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: 20.0Level: HLTClassification code 10016895Term: Follicle centre lymphomas diffuse predominantly small cellSystem Organ Class: 100000004851; 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-IT
• Lead Sponsor: CELGENE CORPORATIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-07
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

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 invest.
3. Subject must have measurable disease as follows:
a. For FL subjects (Cohorts 1, 2, and 3), PET-pos disease with at least one PET-pos lesion and at least one measurable nodal or extranodal lesion greater than 1.5 cm in the long axis (refer to protocol, App F)
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-pos disease is not required for MZL) - refer to protocol, App F
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. 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 syst therapy. At least one of these lines must be a combination which included an antiCD20 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 relapsed after HSCT, OR meet the definition of double refractory (refer to protocol section 4.2)
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+ MZL): received at least 2 prior syst therapies, including at least one line of combination syst therapy, therapy
with an anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent, or relapsed after HSCT. Splenectomy for SMZL is considered as a line of therapy. Antibiotics for extranodal MZL (ENMZL) are not considered as a prior line of
therapy
5. Subject is = 18 years of age the time of signing the ICF
6. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
7. Subject has ECOG performance status of 0 or 1
8. Subject has adequate organ function.
9. Subject has adequate vascular access for leukapheresis procedure.
10. 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.
11. FCBP subjects must:
a. Have 2 neg pregnancy tests as verified by the Investigator (one neg serum 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 documen

Exclusion Criteria

1. Evidence of composite DLBCL and FL, or of transformed FL. Subjects with World Health Organization (WHO) sub-classification of duodenaltype 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: The secondary objectives are: <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<br>health/QoL, physical functioning, fatigue, pain) and FACT-LymS (lymphoma specific symptoms);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);Primary end point(s): Complete response rate (CRR) as assessed by PET-CT (FL) or CT (MZL) using The Lugano Classification.;Timepoint(s) of evaluation of this end point: Up to 24 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Overall response rate (ORR) 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);Timepoint(s) of evaluation of this end point: Up to 24 months for all secondary endpoints.