Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma (TRANSCENDWORLD)
- Conditions
- Aggressive B-cell non-Hodgkin lymphoma (B-NHL)
- Registration Number
- JPRN-jRCT1080224068
- Lead Sponsor
- Bristol-Myers Squibb K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 18
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is >= 18 years of age at the time of signing the informed consent form (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. Investigator considers the subject is appropriate for adoptive T cell therapy
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Subjects not eligible for transplant (TNE) in Cohorts 2 and 3 and subjects in Cohort 5 may be enrolled with ECOG of 2 only if they meet all other inclusion/exclusion criteria.
6. Subjects with one of the following:
- Cohort 1: Subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016 classification (Swerdlow, 2016), after >= 2 lines of therapy*, including an anthracycline and rituximab (or other CD20-targeted agent)
- Cohort 2: Transplant not eligible subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016 classification (Swerdlow, 2016), who failed first line therapy, including an anthracycline and rituximab (or other CD20-targeted agent)
- Transplant not eligible subjects will include those who are deemed ineligible for high-dose chemotherapy and HSCT due to age, performance status or comorbidity, while also having adequate organ function for CAR T cell treatment. At the very least, subjects have to meet one of the following criteria: Age >= 70 years, ECOG performance status >= 2, Impaired pulmonary function (DLCO <= 60%, adjusted for hemoglobin concentration using the Dinakara equation), Impaired cardiac function (LVEF < 50%), Impaired renal function (CrCl < 60 mL/min), Impaired hepatic function (AST/ALT > 2 x ULN, or bilirubin >= 2 mg/dL or cirrhosis Child-Pugh B or C).
- Subjects must fulfill all other inclusion and exclusion criteria.
- Cohort 3 (Japan only): Subjects meeting eligibility criteria for either Cohort 1 or 2
- Cohort 4: Subjects with newly diagnosed HGBL. Subjects must be eligible for anthracycline and rituximab (or other CD20-targeted agent) containing regimen as induction prior to consolidation with JCAR017
- Cohort 5: Subjects with PCNSL who failed first line therapy with HDCT and ASCT, or who failed to proceed to HDCT and ASCT due to failure of PBSC mobilization or insufficient response at the completion of induction therapy with high-dose methotrexate-based polychemotherapy regimen (eg, high dose methotrexate, high dose cytarabine, rituximab and thiotepa [MATRix regimen])
- Cohort 6: (REMOVED)
- Cohort 7: Subjects meeting eligibility criteria for Cohort 1 and suitable for outpatient treatment
7. Histological confirmation of diagnosis at last relapse. Enough tumor material must be available for central confirmation of diagnosis, otherwise a new tumor biopsy is mandated. Note: If the subject did not experience CR since last biopsy, the most recent biopsy will be considered adequate to participate in the trial. For subjects with PCNSL, at a minimum, corresponding pathology report is required if archival tumor material is not available and repeated biopsy not feasible.
8. For subjects with NHL (except Cohort 5): Subjects must have positron emission tomography (PET)-positive disease as per Lugano Classification (Cheson, 2014)
9. For subjects with PCNSL: Subjects must have disease that is objectively measurable by International Workshop to Standardize Baseline Eval
The presence of any of the following will exclude a subject from enrollment:
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 with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), Epstein-Barr virus (EBV) positive DLBCL of the elderly, Burkitt lymphoma, and intraocular lymphoma
5. Subjects with prior history of malignancies, other than aggressive r/r NHL, unless the subject has been in remission for >= 2 years with the exception of the following non-invasive 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.
6. Treatment with any prior gene therapy product
7. Subjects who have received previous CD19-targeted therapy
8. Human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
9. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion
10. Presence of acute or chronic graft-versus-host disease (GVHD)
11. Active autoimmune disease requiring immunosuppressive therapy
12. History of any one of the following cardiovascular conditions within the past 6 months:
- Heart failure class III or IV as defined by the New York Heart Association (NYHA)
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Other clinically significant cardiac disease
13. History or presence of clinically relevant CNS pathology not related to disease under study such as epilepsy, seizure, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
14. Pregnant or nursing women
15. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
16. Use of the following:
- Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
- Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide <= 300 mg/m2) given after leukapheresis to maintain disease control must be stopped >= 7 days prior to LD chemotherapy
- Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 week prior to leukapheresis. Oral anticancer agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis
- Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide > 300 mg/m2, ifosfamide, bendamustine) within 2 weeks prior to leukapheresis
- Experimental agents within 4 weeks prior to leukapheresis unless no res
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Overall Response Rate (ORR) of JCAR017 in participants with Non-Hodgkin Lymphoma (NHL; including secondary central nervous system (CNS) involvement)<br>2. ORR of JCAR017 in participants with relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL)<br>3. Adverse Events (AEs) in participants intended to be treated as outpatients
- Secondary Outcome Measures
Name Time Method