AAML1831, A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations (AAML1831)
A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib to To Treat Newly-diagnosed AML with or without FLT3 Mutations
- All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part
A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens
must be done according to the Manual of Procedures
- Patients must be less than 22 years of age at the time of study enrollment
- Patient must be newly diagnosed with de novo AML according to the 2016 World Health
Organization (WHO) classification with or without extramedullary disease
- Patient must have 1 of the following:
- >= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
- In cases where extensive fibrosis may result in a dry tap, blast count
can be obtained from touch imprints or estimated from an adequate bone
marrow core biopsy
- < 20% bone marrow blasts with one or more of the genetic abnormalities
associated with childhood/young adult AML as provided in the protocol
(sample obtained within 14 days prior to enrollment)
- A complete blood count (CBC) documenting the presence of at least 1,000/uL
(i.e., a white blood cell [WBC] count ≥ 10,000/uL with ≥ 10% blasts or a
WBC count of ≥ 5,000/uL with ≥ 20% blasts) circulating leukemic cells
(blasts) if a bone marrow aspirate or biopsy cannot be performed (performed
within 7 days prior to enrollment)
- ARM C: Patient must be >= 2 years of age at the time of Late Callback
- ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular
Oncology
- ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
- ARM C: Females of reproductive potential must agree to use effective contraception
during treatment and for at least 6 months after the last dose of gilteritinib
- ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib
and for 2 months after the last dose of gilteritinib
- ARM C: Males of reproductive potential must agree to use effective contraception
during treatment and for at least 4 months after the last dose of gilteritinib
- ARM D: Patient must be ≥ 2 years of age at the time of Late Callback
- ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating
mutations as reported by Foundation Medicine
- ARM D: Females of reproductive potential must agree to use effective contraception
during treatment and for at least 6 months after the last dose of gilteritinib
- ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib
and for 2 months after the last dose of gilteritinib
- ARM D: Males of reproductive potential must agree to use effective contraception
during treatment and for at least 4 months after the last dose of gilteritinib
- NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who
transfer to Arm C or Arm D are not eligible
- NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
- NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
- NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to
diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental
retardation)
- NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would
prevent computer use or recognition of visual test stimuli
- 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.
- Fanconi anemia
- Shwachman Diamond syndrome
- Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
- Telomere disorders
- Germline predispositions known, or suspected by the treating physician to increase
risk of toxicity with AML therapy
- Any concurrent malignancy
- Juvenile myelomonocytic leukemia (JMML)
- Philadelphia chromosome positive AML
- Mixed phenotype acute leukemia
- Acute promyelocytic leukemia
- Acute myeloid leukemia arising from myelodysplasia
- Therapy-related myeloid neoplasms
- Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection
fraction (EF) < 50% (preferred method Biplane Simpson's EF) or if EF unavailable,
shortening fraction (SF) < 24%. *Note: if clinically safe and feasible, repeat
echocardiogram is strongly advised in order to confirm cardiac dysfunction following
clinical stabilization, particularly if occurring in the setting of sepsis or other
transient physiologic stressor. If the repeat echocardiogram demonstrates an EF >=
50%, the patient is eligible to enroll and may receive an anthracycline-containing
Induction regimen
- Administration of prior anti-cancer therapy except as outlined below:
- Hydroxyurea
- All-trans retinoic acid (ATRA)
- Corticosteroids (any route)
- Intrathecal therapy given at diagnosis
- In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be
avoided from the time of enrollment until it is determined whether the patient
will receive gilteritinib. Patients receiving gilteritinib will be required to
avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the
study treatment
- 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
- ARM D: Patient does not have any congenital long QT syndrome or congenital heart block
Eligibility last updated 6/20/22. Questions regarding updates should be directed to the study team contact.
Cell Biological Interrogation of Patient-derived AVM Cell Lines (AVM)
Cell Biological Interrogation of Patient-derived Arteriovenous Malformation Cell Lines
- Adult and pediatric patients.
- Undergoing surgical resection of their brain AVM.
- Have not undergone previous stereotactic radiosurgery or endovascular embolization.
- Have undergone previous stereotactic radiosurgery or endovascular embolization.
Eligibility last updated 9/7/22. Questions regarding updates should be directed to the study team contact.
CORT125134-551, A Phase 1b, Open-Label Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production
Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production
- Histologically or cytologically confirmed ACC (advanced unresectable and/or
metastatic)
- Measurable disease based upon RECIST v1.1 as determined by the Investigator.
- Documented GC excess (too much cortisol).
- For patients who have received mitotane within 3 months prior to screening, mitotane
levels must be <4 mg/L at screening.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Adequate organ and bone marrow function (determined through blood and urine tests)
- Negative pregnancy test for patients of childbearing potential at the Screening and
every 6 weeks (+ or
•7 days) in female patients of childbearing potential.
- Major surgery within 4 weeks prior to enrollment. If the participant underwent major
surgery, they must have recovered adequately prior to starting study treatment.
- Have received and responded (complete response [CR] or partial response [PR]) to prior
treatment with any prior checkpoint inhibitor or any other agents targeting T-cell
stimulation pathways
- Taking a concomitant medication that is a strong Cytochrome P450 3A (CYP3A) inducer,
or that is a substrate of CYP3A with a narrow therapeutic index
- Known untreated parenchymal brain metastasis or have uncontrolled central nervous
system (CNS) metastases. Patients must not require steroids and must be neurologically
stable without corticosteroids for a minimum of 3 weeks prior to the commencement of
the study. Patients with neurologic symptoms must undergo a CT/MRI to rule out occult
CNS metastases.
- Requirement for chronic systemic GC treatment, such as active autoimmune disease
requiring systemic treatment (corticosteroids or other immunosuppressive medication)
- Patients requiring inhaled glucocorticoids but have no other alternative treatment
option if their condition deteriorates during the study.
- Clinically relevant toxicity from prior systemic cytotoxic therapies or radiotherapy
that in the opinion of the Investigator has not resolved to NCI-CTCAE v5.0 Grade 1 or
less prior to the first dose of relacorilant.
- Treated with the following prior to the first dose of relacorilant:
1. Any investigational product, systemic anticancer therapy, or radiation therapy
within 21 days
2. Antibodies or anticancer vaccines within 60 days
3. Mifepristone or other GR antagonists within 5 half-lives of these medications
4. Adrenostatic medications within 5 half-lives of these medications
- History of severe hypersensitivity to another monoclonal antibody
- Other concurrent cancer or a history of another invasive malignancy within the last 3
years that has a likelihood of recurrence of >30% within the next 5 years. Adequately
treated basal and squamous skin cancers, ductal carcinoma in situ, cervical cancer,
prostate cancer, non-muscle invasive urothelial cancer or other tumors curatively
treated with no evidence of disease are permissible.
- Human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis
C virus or hepatitis B virus including: Chronic or active hepatitis B as diagnosed by
serologic tests. In equivocal cases, hepatitis B or C polymerase chain reaction may be
performed and must be negative for enrollment.
- Clinically significant uncontrolled condition(s) or a condition which, in the opinion
of the Investigator, may confound the results of the trial or interfere with the
patient's participation, including but not limited to:
1. Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction
3 months before study entry.
2. Active infection that requires parenteral antibiotics.
3. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
Eligibility last updated 7/8/22. Questions regarding updates should be directed to the study team contact.
WO42758 - A Phase I/Ib Global, Multicenter, Open-label Umbrella Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients with Metastatic Colorectal Cancer (Intrinsic) (Intrinsic)
A Study Evaluating the Safety and Effectiveness of Therapies in Patients with Metastatic Colorectal Cancer
- Signed next-generation sequencing (NGS) Biomarker Eligibility Informed Consent Form
- Age >= 18 years at time of signing Informed Consent Form
- Biomarker eligibility as determined at a College of American Pathologists/clinical
laboratory improvement amendments (CAP/CLIA)-certified or equivalently accredited
diagnostic laboratory using a validated test
- Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 1
- Life expectancy >= 3 months, as determined by the investigator
- Histologically confirmed adenocarcinoma originating from the colon or rectum
- Metastatic disease
- Prior therapies for metastatic disease
- Ability to comply with the study protocol, in the investigators judgment
- Measurable disease (at least one target lesion) according to Response Evaluation
Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
- Availability of an archival tissue sample for exploratory biomarker research
- Adequate hematologic and organ function within 14 days prior to initiation of study
treatment
- For women of childbearing potential: Must have a negative serum pregnancy test result
within 14 days prior to initiation of study treatment and agreement to remain
abstinent or use contraceptive measures
- For men: agreement to remain abstinent or use contraceptive measures, and agreement to
refrain from donating sperm
Exclusion Criteria
- Current participation or enrollment in another interventional clinical trial
- Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is
shorter) prior to start of study treatment
- Treatment with investigational therapy within 28 days prior to initiation of study
treatment
- Pregnant or breastfeeding, or intending to become pregnant during the study
- History of or concurrent serious medical condition or abnormality in clinical
laboratory tests that, in the investigator's judgment, precludes the patient's safe
participation in and completion of the study or confounds the ability to interpret
data from the study
- Severe infection within 4 weeks prior to initiation of study treatment or any active
infection that, in the opinion of the investigator, could impact patient safety
- Incomplete recovery from any surgery prior to the start of study treatment that would
interfere with the determination of safety or efficacy of study treatment
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
- Uncontrolled tumor-related pain
- Uncontrolled or symptomatic hypercalcemia
- Clinically significant and active liver disease
- Known HIV infection
- Symptomatic, untreated, or actively progressing CNS metastases
- History of leptomeningeal disease or carcinomatous meningitis
- History of malignancy other than CRC within 2 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death
- Any other disease, unresolved toxicity from prior therapy, metabolic dysfunction,
physical examination finding, or clinical laboratory finding that contraindicates the
use of an investigational drug, may affect the interpretation of the results, or may
render the patient at high risk from treatment complications
- Requirement for treatment with any medicinal product that contraindicates the use of
any of the study treatments, may interfere with the planned treatment, affects patient
compliance, or puts the patient at higher risk for treatment-related complications
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.
Activated Prothrombin Complex Concentrate FEIBA to Optimize Postcardiopulomonary Bypass Hemostasis in Pediatric Cardiac Patients
A Study to Compare FEIBA to Alternative Blood Products in Treating Children After Cardiac Surgery
- Weight ≤ 15 kg.
- Elective cardiac surgery with cardiopulmonary bypass.
- Coagulopathic bleeding after cardiopulmonary bypass.
- Availability and willingness of the parent/legal guardian to provide informed consent.
- Presence of mechanical circulatory support at the time of randomization or POD 0 and 1.
- Patient or family history of coagulopathy and/or thromboses.
- Preoperative anticoagulation (excluding low dose heparin for “line prophylaxis”).
Randomized Double-Blind Placebo-Controlled Adaptive Design Trial Of Intrathecally Administered Autologous Mesenchymal Stem Cells In Multiple System Atrophy
A Study to Evaluate Mesenchymal Stem Cells to Treat Multiple System Atrophy
- Males or females aged 30-70 years, who are willing and able to give informed consent.
- Clinical diagnosis of MSA, fulfillin,g consensus criteria for probable MSA.
- UMSARS I (omitting question 11) between 5 and 17, and able to walk unaided (i.e. abl,e to walk at least 50 yards without the use of a cane or walker, and without other support such as holding on to an arm or touching walls).
- Anticipated survival of at least 3 years in the opinion of the investigator.
- Normal cognition as assessed by the Montreal Cognitive Assessment (MOCA). We will require a value ≥ 26.
- Pregnant or breastfeeding women, and women of childbearing potential who do not agree to practice an acceptable method of birth control. Acceptable methods of birth control in this study are: surgical sterilization, intrauterine devices, partner’s vasectomy, a double-protection method (condom or diaphragm with spermicide), hormonal contraceptive drug (i.e., oral contraceptive, contraceptive patch, long-acting injectable contraceptive) with a required second mode of contraception.
- Participants with a clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect study results. These include conditions causing significant CNS or autonomic dysfunction, clinically significant peripheral neuropathy, active malignant neoplasm, amyloidosis, active autoimmune disease, immunocompromised state, active infection, congestive heart failure (NYHA III or IV), recent (< 6 months) myocardial infarction, history of stoke with residual deficits, uncontrolled diabetes mellitus, alcoholism, orthopedic problems that compromise mobility and activity of daily living, significant liver or kidney disease, thrombocytopenia (< 50 x 10^9/L), disorders affecting coagulation, and patients on active anticoagulation.
- Participants who have taken any investigational products within 90 days prior to baseline, or with expected effects lasting beyond 60 days prior to baseline.
- Medications that could affect clinical evaluations are permitted but need to be withdrawn at least four half-lives prior to study visits. Those include medications used to treat motor symptoms, such as levodopa and other anti-Parkinsonian medications.
- Patients with contraindication to any of the study procedures, in particular MRI scanning.
ALLO-605-201, A Single-Arm, Open-Label, Phase 1/2 Study Evaluating the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-647 and ALLO-605, an Anti- BCMA Allogeneic CAR T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma
Safety and Efficacy of ALLO-605 an Anti-BCMA Allogeneic CAR T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma
- Documented diagnosis of relapsed/refractory multiple myeloma (MM)
- Subjects must have measurable disease
- Subjects must have received ≥ 3 prior MM lines of therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate hematologic, renal, liver, pulmonary, and cardiac functions
- Life expectancy of at least 3 months without treatment
- Subjects with known active or history of central nervous system (CNS) or
leptomeningeal involvement of myeloma or plasma cell leukemia
- Current or history of thyroid disorder (including hyperthyroidism), except for
subjects with hypothyroidism controlled on a stable dose of hormone replacement
therapy
- Autologous stem cell transplantation within last 6 weeks prior to the start of
lymphodepletion
- Any prior allogeneic hematopoietic stem cell transplantation
- Systemic anti-cancer therapy within 2 weeks prior to the start of lymphodepletion
Role of the Neurovascular System in Spontaneous Coronary Artery Dissection (SCAD) (SCAD)
A Study to Analyze the Role of Sympathetic Nervous System in Spontaneous Coronary Artery Dissection
- Having spontaneous coronary artery dissection.
- Sex and age-matched control subjects, 18 years of age and older.
- Individuals under 18 years of age.
A Phase 2 Open-Label Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Nedosiran in Pediatric Patients from Birth to 11 Years of Age with Primary Hyperoxaluria and Relatively Intact Renal Function (PHYOX8)
A Study to Evaluate the Safety, Tolerability and Effectiveness of Nedosiran in Pediatric Patients with Primary Hyperoxaluria and Relatively Intact Renal Function
- Birth to 11 years of age inclusive, at the time of signing the informed consent.
- Documented diagnosis of PH1 or PH2 confirmed by genotyping (historically available genotype information is acceptable for study eligibility).
- Average spot Uox to creatinine ratio at Screening above 2 times the 95th percentile for age (Matos et al, 1999):
- > 0.44 mol/mol in participants < 6 months;
- > 0.34 mol/mol in participants from 6 months to < 12 months;
- > 0.26 mol/mol in participants 12 months to < 2 years;
- > 0.20 mol/mol in participants from 2 to < 3 years; and
- > 0.16 mol/mol in participants from 3 to 5 years.
- Estimated GFR at Screening ≥ 30 mL/min normalized to 1.73 m^2 BSA. For infants aged less than 12 months, serum creatinine below the 97th percentile of a healthy population (Boer et al., 2010).
- Participants must have been on a stable treatment regimen for PH for 3 months prior to Day 1 and parent(s)/legal guardian should be willing to ensure participant remains on the same stable treatment regimen during the study.
- Body weight ≥ 10 kg.
- Male or female.
- Participant’s parent or legal guardian is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow up; accompany the participant to the study site on each assessment day according to the SoA (e.g., able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the rating scales during the scheduled study visits; accurately and reliably dispense study intervention as directed.
- Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations).
- Prior renal or hepatic transplantation; or planned transplantation within the study period.
- Currently receiving dialysis or anticipating requirement for dialysis during the study period.
- Plasma oxalate (Pox) > 30 μmol/L at Screening.
- Documented evidence of clinical manifestations of severe systemic oxalosis (including preexisting retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations).
- Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact participant’s safety including, but not restricted to:
- Severe intercurrent illness;
- Known causes of active liver disease/injury or transaminase elevation (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis [NAFLD/NASH]);
- History of serious mental illness that includes, but is not limited to, schizophrenia, bipolar disorder, or severe depression requiring hospitalization or pharmacological intervention;
- Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological diseases, including dermatological including rash, severe eczema or dermatitis, or connective tissue diseases or disorders.
- Use of an RNAi drug within the last 6 months.
- History of 1 or more of the following reactions to an oligonucleotide-based therapy:
- Severe thrombocytopenia (platelet count ≤ 100,000/μL);
- Hepatotoxicity, defined as ALT or AST > 3 times the upper ULN and total bilirubin > 2 × ULN or INR > 1.5;
- Severe flu-like symptoms leading to discontinuation of therapy;
- Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy;
- Coagulopathy/clinically significant prolongation of clotting time.
- Participation in any clinical study in which they received an IMP within 4 months or 5 times the half-life of the drug (whichever is longer) before Screening:
- For IMPs with the potential to reduce urine and/or plasma oxalate concentrations, these concentrations must have returned to historical baseline levels prior to Screening.
- Liver function test (LFT) abnormalities: ALT and/or AST > 1.5 × ULN for age and gender.
- Known hypersensitivity to nedosiran, or any of its ingredients.
- Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations.
Eligibility last updated 5/11/22. Questions regarding updates should be directed to the study team contact.
COllaborative, National QUality and Efficacy Registry for Tracking Disease Progression in Systemic Sclerosis (Scleroderma) Patients (CONQUER) (CONQUER)
A Registry to Track Scleroderma Progression
- Patients 18 and older, inclusive; AND
- Patients who meet the 2013 ACR/EULAR classification criteria for systemic sclerosis; AND
- < 5 years from onset of first non-RP symptom attributed to systemic sclerosis.
- Patients under 18 years of age.
- Patients with cognitive impairment that will interfere with conducting the study. Study staff should determine if the patient, at that moment, has the cognitive capacity to understand what the study entails, assent to participate, and complete the assessments. If there is question as to whether a patient may meet this criterion, RCs/RAs should defer to the site PI trained on the study to help determine; OR
- Patients who are non-English Speaking. The patient must be able to proficiently read, speak, and understand English in order to be eligible.
The Practical Anemia Bundle for SusTained Blood Recovery (PABST-BR) Trial (PABST-BR)
A Study to Evaluate Practical Anemia Bundle for SusTained Blood Recovery
- Provision of signed and dated informed consent form (may be completed by legal proxies
for those patients unable to provide consent, i.e. sedation/intubation)
- Stated willingness to comply with all study procedures and availability for the
duration of the study, including follow-up assessments
- Current ICU admission at Mayo Clinic Rochester with anticipated ICU duration >48 hours
after enrollment
- Current ICU duration < 7 days
- Patients embedded in the local or regional Mayo Clinic Health System to facilitate
post-hospitalization outcome assessment
- Moderate-to-severe anemia (i.e. hemoglobin concentration < 10 g/dL) at the time of
enrollment, with the hemoglobin concentration assessed no more than 24 hours prior to
enrollment. If RBC transfusion has been administered between the qualifying hemoglobin
assessment and enrollment, a repeat hemoglobin will be required prior to enrollment to
ensure that it remains < 10 g/dL.
- Recent or current iron or erythropoiesis stimulating agent (ESA) use (i.e.
darbepoetin, Aranesp, erythropoietin, Epogen, Procrit, Retacrit) within 30 days of
enrollment, exclusive of oral iron for general nutritional support (e.g. multivitamin
with iron)
- Severe anemia prior to hospitalization (i.e. hemoglobin <9 g/dL within 90 days of
admission)
- Known allergic reactions to iron or EPO
- Inability to complete outcome assessments (i.e. not expected to survive
hospitalization, unable to make follow-up appointments, non-ambulatory, dementia or
other severe cognitive impairment, visual impairment i.e. blind or legally blind)
- Pregnancy or breastfeeding at time of enrollment
- Inability to receive pharmacologic venous thromboembolic prophylaxis except in
patients with recent surgical or gastrointestinal bleeding
- Active or suspected thrombosis (i.e. deep venous thrombosis, pulmonary embolism, acute
arterial thrombus within 3 months)
- Uncontrolled sepsis (i.e. <48 hours of appropriate antimicrobial therapy and/or lack
of definitive source control)
- Having received ≥10 units of allogeneic RBCs in the 48 hours before enrollment
- Acute coronary syndrome or ischemic stroke within 3 months
- Weight less than 40 kg
- Concerns with study enrollment expressed by the clinical team
- Mechanical circulatory support devices
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 9/15/22. Questions regarding updates should be directed to the study team contact.
A Phase I/IIa Theranostic Study of 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (CLP05)
64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECuRE)
- Signed informed consent.
- ≥ 18 years of age.
- Eastern Cooperative Oncology Group performance status of 0 to 2.
- Life expectancy > 6 months;.
- Histological, pathological, and/or cytological confirmation of PCa.
- Positive 64Cu-SAR-bisPSMA PET/CT scan, where 64Cu-SARbisPSMA uptake (standardized uptake value [SUV] max) of at least 1 known lesion is higher than that of the liver on the 1 hour positron emission tomography (PET)/computed tomography (CT) scan.
- NOTE: ALL OTHER ELIGIBILITY CRITERIA MUST BE FULFILLED BEFORE THE 64Cu-SAR-bisPSMA ADMINISTRATION IS PERMITTED. THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE DOSIMETRY PHASE;
- Castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
- Have progressive mCRPC despite prior androgen deprivation therapy and at least either enzalutamide and/or abiraterone (or other such androgen receptor pathway inhibitors). Documented progressive mCRPC will be based on at least 1 of the following criteria:
- Serum/plasma prostate specific antigen (PSA) progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal value for study enrollment is 2.0 ng/mL;
- Soft-tissue progression defined as a ≥ 20% increase in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since the last treatment directed at the metastatic cancer has started (not including hormonal therapy) or the appearance of 1 or more new lesions;
- Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan.
- ≥ 1 metastatic lesion that is present at screening CT, magnetic resonance imaging (MRI), or bone scan imaging obtained ≤ 28 days prior to enrollment into the study.
- Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (prior chemotherapy, radiation, immunotherapy, etc.).
- Participants must have adequate organ function:
- Bone marrow reserve:
- White blood cell (WBC) count ≥ 2.5 x 10⁹/L (2.5 x 109/L is equivalent to 2.5 x 10³/μL and 2.5 x K/μL and 2.5 x 10³/cc and 2500/μL); OR
- Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L (1.5 x 10⁹/L is equivalent to 1.5 x 10³/μL and 1.5 x K/μL and 1.5 x 10³/cc and 1500/μL);
- Platelets ≥ 100 x 10⁹/L (100 x 10⁹/L is equivalent to 100 x 10³/μL and 100 x K/μL and 100 x 10³/cc and 100,000/μL);
- Hemoglobin ≥ 9 g/dL (5.59 mmol/L);
- Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted;
- Alanine aminotransferase or aspartate aminotransferase ≤ 3.0 x ULN OR ≤ 5.0 x ULN for participants with liver metastases;
- Creatinine clearance or estimated glomerular filtration rate ≥ 50 mL/min.;
- For participants who are human immunodeficiency virus infected: Participant must be healthy and have a low risk of Acquired Immune Deficiency Syndrome related outcomes in the opinion of the Investigator;
- For participants who have partners of childbearing potential: Partner and/or participant must use a method of birth control with adequate barrier protection.
- Major surgery within 12 weeks prior to enrollment into the study.
- Brain metastasis.
- Histologic diagnosis of small cell or neuroendocrine prostate cancer.
- Prior history of leukemia or Myelodysplastic Syndrome.
- Diagnosis of Deep Vein Thrombosis or Pulmonary Embolism within 4 weeks prior to enrollment into the study.
- Unmanageable urinary tract obstruction.
- Evidence of progressive lesion(s) on MRI and/or CT (> 1 cm in mean diameter) that is prostate-specific membrane antigen (PSMA) negative on the 1 hour ⁶⁴Cu-SAR-bisPSMA PET/CT scan as determined at screening.
- NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE DOSIMETRY AND DOSE ESCALATION PHASE.
- Previous treatment with any systemic radionuclide (e.g., Lu, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Actinium-225, Radium-223, Iodine-131) within 6 months of treatment initiation;
- Previous treatment with any systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 4 weeks prior to treatment on study with the exception of Luteinizing Hormone Releasing Hormone, any other androgen deprivation therapy (ADT) (if ADT is discontinued prior to enrolment, 14 days must elapse after abiraterone discontinuation and 28 days after enzalutamide before participant can be enrolled) or low dose corticosteroids.
- NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE DOSIMETRY PHASE.
- Previous treatment with any investigational agents within 4 weeks prior enrollment into the study.
- Known hypersensitivity to the components of the investigational products or its analogues.
- Transfusion for the sole purpose of making a participant eligible for study inclusion.
- Spinal metastasis with symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
- Concurrent serious medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that, in the opinion of the Investigator, would impair study participation or cooperation.
- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are participants with adequately treated non-melanoma skin cancer, superficial bladder cancer.
- Any condition or personal situation that would pose an unacceptable radiation safety risk (as per institution guidelines, state and/or national regulations) to the participant or carer at the time of release following the completion of therapy (e.g., uncontrolled urinary incontinence, high dependency care).
- Participants in whom it is known that EBRT is scheduled after enrollment into the study.
- NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE DOSIMETRY PHASE.
Detecting Cancers Earlier Through Elective Plasma-based CancerSEEK Testing – Ascertaining Serial Cancer Patients to Enable New Diagnostic II (DETECT-ASCEND 2) (ASCEND 2)
A Study to Detect Cancers Through Elective Plasma-based CancerSEEK Testing
Inclusion Criteria
•All Subjects:
- ≥ 50 years of age
- Subject understands the study procedures and is able to provide informed consent to participate in the study and authorization for release of relevant protected health information or personal data to the study investigator.
Inclusion Criteria
•Cancer Subjects Only:
- Subject has an untreated primary malignancy of breast, lung, colorectal, prostate, bladder, uterine, kidney/renal pelvis, pancreatic, liver, stomach, ovarian, esophageal cancer, head and neck squamous cell, thyroid, small intestine, cervical, anal, vulva, or testis confirmed through pathology reports and/or clinical/radiographic data; or
- Subject has suspicion of a primary malignancy of pancreatic, bladder, kidney/renal pelvis, testis or ovarian cancer based on imaging.
- Prior or concurrent cancer diagnosis defined as:
- Any previous cancer diagnosis within the past 5 years (with the exceptions of basal cell or squamous cell skin cancers); OR
- Recurrence of the same primary cancer within any timeframe; OR
- Concurrent diagnosis of multiple primary cancers.
- Chemotherapy and/or radiation therapy within 5 years prior to enrollment/sample collection.
- Any treatment for the primary malignancy or sites of metastases. Subject may not have started neo-adjuvant chemotherapy, neo-adjuvant radiation therapy, immunotherapy or other treatment and/or surgery prior to blood sample collection.
- Less than 3 days between fine needle aspiration (FNA) of target pathology and blood collection.
- Less than 7 days between biopsy (other than FNA) of target pathology and blood collection.
- IV contrast (e.g., CT and MRI) within 1 day [or 24 hours] of blood collection.
- Individual has a condition the Investigator believes would interfere with the subject’s ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results or put the person at undue risk.
- Participant has an active febrile infection prior to blood draw.
- History of an allogeneic bone marrow, stem cell transplant, or solid organ transplant.
Eligibility last updated 12/7/21. Questions regarding updates should be directed to the study team contact.
Detecting Cancers Earlier Through Elective Plasma-based CancerSEEK Testing – Ascertaining Serial Cancer Patients to Enable New Diagnostic II (DETECT-ASCEND 2) (ASCEND 2)
A Study to Detect Cancers Through Elective Plasma-based CancerSEEK Testing
Inclusion Criteria
•All Subjects:
- ≥ 50 years of age
- Subject understands the study procedures and is able to provide informed consent to participate in the study and authorization for release of relevant protected health information or personal data to the study investigator.
Inclusion Criteria
•Cancer Subjects Only:
- Subject has an untreated primary malignancy of breast, lung, colorectal, prostate, bladder, uterine, kidney/renal pelvis, pancreatic, liver, stomach, ovarian, esophageal cancer, head and neck squamous cell, thyroid, small intestine, cervical, anal, vulva, or testis confirmed through pathology reports and/or clinical/radiographic data; or
- Subject has suspicion of a primary malignancy of pancreatic, bladder, kidney/renal pelvis, testis or ovarian cancer based on imaging.
- Prior or concurrent cancer diagnosis defined as:
- Any previous cancer diagnosis within the past 5 years (with the exceptions of basal cell or squamous cell skin cancers); OR
- Recurrence of the same primary cancer within any timeframe; OR
- Concurrent diagnosis of multiple primary cancers.
- Chemotherapy and/or radiation therapy within 5 years prior to enrollment/sample collection.
- Any treatment for the primary malignancy or sites of metastases. Subject may not have started neo-adjuvant chemotherapy, neo-adjuvant radiation therapy, immunotherapy or other treatment and/or surgery prior to blood sample collection.
- Less than 3 days between fine needle aspiration (FNA) of target pathology and blood collection.
- Less than 7 days between biopsy (other than FNA) of target pathology and blood collection.
- IV contrast (e.g., CT and MRI) within 1 day [or 24 hours] of blood collection.
- Individual has a condition the Investigator believes would interfere with the subject’s ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results or put the person at undue risk.
- Participant has an active febrile infection prior to blood draw.
- History of an allogeneic bone marrow, stem cell transplant, or solid organ transplant.
Eligibility last updated 12/7/21. Questions regarding updates should be directed to the study team contact.
Detecting Cancers Earlier Through Elective Plasma-based CancerSEEK Testing – Ascertaining Serial Cancer Patients to Enable New Diagnostic II (DETECT-ASCEND 2) (ASCEND 2)
A Study to Detect Cancers Through Elective Plasma-based CancerSEEK Testing
Inclusion Criteria
•All Subjects:
- ≥ 50 years of age
- Subject understands the study procedures and is able to provide informed consent to participate in the study and authorization for release of relevant protected health information or personal data to the study investigator.
Inclusion Criteria
•Cancer Subjects Only:
- Subject has an untreated primary malignancy of breast, lung, colorectal, prostate, bladder, uterine, kidney/renal pelvis, pancreatic, liver, stomach, ovarian, esophageal cancer, head and neck squamous cell, thyroid, small intestine, cervical, anal, vulva, or testis confirmed through pathology reports and/or clinical/radiographic data; or
- Subject has suspicion of a primary malignancy of pancreatic, bladder, kidney/renal pelvis, testis or ovarian cancer based on imaging.
- Prior or concurrent cancer diagnosis defined as:
- Any previous cancer diagnosis within the past 5 years (with the exceptions of basal cell or squamous cell skin cancers); OR
- Recurrence of the same primary cancer within any timeframe; OR
- Concurrent diagnosis of multiple primary cancers.
- Chemotherapy and/or radiation therapy within 5 years prior to enrollment/sample collection.
- Any treatment for the primary malignancy or sites of metastases. Subject may not have started neo-adjuvant chemotherapy, neo-adjuvant radiation therapy, immunotherapy or other treatment and/or surgery prior to blood sample collection.
- Less than 3 days between fine needle aspiration (FNA) of target pathology and blood collection.
- Less than 7 days between biopsy (other than FNA) of target pathology and blood collection.
- IV contrast (e.g., CT and MRI) within 1 day [or 24 hours] of blood collection.
- Individual has a condition the Investigator believes would interfere with the subject’s ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results or put the person at undue risk.
- Participant has an active febrile infection prior to blood draw.
- History of an allogeneic bone marrow, stem cell transplant, or solid organ transplant.
Eligibility last updated 12/7/21. Questions regarding updates should be directed to the study team contact.
(ECTx) A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-21822 Monotherapy and Combination Therapy in Adult Patients with Advanced Solid Tumors Harboring KRAS G12C Mutation
JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation
- Participants must be able to provide an archived tumor sample
- Histologically or cytologically confirmed solid tumors with KRAS G12C mutation
- Must have received at least 1 prior standard therapy
- Must have at least 1 measurable lesion per RECIST v1.1
- Must have adequate organ function
- Must be able to swallow and retain orally administered medication
- Has brain or spinal metastases, except if treated and no evidence of radiographic
progression or hemorrhage for at least 28 days
- Active infection requiring systemic treatment within 7 days
- Active HBV or HCV
- Any severe and/or uncontrolled medical conditions
- LVEF ≤50% assessed by ECHO or QTcF
- QT interval >470 msec
- Experiencing unresolved CTCAE 5.0 Grade >1 toxicities
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 9/7/22. Questions regarding updates should be directed to the study team contact.
The electronic Medical Records and GEnomics (eMERGE) Network Genomic Risk Assessment (eMERGE IV)
A Network Genomic Risk Assessment of the Electronic Medical Records and Genomics
- Adults, 18-75 years of age.
- Children 3 to < 18 years of age.
- Able to read or understand English or Spanish.
- Able to provide a healthcare provider or clinician to receive results.
- Willing to accept GIRA report.
- Inability to provide consent.
- Transplant (solid organ or bone marrow) or transfusion within 8 weeks.
- Research staff and investigators in eMERGE.
- Unable to provide a HCP to receive results.
- Not a patient at parent institution.
Correlation of Spinopelvic Movement with Lateral Radiographs to Assess Spine Motion Prior to Total Hip Arthroplasty
Correlation of Spinopelvic Movement with Lateral Radiographs to Assess Spine Motion Prior to Total Hip Arthroplasty
- Ability to provide informed consent.
- Hip pathology: 20 presenting for total hip arthroplasty, 20 presenting for joint
preservation procedures.
- Patients with lumbosacral hardware, contralateral THA, or DJD in the contralateral hip.
Eligibility last updated 6/21/22. Questions regarding updates should be directed to the study team contact.
Feasibility of the Automated Platelet Aggregation System PlateletWorks® in Cardiac Surgery Patients
A Study to Evaluate Automated Platelet Function Test in Cardiac Surgery Patients
- Age ≥ 18 years old.
- Elective cardiac surgery with cardiopulmonary bypass.
- Informed consent on file.
- Presence of mechanical circulatory support.
- Transfusion of blood products before initiation of cardiopulmonary bypass (CPB).
Rapid dEtection of HyperkAlemia (K+) in the EmergenCy Department Using a SmarTphone-enabled Single-lead EKG (REACT) (REACT)
A Study to Detect Hyperkalemia Using Smartphone-enabled EKG
- Age greater than/equal to 50 years and able to provide consent.
- Patients with eGFR (from serum creatinine) < 45 ml/minute and/or a history of serum potassium > 5.2 mEq/l.
- Patients underage < 50.
- Do not meet inclusion criteria.
- Unstable patients requiring emergent resuscitation.
- Patients unable to provide consent.
DNA Evaluation of Fragments for Early Interception - Lung Cancer Training Study (DELFI-L101 Study) (DELFI-L101)
A Study to Evaluate DNA Evaluation of Fragments for Early Interception - Lung Cancer Training Study
All Subjects:
1. Ability to understand and provide written informed consent
2. Age ≥ 50 years
3. Current or Former Smoker
4. ≥ 20 pack-years (pack years = number of packs per day X number of years smoked)
Inclusion Group 1: High Risk Patients that meet criteria 5 and 6 below:
5. Prior thoracic imaging (computed tomography (CT)) within 12 months of enrollment OR
Planned thoracic imaging (CT) as part of standard of care within 6 weeks of enrollment
AND
6. Meet one of the criteria below:
1. No suspected or confirmed lung cancer diagnosis OR
2. Suspected of lung cancer OR
3. Confirmed, untreated lung cancer
Inclusion Group 2: High Risk Patients with cancer other than lung cancer that meet the
following criteria:
7. Pathologic confirmed, invasive cancer diagnosis, that is not lung cancer with no prior
systemic therapy, definitive therapy, radiation, or surgical resection.
All Subjects:
1. Prior systemic therapy, definitive therapy, radiation, or surgical resection for
cancer within one year prior to enrollment (with the exception of organ biopsies or
surgery for non-melanoma skin cancer)
2. Any history of hematologic malignancies or myelodysplasia
3. Any history of organ tissue transplantation
4. Any history of blood product transfusion
5. Current pregnancy
6. Any condition that in the opinion of the Investigator should preclude the subject's
participation in the study
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 11/16/22. Questions regarding updates should be directed to the study team contact.
A Pilot Study to Compare Short-Term Transcutaneous or Epidural Spinal Stimulation for Enabling Motor Function in Humans with Spinal Cord Injury
Service Line TransPerc
- Spinal cord injury due to trauma located at or above the tenth thoracic vertebrae
(T10)
- American Spinal Injury Association grading scale of A-D (2 from each) below the level
of SCI
- Intact spinal reflexes below the level of SCI
- At least 1-year post-SCI
- At least 22 years of age
- Willing to use medically acceptable methods of contraception, if female and of
child-bearing potential
- Currently a prison inmate, or awaiting trial, related to criminal activity
- Pregnancy at the time of enrollment
- History of chronic and/or treatment resistant urinary tract infection
- Unhealed decubitus ulcer
- Unhealed skeletal fracture
- Untreated clinical diagnosis of depression
- Undergoing, or planning to undergo, diathermy treatment
- Active participation in another interventional clinical trial
- Presence of conditions or disorders which require MRI monitoring
- A history of coagulopathy or other significant cardiac or medical risk factors for
surgery
- Current use of a ventilator
- Clinically diagnosed cardiopulmonary complications such as chronic obstructive
pulmonary disease, cardiac failure, or heart arrhythmia that contraindicate changes in
body position such as supine-to-sit-to-stand activities, prolonged standing, or
stepping
- History of frequent hypotension characterized by light headedness, or loss of
consciousness
- History of frequent hypertension characterized by headache, or bradycardia
- History of frequent, severe, autonomic dysreflexia
- Any illness or condition which, based on the research team's assessment, will
compromise with the patient's ability to comply with the protocol, patient safety, or
the validity of the data collected during this study.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 12/20/22. Questions regarding updates should be directed to the study team contact.
Aortic, Peripheral & Venous (APV) Product Surveillance Registry Platform Base Clinical Investigation
Product Surveillance Registry-APV
- Patient or legally authorized representative (LAR) provides authorization and/or consent per institution and geographical requirements.
- Patient has, or is intended to receive or be treated with, an eligible Medtronic product.
- Patient is consented within the enrollment window of the therapy received, as applicable.
- Patient who is, or is expected to be, inaccessible for follow-up.
- Patient is excluded by local law.
- Patient is currently enrolled in, or plans to enroll in, any concurrent drug/device study that may confound the PSR results (i.e., no required intervention that could affect interpretation of all-around product safety and/or effectiveness).
Research for Individualized Therapeutics in Rare Genetic Disease
Individualized Therapeutics in Rare Genetic Disease
- Has Mayo Clinic or other medical health system ID, or another unique identifier.
- Able to provide informed consent.
- Individual must have evidence of a genetic disorder as determined by a provider or genetic counselor with causative or likely causative genetic variants identified by molecular testing.
- Genetic variants must be hypothesized to be targetable using antisense oligonucleotide drugs (such as: knockdown gain of function alterations, increase protein production for reduced function alterations, or modulate mRNA splicing to correct abnormal splicing, promote normal splicing, or return reading frame to an out-of-frame transcript to restore function, etc.) based on current acceptable understanding of ASO mechanisms of action and tissue/organ targeting efficiency.
- Biological family member of an enrolled individual.
- Would be able to travel to a Mayo Clinic site for ongoing treatment should a therapeutic be developed.
- Treatment at the individual’s current disease state would likely provide benefit based on current clinical data and understanding of the progression of the disease.
Exclusion Criteria
- Individuals who have situations that would limit compliance with the study requirements.
- Institutionalized (i.e., Federal Medical Prison).
Oropharynx (OPX) Salivary Biomarker Study: Microbiome, Virome, and Metabolomics
OPX Saliva Biomarker Study
- Oropharynx or Oral Cavity Squamous Cell Carcinoma Patients: collected under the OPX Biomarker Protocol (IRB: 19-006036).
- Normal Controls:
- Age ≥ 18 years;
- Able to provide informed written consent documenting permission to give saliva sample for research testing;
- Ability to complete questionnaire(s) by themselves or with assistance.
- Oropharynx or Oral Cavity Squamous Cell Carcinoma Patients: collected under the OPX Biomarker Protocol (IRB: 19-006036).
- Normal Controls:
- Any personal history of head or neck cancer including head or neck skin cancer;
- Other active malignancy ≤ 5 years prior to registration.
- EXCEPTIONS: Non-melanotic skin cancer, non-metastatic prostate cancer.
- NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.
- Dry mouth (xerostomia) caused by any chronic (> 30 days) condition (known or unknown) or medication;
- Recent (within 30 days) or active upper aerodigestive tract or anogenital infections.
ACCESS: A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide for Patients with Hematologic Malignancies (ACCESS)
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
Stratum 1 Recipient
1. Age > 18 years and < 66 years (chemotherapy-based conditioning) or < 61 years (total
body irradiation [TBI]-based conditioning) at the time of signing informed consent
2. Planned MAC regimen as defined per protocol
3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with
age < 35 years
4. Product planned for infusion is PBSC
5. HCT Comorbidity Index (HCT-CI) < 5
6. One of the following diagnoses:
1. Acute myeloid leukemia (AML) acute lymphoblastic leukemia (ALL), or other acute
leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating
blasts or evidence of extra-medullary disease. Documentation of bone marrow
assessment will be accepted within 45 days prior to the anticipated start of
conditioning.
2. Patients with myelodysplastic syndrome (MDS) with no circulating blasts and with
< 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to
lack of differences in outcomes with < 5% or 5-10% blasts in MDS). Documentation
of bone marrow assessment will be accepted within 45 days prior to the
anticipated start of conditioning.
7. Cardiac function: Left ventricular ejection fraction > 45% based on most recent
echocardiogram or multigated acquisition scan (MUGA) results
8. Estimated creatinine clearance > 60 mL/min calculated by equation
9. Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO)
corrected for hemoglobin > 50% and forced expiratory volume in first second (FEV1)
predicted > 50% based on most recent pulmonary function test results
10. Liver function acceptable per local institutional guidelines
11. Karnofsky performance status (KPS) of > 70%
12. Subjects ≥ 18 years of age or legally authorized representative must have the ability
to give informed consent according to applicable regulatory and local institutional
requirements.
Stratum 2 Recipient Inclusion Criteria
1. Age > 18 years at the time of signing informed consent
2. Planned NMA/RIC regimen as defined per protocol
3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with
age < 35 years
4. Product planned for infusion is PBSC
5. One of the following diagnoses:
1. Patients with acute leukemia or chronic myeloid leukemia (CML) with no
circulating blasts, no evidence of extramedullary disease, and with < 5% blasts
in the bone marrow. Documentation of bone marrow assessment will be accepted
within 45 days prior to the anticipated start of conditioning.
2. Patients with MDS with no circulating blasts and with < 10% blasts in the bone
marrow (higher blast percentage allowed in MDS due to lack of differences in
outcomes with < 5% or 5-10% blasts in MDS.) Documentation of bone marrow
assessment will be accepted within 45 days prior to the anticipated start of
conditioning.
3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including
prolymphocytic leukemia) with chemosensitive disease at time of transplantation
4. Patients with lymphoma with chemosensitive disease at the time of transplantation
6. Cardiac function: Left ventricular ejection fraction > 45% based on most recent
echocardiogram or MUGA results with no clinical evidence of heart failure
7. Estimated creatinine clearance > 60 mL/min calculated by equation
8. Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted > 50% based
on most recent pulmonary function test results
9. Liver function acceptable per local institutional guidelines
10. KPS of > 60%
11. Subjects ≥ 18 years of age or legally authorized representative must have the ability
to give informed consent according to applicable regulatory and local institutional
requirements.
Stratum 3 Recipient Inclusion Criteria
1. Age > 1 years and < 21 years at the time of signing informed consent
2. Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35
years
3. Product planned for infusion is BM
4. Planned MAC regimen as defined per protocol
5. One of the following diagnosis:
1. AML in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts or
evidence of extra-medullary disease. Pre-transplant MRD testing will be performed
as per standard of practice at the treating institution. Patients with any MRD
status are eligible and should be enrolled at the discretion of provider.
Documentation of bone marrow assessment will be accepted within 45 days prior to
the anticipated start of conditioning.
2. Patients MDS with no circulating blasts and less than 10% blasts in the bone
marrow. Documentation of bone marrow assessment will be accepted within 45 days
prior to the anticipated start of conditioning.
3. ALL in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts, or
evidence of extra-medullary disease. Pre-transplant MRD testing will be performed
as standard practice at the treating institution with the goal of achieving MRD
of <0.01%. Patients with any MRD status are eligible and should be enrolled at
the discretion of provider. Documentation of bone marrow assessment will be
accepted within 45 days prior to the anticipated start of conditioning.
4. Other leukemia (mixed-phenotype acute leukemia [MPAL], CML, or other leukemia) in
morphologic remission with ≤ 5% marrow blasts and no circulating blasts or
evidence of extramedullary disease. Documentation of bone marrow assessment will
be accepted within 45 days prior to the anticipated start of conditioning.
5. Chemotherapy sensitive lymphoma in at least partial remission (PR)
6. KPS or Lansky performance score ≥ 70%
7. Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction
of ≥ 27% based on most recent echocardiogram
8. Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine
scan or calculated from a 24 hour urine collection
9. Pulmonary function: DLCO corrected for hemoglobin, FEV1, and Forced Vital Capacity
(FVC) of ≥50% if able to perform pulmonary function tests. If unable to perform
pulmonary function tests, must have a resting pulse oximetry of >92% without
supplemental oxygen.
10. Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate
aminotransferase (AST) < 3x the upper limit of normal
11. Legal guardian permission must be obtained for subjects < 18 years of age. Pediatric
subjects will be included in age appropriate discussion in order to obtain assent.
12. Subjects ≥ 18 years of age or legally authorized representative must have the ability
to give informed consent according to applicable regulatory and local institutional
requirements.
Donor
1. Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or
7/8 (HLA-A, -B, -C, and -DRB1)
2. Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DRB1, -DQB1,
and -DPB1
3. Age > 18 years and < 35 years at the time of signing informed consent
4. Meet the donor registries' medical suitability requirements for PBSC or BM donation
5. Must undergo eligibility screening according to current Food and Drug Administration
(FDA) requirements. Donors who do not meet one or more of the donor screening
requirements may donate under urgent medical need.
6. Must agree to donate PBSC (or BM for stratum 3)
7. Must have the ability to give standard (non-study) informed consent according to
applicable donor regulatory requirements
Recipient Exclusion Criteria (Strata 1, 2 and 3):
1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
2. Subject unwilling or unable to give informed consent, or unable to comply with the
protocol including required follow-up and testing
3. Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia,
polycythemia vera, or MDS with grade 4 marrow fibrosis
4. Subjects with a prior allogeneic transplant
5. Subjects with an autologous transplant within the past 3 months
6. Females who are breast-feeding or pregnant
7. Uncontrolled bacterial, viral or fungal infection at the time of the transplant
preparative regimen
8. Concurrent enrollment on other interventional GVHD clinical trial (enrollment on
supportive care trials may be allowed after discussion with Principal Investigators)
9. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to
transplant.
10. Patients who are HIV+ with persistently positive viral load. HIV-infected patients on
effective anti-retroviral therapy with undetectable viral load within 6 months are
eligible for this trial.
Donor
1. Donor unwilling or unable to donate
2. Recipient positive anti-donor HLA antibodies against a mismatched HLA in the selected
donor determined by either:
1. a positive crossmatch test of any titer (by complement-dependent cytotoxicity or
flow cytometric testing) or
2. the presence of anti-donor HLA antibody to any HLA locus (HLA-A, -B, -C, -DRB1,
-DQB1, -DQA1, -DPB1, -DPA1) with mean fluorescence intensity (MFI) >3000 by solid
phase immunoassay
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 Phase 3, 52-week, Open-label, Single-arm Study to Investigate the Efficacy and Safety of Mepolizumab SC in Participants Aged 6 to 17 years with Hypereosinophilic Syndrome (SPHERE)
Study in Pediatrics with HypEREosinophilic Syndrome
- Participant must be aged 6 to 17 years, inclusive, at Screening (Visit 1).
- Participants who have been diagnosed with HES for at least 6 months prior to enrolment (Visit 2).
- A history of 2 or more HES flares within the past 12 months prior to Screening (Visit 1).
- Participants must have blood eosinophil count ≥ 1000 cells per microliter (/mcL) present at Screening.
- Participants must be on a stable dose of HES therapy for the 4 weeks prior to the first dose of mepolizumab (Visit 2).
- Male and/or female.
- Signed written informed consent.
- Life-threatening HES or life-threatening HES co-morbidities.
- Other concurrent medical conditions that may affect the participant's safety.
- Eosinophilia of unknown significance.
- Fusion tyrosine kinase gene translocation [FIP1L1.
- Platelet-derived Growth Factor Receptor (PDGFRα) (F/P)] positivity.
- Clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA).
- Participants with chronic or ongoing active infections requiring systemic treatment, as well as participants who have experienced clinically significant infections due to viruses, bacteria, and fungi within 4 weeks prior to enrolment (Visit 2).
- Participants with a pre-existing parasitic infestation within 6 months prior to enrolment (Visit 2).
- Participants with a known immunodeficiency (e.g., Human immunodeficiency virus [HIV]), other than that explained by the use of OCS or other therapy taken for HES
- Participants with documented history of any clinically significant cardiac damage prior to Screening (Visit 1) that, in the opinion of the investigator, would impact the participant's participation during the study.
- Participants with a history of or current lymphoma.
- Participants with current malignancy or previous history of cancer in remission for less than 12 months prior to Screening (Visit 1).
- Participants who are not responsive to OCS based on clinical response or blood eosinophil counts.
- Participants who have previously received mepolizumab in the 4 months prior to enrolment (Visit 2).
- Participants receiving non-oral systemic corticosteroids in the 4-week period prior to enrolment (Visit 2).
- Participants who have received any other monoclonal antibodies within 30 days or 5 half-lives, whichever is longer, of enrolment (Visit 2).
- Participants who have received treatment with an investigational agent (biologic or non-biologic) within the past 30 days or 5 drug half-lives, whichever is longer, prior to enrolment (Visit 2).
- Use of candidate Coronavirus disease 2019 (COVID-19) vaccines that have not received limited, accelerated, or full authorization/approval, and are only in use as part of a clinical trial.
- Participants who are currently participating in any other interventional clinical study.
- Participants with any history of hypersensitivity to any monoclonal antibody (including mepolizumab).
- Evidence of clinically significant abnormality in the hematological, biochemical, or urinalysis screen from the sample collected at Screening (Visit 1), that could put the participant's safety at risk by participating in the study, as judged by the investigator.
International Patient Education with Cultural Emphasis (I-PECE) (I-PECE)
Cross-Cultural Patient Education
- Age 18- 90 years.
- Able to communicate and participate in their own care.
- Speak a language that we do not have in-person translator at the clinic.
North American Prodromal Synucleinopathy Consortium for RBD, Stage 2 (NAPS2) (NAPS2)
North American Prodromal Synucleinopathy Consortium for RBD
Inclusion Criteria
•RBD Group:
- All participants must have polysomnogram-confirmed RBD by ICSD-3 criteria [AASM 2014]. An EDF of a polysomnogram demonstrating RSWA must be available from NAPS1 or obtainable from elsewhere to verify this entry criterion.
- Capable of providing informed consent at time of NAPS2 study enrollment, unless the participant previously enrolled in NAPS1:
- For individuals previously enrolled in NAPS1 who developed cognitive decline and are no longer able to provide informed consent prior to enrollment in NAPS2, informed consent will be obtained from the legally authorized representative, and written assent obtained from the participant;
- Individuals who enroll in NAPS2 will identify a proxy at initial enrollment. If a participant subsequently develops cognitive decline and is no longer able to provide informed consent for revised consent documents during follow-up visits, the proxy or legally authorized representative (depending on local regulations) will be asked to provide informed consent, and written assent obtained from the participant.
- Age ≥ 18 years.
Exclusion Criteria
•RBD Group:
- PD, dementia of any type, or MSA unless the individual was previously enrolled in NAPS1. Participants who phenoconvert during NAPS2 will be eligible to continue participation if they enrolled at a time when they were capable for providing informed consent.
- Coexisting cognitive, motor, or autonomic symptoms are permitted in the RBD group provided that a diagnosis of dementia, PD, MSA, or any other overt neurodegenerative phenotype is not present;
- The presence of “soft” cognitive, motor, autonomic, or other neurologic symptoms are appropriate for inclusion since 1) such features are common among RBD patients in the clinical setting, 2) such features are common in NAPS1participants,3) the NAPS2 program is designed to mimic recruitment of RBD patients who may be appropriate for participation in clinical trials, and 4) a primary goal of NAPS2 is to identify those at short-term risk of phenoconversion since clinical trials will focus on such RBD patient.
- Narcolepsy-associated RBD.
- RBD secondary to any known cause except prodromal synucleinopathy.
- Participation in a clinical trial, except by specific permission by the Executive Committee.
- In the opinion of the investigator, the participant has a clinically significant uncontrolled medical condition that would impede safe completion of the study protocol.
Exclusions for Specific Procedures - RBD Group:
RBD participants will not be excluded from NAPS2 for the following exclusions; they will be excluded from undergoing the specific procedure(s).
- Exclusions specific for MRI include any of the following:
- metal implant or pacemaker;
- Pregnancy;
- Head/shoulder or body girth/weight unable to fit in the MRI scanner and coils;
- Note that RBD participants who have claustrophobia or other issues completing MRI will not be excluded necessarily from MRI;
- Exclusions specific for DaTscan SPECT include any of the following:
- Pregnancy;
- Head/shoulder or body girth/weight unable to fit in the SPECT scanner;
- Note that RBD participants who have claustrophobia or other issues completing DaTscan will not be excluded necessarily from DaTscan;
- Note that RBD participants who take concomitant medications that are potentially interfering for DaTscan as listed in the NI Manual of Procedures will not be excluded necessarily from DaTscan, but the specific medication(s) will be held if possible per site-specific protocols and at the discretion of the local Site Investigator. Any such medications will be noted in source documents at the time of scan.
- History of an allergic reaction to iodine and iodine-containing products such as IV contrast dye (used for CT scans, IVPs, etc.). An allergy to shellfish is not exclusionary.
- Exclusions specific for lumbar puncture include any of the following:
- Diagnosis of a bleeding disorder;
- Anticoagulant medication (coumadin, aspirin, etc.) is at the discretion of the local Site Investigator. Site-specific procedures for lumbar puncture should be followed.
Inclusion Criteria
•Control Group:
- Ability to provide written consent.
- Age ≥ 18 years
- Must meet age, sex, and race matching criteria per the DMS core recommendations for the site.
- Must be willing and able to undergo all testing procedures, including neuroimaging and lumbar puncture.
- Normal capacity to perform complex activities of daily living independently based on informant or physician report.
Exclusion Criteria
•Control Group:
- History of dream enactment behavior to suggest RBD
- Parkinsonism, MSA, dementia, or mild cognitive impairment
- Active central nervous system, systemic, psychiatric condition or use of psychoactive medication that would adversely affect cognitive, neuropsychiatric, motor, or autonomic functioning:
-
- Since the goal is to include typical normal persons, the Controls may include participants with adequately controlled medical and psychiatric conditions (based on physician determination and stratification in the RBD cohort);
- This includes the use of stable doses of antidepressant medications, and their presence will be factored into any RBD vs Controls analyses.
- Contraindications to complete MRI, including any of the following:
- metal implant or pacemaker;
- too claustrophobic to complete MRI scans;
- previous issue completing an MRI;
- Pregnancy;
- Head/shoulder or body girth unable to fit in the MRI scanner and coils;
- Body mass index > 35 kg/m^2 or weight > 300 lbs, due to neuroimaging scanner limits;
- Participation in a clinical trial, except by specific permission by the Executive Committee;
- In the opinion of the investigator, the participant has a clinically significant uncontrolled medical condition.
- Contraindications to complete lumbar puncture:
- Diagnosis of a bleeding disorder;
- Anticoagulant medication (coumadin, aspirin, etc.) is at the discretion of the local Site Investigator. Site-specific procedures for lumbar puncture should be followed.
Eligibility last updated 1/14/22. Questions regarding updates should be directed to the study team contact.
A Minimal-Risk, Multi-Center, Prospective, Clinical Trial to Evaluate the PrevisEA Device for Predicting Gastrointestinal Impairment (Entac)
Clinical Trial to Evaluate the PrevisEA Device for Predicting Gastrointestinal Impairment
- ≥ 18 and ≤ 90 years of age.
- Patient undergoing elective intestinal resection surgery including open, laparoscopic, robotic, or hand-assist technique for:
- Segmental ileocolic resection with or without diversion;
- Segmental colon resection with or without diversion;
- Segmental coloproctectomy with or without diversion;
- Low anterior resection with or without diversion;
- Abdominoperineal resection;
- Total abdominal colectomy with or without diversion;
- Proctocolectomy with or without end ileostomy or diversion;
- Closure of end colostomy (Hartmann’s reversal).
- Allergies to any of the device components (i.e., adhesive).
- Inability to have prototype device applied to their abdominal wall due to disease conditions or surgical alterations (e.g., fistulas, stomas, drains, etc.).
- Patients undergoing:
- Small bowel resection without colonic resection;
- Transanal proctectomy without transabdominal approach;
- Perineal proctosigmoidectomy;
- Closure of loop colostomy or ileostomy.
- Patients with preoperative evidence of an anastomotic leak, deep wound infection, organ space infection, or urinary tract infection.