Health Studies MN
A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
All
180 Days to 22 Years old
Phase 2
NCT05828069
Inclusion Criteria:
• 180 days- < 22 years (at time of study enrollment)
• Patients with multifocal progressive, relapsed, or recurrent LCH with measurable disease at study entry
• Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
• Tissue confirmation of relapse is recommended but not required
• Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
• Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent biopsies) will be required for retrospective central confirmation of diagnosis and molecular studies
• Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included
• Patients must have measurable disease, documented by radiographic imaging (LCH- specific response criteria (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary).
• Patients must have progressive or refractory disease or experience relapse after at least one previous systemic chemotherapy treatment strategy
• Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50% for patients =< 16 years of age
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study
• Investigational agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent for at least 14 days prior to planned start of tovorafenib (DAY101)
• Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT
• Patients must have fully recovered from any prior surgery
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy with toxicities reduced to Grade 1 or less (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
• Steroids: < 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to study enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to study enrollment
• Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation
• Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation
• Peripheral absolute neutrophil count (ANC) >= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
• Platelet count >= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
• Patients with marrow disease must have platelet count of >= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented
• Hemoglobin >= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin >= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented
• Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta [registered trademark]) or 7 days for short-acting growth factor
• A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
• Age: 6 months to < 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
• Age: 1 to < 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
• Age: 2 to < 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
• Age: 6 to < 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
• Age: 10 to < 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
• 13 to < 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
• Age: >= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
• OR- a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2
• OR- a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
• Alanine aminotransferase (ALT) =< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
• Serum albumin >= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
• For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease
• Fractional shortening (FS) of >= 25% or ejection fraction of >= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
• No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH
• Central Nervous System Function Defined As:
• Patients with seizure disorder may be enrolled if well controlled
• Central nervous system (CNS) toxicity =< Grade 2
• Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication
Exclusion Criteria:
• LCH arising along with other hematologic malignancy (e.g. mixed LCH with acute lymphoblastic leukemia) or any history of non-histiocytic malignancy
• Disease scenarios as below will be excluded
• Skin-limited disease
• Single bone lesion
• Gastrointestinal (GI) tract involvement only (those that have disease that can be determined by endoscopic biopsies only)
• LCH-associated neurodegeneration (LCH-ND) without parenchymal lesions or other systemic lesions
• Patients with activating mutations in MAP2K1 are not eligible for this study due to drug target specificity. Mutation status will be submitted to study team within 7 days of enrollment
• Patient must not have received any prior MAPK pathway inhibitor therapy
• Refractory nausea and vomiting, malabsorption, or external biliary shunt that would preclude adequate absorption of tovorafenib (DAY101)
• Uncontrolled systemic bacterial, viral, or fungal infection
• Major surgical procedure or significant traumatic injury within 14 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days of study enrollment (provided that the wound has healed)
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
• History of solid organ or hematopoietic bone marrow transplantation
• Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged QT interval > 440 ms based on triplicate electrocardiogram (ECG) average
• History of Grade >= 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of study entry
• History of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS) or who are allergic to tovorafenib (DAY101) or any of its components
• CTCAE version (V). 5.0 Grade 3 symptomatic creatinine kinase (CPK) elevation ( > 5 x ULN)
• Female patients who are pregnant are ineligible. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants are ineligible
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are ineligible. Participants (male and female) who are sexually active must use two forms of an acceptable method of birth control (for men, one form must be a barrier method) from start of therapy through 180 days following last dose of tovorafenib (DAY101)
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Computed Tomography, Procedure: Echocardiography, Procedure: FDG-Positron Emission Tomography and Computed Tomography Scan, Procedure: Lumbar Puncture, Procedure: Multigated Acquisition Scan, Drug: Tovorafenib
Recurrent Langerhans Cell Histiocytosis, Refractory Langerhans Cell Histiocytosis
A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab
All
5 Years to 60 Years old
Phase 3
NCT05675410
Inclusion Criteria:
• Patients must be 5 to 60 years of age at the time of enrollment
• Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]) with stage I or II disease
• Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm)
• Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained
• Pediatric patients (age 5-17 years) must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease. Adult patients must have either a CXR or CT chest
• Patients >= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2
• Patients =< 17 years of age must have a Lansky performance score of >= 50
• Pediatric patients (age 5-17 years): A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• 2 to < 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female)
• 6 to < 10 years (age): 1 mg/dL (male), 1 mg/dL (female)
• 10 to < 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female)
• 13 to < 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• For adult patients (age 18 years or older) (within 7 days prior to enrollment): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
• Total bilirubin =< 2 x upper limit of normal (ULN) (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Aspartate aminotransferase (AST) =< 3 x ULN (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Alanine aminotransferase (ALT) =< 3 x ULN (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Shortening fraction of >= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 7 days prior to enrollment) or ejection fraction of >= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 7 days prior to enrollment)
• Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 7 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of > 92% on room air
• Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
• Patients with nodular lymphocyte predominant Hodgkin lymphoma
• Patients with a history of active interstitial pneumonitis or interstitial lung disease
• Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients
• Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills
• Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to > 10 mg daily prednisone for patients >= 18 years or > 0.5 mg/kg [up to 10 mg/day] for patients < 18 years) or other immunosuppressive medications within 14 days prior to enrollment
• Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=< 10 mg daily for patients >= 18 years or =< 0.5 mg/kg [up to 10 mg/day] prednisone equivalents) are permitted in the absence of active autoimmune disease
• Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1
• Patients with peripheral neuropathy > grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL
• Prior solid organ transplant
• Prior allogeneic stem cell transplantation
• Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, bacillus calmette guerin [BCG], oral polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment
• Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of < 1% per year when used consistently and correctly) for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer
• Men and women of childbearing potential must continue contraception for a period of 6 months after last dose of brentuximab vedotin
• Women of child-bearing potential (WOCBP) must continue contraception for a period of at least 5 months after the last dose of nivolumab
• 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
Procedure: Biospecimen Collection, Biological: Bleomycin Sulfate, Drug: Brentuximab Vedotin, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Dacarbazine, Drug: Doxorubicin Hydrochloride, Drug: Etoposide, Drug: Etoposide Phosphate, Other: Fludeoxyglucose F-18, Radiation: Involved-site Radiation Therapy, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Procedure: Positron Emission Tomography, Drug: Prednisolone, Drug: Prednisone, Drug: Procarbazine Hydrochloride, Other: Questionnaire Administration, Drug: Vinblastine Sulfate, Drug: Vincristine Sulfate
Lugano Classification Limited Stage Hodgkin Lymphoma AJCC v8
Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma
Female
18 Years and over
Phase 2/Phase 3
NCT05256225
Inclusion Criteria:
• Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IVB, non-recurrent, chemotherapy (chemo)-naive, HER2-positive endometrial serous carcinoma or endometrial carcinosarcoma
• Histologic confirmation of the original primary tumor is required. Submission of surgical pathology report (or endometrial biopsy pathology report in patients who never undergo hysterectomy) is required
• Patients must be within 8 weeks of primary surgery (or endometrial biopsy in patients who never undergo hysterectomy) at the time of study registration
• Patients may have measurable disease, non-measurable disease, or no measurable disease. In patients with measurable disease, lesions will be defined and monitored by RECIST v 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• For patients with uterine-confined (stage I) disease, the tumor must be invasive into the myometrium. Any amount of myoinvasion is acceptable for eligibility. Patients with non-invasive disease, endometrial intraepithelial carcinoma alone, or disease confined to a polyp will be excluded
• Additionally, patients must have the following histologic types to be eligible:
• Serous adenocarcinoma (may include =< 10% non-serous histology)
• Carcinosarcoma with serous epithelial component (only the serous component needs to be HER2 positive; may include =< 10% non-serous histology)
• In cases where determination of serous is equivocal or challenging, aberrant p53 immunohistochemistry (IHC) (defined as overexpression of p53 compared to internal controls) will be sufficient for inclusion
• All patients must have tumors that are HER2 positive as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 Breast Cancer guidelines (https://documents.cap.org/documents/algorithim-evaluation-her2.pdf. In general HER2 positivity is defined as any of the following:
• 3+ immunohistochemistry (IHC),
• 2+ IHC with positive in situ hybridization (ISH)
• Average HER2 copy number >= 6.0 signals/cell
• Average HER2 copy number >= 4.0 and < 6.0 signals/cell, with concurrent IHC 3+
• HER2/CEP17 ratio >= 4.0 signals/cell
• HER2/CEP 17 ratio >= 2.0 and < 4.0, with concurrent IHC 3+ IHC and ISH testing will be done locally, at each participating institution and interpreted by local pathologists. Alternatively, patients could be eligible if next generation sequencing (NGS) demonstrates HER2 (ERBB2) amplification. NGS testing can be performed through any designated labs as per the National Cancer Institute (NCI) MATCH/NCI Combo-MATCH trial (https://ecog-acrin.org/nci-match-eay131-designated-labs). Pathology report showing results of institutional HER2 testing (or NGS testing results) must be submitted. Sites must submit all results available (IHC, ISH, and NGS)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Age >= 18
• Platelets >= 100,000/mcl (within 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) or estimated Glomerular filtration rate (eGFR) >= 50 mL/min using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR). (within 14 days prior to registration)
• Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
• Although the uterus will have been removed in the vast majority of patients, for patients of child-bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. Patients will be considered of non-reproductive potential if they are either:
• Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR
• Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to registration
• Have a congenital or acquired condition that prevents childbearing
• 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. NOTE: Patients with prior anthracycline exposure are NOT eligible
• Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Prior Therapy:
• Patients must NOT have received prior chemotherapy, biologic therapy, or targeted therapy for treatment of endometrial carcinoma
• Patients must NOT have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation includes external beam pelvic radiation therapy, external beam extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy
• NOTE: Vaginal brachytherapy for treatment of endometrial cancer is permitted during study treatment. Planned use of vaginal brachytherapy must be declared at time of registration
• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to registration
• Patients may not have a planned interval cytoreduction or hysterectomy, prior to documentation of progression, after study registration
• Patients may not have planned external beam radiotherapy, prior to documentation of progression, after study registration
• Significant cardiovascular disease including:
• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg despite antihypertensive medications
• Myocardial infarction or unstable angina within 6 months prior to registration
• New York Heart Association functional classification II, III or IV
• Serious cardiac arrhythmia requiring medication. This does not include asymptomatic, atrial fibrillation with controlled ventricular rate
• Significant lung disease: dyspnea at rest grade 2 or greater (resulting from extensive tumor involvement or other causes), pneumonitis grade 2 or greater, interstitial lung disease grade 2 or greater, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Patients with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), uncontrolled interstitial lung disease, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
• Treatment with strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to registration
• Women who are unwilling to discontinue nursing
Drug: Carboplatin, Procedure: Echocardiography, Drug: Hyaluronidase-zzxf/Pertuzumab/Trastuzumab, Procedure: Multigated Acquisition Scan, Drug: Paclitaxel, Other: Quality-of-Life Assessment, Drug: Trastuzumab/Hyaluronidase-oysk
Endometrial Serous Adenocarcinoma, Uterine Corpus Carcinosarcoma
Oral N-acetylcysteine for Retinitis Pigmentosa (NAC Attack)
All
18 Years to 65 Years old
Phase 3
NCT05537220
Inclusion Criteria:
General
• Ability and willingness to provide informed consent
• Age ≥ 18 and ≤65 years at time of signing Informed Consent Form
• Ability and willingness to comply with the study protocol and to participate in all study visits and assessments in the investigator's judgement
• For candidates of childbearing potential: willingness to use a method of contraception
• Agreement not to take supplements other than vitamin A Ocular Inclusion Criteria
• Both eyes must exhibit the RP phenotype with evidence of loss of night vision, gradual constriction of visual fields, and maintenance of visual acuity;
• In addition, an eye must meet the following criteria to be included in the study:
• Gradable EZ on a horizontal SD-OCT scan through the fovea center with width ≤ 8000 µm and ≥1500 µm and with well-defined truncation at both the nasal and temporal sides;
• BCVA ≥ ETDRS letter score of 61 (20/60 Snellen equivalent);
• Sufficiently clear ocular media and adequate pupillary dilation to allow good quality images sufficient for analysis and grading by central reading center.
Exclusion Criteria:
General Exclusion Criteria
• Active cancer within the past 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score ≤ 6 and stable prostate specific antigen for > 12 months
• Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis during the study
• Liver disease, cystic fibrosis, asthma, or chronic obstructive pulmonary disease (COPD), history of thrombocytopenia not due to a reversible cause or other blood dyscrasia
• Uncontrolled blood pressure (defined as systolic > 180 and/or diastolic > 100 mmHg while at rest) at screening. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient's blood pressure must be controlled by antihypertensive medication, the patient may become eligible if medication is taken continuously for at least 30 days.
• History of other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion that oral NAC may be contraindicated or that follow up may be jeopardized
• Cerebrovascular accident or myocardial infarction within 6 months of screening
• Participation in an investigational study that involves treatment with any drug or device within 6 months of screening
• Three relatives already enrolled in study
• Pregnant, breast feeding, or intending to become pregnant during the study treatment period. Women of childbearing potential who have not had tubal ligation must have a urine pregnancy test at screening.
• Known history of allergy to NAC
• Having taken NAC in any form in the past 4 months
• Phenylketonuria
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• Abnormal laboratory value including the value of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin being greater than 1.5 x the upper limit of normal
• Any major abnormal findings on blood chemistry, hematology, and renal function lab tests that in the opinion of the Site Investigator and/or the Study Chair makes the candidate not suitable to participate in the trial
• HIV or hepatitis B infection Ocular Exclusion Criteria
• Evidence of cone-rod dystrophy or pattern dystrophy including focal areas of atrophy or pigmentary changes in the central macula
• Cystoid spaces involving the fovea substantially reducing vision
• Glaucoma or other optic nerve disease causing visual field loss or reduced visual acuity
• Intra ocular pressure >27 mm Hg from two measurements. If a patient's initial measurement exceeds 27 mm Hg, a second reading must be taken.
• Any retinal disease other than RP causing reduction in visual field or visual acuity
• Any prior macular laser photocoagulation
• Intraocular surgery within 3 months prior to screening
• High myopia with spherical equivalent refractive error > 8 diopters. If an eye has had cataract surgery or refractive surgery, a pre-operative refractive error spherical equivalent > 8 diopters is an exclusion
• Any concurrent ocular condition that might affect interpretation of results
• History of uveitis in either eye
Drug: N-acetylcysteine, Drug: Placebo
Retinitis Pigmentosa
N-acetylcysteine, Ellipsoid zone, Macular sensitivity, Best corrected visual acuity, Ellipsoid zone width, Ellipsoid zone area, Oxidative damage, Usher Syndrome, Antioxidants
A Qualitative Study of the Use of Cold Caps to Prevent Hair Loss During Chemotherapy
A Study of the Use of Cold Caps to Prevent Hair Loss in Chemotherapy Patients
Aminah Jatoi
All
18 years and over
0000-121929-H01-RST
19-002573
Inclusion Criteria:
- Patients who have used a cold cap at least once for purposes of hair loss prevention during chemotherapy treatment.
Exclusion Criteria:
- None.
A Randomized, Double-Blind, Phase 2 Pilot Study of VLX-1005 Versus Placebo in Participants With Suspected Heparin Induced Thrombocytopenia Treated With Background Standard of Care
A Phase 2 Study of VLX-1005 Versus Placebo in Suspected Heparin Induced Thrombocytopenia
Damon Houghton
All
18 years and over
Phase 2
2023-312080-P01-RST
23-005715
Inclusion Criteria:
1. Adult participants ≥ 18 years of age.
2. Able to provide informed consent or have informed consent provided on their behalf by
a primary caregiver prior to study-related activities being initiated.
3. Recent unfractionated heparin or low-molecular-weight heparin exposure.
4. Qualifying platelet count < 150 X 10^9/L and clinical 4T score of ≥ 4; candidate for
argatroban or bivalirudin treatment.
5. Positive PF4-immunoassay (eg, ELISA [≥ 1.0 optical density units], LIA [≥ 1.0 U/mL],
CLIA [≥ 1.0 U/mL]).
-Exclusion Criteria:
1. Previous treatment with argatroban or bivalirudin for > 48 hr prior to randomization.
2. Participants cannot receive other anti-coagulants, such as fondaparinux and
danaparoid, or direct oral anti-coagulants, such as rivaroxaban as initial standard of
care.
3. QT interval corrected by the method of Fridericia (QTcF) > 450 msec for males, > 470
msec for females.
4. History of hepatitis C antibody, hepatitis B surface antigen, or human
immunodeficiency virus (HIV) antibody at screening.
5. Current renal disease with a calculated creatinine clearance less than 30 mL/min.
6. Participants with a history of substance abuse or dependency or history of
recreational IV drug use (by self-declaration).
7. Participant has a suspected history of alcohol abuse in the 6 months prior to
screening.
8. Participants who are unlikely to comply with the study protocol or, in the opinion of
the investigator, would not be a suitable candidate for participation in the study.
9. Participants with cancer, having a life expectancy of < 12 months.
10. Current diagnosis of or any other clinically significant indication of active sepsis
11. Pregnant or lactating women.
12. Have participated in any other investigational drug trial within 30 days of dosing or
5 half-lives (whichever is longer) in the current study.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 7/6/23. Questions regarding updates should be directed to the study team contact.
Drug
A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)
All
Not specified
Phase 3
NCT04573023
Inclusion Criteria:
• A patient who voluntarily signs an Institutional Review Board or Independent Ethics Committee-approved written informed consent form. If the patient is aged under 18 years (aged under 16 years in the UK) at the time of enrollment or willingness to participate in the study cannot be confirmed due to MPS II-related intellectual disability, the patient's legally acceptable representative (e.g., his/her parents or guardians) may sign the informed consent on behalf of the patient. Written informed assent should be obtained from the patient, wherever possible.
• Patients with confirmed diagnosis of MPS II
• Naïve patients or patients who are receiving stable enzyme replacement therapy with idursulfase for more than 12 weeks before starting administration of JR-141 or idursulfase for this study.
• Patients or patients whose partners are of child-bearing potential agree to use a medically accepted, highly effective method of contraception being use of condoms from the time of informed consent.
• Patients aged 36-42 months old at the time of ICF signing: patients must have a standard score measured by the BSID-III of 85 or less at screening.
• Patients aged 43-71 months old at the time of ICF signing: patients must EITHER have (1) A DQ measured by BSID-III of 20 to 85 at screening OR (2) A composite standard score on NVI measured by KABC-II of 85 or less at screening (only who can perform KABC-II)
• Patients aged 30-35 months old at the time of randomization and who are judged as having the severe phenotype by the Expert Board.
• Patients 6 years of age or older at the time of ICF signing and whose IQ are 70 and higher.
• Enrollment of subjects in Cohort B is contingent on the availability in that country of a validated country-specific version of the test (either WISC-V, WAIS-IV, or T.O.V.A.).
• Attenuated patients with 1 SD deficiency in the omission errors or variability domains of the T.O.V.A..
Exclusion Criteria:
• A patient with a history of HSCT with successful engraftment.
• A patient who has received gene therapy treatment at any point.
• Unable to undergo lumbar puncture.
• A patient who is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 4 months before obtaining informed consent.
• Unable to comply with the protocol as determined by the principal investigator or subinvestigator.
• Judged by the principal investigator or subinvestigator to be ineligible to participate in the study due to a history of serious drug allergy or sensitivity including anesthesia or hypersensitivity to any component of JR-141.
• A patient who has a known or suspected local or general infection or is at risk of abnormal bleeding due to medical conditions or therapies.
• A patient who has documented mutation of other genes, including loci adjacent to the IDS gene that are known to be associated with developmental delay, seizures, or other significant CNS disorders.
• A patient who has documented loss of activity of sulfatases other than IDS.
• A patient who has had a ventriculoperitoneal shunt placed or any other brain surgery, or has a clinically significant ventriculoperitoneal shunt malfunction within 30 days of screening.
• full time employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members.
• A patient who otherwise is judged by the principle investigator or sub-investigator to be ineligible to participate in the study. [Only in France]
• Persons deprived of their liberty by a judicial or administrative decision, according to article L.1121-6 the Public Health Code (Code de la santé publique), adults who are the subject of a measure of legal protection or unable to express their consent according to article L. 1121-8 of the Code de la santé publique)
Drug: JR-141, Drug: Idursulfase, Drug: JR-141 or Idursulfase
Mucopolysaccharidosis II
Janus Kinase (JAK) Inhibitors to Preserve C-Peptide Production in New Onset Type 1 Diabetes (T1D)
All
12 Years to 35 Years old
Phase 2
NCT05743244
Inclusion Criteria:
1. Provide informed consent or assent as appropriate and, if < 18 years of age have a
parent or legal guardian provide informed consent
2. Age 12-35 years (both inclusive) at the time of signing informed consent and assent
3. Diagnosis of T1D within 100 days of the baseline visit (V0).
4. Positive for at least one islet cell autoantibody; Glutamate decarboxylase (GAD)65A,
mIAA (if obtained within 10 days of the onset of insulin therapy), IA-2A, ICA, or
ZnT8A
5. Stimulated C-peptide of ≥0.2 pmol/mL measured during mixed-meal tolerance test (MMTT)
conducted at least 21 days from diagnosis of diabetes
6. HbA1c ≤ 10 %
7. Body weight ≥ 35kg at screening
8. Willing to comply with intensive diabetes management and wear a Continuous Glucose
Monitoring Device (CGM)
9. Participants who are Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV)
seronegative at screening must be CMV and/or EBV Polymerase chain reaction (PCR)
negative within 30 days of randomization and may not have had signs or symptoms of a
CMV and/or EBV-compatible illness lasting longer than 7 days within 30 days of the
baseline visit (V0).
10. Be up to date on recommended immunizations; participants are required to receive
killed influenza vaccination at least 2 weeks prior to the baseline visit (V0) when
vaccine for the current or upcoming flu season is available. Enrollment must be
delayed at least 4 weeks from administration of a killed vaccine other than influenza
and 6 weeks from a live vaccination. Vaccinations should not be given while on study
drug and be postponed at least 3 months after the last dose of study drug.
11. Participants are required to be fully vaccinated including eligible boosters and
should receive an authorized non-live COVID-19 vaccination series or COVID-19 vaccine
at least 2 weeks prior to the baseline visit (V0).
12. If participant is female with reproductive potential, she must have a negative
pregnancy test at screening and be willing to avoid pregnancy using a highly-effective
contraceptive method for the duration of the study
13. Males of reproductive age must use a highly-effective contraceptive method during the
treatment phase and for 3 months following last dose of study drug
Exclusion Criteria:
1. Current or ongoing use of non-insulin pharmaceuticals or medication that affect
glycemic control or glucose homeostasis within 7 days prior to screening or any
prohibited concomitant medication listed in section 4.8
2. Untreated hypothyroidism or active Graves' disease
3. Concurrent treatment with other immunosuppressive agents (including biologics or
steroids), other than inhaled or topical glucocorticoids
4. Active acute or chronic infection requiring treatment with oral antibiotics,
antivirals, antiparasitics, antiprotozoals, or antifungals within 1 month prior to Day
0 or superficial skin infection within 1 week prior to Day 0
5. Active acute or chronic infection requiring treatment with intravenous therapy (IV)
within a minimum 1 month prior to Day 0
a. Specific cases should be reviewed by Infectious Disease Committee prior to
enrollment
6. Have active signs or symptoms of acute infection at the time of the baseline visit
(V0).
7. Significant trauma or major surgery within 1 month of signing informed consent.
8. Considered in imminent need for surgery or with elective surgery scheduled to occur
during the study
9. History of disseminated herpes zoster or disseminated herpes simplex or a recurrent
(more than one episode of) localized, dermatomal herpes zoster
10. Have evidence of prior or current tuberculosis infection as assessed by Purified
Protein Derivative (PPD), interferon gamma release assay (IGRA) or by history
11. Have evidence of current or past HIV or Hepatitis B infection
12. Have evidence of active Hepatitis C infection
13. Have current, confirmed COVID-19 infection
14. Current or history of Deep vein thrombosis (DVT), Pulmonary embolism (PE), or other
thromboembolic events or history of inherited coagulopathies
15. First degree relative with a history of unprovoked venous thromboembolism (i.e.
without known underlying cause such as trauma, surgery, immobilization, prolonged
travel, pregnancy, hormone use, or plaster cast), which suggests that a participant
may be at increased risk of inherited coagulation disorder
16. Any present malignancies or history of malignancy, other than a successfully treated
nonmelanoma skin cancer
17. History of any lymphoproliferative disorder such as EBV-related lymphoproliferative
disorder, history of lymphoma, history of leukemia, or signs and symptoms suggestive
of current lymphatic or lymphoid disease
18. Known or suspected polymorphism in the Cytochrome P450 2C19 (CYP2C19 gene, resulting
in classification as a poor CYP2C19 metabolizer).
19. Have renal impairment (eGFR< 60 mL/min)
20. Currently on anti-platelet therapies, excluding low dose aspirin
21. One or more screening laboratory values as stated
1. Neutrophils < 1,500 /μL
2. Lymphocytes < 800 /μL
3. Platelets < 150,000 / μL
4. Hemoglobin < 6.2 mmol/L (10.0 g/dL)
5. Potassium > 5.5 mmol/L or <3.0 mmol/L
6. Sodium > 150mmol/L or < 130mmol/L
7. AST or ALT ≥ 2.5 times the upper limit of normal
8. Bilirubin ≥ 1.5 times upper limit of normal unless diagnosed with Gilbert's
syndrome
9. LDL >160 mg/dL
22. Vaccination with a live virus within the last 6 weeks and killed vaccine within 4
weeks (except 2 weeks for flu vaccine and COVID vaccine)
23. Be currently pregnant or lactating or anticipate becoming pregnant during the study
24. Male participants able to father children and female participants of childbearing
potential who are unwilling or unable to use 2 effective methods (at least 1 highly
effective method) of contraception, including abstinence, as outlined in this protocol
for the duration of the study and for at least 3 months after the last dose of
investigational product
25. Be currently participating in another T1D treatment study
26. Have hearing loss with progression over the previous 5 years, or sudden hearing loss,
or middle or inner ear disease such as otitis media, cholesteatoma, Meniere's disease,
labyrinthitis, or other auditory condition that is considered acute, fluctuating, or
progressive
27. Acute coronary syndrome (e.g., myocardial infarction, unstable angina pectoris) and
any history of cerebrovascular disease within 24 weeks before screening; Heart failure
NYHA (New York Heart Association) III, NYHA IV
28. ANY of the following conditions at screening:
a. Screening 12-lead electrocardiogram (ECG) that demonstrates: i. Clinically
significant abnormalities requiring treatment (eg, acute myocardial infarction,
serious tachy- or brady-arrhythmias) or indicating serious underlying heart disease
(eg, cardiomyopathy, Wolff-Parkinson- White syndrome); ii. Confirmed QT corrected
using Fridericia's correction factor (QTcF) prolongation (>450 milliseconds).
b. Long QT Syndrome, a family history of Long QT Syndrome, or a history of Torsades de
Pointes (TdP).
29. History of chronic alcohol abuse or intravenous drug abuse or other illicit drug abuse
within 2 years prior to screening
30. Current or past use of tobacco or nicotine containing products more than the
equivalent of 5 cigarettes per day
31. Participant is the investigator or any sub-investigator, research assistant,
pharmacist, study coordinator, other staff or relative thereof directly involved in
the conduct of the trial
32. Have any complicating medical issues or abnormal clinical laboratory results that may
interfere with study conduct, or cause increased risk
33. Any condition that in the investigator's opinion may adversely affect study
participation or may compromise the study results
Drug: Abrocitinib 200 MG Oral Tablet, Drug: Ritlecitinib, Drug: Placebo
Diabetes Mellitus, Type 1
TrialNet, T1D
Multi-Center Molecular Diagnosis and Host Response of Respiratory Viral Infections in Pediatric Transplant Recipients
All
up to 18 Years old
NCT05550298
Recipient Inclusion Criteria
• Less than 18 years at the time of anticipated transplant
• Participant meets one of the following criteria: 1. scheduled to receive allogeneic hematopoietic cell transplant within 14 days of enrollment or 2. Scheduled to or received solid organ transplant within 7 days before or after enrollment
• Participant is receiving care at the time of enrollment at one of the study participating institutions.
• Parent/guardian willing and able to provide informed consent, and if appropriate, child willing and able to provide informed assent. Donor Inclusion Criteria
• Donor for HCT recipient enrolled on the VIPER study.
• Willing and able to provide informed consent.
• Is not an HCT donor for a participant enrolled on the VIPER study.
• Not available to provide pre-transplant research blood sample.
• Less than 18 years at the time of anticipated transplant
• Participant meets one of the following criteria: 1. scheduled to receive allogeneic hematopoietic cell transplant within 14 days of enrollment or 2. Scheduled to or received solid organ transplant within 7 days before or after enrollment
• Participant is receiving care at the time of enrollment at one of the study participating institutions.
• Parent/guardian willing and able to provide informed consent, and if appropriate, child willing and able to provide informed assent. Donor Inclusion Criteria
• Donor for HCT recipient enrolled on the VIPER study.
• Willing and able to provide informed consent.
Exclusion Criteria:
Recipient Exclusion Criteria
None
Donor Exclusion Criteria
• Is not an HCT donor for a participant enrolled on the VIPER study.
• Not available to provide pre-transplant research blood sample.
Hematopoietic Cell Transplant, Solid Organ Transplant, Respiratory Viral Infection
STOP-T1D Low-Dose (ATG) (TN28)
All
12 Years to 34 Years old
Phase 2
NCT04291703
Inclusion Criteria:
1. Willing to provide informed consent or have a parent or legal guardian provide
informed consent when the subject is <18 years of age.
2. Age greater than or equal to 12 and < 35 years
3. At least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA,
IA-2A, ZnT8A) present on the same sample. In the absence of other antibodies, ICA and
GADA positivity alone will not suffice for eligibility in this trial.
4. Weight greater than the 5th percentile for age and sex.
5. BMI < 95th and > 5th percentile for age for those under age 18 years and < 30 and > 15
for adults (≥ 18)
6. ADA Stage 2 criteria* AND at least one of the following high-risk markers (occurring
at the same visit) within 7 weeks (52 days) of randomization, defined below (for
defining a 2-year 50% risk for progression to Stage 3 T1D):
a. HbA1c ≥ 5.7 and <6.5% b. Index60 ≥ 1.4 i. Index60 = 0.3695 × (log fasting C-peptide
[ng/mL]) + 0.0165 × 60-min glucose (mg/dL)•0.3644 × 60-min C-peptide (ng/mL) c. DPTRS ≥ 7.4 DPTRS = (1.57 x log BMI)
•(0.06 x age) + (0.81 x glucose sum from 30 to 120 min/100)
•(0.85 x C-peptide sum from 30 to 120 min/10) + (0.48 x log fasting C-peptide) *Dysglycemia is defined as 2-hr glucose ≥ 140 and <200 mg/dL or fasting glucose ≥ 110 and <126 7. All subjects must be CMV and EBV PCR negative within 30 days of randomization and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days of randomization 8. Seated blood pressure less than 130/80 mmHg for participants ≥ 18 years. For participants < 18 years seated blood pressure less than 95th percentile for age, sex and height. 9. Be at least 4 weeks from last live immunization 10. Participants are required to receive non-live influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available. 11. Participants are required to receive an authorized non-live COVID-19 vaccination and be fully vaccinated, including eligible boosters at least two weeks prior to randomization. Participants must also have a negative COVID-19 PCR test within 3 days of the first day of treatment. 12. Willingness to comply with study directed social distancing and protection from SARS-Cov-2 infection. 13. Be willing to forgo vaccines (other than killed influenza) during the 3 months after study drug treatment period (Days 0 and 1) 14. Be up to date on all recommended vaccinations based on age of subject* 15. With the exception of stage 2 T1D, subjects must be healthy, as defined by absence of any other untreated diagnoses that the protocol committee deems to be a potential confounder. 16. If a female participant with reproductive potential, willing to avoid pregnancy (abstinence or adequate contraceptive method) through the completion of the study infusions and up to 3 months after study drug administration and undergo pregnancy testing prior to each study visit. 17. Must be residing or have accommodations within 1 hour of the infusion site during the two days of study drug infusions and must be within 1 hour of a medical care facility for 1 day after completion of infusion 2. 18. Participants must live in a location with rapid access to emergency medical services.
• Adult subjects must be fully immunized. Pediatric subjects who have not completed their primary vaccination schedule must receive all vaccinations allowable per the AAP immunization guidelines for their current age prior to study drug delivery. Any remaining vaccinations should be given and continue per the schedule at least 3 months after study drug is administered.
Exclusion Criteria:
1. Immunodeficiency or clinically significant chronic lymphopenia: (Leukopenia (< 3,000
leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800
lymphocytes/μL), thrombocytopenia (<100,000 platelets/μL).
2. Hemoglobin less than 13.5 g/dL for adult men and less than 12 g/dL for adult females
and less than 11 g/dL for participants under age 18
3. Active signs or symptoms of acute infection at the time of randomization including
SARS-Cov-2.
4. Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must be
well controlled for the previous 6 months).
5. Evidence of prior or current tuberculosis infection as assessed interferon gamma
release assay (QuantiFERON).
6. Currently pregnant or lactating or anticipate getting pregnant within the study
period.
7. Require use of other immunosuppressive agents including chronic use of systemic
steroids.
8. Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
9. Any complicating medical issues or abnormal clinical laboratory results that may
interfere with study conduct, or cause increased risk to include pre-existing cardiac
disease, COPD, sickle cell disease, neurological disease, or blood count
abnormalities.
10. A history of malignancies other than of skin.
11. Evidence of liver dysfunction with AST or ALT outside of the reference range.
12. Evidence of renal dysfunction with creatinine outside of the reference range.
13. Increased bilirubin (total and direct) outside of the normal limit (Participants with
documentation of Gilbert's Disease permitted).
14. Vaccination with a live virus within the last 4 weeks.
15. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control
within 7 days of screening
16. Prior treatment with Teplizumab (either in a previous clinical trial or clinically).
17. Has participated in a clinical trial for diabetes prevention previously and received
active study agent within 3 months of randomization.
18. Known allergy to ATG
19. Prior treatment with ATG or known allergy to rabbit-derived products
20. Prior adverse reactions to heparin.
21. Any condition that in the investigator's opinion may adversely affect study
participation will be reviewed by the Study Chair to ensure consistency and adjudicate
whether or not the subject may compromise the study results
22. Any screening/baseline laboratory result not otherwise stated out of normal reference
range and/or medical history that may increase the risk of the subject's participation
in this trial.
23. Previously diagnosed with Stage 3 TID according to ADA criteria76 (see Appendix 3 for
Criteria for diagnosis of diabetes)
Drug: Antithymocyte Globulin, Drug: Placebo (for ATG)
Diabetes Mellitus, Type 1
TrialNet, T1D
A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)
All
18 Years and over
Phase 2
NCT04225117
Inclusion Criteria:
• Subject is considered an adult according to local regulation at the time of signing the informed consent form (ICF).
• Subject has measurable disease by RECIST Version 1.1.
• Subject has accessible archival tumor tissue from either the primary tumor or a metastatic site, for which source and availability have been confirmed prior to study treatment. If no archival tumor tissue is available, the subject will have a biopsy to obtain tumor tissue prior to study treatment. If the subject is unable to undergo a biopsy due to safety concerns, enrollment into the study must be discussed with the medical monitor.
• For cohort 9 only: Subject should submit archival or fresh tumor tissue sample for programmed cell death-ligand 1 (PD-L1) central testing during screening if no local PD-L1 test result is available. Central test result for PD-L1 will be required prior to subject enrollment. For cohort 9 subjects with local PD-L1 test result confirming CPS ≥ 1, archival or fresh tissue sample for exploratory analysis should be submitted within 5 days of enrollment.
• Subject has ECOG performance status of 0 or 1.
• Subject has the following baseline laboratory data. If a subject has received a recent blood transfusion, the hematology tests must be obtained ≥ 28 days after any blood transfusion.
• absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
• platelet count ≥ 100 × 10^9/L
• hemoglobin ≥ 9 g/dL
• serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
• creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl).
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Subject agrees not to participate in another interventional study while receiving study treatment in the present study.
• Additional contraceptive requirements exist for male and female subjects. Disease Specific
Inclusion Criteria:
• Evidence of progression on or after the last regimen received.
• Locally advanced or metastatic disease that is not amenable to curative intent treatment. Cohort 1: HR+/HER2- breast cancer
• Subject has evidence of radiographic progression on or after the last regimen received.
• Subject has histologically- or cytologically-confirmed HR+/HER2- (estrogen receptor [ER] positive and/or progesterone receptor [PR] positive, and HER2 negative) breast cancers and are not considered a candidate for further hormonal therapy. Subject will be considered HR+ if biopsies show ≥ 1% expression of ER or PR as per current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will count as a prior cytotoxic regimen if disease recurrence occurred during or within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at least 1 prior standard of care cytotoxic regimen in the incurable, unresectable locally advanced or metastatic setting, and has not received > 2 prior lines of cytotoxic therapy in the locally advanced or metastatic setting. No limit applies to endocrine therapies. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
• Subject has progressed, relapsed, or discontinued for toxicity during or after receiving endocrine therapy or with hormonally-directed therapy with cyclin-dependent kinase (CDK) inhibitors. Prior therapy with CDK inhibitors is not required. Cohort 2: triple negative breast cancer (TNBC)
• Subject has evidence of radiographic progression on or after the last regimen received.
• Subject has histologically- or cytologically-confirmed TNBC; defined as unequivocal TNBC histology (ER-negative/PR-negative/HER2-negative). This is defined by < 1% expression of ER and PR by immunohistochemistry (IHC), and that are, for HER2, either 0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not amplified) as per current ASCO/CAP guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will count as a prior cytotoxic regimen if disease recurrence occurred during or within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at least 1 prior standard of care cytotoxic regimen in the incurable, unresectable locally advanced or metastatic setting, and has not received > 2 prior lines of cytotoxic therapy in the locally advanced or metastatic setting. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
• Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1) or an anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohort 3: squamous non-small cell lung cancer (NSCLC)
• Subject has evidence of radiographic progression on or after the last regimen received.
• Subject has histologically or cytologically-confirmed squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any component of neuroendocrine histology.
• Subjects with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are eligible if treated with mutation targeted therapy and have progressed, relapsed, or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting. 1. Subjects with locally advanced disease who previously received curative intent treatment with platinum-based standard of care regimen in the adjuvant or neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible if they have progressed or relapsed within 6 months of completion. 2. Maintenance therapy does not constitute a new chemotherapy regimen provided there was no progression after the initial platinum-based regimen. 3. Changing chemotherapy agents during platinum-based treatment for the management of toxicities does not constitute a new chemotherapy regimen provided no progression had occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohort 4: non-squamous non-small cell lung cancer
• Subject has evidence of radiographic progression on or after the last regimen received.
• Subject has histologically- or cytologically-confirmed non-squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any component of neuroendocrine histology.
• Subjects with known EGFR, ALK, ROS, BRAF, or other actionable mutations are eligible if treated with mutation targeted therapy and have progressed, relapsed, or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting. 1. Subjects with locally advanced disease who previously received curative intent treatment with platinum-based standard of care regimen in the adjuvant or neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible if they have progressed or relapsed within 6 months of completion. 2. Maintenance therapy does not constitute a new chemotherapy regimen provided there was no progression after the initial platinum-based regimen. 3. Changing chemotherapy agents during platinum-based treatment for the management of toxicities does not constitute a new chemotherapy regimen provided no progression has occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohort 5: second-line or later head and neck cancer
• Subject has evidence of radiographic progression on or after the last regimen received.
• Subject has histologically- or cytologically-confirmed head and neck cancer.
• Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors and/or parotid gland tumors are not eligible for Cohort 5.
• Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting.
• Subjects with locally advanced disease who previously received curative intent treatment with platinum-based standard of care regimen in the adjuvant or neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible if they have progressed or relapsed within 6 months after completion.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohorts 6, 7 and 8: gastric or gastroesophageal junction (GEJ) or esophageal adenocarcinoma
• Subject has evidence of radiographic progression on or after the last regimen received.
• Subject has histologically- or cytologically-confirmed gastric, GEJ, or esophageal cancer.
• Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
• Subject has progressed, relapsed, or discontinued due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting.
• Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if relapsed or progressed ≤ 6 months after completion.
• Subject must have received a HER2 directed therapy if known to have HER2 positive cancer.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohort 9: 1L HNSCC
• Subject has histologically- or cytologically-confirmed head and neck squamous cell carcinoma. a. Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors and/or parotid gland tumors are not eligible for Cohort 9.
• Subject has recurrent or metastatic disease that is incurable by local therapies.
• Subject's tumor sample has PD-L1 combined positive score (CPS) of ≥ 1 as determined by local or central IHC testing.
• Subject has had no prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease). Subjects who have received a PD-1 or PD-L1 inhibitor in the curative setting are eligible if it has been at least 12 months since last dose of the anti PD-L1 agent.
• Subject has ANC ≥ 1.5 × 10^9/L.
• International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin (aPTT) both ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range of intended use of anticoagulants. PTT may be used if local lab is unable to perform aPTT.
• For subjects with oropharynx tumors, subject has results from testing of HPV status by p16 testing.
Exclusion Criteria:
For All Cohorts:
• Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
• Subject has active central nervous system (CNS) metastases. Subjects with treated CNS metastases are permitted on study if all the following are true:
• CNS metastases have been clinically stable for ≥ 6 weeks prior to screening
• If requiring steroid treatment for CNS metastases, the subject is on a stable dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks
• Baseline imaging scans show no evidence of new or enlarged brain metastasis
• Subject does not have leptomeningeal disease
• Subject has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
• Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or subjects with other immunotherapy-related AEs requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), are excluded. Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well maintained/controlled on a stable dose of hormone replacement therapy (if indicated).
• Subject has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes (within 3 months before first dose) is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. The lowest HbA1c during the screening period will be used to determine eligibility.
• Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE) based antibody-drug conjugates (ADCs).
• Subject has a second malignancy diagnosed within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
• Subject is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of study treatment. Routine antimicrobial prophylaxis is permitted.
• Subject has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is detected).
• Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).
• Subject has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.
• Subject has major surgery within 4 weeks prior to first dose of study drug.
• Subject had radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug.
• Subject has known hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate and polysorbate 20) OR subject has known hypersensitivity to biopharmaceutical produced in Chinese hamster ovary cells.
• Subject has known active keratitis or corneal ulcerations. Subject with superficial punctate keratitis is allowed if the disorder is being adequately treated.
• Subject has any condition which makes the subject unsuitable for study participation. Cohort 9: 1L HNSCC
• Had PD within 6 months of completion of curatively intended systematic treatment for locoregionally advanced HNSCC.
• Has had an allogeneic tissue/solid organ transplant. 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 a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g. tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 1. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 2. Brief (<7 days) use of systemic corticosteroids is allowed when use is considered standard of care. 3. Subjects with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded. 4. Subjects requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded. 5. Subjects with hypothyroidism that is stable with hormone replacement or Sjögren's syndrome will not be excluded.
• Has an active infection requiring systemic therapy.
• Has received prior therapy with an anti-PD-1 or anti-PD-L1 agent in the recurrent/metastatic setting. If anti-PD-1 or anti-PD-L1 agent was given as part of curative intent therapy, it must be at least 1 year since last dose.
• Has received a live vaccine within 30 days of planned start of study therapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Subject has active tuberculosis
Drug: enfortumab vedotin, Drug: pembrolizumab
Locally Advanced or Metastatic Malignant Solid Tumors
Squamous NSCLC, Triple negative breast cancer (TNBC), ASG-22CE, non-small cell lung cancer (NSCLC), Hormone receptor-positive/ human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, non-squamous NSCLC, locally advanced or metastatic malignant solid tumors, Head and neck cancer, EV-202, Gastric or gastroesophageal junction (GEJ) or esophageal cancer
Clinical Research in Hairy Cell Leukemia: Surveillance and Documentation of Clinical Outcomes in a Rare Form of Adult Leukemia (HCL-PDR)
Hairy Cell Leukemia Patient Data Registry
Sameer Parikh
All
18 years and over
2022-308076-P01-RST
22-004578
Inclusion Criteria:
- Patients with classic hairy cell leukemia.
- Patients with the variant of hairy cell leukemia.
Exclusion Criteria:
- Children are excluded from the study, since Hairy Cell Leukemia wasn't described in children.
A Phase 1b, Open Label, Multi-center, Dose Optimization and Dose Expansion Study to Assess the Safety and Efficacy of DFV890 in Adult Patients With Myeloid Diseases
Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases
Abhishek Mangaonkar
All
18 years and over
Phase 1
2022-309532-P01-RST
22-012678
Inclusion Criteria:
- Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF)
- The Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
- Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and must be willing to undergo a bone marrow aspirate.
- Patients must have one of the following for eligibility into the study:
- In dose optimization and expansion: IPSS-R defined very low, low or intermediate risk Myelodysplastic Syndrome (LR MDS) who failed to respond to or did not tolerate ESAs or luspatercept or HMAs and patients with del 5q who failed to respond to or did not tolerate lenalidomide; or
- In dose optimization and expansion: IPSS-R defined very low, low or intermediate risk Chronic Myelomonocytic Leukemia (LR CMML) who failed to respond to or did not tolerate hydroxyurea or HMAs.
Exclusion Criteria:
- Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or any experimental therapy within 28 days or 5 half-lives, whichever is longer, and recovered from the toxicities before the first dose of study treatment. For patients that received antibodies the washout period is 4 weeks prior to study treatment.
- History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
- Patients who have previously been treated with agents that have the same mechanism of action as DFV890 as defined in Table 6-8, list of prohibited medications (e.g., drugs targeting the NLRP3 inflammasome pathway and the IL-1 pathway (canakinumab and anakinra)).
- Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents anytime ≤ 1 week (or 5 half lives, whichever is longer) prior to start of study treatment.
- Patients receiving:
- concomitant medications that are known to be modulators of cytochrome P450 enzymes CYP2C9 and/or CYP3A (specifically strong or moderate inducers of CYP2C9, strong inducers of CYP3A enzymes, strong inhibitors of CYP2C9 and/or strong or moderate dual inhibitors of CYP2C9/CYP3A); and
- patients, who are poor CYP2C9 metabolizers receiving concomitant medications known to be strong or moderate inhibitors of CYP3A, whose concomitant medications cannot be discontinued or switched to a different medication within 5 half-lives or 1 week (whichever is longer) prior to start of study treatment and for duration of the study.
- Known malignancy, unless the diagnosis unde the study, which is progressing or has active treatment within the lat 12 months. Exceptions to this exclusion include the following:
- completely resectd basal cell and squamous cell skin cancers; and
- completely resected carcinoma in situ of any type.
- Patients with secondary MDS or therapy-related myeloid neoplasms.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 11/29/23. Questions regarding updates should be directed to the study team contact.
Drug
Hyperbaric Oxygen Therapy for Ulcerative Colitis Patients Hospitalized for Moderate to Severe Flares: A Phase 3 Multi-Center, Randomized, Double-Blind, Sham-Controlled Trial
Hyperbaric Oxygen Therapy for Ulcerative Colitis (HBOT-UC)
Laura Raffals
All
18 years to 85 years old
Phase 3
2022-309994-P01-RST
22-011550
Inclusion Criteria:
- Participants with known or newly diagnosed UC who require hospitalization for an acute moderate to severe flare.
- Age 18-85.
- Consented and able to receive first HBOT session within first 48 hours of initiation of intravenous steroids.Exclusion Criteria:
- Complication requiring urgent surgical intervention.
- Toxic megacolon.
- Inability to receive intravenous steroids.
- Historically failed 3 or more classes of advanced therapeutic options.
- Known or suspected diagnosis of Crohn's colitis, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic
colitis or infectious colitis.
- Received any investigational drug within 30 days.
- Clinically significant cardiac, renal, neurological, endocrine, respiratory or hepatic impairment that increases the risk for HBOT toxicity.
- Women who are pregnant or nursing.
- Unwillingness to complete course of HBOT.
- Active SARS CoV 2 infection.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 12/14/23. Questions regarding updates should be directed to the study team contact.
Device, Other
APEX: Alzheimer's Plasma Extension (APEX)
AHEAD Plasma Extension Study
Jonathan Graff-Radford
All
55 years to 80 years old
2023-311807-P01-RST
23-004687
Inclusoin Criteria:
- Documentation of the participant’s informed consent to study procedures and for the use of PHI (HIPAA Authorization, if applicable):
- NOTE: Informed consent processes and documentation must adhere to state laws/local requirements, including consent provided by the participant’s legally authorized representative (LAR), responsible next of kin, surrogate consent with assent, etc.
- Previously consented to participate in A3-45 screening.
- Has A3-45 screening plasma biomarker results required for determining eligibility to participate in the A3-45 trial.
- If an amyloid PET scan was conducted in A3-45, the scan was determined to be below the 20 centiloid cutpoint required for eligibility into the treatment arms of the A3 or A45 trial.
- As assessed by the site PI, participant is likely to be able to comply with the protocol, including completion of all required procedures for the duration of the study, and has adequate vision, hearing (hearing aid permitted), and literacy in English or Spanish sufficient for compliance with required testing procedures.
Exclusion Criteria:
- Current treatment with an FDA approved medication for Alzheimer’s disease, including prior or current treatment with a prohibited medication as described in section 6.2.1.
- Enrollment in another investigational study, or intake of investigational drug, within 30 days prior to screening, or five halflives of the investigational drug, whichever is longer, unless it can be documented that the participant was in the placebo treatment arm.
- NOTE: Participants enrolled in other observational studies may be permitted with Medical Monitor review and approval.
- Screen failed from A3-45 due to not meeting basic inclusion criterion (i.e., age requirement; current diagnosis of AD dementia).
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 5/4/23. Questions regarding updates should be directed to the study team contact.
Accuracy of 18F-FDG PET/MRI in Predicting Complete Pathologic Response Following Neoadjuvant Chemoradiotherapy in Resectable, Locally Advanced Rectal Cancer
Determining if a PET/MRI can predict complete response from chemoradiotherapy before surgery in patients with locally advanced rectal cancer
Shannon Sheedy
All
18 years and over
0000-118151-H01-RST
15-009170
Inclusion Criteria
- Histologically confirmed primary adenocarcinoma, clinical Stage II disease (T3-4, N0) or Stage III disease (any T, N1-2)
- No known distant metastatic disease at initial staging
- Patients for whom the interdisciplinary treatment team has selected standard CRT followed by TME as the treatment plan
- Pre-treatment staging MRI available
- Blood sugar levels less than 200 mg/dl at the time of the exam
- A negative pregnancy test is required for female subjects of child-bearing potential within 48 hours of F-18 FDG injection
- Informed consent for dual modality PET/MRI without IV contrast material
- Age greater than 18, male or female
Exclusion Criteria
- No available initial staging MR exam.
- Any contraindication for MRI, including pacemakers, aneurysm clips, cochlear implants, and certain spinal stimulation devices.
- Subjects with a metallic prosthesis in the pelvis that may interfere with the MR and PET imaging.
- Nonsurgical candidates.
- Patients with uncontrolled diabetes.
- Patients with known distant metastatic disease (M1) at the time of initial staging.
- Patients with evidence of mucinous subtype of adenocarcinoma on biopsy and/or on initial staging MR exam.
- Prior pelvic radiation.
- Prior chemotherapy or surgery for rectal cancer.
- Patients in whom neoadjuvant therapy is contraindicated.
- Female subjects who are breast-feeding or with a positive pregnancy test.
- Patients with a known history of claustrophobia.
- Subjects unable to provide informed consent.
Cancer, Rectal cancer
Digestive system, Malignant tumor of rectum, Medical Oncology, PET/MRI scan
Long Term Evaluation of Thymoma Recurrence
A Study to Evaluate Thymoma Recurrence
Dennis Wigle
All
18 years to 99 years old
0000-122681-H01-RST
19-009562
Inclusion Criteria:
- ≥ 18 years old.
- Previous thymectomy at Mayo Clinic.
Exclusion Criteria:
-
Pathology other than thymoma or thymic carcinoma.
Intercept Somatic (Intercept Somatic)
Intercept Somatic
Niloy Jewel Samadder
All
18 years and over
0000-122824-H01-RST
19-010300
RETROSPECTIVE STUDY
•NO PARTICIPANT CONTACT
Patient Experience and Understanding of Genetic Testing in Ovarian Cancer
Patient Experience and Understanding of Genetic Testing in Ovarian Cancer
Casey Lawler
Female
18 years and over
0000-123033-H01-RST
19-012459
Inclusion Criteria:
- Initial diagnosis of ovarian cancer.
- Patients undergoing primary debulking surgery followed by adjuvant chemotherapy.
Exclusion Criteria:
- Non-English speaking.
Description of perceived cancer risk, screening, and risk reduction practices among women with Lynch syndrome
Cancer screening practices of individuals with Lynch Syndrome
Jamie Bakkum-Gamez
All
18 years and over
0000-123274-H01-RST
20-001757
Men and women over the age of 18 who have a diagnosis of Lynch Syndrome
Olpasiran Trials of Cardiovascular Events and Lipoprotein(a) Reduction (OCEAN(a)) - Outcomes Trial
All
18 Years to 85 Years old
Phase 3
NCT05581303
Inclusion Criteria:
• Age 18 to ≤ 85 years
• Lp(a)≥ 200 nmol/L during screening
• History of ASCVD as evidenced by history of either:
• Myocardial infarction (presumed type 1 event due to plaque rupture/erosion) and/or
• Coronary revascularization with percutaneous coronary intervention AND at least 1 additional risk factor.
Exclusion Criteria:
• Severe renal dysfunction
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN), or total bilirubin (TBL) > 2 x ULN during screening
• History of hemorrhagic stroke
• History of major bleeding disorder
• Planned cardiac surgery or arterial revascularization
• Severe heart failure
• Current, recent, or planned lipoprotein apheresis
• Previously received ribonucleic acid therapy specifically targeting Lp(a)
Drug: Placebo, Drug: Olpasiran
Atherosclerotic Cardiovascular Disease
Atherosclerotic Cardiovascular Disease, ASCVD, AMG 890, Olpasiran
First-in-Human Study of TAK-280 in Participants With Unresectable Locally Advanced or Metastatic Cancer
All
18 Years and over
Phase 1/Phase 2
NCT05220098
Inclusion Criteria
• Age greater than or equal to (>=)18 years or >= the local legal age of majority, as applicable.
• Criteria for disease state in dose escalation and cohort expansion. 1. Tumor histologies during dose escalation: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers. 2. Tumor histologies during cohort expansion: Participants will be eligible if they have histologically proven, unresectable, locally advanced or metastatic malignant neoplasms.
• Eastern Cooperative Oncology Group performance status (less than or equal to [<=]) 1.
• Measurable disease per RECIST V1.1 by investigator except for participants with PC and only bone metastases (these participants are allowed in the study). Exclusion Criteria
• History of known autoimmune disease.
• Major surgery or traumatic injury within 8 weeks before the first dose of TAK-280.
• Unhealed wounds from surgery or injury.
• Ongoing or active infection of Grade >=2.
• Oxygen saturation less than (<) 92 percent (%) on room air at screening or during Cycle 1 Day 1 (C1D1) predose assessment.
• Inflammatory process that has not resolved for >= 4 weeks before the first dose of study drug. Participants with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of their duration.
• Vaccination with any live virus vaccine within 4 weeks or other vaccines within 2 weeks before the initiation of study drug. Inactivated annual influenza vaccination is allowed.
• Known hypersensitivity to TAK-280 or any excipient.
• Age greater than or equal to (>=)18 years or >= the local legal age of majority, as applicable.
• Criteria for disease state in dose escalation and cohort expansion. 1. Tumor histologies during dose escalation: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers. 2. Tumor histologies during cohort expansion: Participants will be eligible if they have histologically proven, unresectable, locally advanced or metastatic malignant neoplasms.
• Eastern Cooperative Oncology Group performance status (less than or equal to [<=]) 1.
• Measurable disease per RECIST V1.1 by investigator except for participants with PC and only bone metastases (these participants are allowed in the study). Exclusion Criteria
• History of known autoimmune disease.
• Major surgery or traumatic injury within 8 weeks before the first dose of TAK-280.
• Unhealed wounds from surgery or injury.
• Ongoing or active infection of Grade >=2.
• Oxygen saturation less than (<) 92 percent (%) on room air at screening or during Cycle 1 Day 1 (C1D1) predose assessment.
• Inflammatory process that has not resolved for >= 4 weeks before the first dose of study drug. Participants with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of their duration.
• Vaccination with any live virus vaccine within 4 weeks or other vaccines within 2 weeks before the initiation of study drug. Inactivated annual influenza vaccination is allowed.
• Known hypersensitivity to TAK-280 or any excipient.
Drug: TAK-280
Unresectable Locally Advanced or Metastatic Cancer
ONC201 for the Treatment of Newly Diagnosed H3 K27M-mutant Diffuse Glioma Following Completion of Radiotherapy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study (ACTION)
ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)
Michael Ruff
All
Not specified
Phase 3
2022-309982-P01-RST
23-004591
Inclusion Criteria:
1. Able to understand the study procedures and agree to participate in the study by
providing written informed consent (by participant or legally authorized
representative), and assent when applicable.
2. Body weight ≥ 10 kg at time of randomization.
3. Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a
missense K27M mutation in any histone H3-encoding gene detected by testing of tumor
tissue (immunohistochemistry [IHC] or next-generation sequencing [NGS] in a Clinical
Laboratory Improvement Amendments [CLIA]-certified or equivalent laboratory). [Site to
provide (as available): ≥ 10 unstained formalin-fixed paraffin-embedded (FFPE) slides
from tumor tissue.]
4. At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to
starting radiotherapy for submission to sponsor's imaging vendor for central read. For
participants who had a surgical resection, this scan must be post-resection; for
participants who did not have a resection, this scan may be pre- or post-biopsy.
5. At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks
after completion of frontline radiotherapy. [Site to also provide all available MRIs
completed prior to initiating treatment with study intervention.]
6. Completed standard frontline radiotherapy within 2 to 6 weeks prior to randomization.
Standard frontline radiotherapy is defined as a dose of 54 to 60 Gy at 1.8 to 2.2
Gy/fraction. Radiotherapy must be initiated within 12 weeks from initial diagnosis of
H3 K27M-mutant diffuse glioma and within 8 weeks of most recent surgical
resection/biopsy.
7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of
randomization.
8. Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days
prior to randomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day
increase (based on dexamethasone dose or equivalent dose of an alternative steroid).Exclusion Criteria:
1. Primary spinal tumor.
2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter
and diffuse involvement of the pons.
3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.
4. Any known concurrent malignancy.
5. New lesion(s) outside of the radiation field.
6. Received whole-brain radiotherapy.
7. Received proton therapy for glioma.
8. Use of any of the following treatments within the specified time periods prior to
randomization:
1. ONC201 or ONC206 at any time.
2. Bevacizumab (includes biosimilars) at any time.
3. Temozolomide within past 3 weeks.
4. Tumor treating fields at any time.
5. DRD2 antagonist within past 2 weeks.
6. Any investigational therapy within past 4 weeks.
7. Strong CYP3A4/5 inhibitors within 3 days.
8. Strong CYP3A4/5 inducers (includes enzyme-inducing antiepileptic drugs) within 2
weeks.
9. Laboratory test results meeting any of the following parameters within 2 weeks prior
to randomization:
1. Absolute neutrophil count < 1.0 × 109/L or platelets < 75 × 109/L.
2. Total bilirubin > 1.5 × upper limit of normal (ULN) (participants with Gilbert's
syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is
≤ 1.5 × ULN).
3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN.
4. Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation
(or estimated glomerular filtration rate < 60 mL/min/1.73 m2).
10. QTc > 480 msec (based on mean from triplicate electrocardiograms) during screening.
11. Known hypersensitivity to any excipients used in the study intervention formulation.
12. Pregnant, breastfeeding, or planning to become pregnant while receiving study
intervention or within 3 months after the last dose. Participants of childbearing
potential must have a negative serum pregnancy test within 72 hours prior to receiving
the first dose of study intervention.
13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring systemic therapy or psychiatric illness/social situations that
would limit compliance with study requirements.
14. Any other condition (e.g., medical, psychiatric, or social) that, in the opinion of the
investigator, may interfere with participant safety or the ability to complete the
study according to the protocol.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 11/2/22. Questions regarding updates should be directed to the study team contact.
Drug, Other
A Phase 2a, Double-blind, Placebo-controlled, Multi-center, Randomized Study Evaluating LSTA1 When Added to Standard of Care (SoC) Versus Standard of Care Alone in Subjects with Advanced Solid Tumors (BOLSTER)
A Study of LSTA1 When Added to Standard of Care Versus Standard of Care Alone in Patients With Advanced Solid Tumors
Nguyen Tran
All
18 years and over
Phase 2
2023-311835-P01-RST
23-007617
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Life expectancy ≥ 3 months.
- At least one measurable metastatic lesion as assessed by RECIST 1.1.
- Adequate organ and marrow function.
- Adequate contraception.
Patients with any of the following:
- Histologically confirmed recurrent or metastatic HNSCC that is unresectable or considered incurable by local therapies and that has progressed after first-line immunotherapy. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Patients may not have primary tumor sites of the skin, paranasal sinuses, or the nasopharynx (any histology).
- Histologically or cytologically confirmed locally advanced unresectable or metastatic ESCC. ESCC subjects have documented clinical or radiographic disease progression by RECIST 1.1 after first-line immunotherapy.
- Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization). Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible.
Exclusion Criteria:
-
Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to:
- Any major surgery or irradiation less than 4 weeks prior to baseline disease assessment
- Active infection (viral, fungal, or bacterial) requiring systemic therapy
- Known active hepatitis B virus, hepatitis C virus, or HIV infection
- Active tuberculosis as defined per local guidance
- History of allogeneic tissue/solid organ transplant
- Prior malignancy requiring active treatment within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
- Clinically significant or symptomatic cardiovascular/cerebrovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before randomization
- Treatment in another interventional clinical study within the last 1 year
- History or clinical evidence of symptomatic central nervous system (CNS) metastases
- Has had prior targeted small molecule therapy, or radiation therapy for unresectable or metastatic HNSCC or ESCC
- For cholangiocarcinoma, active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with Type 1 diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 7/26/23. Questions regarding updates should be directed to the study team contact.
Biologic/Vaccine, Drug, Other
Water Vapor Ablation for Localized Intermediate Risk Prostate Cancer (VAPOR 2)
Male
50 Years and over
N/A
NCT05683691
Inclusion Criteria:
1. ≥50 years of age; with life expectancy of ≥10 years
2. 20-80 cc prostate size determined by MRI Central Imaging
3. ≤15 ng/ml PSA
4. Cancer stage less than or equal to T2c
5. Within 12 months prior to signing consent have had a multiparametric MRI. Within 6
months prior to signing consent, have undergone a multiparametric MRI software guided
fusion biopsy of the prostate (transrectal or transperineal). This must include a
standard sector biopsy obtaining a minimum of 10-16 cores.
6. <15mm diameter of qualifying lesion as measure by greatest diameter
7. Subject is willing and able to adhere to specific protocol visits and required testing
throughout study
8. Is geographically stable and near the site or able and willing to travel back to site
for follow-up visits involving diagnostic tests or treatment
9. Able and willing to provide written consent to participate in the study.
Exclusion Criteria:
1. Patients with >GGG3 cores anywhere in the prostate
2. MRI evidence of extracapsular extension of cancer (MRI read as "definite", "frank" or
"gross" ECE)
3. All PI-RADS 5 lesions
4. All MRI Central Imaging confirmed by PI-RADS 4 lesions negative on biopsy
5. Contraindications to MRI
6. Subjects with an installed pacemaker or other potentially electrically conductive
implants implanted within 200mm (8 inches) of the procedure area. Implants that are
within 200mm (8 inches) and can be turned off for the duration of the study procedure
are acceptable.
7. Any prior surgery, intervention, or minimally invasive therapy, (MIST) for the
prostate cancer or bladder neck.
8. Treated within the past 5 years for genital cancer
9. Presence of any urethral or prostatic condition that precludes water vapor ablation
per Instructions for Use
10. Currently taking medications that have hormonal effects on the prostate or PSA, such
as: 5 alpha reductase inhibitors (if on for <6 months), Androgen blockers, Luteinizing
hormone-releasing hormone (LHRH) agonists or antagonists (12 month wash-out), or
Testosterone supplementation
11. Active urinary tract infection
12. Active or clinically chronic prostatitis or granulomatous prostatitis
13. Treated within the past 5 years for a lower and/or upper urinary tract malignancy
(excluding prostate cancer meeting the inclusion criteria)
14. Any rectal pathology, anomaly or previous treatment that could change properties of
rectal wall or insertion and use of TRUS
15. Unable to stop taking antiplatelet medications or other blood thinning agents
16. Known allergy to nickel
17. Allergic to medication required by the study such as MRI contrast or anesthesia
18. Any significant medical history that would pose an unreasonable risk or make the
subject unsuitable for the study
19. Any cognitive or psychiatric condition that interferes with or precludes direct and
accurate communication with the study Investigator regarding the study or affects the
ability to complete the study quality of life questionnaires
20. Subject currently participating in other premarket investigational studies unless
approved by Sponsor in writing
21. Subject is considered vulnerable such as incarcerated or cognitively impaired.
Device: Vanquish System
Prostate Cancer
Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA)
All
8 Years to 21 Years old
N/A
NCT04891640
Inclusion Criteria:
1. Males or females age 8 to 21 years
2. Juvenile SpA diagnosis (symptom onset before their 16th birthday):
Pediatric Rheumatology International Trials Organization (PRINTO) revision of the The
International League of Associations for Rheumatology (ILAR) criteria
enthesitis/spondylitis-related Juvenile idiopathic arthritis (JIA)
• Peripheral arthritis and enthesitis, or
• Arthritis or enthesitis, plus ≥ 3 months of inflammatory back pain and sacroiliitis on imaging, or
• Arthritis or enthesitis plus 2 of the following: (1) sacroiliac joint tenderness; (2) inflammatory back pain; (3) presence of Human leukocyte antigen (HLA-B27) ; (4) acute (symptomatic) anterior uveitis; and (5) history of a SpA in a first-degree relative 3. Currently taking one of the following TNFi therapies (Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab) at standard doses and dosing intervals 4. Have reached a clinically inactive disease state for a minimum of six months, as determined by treating physician 5. English speaking or Spanish speaking 6. Interested and willing to de-escalate TNFi therapy
Exclusion Criteria:
1) History of inflammatory bowel disease, history of uveitis that was not adequately
controlled with localized ophthalmic treatment or psoriasis that pre-dates the start of
TNFi therapy or psoriasis that started after TNFi therapy and has required more than
topical therapy for control
Other: Standard TNFi Therapy, Other: TNFi fixed longer dosing intervals, Other: Stop TNFi treatment
Juvenile Spondyloarthritis
A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
All
12 Months to 21 Years old
Phase 1/Phase 2
NCT05099003
Inclusion Criteria:
• STEP 0: Patients must be >= 12 months and =< 21 years of age at the time of enrollment on Step 0.
• Please note:
• This age range includes pre-screening for all HGG patients. Individual treatment protocols may have different age criteria.
• Non-DIPG patients with tumors that do not harbor an H3K27M-mutation and are >= 18 years of age will not be eligible to enroll on ACNS1821 (Step 1).
• STEP 0: Patient is suspected of having localized, newly diagnosed HGG, excluding metastatic disease, OR patient has an institutional diagnosis of DIPG
• STEP 0:
• For patients with non-pontine tumors: Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
• For patients with DIPG: Patient and/or their parents or legal guardians have signed informed consent for ACNS1821.
• STEP 0:
• For patients with non-pontine tumors only, the specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 ASAP, preferably within 5 calendar days of definitive surgery
• STEP 1: Patients must be >= 12 months and =< 21 years of age at the time of enrollment
• STEP 1: Patients must have newly-diagnosed DIPG or HGG (including DMG).
• STEP 1: Stratum DIPG
• Patients with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons on at least 1 axial T2 weighted image, are eligible. No histologic confirmation is required.
• Patients with pontine tumors that do not meet radiographic criteria for typical DIPG (e.g., focal tumors or those involving less than 2/3 of the pontine cross-sectional area with or without extrapontine extension) are eligible if the tumors are biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma, glioblastoma, high-grade glioma not otherwise specified [NOS], and/or H3 K27M-mutant) by institutional diagnosis.
• STEP 1: Stratum DMG (with H3 K27M mutation)
• Patients must have newly-diagnosed non-pontine H3 K27M-mutant HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
• Note: Patients need not have either measurable or evaluable disease, i.e., DMG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment. For rare H3 K27M-mutant HGG in non-midline structures (e.g., cerebral hemispheres), these patients will be considered part of Stratum DMG.
• STEP 1: Stratum HGG (without H3 K27M mutation)
• Patients must have newly-diagnosed non-pontine H3 K27M-wild type HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
• Please note:
• Patients who fall in this category and who are >= 18 years of age are not eligible due to another standard-of-care regimen (radiation/temozolomide) that is available
• Patients need not have either measurable or evaluable disease, i.e., HGG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment
• STEP 1: Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =<16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• STEP 1: Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to step 1 enrollment)
• STEP 1: Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to step 1 enrollment)
• STEP 1: Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to step 1 enrollment)
• STEP 1: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to step 1 enrollment) or A serum creatinine based on age/gender as follows (within 7 days prior to step 1 enrollment):
• Age / Maximum Serum Creatinine (mg/dL)
• 1 to < 2 years / male: 0.6; female: 0.6
• 2 to < 6 years / male: 0.8; female: 0.8
• 6 to < 10 years / male: 1; female: 1
• 10 to < 13 years / male: 1.2; female: 1.2
• 13 to < 16 years / male: 1.5; female: 1.4
• >= 16 years / male: 1.7; female: 1.4
• STEP 1: Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• STEP 1: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
• STEP 1: Serum amylase =< 1.5 x ULN
• STEP 1: Serum lipase =< 1.5 x ULN
• STEP 1: No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
• STEP 1: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
• STEP 1: Patients must be enrolled and protocol therapy must begin no later than 31 days after the date of radiographic diagnosis (in the case of non-biopsied DIPG patients only) or definitive surgery, whichever is the later date (Day 0). For patients who have a biopsy followed by resection, the date of resection will be considered the date of definitive diagnostic surgery. If a biopsy only was performed, the biopsy date will be considered the date of definitive diagnostic surgery.
Exclusion Criteria:
• STEP 1: Patients must not have received any prior therapy for their central nervous system (CNS) malignancy except for surgery and steroid medications.
• STEP 1: Patients who are currently receiving another investigational drug are not eligible.
• STEP 1: Patients who are currently receiving other anti-cancer agents are not eligible.
• STEP 1: Patients >=18 years of age who have H3 K27M-wild type HGG.
• STEP 1: Patients who have an uncontrolled infection.
• STEP 1: Patients who have received a prior solid organ transplantation.
• STEP 1: Patients with grade > 1 extrapyramidal movement disorder.
• STEP 1: Patients with known macular degeneration, uncontrolled glaucoma, or cataracts.
• STEP 1: Patients with metastatic disease are not eligible; MRI of spine with and without contrast must be performed if metastatic disease is suspected by the treating physician.
• STEP 1: Patients with gliomatosis cerebri type 1 or 2 are not eligible, with the exception of H3 K27M-mutant bithalamic tumors.
• STEP 1: Patients who are not able to receive protocol specified radiation therapy.
• STEP 1:
• Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
• Lactating females are not eligible unless they have agreed not to breastfeed their infants. It is not known whether selinexor is excreted in human milk.
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use two effective methods of birth control (including a medically accepted barrier method of contraception, e.g., male or female condom) for the duration of their study participation and for 90 days after the last dose of selinexor. Abstinence is an acceptable method of birth control.
Procedure: Biopsy, Procedure: Magnetic Resonance Imaging, Radiation: Radiation Therapy, Drug: Selinexor
Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified, Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Glioblastoma, Glioblastoma, Not Otherwise Specified, Malignant Glioma
An Open-label Extension Study for Participants Who Completed Study IMVT-1401-3201 or Study IMVT-1401-3202 to Assess the Efficacy and Safety of Batoclimab for the Treatment of Thyroid Eye Disease (TED)
Extension Study to Assess Batoclimab in Participants With Thyroid Eye Disease
Marius Stan
All
18 years and over
Phase 3
2022-309692-P01-RST
22-010513
Inclusion Criteria
•For All Participants:
- Have completed the Week 24 visit of the feeder study.
Inclusion Criteria
•For Participants Assigned to the Open-label Treatment Cohort:
- Do not require immediate surgical intervention and is not planning corrective surgery/irradiation or medical therapy for TED during the course of the study.
- Did not permanently discontinue batoclimab.
Exclusion Criteria
•For All Participants:
- In the Investigator's judgement, the benefits of entry in the study do not outweigh the risk.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 9/30/22. Questions regarding updates should be directed to the study team contact.
Other, Drug
Brachial plexus patients undergoing upper limb amputation
Fantley Smither
All
18 years and over
2023-311936-H01-RST
23-005220
Inclusion Criteria:
- 18 years of age or older.
- Severe brachial plexus injury.
- Considering upper limb amputation.
Exclusion Criteria:
- 17 years old or younger.
- Declined upper limb amputation.
Eligibility last updated 5/18/23. Questions regarding updates should be directed to the study team contact.
A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)
All
18 Years and over
Phase 1
NCT04970901
Inclusion Criteria:
• Male or female participant aged 18 years or older
• Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) B-NHL (2016 World Health Organization classification) who have failed, or been intolerant to any approved therapy and had received at least two systemic treatment regimens in dose-escalation part; and at least one systemic treatment regimen in dose-expansion part
• DLBCL (including transformed diseases, but for Arms E and F, including transformed FL only)
• HGBCL
• FL
• MZL
• MCL (for Arm C only)
• BL (for Arm C only)
• Life expectancy of at least 24 weeks according to Investigator's judgement
• Need of systemic treatment for any of the listed indications as assessed by the investigator, including indolent B-NHLs (e.g. FL and MZL)
• Measurable disease as defined by the 2014 Lugano Classification
• Availability of formalin-fixed paraffin-embedded tumor tissue block
• ECOG performance status 0 to 2
• Adequate organ function
• Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent the first dose until at least 7 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period. For the arm that includes glofitamab, WOCBP must agree to use contraceptive methods that result in a failure of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 18 months after pretreatment with obinutuzumab. For the arm that includes mosunetuzumab, WOCBP must agree to use contraceptive methods that result in a failure of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable).
Exclusion Criteria:
• Known history of hypersensitivity resulting in treatment discontinuation to or positive serum human ADA to a CD19 antibody
• Previous therapy with loncastuximab tesirine
• Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied to relevant arm and/or cohort of the specific drug administered)
• Participants who received previous treatment of polatuzumab vedotin containing regimen will be excluded from Arm C
• Participants who received previous treatment of glofitamab containing regimen will be excluded from Arm E
• Participants who received previous treatment of mosunetuzumab containing regimen will be excluded from Arm F
• Allogenic or autologous stem cell transplant within 60 days prior to start of study drug (C1 D1)
• Human immunodeficiency virus (HIV) seropositive
• Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
• Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
• History of confirmed progressive multifocal leukoencephalopathy
• History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)
• Lymphoma with active central nervous system (CNS) involvement at the time of screening, including leptomeningeal disease
• Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
• Breastfeeding or pregnant
• Significant medical comorbidities
• Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drugs (C1 D1), except shorter if approved by the Sponsor
• Live vaccine within 4 weeks prior to C1D1
• Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (Grade ≤2 alopecia) due to previous therapy prior to screening
• Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary Extra Exclusion Criteria for Arms E (includes glofitamab) and F (includes mosunetuzumab) Note: as applicable, the arm-specific exclusion criteria may supersede the general ones, such as stem cell transplant.
• Prior allogeneic stem cell transplant and solid organ transplant
• Autologous stem cell transplant within 100 days prior to C1D1
• History of CNS lymphoma or leptomeningeal infiltration
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Known active infection, reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within four weeks prior to C1D1
• Active or history of autoimmune disease or immune deficiency, including but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain Barré syndrome, or multiple sclerosis, with certain exceptions
• Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinase inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not limited to, cluster of differentiation 137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death protein 1 (PD1), and anti-programmed death ligand 1 (PDL1) therapeutic antibodies, radio-immunoconjugates, ADCs, immune/cytokines and monoclonal antibodies) or treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of need for systemic immunosuppressive medication during study treatment, with certain exceptions
• Prior treatment with chimeric antigen receptor T-cell therapy within 30 days prior to C1D1
• Toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed with replacement therapy and stable vitiligo
• Any history of immune-related Grade ≥3 AE with the exception of endocrinopathy managed with replacement therapy
• Ongoing corticosteroid use >25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment
• Administration of a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment Extra Exclusion Criteria for Arm E (includes glofitamab) only. • Known history of hypersensitivity to obinutuzumab
Drug: Loncastuximab Tesirine, Drug: Polatuzumab Vedotin, Drug: Glofitamab, Drug: Mosunetuzumab, Drug: Obinutuzumab
B-Cell Non-Hodgkin Lymphoma, Relapsed B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma
B-Cell Non-Hodgkin Lymphoma, Relapsed B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Loncastuximab Tesirine