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

NCT03355859 | Unknown Phase 1

• 1 other identifier: JWCAR029-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Conditions

Non Hodgkin Lymphoma

Keywords

Non Hodgkin Lymphoma; CD19-targeted chimeric antigen receptor; JWCAR029

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Maximum concentration (Cmax) of JWCAR029 in the peripheral blood and bone marrow

  1 year after JWCAR029 infusion

• Time to maximum concentration (Tmax) of JWCAR029 in the peripheral blood and bone marrow

  1 year after JWCAR029 infusion

• Area-under the concentration-vs-time-curve (AUC) of JWCAR029 in the peripheral blood and bone marrow

  1 year after JWCAR029 infusion

• Complete response (CR) rate

  2 years

• Duration of response

  2 years

Study Arms (1)

JWCAR029

EXPERIMENTAL

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

Interventions

JWCAR029 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.

JWCAR029

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be enrolled in this study:
• Age ≥ 18 years at the time of consent
• Signed written informed consent obtained prior to any study procedures
• Relapsed or refractory B-cell NHL.
• PET-positive disease BY Lugano classification
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow, renal, hepatic, pulmonary and cardiac function
• Adequate vascular access for leukapheresis procedure
• Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
• Subjects must agree to use appropriate contraception.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from participation in this study:
• Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
• History of another primary malignancy that has not been in remission for at least 2 years.
• Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
• Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of screening
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or JWCAR029 administration
• Presence of acute or chronic graft-versus-host disease (GVHD)
• History of cardiovascular disease
• 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
• Pregnant or nursing women.
• 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

Sponsors & Collaborators

• Zhao Weili: lead
• Shanghai Mingju Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Ruijin hospital

Shanghai, Shanghai Municipality, 200025, China

Location

Related Publications (2)

• 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.

  PMID: 34515338 DERIVED

• 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.

  PMID: 31444250 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

relmacabtagene autoleucel

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: November 28, 2017
• Study Start: January 5, 2018
• Primary Completion: December 1, 2019
• Study Completion: March 1, 2022
• Last Updated: July 12, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)