A phase 3 study to assess the efficacy and safety of JCAR017, a CAR-T cell therapy, in adults with aggressive B-Cell non-Hodgkin lymphoma

Phase 1

• Conditions: Transplant-eligible relapsed or refractory (R/R) aggressive B-cell Non Hodgkin Lymphoma (B-NHL); MedDRA version: 20.0Level: LLTClassification code 10029593Term: Non-Hodgkin's lymphoma NOSSystem Organ Class: 100000004864; MedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2018-000929-32-ES
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-21
• Last Update Posted: 20 August 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 182

Inclusion Criteria

1. Subject is = 18 years and = 75 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. ECOG performance status = 2.

5. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed FL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]) or follicular lymphoma grade 3B. Enough tumor material must be available for confirmation by central pathology. If archival sample is before most recent relapse or no or insufficient archival sample is available, a new tumor biopsy is mandated to confirm diagnosis.
Note: Subjects with secondary CNS involvement are eligible.

6. Refractory (SD, PD, PR or CR with relapse before 3 months) or relapsed (CR with relapse on or after 3 months) within 12 months from CD20 antibody and anthracycline containing first line therapy.

7. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening.

8. Adequate organ function, defined as:
- Adequate bone marrow function as assessed by the Investigator
- Serum creatinine < 1.5 x age-adjusted upper limit of normal (ULN) or creatinine clearance > 30 mL/min (estimated glomerular filtration rate [eGFR] by Cockcroft Gault see Appendix D for calculation)
- Alanine aminotransferase (ALT) = 5 x ULN and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver)
- Adequate pulmonary function, defined as = Grade 1 dyspnea according to Common Terminology Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) = 92% on room air
- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) = 40% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) performed within 4 weeks of randomization

9. Adequate vascular access for leukapheresis

10. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals while receiving as well as within 12 months after the JCAR017 infusion and until CAR T cells are no longer present by quantitative polymerase chain reaction (qPCR) on 2 consecutive tests, whichever occurs last.

11. Females of childbearing potential (FCBP) must:
- Have a negative pregnancy test as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
- 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. Contraception methods must include 1 highly effective and 1 additional effective (barrier) method of contraception from screening until at least 12 months after the JCAR017 infusion and until CAR T cells are no longer present by qPCR on 2 consecutive tests, whichever is later (Arm B) and until 12 months after the last chemotherapy (Arm A),
- Agree to abstain from breastfeeding during study participation and for at least 3 months after the last dose of JCAR017 or until CAR

Exclusion Criteria

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 not eligible for hematopoietic stem cell transplantation (HSCT).

5. Subjects planned to undergo allogeneic stem cell transplantation.

6. Subjects with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), EBV (Epstein-Barr virus) positive DLBCL of the elderly and Burkitt lymphoma, transformed indolent NHL except transformed FL.

7. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for = 2 years with the exception of the following noninvasive 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

8. Treatment with any prior gene therapy product

9. Subjects who have received previous CD19-targeted therapy.

10. History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

11. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.

12. Active autoimmune disease requiring immunosuppressive therapy.

13. History of any one of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.

14. History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

15. Pregnant or nursing (lactating) women.

16. Use of the following:
- Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to unstimulated leukapheresis. Physiologic replacement, topical, and inhaled steroids are permitted.
- Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) must be stopped = 7 days prior to unstimulated leukapheresis.
- Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) prior to unstimulated leukapheresis.
- Experimental agents within 4 weeks prior to signing the ICF unless no response or progressive disease (PD) is documented on the experimental therapy and at least 3 half-lives have elapsed prior to unstimulated leukapheresis.
- Immunosuppressive therapies within 4 weeks prior to unstimulated leukapheresis (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-tumor necrosis fac

Study & Design

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