaking;
- Eligible cancer type and planned intravenous multi-agent chemotherapy regimen:
- Breast cancer patients
1. Patients with stage 1-3 breast cancer diagnosed within previous 9 months
2. Planned to receive multi-agent intravenous adjuvant and/or neoadjuvant
chemotherapy during their treatment course
3. Patients should be enrolled prior to receipt of cytotoxic chemotherapy for breast
cancer.
4. Patients with concurrent/prior/future immunotherapy/radiotherapy, targeted
therapy and endocrine therapy for breast cancer can be included
5. Eligible regimens include:
i) Taxotere-Cytoxan (TC) ii) Adriamycin-Cytoxan followed by Taxol +/- carboplatin
(AC-T +/- carbo) iii) Taxol +/- carbo followed by Adriamycin-Cytoxan (T +/- carbo-AC)
iv) Taxotere-Carboplatin-Herceptin (TCH) v) Taxotere-Carboplatin-Herceptin-Perjeta
(TCH-P) vi) AC-T-Herceptin (AC-TH) vii) AC-T-Herceptin-Perjeta (AC-THP) viii) Other
similar multi-agent frontline chemotherapy depending on the state of the field and
with approval from the study PI or co-investigators. Ado-trastuzumab (TDM1),
capecitabine and immunotherapy are allowed in addition to or following a multi-agent
regimen.
- Lymphoma patients a) Newly diagnosed high grade/aggressive lymphoma patients of any
stage, including: i) High grade/aggressive B cell lymphoma per the 2016 revision of
the World Health Organization (WHO) classification of lymphoid neoplasms62 (including
composite, discordant or transformed disease, if applicable).
ii) High grade/aggressive T cell lymphoma per the 2016 revision of the WHO classification
of lymphoid neoplasms (including composite, discordant or transformed disease, if
applicable).
iii) Hodgkin lymphoma (including composite, discordant or transformed disease, if
applicable).
iv) Planned to receive multi-agent chemotherapeutic regimens for a fixed period (4-6
months) on an outpatient basis.
v) Patients should be enrolled prior to receipt of cytotoxic chemotherapy for lymphoma.
vi) Patients with pre-existing low-grade lymphoma who transform to higher grade histology
are eligible if the transformation is newly diagnosed and the patient has not previously
received cytotoxic chemotherapy b) Eligible regimens include: i) Cyclophosphamide,
doxorubicin, vincristine and prednisone (CHOP) ii) Rituximab, cyclophosphamide,
doxorubicin, vincristine and prednisone (R-CHOP) iii) Brentuximab vedotin,
cyclophosphamide, doxorubicin, prednisone (BV-CHP) iv) Rituximab, etoposide, prednisone,
vincristine, cyclophosphamide, doxorubicin (Outpatient R-EPOCH) v) Doxorubicin, bleomycin,
vinblastine, dacarbazine (ABVD) vi) Brentuximab vedotin, doxorubicin, vinblastine,
dacarbazine (BV+AVD) vii) Cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone
(CHOEP) viii) Cyclophosphamide, etoposide, vincristine, prednisone (CEOP) ix) Rituximab
with cytarabine alternating with rituximab with maxi-CHOP (Nordic regimen) x) Other similar
multi-agent frontline chemotherapy depending on the state of the field and with approval
from the study PI or co-investigators. Patient planned to receive radiation, maintenance
chemotherapy or consolidation stem cell transplant may also be included.
- If patients are receiving the above standard therapies as part of a frontline clinical
trial which may include a novel agent or combination, they are also eligible for the
present study if the therapeutic protocol permits enrollment in both studies;
- Receiving chemotherapy on a primarily outpatient basis;
- Willing and able to give consent and participate in study;
- Able to access a mobile device (smartphone or tablet) or computer with web access
every day to complete study surveys; able to connect Fitbit to a device that can
regularly link to Hugo for data transfer;
- Willing and able to perform an in-clinic 6-minute walk test (gait aides are permitted
if regularly used by the patient)
- Willing to use the health data sharing platform. Potential subjects who do not meet
all of the enrollment criteria will not be enrolled. Any deviations from these
criteria must be reported in accordance with Institutional Review Board (IRB) Policies
and Procedures.
- Lack of access to a mobile device (smartphone or tablet) or computer with web access
- Unable or unwilling to connect Fitbit to device
- Unable or unwilling to use the health data sharing platform
- Unable to give consent and be enrolled in person
- Prior receipt of cytotoxic chemotherapy within 12 months of study start date
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 8/16/22. Questions regarding updates should be directed to the study team contact
A Phase II/III Randomized, Placebo controlled, Double-blind Study to Evaluate the Effects of up to 24 Weeks of Low Dose Pazopanib on Hereditary Hemorrhagic Telangiectasia Related Epistaxis and Anemia
Effects of Pazopanib on Hereditary Hemorrhagic Telangiectasia Related Epistaxis and Anemia (Paz)
- A definite diagnosis of hereditary hemorrhagic telangiectasia is defined as having at least 3 of the following criteria:
- Spontaneous and recurrent epistaxis;
- Multiple telangiectasias at characteristic sites: lips, oral cavity, fingers, nose;
- Visceral lesions: GI telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs.
- A first degree relative with hereditary hemorrhagic telangiectasia according to these criteria OR a definite diagnosis of hereditary hemorrhagic telangiectasia is defined as having a gene sequencing diagnosis of hereditary hemorrhagic telangiectasia:
- Epistaxis due to hereditary hemorrhagic telangiectasia at least 2 x per week, for a cumulative duration of at least 25 minutes per week;
- Epistaxis is clinically stable during the 12 weeks prior to screening in the clinical judgment of the investigator (i.e., no major changes in frequency or duration of epistaxis);
- Participant agrees not to undergo cautery of nasal telangiectasias or take any experimental therapies for hereditary hemorrhagic telangiectasia other than the study drug while participating in the study.
- Male or female [non-child bearing potential].
- Participant has known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib that in the opinion of the investigator contradicts their participation.
- Currently has untreated cerebral arterio-venous malformations (AVMs), cerebral arteriovenous fistulae, or cerebral cavernous malformations (CCMs) (Note: MRI scan does not need to be repeated at screening if AVMs, arterio-venous fistulas and CCMs were absent on a scan at age ≥ 18 years).
- Currently has perfused pulmonary AVMs with feeding artery diameter > 3mm.
- Known significant bleeding sources other than nasal or gastrointestinal.
- Systemic use of a vascular endothelial growth factor inhibitor in the past 3 months or previous enrollment in this study.
- Active and recent onset of clinically significant diarrhea.
- Current or recent (in the last 5 years) malignancies (except non-melanoma skin cancers).
- Participant has had major surgery (e.g., surgical ligation of an AVM) or trauma within 28 days or had minor surgical procedures (e.g., central venous access line removal) within 7 days prior to dosing, the latter representing a recent wound, fracture or ulcer.
- Participant has a planned surgery during the period to include active treatment and 6 weeks of follow up.
- Participant has clinically significant gastrointestinal abnormalities (other than hereditary hemorrhagic telangiectasia related vascular lesions).
- Participant during the 6 months prior to first dose of study drug has a history of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, untreated deep vein thrombosis (DVT), myocardial infarction, or any other thrombotic event.
- QT corrected interval ≥ 450 msec, based on averaged QT corrected interval values of triplicate ECGs obtained over a brief recording period.
- Hemoglobin < 6 g/dL.
- Platelets < 100 x 10^9/L.
- International normalized ratio (INR) >1.2 x upper limit of normal and activated partial thromboplastin time (aPTT) > 1.2 x upper limit of normal.
- Alanine Transaminase > 2 x upper limit of normal.
- Bilirubin > 1.5 x upper limit of normal (isolated bilirubin > 1.5 x upper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
- Participant has poorly controlled hypertension [defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg.
- Substantive renal disease (eGFR < 30 mL/min/1.73m^2 calculated using the Cockcroft-Gault formula).
- Echo derived left ventricular ejection fraction < 30%.
- Thyroid stimulating hormone > upper limit of normal.
- Urine protein to creatinine ratio > 0.3.
- Neutrophil count < 1500/mm^3.
Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.
A Phase 3, Multicenter, Prospective, Randomized, Double-blind, Efficacy and Safety Study of Rezafungin for Injection Versus the Standard Antimicrobial Regimen for the Prevention of Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation (The ReSPECT Study) (ReSPECT)
Study of Rezafungin Compared to Standard Antimicrobial Regimen for Prevention of Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation (ReSPECT)
- Willing and able to provide written informed consent.
- Males or females, ≥ 18 years of age.
- Receiving a human leukocyte antigen (HLA) matched allogeneic peripheral BMT from a family or unrelated donor, HLA-mismatched related or unrelated donor, or haploidentical donor.
- Diagnosed with 1 of the following underlying diseases:
- Refractory anemia;
- Refractory anemia with ringed sideroblasts;
- Refractory cytopenia with multilineage dysplasia;
- Refractory cytopenia with multilineage dysplasia and ringed sideroblasts;
- Refractory anemia with excess blasts
•1 (5-10% blasts); - Refractory anemia with excess blasts
•2 (10-20% blasts); - Myelodysplastic syndrome, unclassified;
- Myelodysplastic syndrome associated with isolated del (5q);
- Chronic myelomonocytic leukemia;
- Lymphoma (including Hodgkin's) with chemosensitive disease (i.e., response to chemotherapy) and receiving a related donor transplant;
- Aplastic anemia;
- Primary or secondary myelofibrosis.
- Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
- Acute lymphoblastic leukemia, in first or second complete remission.
- Acute undifferentiated leukemia in first or second remission.
- Acute biphenotypic leukemia in first or second complete remission.
- Chronic myelogenous leukemia in either chronic or accelerated phase.
- One of the following myelodysplastic syndrome(s) defined by the following:
- Receiving myeloablative or reduced-intensity conditioning regimens.
- Adequate renal and hepatic function, within 6 weeks of initiation of conditioning, as measured by:
- Hepatic (within 72 hours of Day 0): alanine aminotransferase;
- Renal (within 72 hours of Day 0): Serum creatinine within normal range for age or if serum creatinine above ULN range for age, a creatinine clearance [CrCl]) ≥60 mL/min.;
- Baseline blood samples drawn for serum Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 14 days before randomization, with results available prior to randomization;
- Baseline Toxoplasma serologies available within 6 weeks prior to randomization;
- Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency testing with no evidence of G6PD deficiency performed within 6 weeks prior to randomization.
- Female subjects of child-bearing potential < 2 years post-menopausal must agree to and comply with using 1 barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence while participating in this study. Male subjects must be vasectomized, abstain from sexual intercourse, agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm while participating in the study and for 120 days from the last IV dose of study drug.
- Diagnosis of AML not in morphological remission.
- Diagnosis of chemotherapy-resistant lymphoma.
- Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of screening.
- Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤ 40%, LVEF > 40% but fails to improve with exercise, or shortening fraction ≤ 26%.
- Personal or family history of Long QT interval on ECG (QT) syndrome or a prolonged QT interval corrected (QTc) interval (> 470 msec in males and > 480 msec in females); or concurrent administration of terfenadine, cisapride, astemizole, erythromycin, pimozide, or quinidine.
- Diagnosed reduced lung function with either diffusion capacity (corrected for hemoglobin), forced expiratory volume 1, forced vital capacity ≤ 45% of predicted value, or O2 saturation ≤ 85% on room air.
- Suspected or documented PCP within 2 years of screening.
- Positive baseline serum Platelia GM EIA (≥ 0.5) and/or β-D glucan assay (≥ 80 pg/mL).
- Receipt of previous allogeneic BMT.
- Planned receipt of cord blood for transplantation.
- Planned peripheral blood or marrow autograft.
- Underlying diagnosis of multiple myeloma.
- Grade 2 or higher ataxia, tremor, motor neuropathy, or sensory neuropathy, per NCI CTCAE version 5.0.
- History of severe ataxia, neuropathy or tremors; or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease or Huntington's disease).
- Planned or ongoing therapy at screening with a known neurotoxic medication for a complete list of prohibited neurotoxic medications).
- Known hypersensitivity to Rezafungin for Injection, any echinocandin, fluconazole, posaconazole, other azole antifungal, or to any of their excipients.
- Known hypersensitivity or inability to receive TMP/SMX or any of its excipients.
- Recent use of an investigational medicinal product within 28 days of the first dose of prophylactic study drug or presence of an investigational device at the time of screening.
- Known infection with HIV.
- Pregnant or lactating females.
- The Principal Investigator (PI) determines that the subject should not participate in the study.
- Considered unlikely to follow up for 90 days after receipt of the BMT due to logistic concerns (i.e., location relative to transplant center).
Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.
A PhAse 1a/b, Dose finding, open-label study to eValuate sAfety and toxicity, of iNtravesiCal instillation of TARA-002 in adults with high-gradE non-muscle invasive blaDder cancer (ADVANCED-1)
Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults with High-grade, Non-muscle Invasive Bladder Cancer
- Male or female subjects 18 years of age or older at the time of signing the informed
consent
- Subjects who have voluntarily given written informed consent after the nature of the
study has been explained according to applicable requirements prior to study entry
- Subjects with a histologically confirmed, high-grade Ta or CIS (including CIS with
concomitant Ta) urothelial cell carcinoma of the bladder on central review
- Subjects who are treatment naïve, are unable to obtain intravesical BCG for the
treatment of NMIBC, have received at least one dose of intravesical BCG, or at least
one dose of intravesical chemotherapy
- Penicillin allergy (subjects with a questionable history of allergy to penicillin or
no history of penicillin use will undergo penicillin blood allergy testing prior to
inclusion in the study)
- Predominant (defined as > 50%) adenocarcinoma, squamous cell carcinoma, or
histological variants including plasmacytoid, sarcomatoid, or squamous components
according to central review
- Concomitant prostatic or upper tract urothelial involvement, per Investigator's
assessment
- Nodal involvement or metastatic disease that existed at any time (past or present
disease)
- Bladder cancer stage ≥ T1 within the last 36 months according to central histology
review
- Bladder cancer stage CIS with concomitant T1
For more information on eligibility criteria, please contact the sponsor.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 12/13/22. Questions regarding updates should be directed to the study team contact.
A Study Comparing Bi-parametric MRI to Multi-parametric MRI in the Diagnosis of Clinically Significant Prostate Cancer (PRIME)
Prostate Imaging Using MRI +/- Contrast Enhancement
- Men at least 18 years of age referred with clinical suspicion of prostate cancer.
- Serum PSA ≤ 20ng/ml.
- Fit to undergo all procedures listed in protocol.
- Able to provide written informed consent.
- Prior prostate biopsy.
- Prior treatment for prostate cancer.
- Prior prostate MRI on a previous encounter.
- Contraindication to MRI.
- Contraindication to prostate biopsy.
- Unfit to undergo any procedures listed in protocol.
Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.
A Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Effect of Obinutuzumab versus Rituximab in PR3-Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (PRRR)
PR3-AAV Resilient Remission or PRRR
- Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis or microscopic
polyangiitis).
- Positivity for ANCA, directed against proteinase-3 (PR3)
- Severe newly-diagnosed disease or severe relapsing disease. Severe relapsing disease is defined as at least one major BVAS/WG item or a score ≥ 3 and the investigator
deems standard treatment for severe disease is necessary.
- Minimum BVAS/WG of 3
- Relapsing patients must have B cells detectable in the peripheral blood.
- Patients must have completed COVID-19 vaccination (per current recommended CDC guidelines) at least 4 weeks prior to enrollment. Patients who have recovered from COVID-19 prior to screening with a positive spike protein antibody test result but have not been vaccinated are also eligible.
- Female subjects of childbearing potential who are not sterile must agree to use an acceptable method of contraception for 18 months after the last dose of infusion medication. Male subjects who are not sterile whose female partners are of
childbearing potential must agree to use an acceptable method of contraception for 180 days after the last dose of infusion medication.
- Females of childbearing potential include any female who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (to be considered
postmenopausal, the patient must have had amenorrhea for >12 consecutive months).
- Acceptable methods of contraception include the use of at least two of the following: 1) intrauterine device; 2) hormonal contraceptives for at least 30 days prior to first dose infusion (oral, injectable, implant or ring); 3) barrier contraceptives (condom or diaphragm) with spermicide; or 4) abstinence.
- Diagnosis with eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) as defined by the Chapel Hill Consensus Conference.
- Positive serum assays for ANCA directed against myeloperoxidase (MPO-ANCA)
- Non-severe AAV, defined as disease that does not justify treatment with both B cell depletion and a four-month glucocorticoid taper.
- Any of the co-morbidities:
- Allergies: a history of severe allergic reactions to human or chimeric monoclonal antibodies or murine protein.
- Infection (systemic): an active systemic infection at screening visit
- Infection (deep space): have been diagnosed as having a deep-space infection, such as osteomyelitis, septic arthritis, or pneumonia complicated by empyema or lung abscesses, within 6 months prior to the screening visit
- Infection (blood borne): active hepatitis B or active hepatitis C or a documented history of HIV, hepatitis B, or hepatitis C
- Infection (history): History of recurrent significant infection or history of recurrent bacterial infections
- Liver disease: acute or chronic liver disease that is deemed sufficiently severe to impair their ability to participate in the trial.
- Renal disease: a history of documented anti-glomerular basement membrane disease (anti-GBM disease).
- Malignancy: Active or history of malignancy in the last 5 years. Individuals with squamous cell or basal cell skin carcinomas and individuals with cervical or ductal carcinoma in situ may be enrolled if they have received curative surgical
treatment.
- Active COVID-19 infection.
- Uncontrolled disease: evidence of glucocorticoid dependent disease (such as asthma, COPD, psoriasis or IBD, etc.) requiring consistently greater than 10 mg of prednisone for disease control which might affect endpoint assessment or,
- Other uncontrolled diseases, including any uncontrolled psychiatric disorders, drug and alcohol abuse, that could interfere with participation in the trial according to the protocol.
- Known diagnosis of human anti-chimeric antibodies (HACA) formation.
- Subjects who are premenopausal and are:
- Pregnant on the basis of a serum pregnancy test,
- Breastfeeding, or
- Do not agree to use effective method(s) of contraception
- Use of prohibited medications: They have used any of the prohibited medication listed in Section 5.9.1.
- Plasma exchange: They have been treated with plasma exchange within the 3 months preceding the screening visit.
- History of intolerance to rituximab or other chimeric monoclonal antibodies (e.g., infliximab).
- Recent vaccination: They have had a live vaccine fewer than 4 weeks (28 days) before or during randomization (vaccination with live vaccine through the end of study
participation is contraindicated).
- Daily use of non-steroidal anti-inflammatory drugs (NSAIDs)
- Exclusion criteria related to laboratory parameters:
- Bone marrow suppression as evidenced by a total white count < 4 x10 /l, hemoglobin < 7 gm/dl or platelet count < 100,000/?l
- Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the upper limit of normal, unless attributed to vasculitis
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 11/20/23. Questions regarding updates should be directed to the study team contact.
The Role of the Comprehensive Geriatric Assessment in Elderly Patients with Multiple Myeloma: a Single Center Prospective Study
The Impact of a Geriatric Assessment in Elderly Patients with Multiple Myeloma
- Age ≥ 65 years.
- Diagnosis of MM based on IMWG diagnostic criteria 64.
- Newly diagnosed or have received 1 prior line of treatment.
- Planned to start a new treatment for MM within 30 days.
- Transplant eligible or ineligible.
- Fluent in English (all assessment tools are in English).
- Able to provide written informed consent.
- Received > 1 prior line of treatment.
- Patients included in an interventional therapeutic trial.
- Not able to give informed consent.
- Severe mental or cognitive disorder precluding geriatric assessment.
Eligibility last updated 1/20/22. Questions regarding updates should be directed to the study team contact.
Physiological Regulation of Energy Intake - The FOOD-PRINT Study Identifying the Hormonal and Neural Footprints of the Visceroceptive, Homeostatic, and Hedonic Components of Food Intake Regulation in Humans (FOODPRINT)
Studying the Hedonic and Homeostatic Regulation of Food Intake using Functional MRI
- BMI 18-25 kg/m^2.
- Age > 21 and < 50 years.
- Weight stable for 3 months prior to study entry.
- For females: study days will be scheduled during the follicular phase of their menstrual cycle (i.e., the first 13 days (about 2 weeks) of the cycle).
- Able to provide written informed consent prior to any study procedures and be willing and able to follow study procedures.
- Ability to perform light to moderate physical activity.
- Any contraindication for MRI scanning.
- Any history of childhood (> 95th percentile) or adult obesity (BMI >30 kg/m^2).
- Claustrophobia.
- High intensity training or physical activity.
- Any contraindication for intragastric balloon insertion.
- Any allergies to the study meals.
- Any history of eating disorder.
- Any substance abuse disorder (including alcohol and tobacco).
- Any history of psychiatric disorders.
- Any cardiovascular, endocrine, pulmonary, neurological, or gastrointestinal comorbidities.
- Pregnancy or nursing.
- Any history of bariatric surgery or endoscopic bariatric procedure.
- Use of any medication or supplement that alters appetite.
- Patient has a known history of any condition or factor judged by the investigator to prevent participation in the study or which might hinder study adherence.
Eligibility last updated 10/6/21. Questions regarding updates should be directed to the study team contact.
A Phase 3, Randomized, Double-blind, Two-period, Crossover, Withdrawal Study to Assess the Efficacy and Safety of AVTX-803 in Subjects with Leukocyte Adhesion Deficiency Type II (LAD II) (AVTX-803)
A Study to Assess the Efficacy and Safety of AVTX-803 in Subjects with Leukocyte Adhesion Deficiency Type II (LAD II)
- Subject must be between 6 months and 75 years old
- Subject has biochemically and genetically proven LAD II (SLC35C1-CDG)
- Subject has a documented history of Lewis antigen deficiency
- Subject has a history of recurrent infections, opportunistic infections or infections
that did not respond well to standard of care treatment
- Subject or parent (for subjects under legal age for consent) has provided written
informed consent for this study. Additionally, written informed assent has been
provided, as appropriate, for minors of older age, per local institutional review
board (IRB)/ethics committee (EC) policy and requirements
- Subject is willing and able to comply with the protocol
- Women of childbearing potential (WOCBP) meeting the criteria below:
1. Non-lactating and has a negative pregnancy test at screening -AND-
2. Uses an acceptable double-barrier method of contraception as determined by the
investigator or sub-investigator for the duration of the study and 30 days
following the last dose of study drug.
- Male subjects must agree to use an acceptable double-barrier method of contraception
with their partner as determined by the investigator or sub-investigator for the
duration of the study and 30 days following the last dose of study drug.
- Subject has severe anemia defined as hemoglobin <8.0 g/dL (<4.9 mmol/L)
- Subject has impaired renal function as defined by an eGFR <90 mL/min
- Subject has a total absence of fucosylation on red blood cells and the presence of
anti-H antigen
- Subject has known or suspected intolerance or hypersensitivity to fucose or any
ingredients of the investigational product
- In the investigator's opinion, subject has a history of failure to respond to fucose
at adequate dosing
- In the investigator's opinion, subject is not able or not willing to comply with the
study requirements.
- Subject is pregnant
Eligibility last updated 7/20/22. Questions regarding updates should be directed to the study team contact.