A 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: Aggressive B-cell Non Hodgkin Lymphoma (B-NHL); MedDRA version: 23.0Level: 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: EUCTR2017-000106-38-FI
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-12
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

1. Subject is = 18 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. Investigator considers the subject is appropriate for adoptive T cell therapy.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Subjects not eligible for transplant (TNE) in Cohorts 2 and 3 and subjects in Cohort 5 may be enrolled with ECOG of 2 only if they meet all other inclusion/exclusion criteria.

6. Subjects with one of the following:
• Cohort 1: Subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016 classification (Swerdlow, 2016), after = 2 lines of therapy*, including an anthracycline and rituximab (or other CD20-targeted agent).
• Cohort 2: Transplant not eligible subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016 classification (Swerdlow, 2016), who failed first line therapy* including an anthracycline and rituximab (or other CD-20-targeted agent).
- Transplant not eligible subjects will include those who are deemed ineligible for high-dose chemotherapy and HSCT due to age, performance status or comorbidity, while also having adequate organ function for CAR T cell treatment. At the very least, subjects have to meet one of the following criteria:
a)age = 70 years
b) ECOG performance status = 2
c) impaired pulmonary function (DLCO = 60% adjusted for hemoglobin concentration using the Dinakara equation)
d) impaired cardiac function (LVEF < 50%)
e) impaired renal function (CrCl < 60 mL/min)
f) Impaired hepatic function (AST/ALT > 2x ULN, bilirubin > 2 mg/dL or cirrhosis Child-Pugh B or C).
- Subjects must fulfill all other inclusion and exclusion criteria
• Cohort 3: (Japan only): Subjects meeting eligibility criteria for either Cohort 1 or 2.
• Cohort 4: Subjects with newly diagnosed HGBL. Subjects must be eligible for anthracycline and rituximab (or other CD20-targeted agent) containing regimen as induction prior to consolidation with JCAR017**
• Cohort 5: Subjects with PCNSL who failed first line therapy with HDCT and ASCT or who failed to proceed to HDCT and ASCT due to failure of
PBSC mobilization or insufficient response at the completion of induction
therapy with high-dose methotrexate-based polychemotherapy regimen
(eg, high dose methotrexate, high dose cytarabine, rituximab and
thiotepa [MATRix regimen])
• Cohort 6: (REMOVED)
• Cohort 7: Subjects meeting eligibility criteria for Cohort 1 and suitable for outpatient treatment***
*For subjects with transformed disease, the subject should have had at least 2 lines of systemic therapy for his/her transformed disease (i.e. DLBCL) for Cohort 1 and 1 line for Cohort 2 to be eligible. Lines of therapy do not include those given for a previously indolent condition (i.e. follicular lymphoma). Subjects do NOT have to have anthracycline for their DLBCL if received for indolent disease.
** For subjects already undergoing anthracycline and rituximab containing regimen, eligibility is to be discussed with Medical Monitor. Subjects with complete metabolic response after 2 cycles of induction will proceed with JCAR017 infusion only at time of relapse, if applicable.
*** Subjects must meet the conditions for outpatient treatment and monitoring as outlined in the Outpatient Administration and Monitoring Guidanc

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 with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), Epstein-Barr virus (EBV) positive DLBCL of the elderly, Burkitt lymphoma, and intraocular lymphoma.

5. Subjects with prior history of malignancies, other than aggressive r/r NHL, unless the subject has been in remission for 2 years with the exception of the following non-invasive 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

6. Treatment with any prior gene therapy product.

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

8. Human immunodeficiency virus (HIV) infection , hepatitis B, or hepatitis C:
• Subjects with a history of or active HIV are excluded
• Subjects with active hepatitis B, or active hepatitis C are excluded
- Subjects with a negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy

9. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion.

10. Presence of acute or chronic graft-versus-host disease (GVHD).

11. Active autoimmune disease requiring immunosuppressive therapy.

12.History of any one of the following cardiovascular conditions within the past 6 months:
• Heart failure class III or IV as defined by the New York Heart Association (NYHA)
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Other clinically significant cardiac disease

13. History or presence of clinically relevant CNS pathology not related to disease under study such as epilepsy, seizure, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

14. Pregnant or nursing women.

15. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis

16. Use of the following (see Section 8.2 for full details):
• Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or
72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
• Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide = 300 mg/m2) given after leukapheresis to maintain disease control must be stopped = 7 days prior to LD chemotherapy.
• Cytotoxic chemotherapeutic agents

Study & Design

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