A study to evaluate the efficacy and safety of JCAR017 in adult subjects with a type of cancer that affects B-cells, a type of white blood cell.
- Conditions
- Relapsed or refractory indolent B-cell Non-Hodgkin Lymphoma (NHL)MedDRA version: 24.0Level: HLTClassification code: 10016895Term: Follicle centre lymphomas diffuse predominantly small cell Class: 10029104MedDRA version: 21.1Level: PTClassification code: 10029460Term: Nodal marginal zone B-cell lymphoma Class: 100000004864MedDRA version: 20.0Level: PTClassification code: 10076596Term: Marginal zone lymphoma Class: 100000004864Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- CTIS2024-510966-18-00
- Lead Sponsor
- Celgene Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 204
Subject has FL (Grade 1, 2, or 3a) or MZL histologically confirmed within 6 months of screening, as assessed by local pathology., Subject has adequate vascular access for leukapheresis procedure., Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy., Females of childbearing potential (FCBP) subjects must: a. Have 2 negative pregnancy tests as verified by the Investigator (one negative serum beta-human chorionic gonadotropin [ß-hCG] pregnancy test result at screening, and within 7 days prior to the first dose of lymphodepleting chemotherapy). b. 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. c. Agree to abstain from breastfeeding during study participation and for at least 12 months following lymphodepleting chemotherapy., Male subjects must: a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for 12 months after lymphodepleting chemotherapy even if he has undergone a successful vasectomy., Refer to protocol section 4.2 for list of inclusion criteria., Subject must have relapsed or refractory disease, as assessed by the investigator., Subject must have measurable disease as follows: a. For FL subjects (Cohorts 1, 2, and 3), PET-positive disease with at least one PET-positive lesion and at least one measurable nodal or extranodal lesion greater than 1.5 cm in the long axis (refer to protocol, Appendix G) b. MZL subjects (Cohort 4) with PET non-avid disease should have at least one measurable nodal lesion greater than 2.0 cm in the long axis (PET-positive disease is not required for MZL) - refer to protocol, Appendix G., Subject must have received the following, depending on cohort assignment: a. Cohort 1 (4L+ r/r FL): received at least 3 prior lines of systemic therapy. At least one of these lines must be a combination which included an anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent. Prior HSCT is permitted as a prior line of therapy. A group of 4L+ double-refractory subjects will be enrolled in this cohort (refer to protocol section 4.2). b. Cohort 2 (3L r/r FL): received 2 prior lines of systemic therapy. At least one of these lines must be a combination which included an antiCD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent. Prior HSCT is permitted as a prior line of therapy. c. Cohort 3 (2L r/r FL): received 1 prior line of combination systemic therapy, which included an anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent. A group of POD24 subjects, defined as having progressive disease within 24 months of diagnosis and have received treatment within 6 months of the original FL diagnosis, will be enrolled to this cohort. The 2L subjects that do not meet this POD24 definition must instead meet one of the modified GELF criteria (NCCN, 2019) as outlined in protocol section 4.2, number 5. d.Cohort 4 (3L+ r/r MZL): received at least 2 prior systemic therapies, including at least one line of combination systemic therapy, therapy with an anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent, or relapsed after HSCT. Splenectomy for Splen
Evidence or history of composite DLBCL and FL, or of transformed FL. Subjects with World Health Organization (WHO) sub-classification of duodenal-type FL, Active hepatitis B or active hepatitis C., Uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment., Active autoimmune disease requiring immunosuppressive therapy., Presence of acute or chronic graft-versus-host disease (GVHD)., History of specific cardiovascular conditions within the past 6 months prior to signing the ICF (see protocol section 4.3)., History or presence of clinically relevant central nervous system (CNS) pathology not related to disease under study. (see protocol section 4.3), Subject is a pregnant or nursing (lactating) woman., Subject has an intolerance to dimethyl sulfoxide (DMSO) and/or dextran, Progressive vascular tumor invasion, thrombosis, or embolism, Venous thrombosis or embolism not managed on a stable regimen of anticoagulation, Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on investigator's judgement., Subject has received or undergone the following (See section 4.3 for additional details).a. Therapeutic doses of corticosteroids (defined as >20 mg/day prednisone or equivalent) within 7 days prior to unstimulated leukapheresis. b. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic and intrathecal chemotherapy must be stopped > 7 days prior to unstimulated leukapheresis c. Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide > 300 mg/m2, ifosfamide, bendamustine) 2 weeks prior to unstimulated leukapheresis. d. Experimental agents within 4 weeks prior to signing the ICF unless no response or PD is documented on the experimental therapy e. Ibrutinib, lenalidomide and PI3Ki within 3 half-lives prior to unstimulated leukapheresis f. Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion g. Donor lymphocyte infusion (DLI) within 6 weeks prior to JCAR017 infusion h. Radiation within 6 weeks of leukapheresis. i. Systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to JCAR017 infusion. j. Allo-HSCT within 90 days of leukapheresis., Refer to protocol section 4.3 for list of inclusion criteria, Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study based on investigator's judgement., Any condition that confounds the ability to interpret data from the study based on investigator's judgement., Central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)., History of another primary malignancy that has not been in remission for at least 2 years For specific exceptions, see protocol section 4.3, Previous treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis., Prior CAR T-cell or other genetically-modified cell therapy., History of or active human immunodeficiency virus (HIV).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to evaluate the efficacy of JCAR017 in subjects with relapsed/refractory (r/r) follicular lymphoma (FL) and marginal zone lymphoma (MZL).;Secondary Objective: To evaluate other measures of efficacy, To evaluate the safety of JCAR017, To characterize the pharmacokinetic (PK) profile of JCAR017, To evaluate the Health-Related-Quality of Life (HRQoL) using preselected primary domains of interest in the EORTC QLQ-C30 (global health/QoL, physical functioning, cognitive functioning, fatigue, pain) and FACT-LymS (lymphoma specific symptoms);Primary end point(s): Overall response rate (ORR) as assessed by PET-CT (FL) or CT (MZL) using The Lugano Classification.
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Complete response rate (CRR) as assessed by PET-CT (FL) or CT (MZL) using The Lugano Classification.;Secondary end point(s):Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using The Lugano Classification.;Secondary end point(s):Duration of Response (DOR) as assessed by PET-CT and/or CT using The Lugano Classification.;Secondary end point(s):Progression Free Survival (PFS) as assessed by PET-CT and/or CT using The Lugano Classification.;Secondary end point(s):Overall Survival (OS);Secondary end point(s):Safety;Secondary end point(s):Pharmacokinetics (PK);Secondary end point(s):Health-related quality of life (HRQoL)