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

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)

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 patients with relapsed and refractory B-cell Non-Hodgkin lymphoma.

Study Overview

• Status: Unknown
• Conditions: Non Hodgkin Lymphoma
• Intervention / Treatment: Biological: JWCAR029

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JWCAR029; The safety and efficacy of JWCAR029 will be evaluated in a standard 3+3 dose escalation approach. 4 CAR T dosage will be tested in this study: 1×10^7, 2.5×10^7, 5×10^7, 1×10^8 CAR+ T cells.

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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhao Weili
• Collaborators: Shanghai Mingju Biotechnology Co., Ltd.

Publications and helpful links

General Publications

• 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.
• Yan ZX, Li L, Wang W, OuYang BS, Cheng S, Wang L, Wu W, Xu PP, Muftuoglu M, Hao M, Yang S, Zhang MC, Zheng Z, Li J, Zhao WL. Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma. Clin Cancer Res. 2019 Dec 1;25(23):6995-7003. doi: 10.1158/1078-0432.CCR-19-0101. Epub 2019 Aug 23.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: November 22, 2017
• First Submitted That Met QC Criteria: November 22, 2017
• First Posted (Actual): November 28, 2017

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Non Hodgkin Lymphoma; JWCAR029; CD19-targeted chimeric antigen receptor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: JWCAR029-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No