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

Phase 1

• Conditions: Non Hodgkin Lymphoma
• Interventions: Biological: JWCAR029

• Registration Number: NCT03344367
• Lead Sponsor: Peking University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-10
• Study First Submitted QC: 2017-11-15
• Study Start: 2017-11-16
• Study First Posted: 2017-11-17
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-10
• Last Update Posted: 2019-07-12
• Primary Completion: 2019-10
• Study Completion: 2022-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
JWCAR029	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.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicities of JWCAR029	28 days after JWCAR029 infusion	Physiological parameter
Treatment-related adverse events (AEs)	2 years	Physiological parameter
Objective response rate (ORR)	2 years	Lugano criteria

Secondary Outcome Measures

Name	Time	Method
Maximum concentration (Cmax) of JWCAR029 in the peripheral blood and bone marrow	1 year after JWCAR029 infusion	Flow cytometry and qPCR
Time to maximum concentration (Tmax) of JWCAR029 in the peripheral blood and bone marrow	1 year after JWCAR029 infusion	Flow cytometry and qPCR
Health-related quality of life (HRQoL)	2 years	Questionnaire
Area-under the concentration-vs-time-curve (AUC) of JWCAR029 in the peripheral blood and bone marrow	1 year after JWCAR029 infusion	Flow cytometry and qPCR
Duration of response	2 years	Lugano criteria
Progression-free survival (PFS) and PFS ratio	2 years	Lugano criteria
Complete response (CR) rate	2 years	Lugano criteria
Overall survival	2 years	Physiological parameter

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, China