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.

Phase 1

• Conditions: Relapsed or refractory indolent B-cell Non-Hodgkin Lymphoma (NHL); MedDRA version: 24.0Level: HLTClassification code 10016895Term: Follicle centre lymphomas diffuse predominantly small cellSystem Organ Class: 10016895 - Follicle centre lymphomas diffuse predominantly small cell; MedDRA version: 20.0Level: PTClassification code 10076596Term: Marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029460Term: Nodal marginal zone B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2019-004081-18-AT
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-02-26
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 213

Inclusion Criteria

1. Subject has FL (Grade 1, 2, or 3a) or MZL histologically confirmed within 6 months of screening, as assessed by local pathology.
2. Subject must have relapsed or refractory disease, as assessed by the investigator.
3. 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
4. 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.
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 anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent. In addition to this requirement, subjects must meet one of the following high-risk criteria: have relapsed or refractory disease within 12 months of completion of a prior line of therapy and have received prior combination therapies, OR
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 Splenic MZL (SMZL) is considered as a line of therapy. Antibiotics for extranodal MZL (ENMZL) are not considered as a prior line of therapy.
5. Cohort 3 (2L r/r FL) subjects must meet at least one criterion of the modified GELF criteria listed below (a-d) (NCCN, 2019) if they do not meet criteria of POD24 (having progression of disease within 24 months from diagnosis and must have received treatment for FL within 6 months
of diagnosis):
a. Symptoms attributable to FL (not limited to B symptoms)
b. Threatened end-organ function; OR cytopenia secondary to lymphoma; OR bulky disease (single mass > 7 cm or 3 or more masses > 3 cm)
c. Splenomegaly
d. Steady progression over at least 6 months
6. Subject is = 18 years of age the time of signing the informed consent form (ICF).
7. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
8. Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Subject has adequate organ function.
10. Subject has adequate vascular access for leukapheresis procedure.
11. Subjects must agree to no

Exclusion Criteria

1. Evidence or history of composite DLBCL and FL, or of transformed FL. Subjects with World Health Organization (WHO) sub-classification of duodenal-type FL
2. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on investigator’s judgement.
3. 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.
4. Any condition that confounds the ability to interpret data from the study based on investigator’s judgement.
5. Central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study).
6. History of another primary malignancy that has not been in remission for at least 2 years For specific exceptions, see protocol section 4.3
7. Previous treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis.
8. Prior CAR T-cell or other genetically-modified T-cell therapy.
9. History of or active human immunodeficiency virus (HIV).
10. Active hepatitis B or active hepatitis C.
11. Uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
12. Active autoimmune disease requiring immunosuppressive therapy.
13. Presence of acute or chronic graft-versus-host disease (GVHD).
14. History of specific cardiovascular conditions within the past 6 months prior to signing the ICF (see protocol section 4.3).
15. History or presence of clinically relevant central nervous system (CNS) pathology not related to disease under study. (see protocol section 4.3)
16. Subject is a pregnant or nursing (lactating) woman.
17. Subject has an intolerance to dimethyl sulfoxide (DMSO) and/or dextran
18. Progressive vascular tumor invasion, thrombosis, or embolism
19. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
20. 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. Experimental agents within 4 weeks prior to signing the ICF unless no response or PD is documented on the experimental therapy
d. Ibrutinib, lenalidomide and PI3Ki within 3 half-lives prior to unstimulated leukapheresis
e. Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion
f. Donor lymphocyte infusion (DLI) within 6 weeks prior to JCAR017 infusion
g. Radiation within 6 weeks of leukapheresis.
h. 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

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: The secondary objectives are: <br><br>-To evaluate other measures of efficacy <br>-To evaluate the safety of JCAR017 <br>-To characterize the pharmacokinetic (PK) profile of JCAR017 <br>-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) <br>;Primary end point(s): Overall response rate (ORR) as assessed by PET-CT (FL) or CT (MZL) using The Lugano Classification”. <br>;Timepoint(s) of evaluation of this end point: Up to 60 months

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”.<br>-Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using The Lugano Classification”.<br>-Duration of Response (DOR) as assessed by PET-CT and/or CT using The Lugano Classification”.<br>-Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using The Lugano Classification”.<br>-Overall Survival (OS) <br>-Safety<br>-Pharmacokinetics (PK)<br>-Health-related quality of life (HRQoL)<br><br><br><br><br>;Timepoint(s) of evaluation of this end point: Up to 60 months for all secondary endpoints EXCEPT HRQoL - which is up to 24 months.