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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

3 Jun 2024 → ongoing

Decision date (initial)

2024-06-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-510966-18-00

EudraCT number

2019-004081-18

WHO UTN

U1111-1244-9768

ClinicalTrials.gov

NCT04245839

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacogenomic, Safety, Others, Pharmacoeconomic, Pharmacogenetic, Pharmacokinetic, Efficacy, Therapy

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 objectives 4

1. To evaluate other measures of efficacy
2. To evaluate the safety of JCAR017
3. To characterize the pharmacokinetic (PK) profile of JCAR017
4. 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)

Conditions and MedDRA coding

Relapsed or refractory indolent B-cell Non-Hodgkin Lymphoma (NHL)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

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, 3 and 3 Extension), 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. 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 3 Extension (2L r/r FL): received no more than 1 prior line of combination systemic therapy, which included an anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent, and i. has relapsed or refractory disease that has progressed within 24 months of initiation of first-line chemoimmunotherapy (POD24) OR ii. must meet at least one of the modified GELF criteria (NCCN, 2019), as outlined in Inclusion Criterion 5.e.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) and Cohort 3 Extension (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 (as defined for Cohort 3 and Cohort 3 Extension respectively) 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 not donate blood, organs, sperm or semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy.
12. 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.
13. 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.
14. Refer to protocol section 4.2 for list of inclusion criteria.

Exclusion criteria 21

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 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. 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.
21. Refer to protocol section 4.3 for list of inclusion criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR) as assessed by PET-CT (FL) or CT (MZL) using "The Lugano Classification".

Secondary endpoints 8

1. Complete response rate (CRR) as assessed by PET-CT (FL) or CT (MZL) using "The Lugano Classification".
2. Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using "The Lugano Classification".
3. Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification".
4. Progression Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification".
5. Overall Survival (OS)
6. Safety
7. Pharmacokinetics (PK)
8. Health-related quality of life (HRQoL)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 5

Locations

6 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications