A phase 3 study to assess the efficacy and safety of JCAR017, a CAR-T cell therapy, in adults with aggressive B-Cell non-Hodgkin lymphoma
- Conditions
- Transplant-eligible relapsed or refractory (R/R) aggressive B-cell Non Hodgkin Lymphoma (B-NHL)MedDRA version: 21.1 Level: LLT Classification code 10029593 Term: Non-Hodgkin's lymphoma NOS System Organ Class: 100000004864MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-000929-32-NL
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 182
1. Subject is = 18 years and = 75 years of age at the time of signing the ICF. 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 4. ECOG performance status = 1. 5. Histologically proven DLBCL NOS (de novo or transformed FL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]) , primary mediastinal (thymic) large B-cell lymphoma (PMBCL), T cell/histiocyte-rich large B-cell lymphoma (THRBCL), or follicular lymphoma grade 3B. Enough tumor material must be available for confirmation by central pathology. If archival sample is before most recent relapse or no or insufficient archival sample is available, a new tumor biopsy is mandated to confirm diagnosis. Note: Subjects with secondary CNS involvement are eligible. Subject selection must consider clinical risk factors for severe AEs and alternative treatment options. Subjects should only be enrolled if the Investigator assesses that the potential benefit outweighs the risk for the subject.6. Refractory (SD, PD, PR or CR with relapse before 3 months) or relapsed (CR with relapse on or after 3 months) within 12 months from CD20 antibody and anthracycline containing firstline therapy. Note: The time of relapse is calculated from the date of the first disease assessment confirming a CR obtained with firstline treatment for disease under study, to the date of first assessment demonstrating a relapse. 7. [18F] FDG PET positive lesion per Lugano criteria at screening. 8. Adequate organ function, defined as: Adequate bone marrow function as assessed by the Investigator; Serum creatinine < 1.5 x age-adjusted ULN or creatinine clearance > 45 mL/min (eGFR by Cockcroft Gault; see Appendix D for calculation); ALT = 5 x ULN and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert's syndrome orlymphomatous infiltration of the liver); Adequate pulmonary function, defined as = Grade 1 dyspnea according to CTCAE and oxygen saturation (SaO2) = 92% on room air and FEV1 = 50%; Adequate cardiac function, defined as LVEF = 40% as assessed by ECHO or MUGA performed within 4 weeks of randomization. 9. Adequate vascular access for leukapheresis. 10. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals while receiving as well as within 12 months after the JCAR017 infusion and until CART cells are no longer present by qPCR on 2 consecutive tests, whichever occurs last. 11. Females of CBP must: Have a neg. pregnancy test as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact; Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption. Contraception methods must include 1 highly effective and 1 additional effective (barrier) method of contraception from screening until at least 12 months after the JCAR017 infusion and until CAR T cells are no longer present by qPCR on 2 consecutive tests, whichever is later (Arm B) and until
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if participating in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
5. Subjects planned to undergo allogeneic stem cell transplantation.
6. Subjects with primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus) positive DLBCL of the elderly and Burkitt lymphoma
7. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for = 2 years with the exception of the following noninvasive malignancies:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
- Other completely resected stage 1 solid tumor with low risk for recurrence
8. Treatment with any prior gene therapy product
9. Subjects who have received previous CD19-targeted therapy.
10. History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
11. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
12. Active autoimmune disease requiring immunosuppressive therapy.
13. History of any one of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
14. History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
15. Tumor invasion of venous or arterial vessels.
16. Deep venous thrombosis (DVT)/ Pulmonary embolism (PE) within 3
months prior to leukapheresis, and/or DVT/ PE that requires ongoing
therapeutic levels of anti-coagulation.
17. Pregnant or nursing (lactating) women.
18. Use of the following:
- Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to unstimulated leukapheresis. P
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method