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

Non Hodgkin Lymphoma Clinical Trial

Official title:

A Phase 1, Open-Label Study of JWCAR029, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Adult Subjects With Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03344367
• Other study ID #: JWCAR029-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 16, 2017
• Est. completion date: March 2022

Study information

• Verified date: July 2019
• Source: Peking University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: March 2022
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University	Shanghai Mingju Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related adverse events (AEs)	Physiological parameter	2 years
Primary	Dose-limiting toxicities of JWCAR029	Physiological parameter	28 days after JWCAR029 infusion
Primary	Objective response rate (ORR)	Lugano criteria	2 years
Secondary	Maximum concentration (Cmax) of JWCAR029 in the peripheral blood and bone marrow	Flow cytometry and qPCR	1 year after JWCAR029 infusion
Secondary	Time to maximum concentration (Tmax) of JWCAR029 in the peripheral blood and bone marrow	Flow cytometry and qPCR	1 year after JWCAR029 infusion
Secondary	Area-under the concentration-vs-time-curve (AUC) of JWCAR029 in the peripheral blood and bone marrow	Flow cytometry and qPCR	1 year after JWCAR029 infusion
Secondary	Complete response (CR) rate	Lugano criteria	2 years
Secondary	Duration of response	Lugano criteria	2 years
Secondary	Progression-free survival (PFS) and PFS ratio	Lugano criteria	2 years
Secondary	Overall survival	Physiological parameter	2 years
Secondary	Health-related quality of life (HRQoL)	Questionnaire	2 years