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

NCT03344367 | Unknown Phase 1

• 1 other identifier: JWCAR029-001
• Study Type: interventional
• Target: 20
• 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 subjects 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. 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.

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

• Peking University: lead
• Shanghai Mingju Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Beijing Cancer Hospital

Beijing, 100142, China

Location

Related Publications (1)

• 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

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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 10, 2017
• First Posted: November 17, 2017
• Study Start: November 16, 2017
• Primary Completion: October 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)