Study Evaluating the Safety and Efficacy of JWCAR029 in Adult Subjects With Relapsed and Refractory B-cell Non-Hodgkin Lymphoma

NCT ID: NCT03344367

Last Updated: 2019-07-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-16
• Study Completion Date: 2022-03-31

Brief Summary

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infusion of autologous CD19-targeted chimeric antigen receptor (CD19 CAR) T cells in adult subjects with relapsed and refractory B-cell Non-Hodgkin lymphoma.

Conditions

Non Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

JWCAR029

The safety and efficacy of JWCAR029 will be evaluated in a standard 3+3 dose escalation approach. 5 CAR T dosage will be tested in this study: 1×10\^7, 2.5×10\^7, 5×10\^7, 1×10\^8, 1.5\^108 CAR+ T cells.

Group Type: EXPERIMENTAL

JWCAR029

Intervention Type: BIOLOGICAL

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWCAR029. During JWCAR029 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with JWCAR029 by intravenous (IV) injection.

Interventions

JWCAR029

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWCAR029. During JWCAR029 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with JWCAR029 by intravenous (IV) injection.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Subjects must meet all of the following criteria to be enrolled in this study:

1. Age ≥ 18 years at the time of consent

2. Signed written informed consent obtained prior to any study procedures

3. Relapsed or refractory B-cell NHL.

4. PET-positive disease BY Lugano classification

5. Archived tumor biopsy tissue available from the last relapse and corresponding pathology report available or, if at least one tumor-involved site is deemed accessible at time of screening, willing to undergo pre-treatment biopsy (excisional when possible) for disease confirmation. If a subject has never had a complete response, a sample from the most recent biopsy is acceptable.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function

8. Adequate vascular access for leukapheresis procedure

9. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy

10. Subjects must agree to use appropriate contraception.

Exclusion Criteria

• Subjects who meet any of the following criteria will be excluded from participation in this study:

1. Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)

2. History of another primary malignancy that has not been in remission for at least 2 years.

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

4. Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of screening

5. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or JWCAR029 administration

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

7. History of cardiovascular disease

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

9. Pregnant or nursing women.

10. Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JWCAR029 treatment in this protocol for subjects receiving retreatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Mingju Biotechnology Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Jun Zhu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Cancer Hospital

Beijing, , China

Countries

China

References

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

Other Identifiers

JWCAR029-001

Identifier Type: -

Identifier Source: org_study_id