CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Mantle Cell Lymphoma

A Phase II Open-Label, Single-Arm, Multicenter Study of JWCAR029, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells for Relapsed and Refractory (R/R) Mantle Cell Lymphoma

This is a phase II, open-label, single-arm, multicenter study to assess the efficacy and safety of JWCAR029 in adult R/R Mantle Cell Lymphoma subjects in China.

Study Overview

• Status: Recruiting
• Conditions: Mantle Cell Lymphoma
• Intervention / Treatment: Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells

Detailed Description

This is a phase II, open-label, single-arm, multicenter study conducted in adult subjects with relapsed and refractory (R/R) mantle cell lymphoma (MCL) in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and immune response after JWCAR029 treatment.

R/R MCL patients will be enrolled in dose level of 1.0 x 10^8 CAR+ T cells. All subjects will be followed for 2 years following JWCAR029 infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Peking University Cancer Hospital
  • Fujiang
    • Fuzhou, Fujiang, China
      • Recruiting
      • Fujian Medical University Consonancy Hospital
  • Guangdong
    • Guanzhou, Guangdong, China
      • Recruiting
      • Guangdong Province People Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Province Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Province People Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Zhongshan Hospital affiliated to Fudan University
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Cancer Hospital
      • Contact: Lanfang Li
    • Tianjin, Tianjin, China
      • Recruiting
      • Institute of Hematology, Chinese Academy of Medical Sciences
      • Contact: Dehui Zou
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Province Cancer 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:

• ≥ 18 years old;
• Sign on the informed consent;
• Subject must have histologically confirmed mantle cell lymphoma;
• Relapsed/refractory patients;
• Subjects have accessible PET-positive lesion and have measurable CT-positive lesion according to Lugano Classification;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Expected survival is greater than 12 weeks;
• Adequate organ function;
• Adequate vascular access for leukapheresis procedure;
• Subjects who have previously received CD19 targeted therapy must confirm that lymphoma lesions still express CD19;
• Women of childbearing potential must agree to use highly effective methods of contraception for 1 year after the last dose of JWCAR029;
• Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after the last dose of JWCAR029.

Exclusion Criteria:

• Central nervous system (CNS) only involvement by malignancy or primary CNS lymphoma;
• History of another primary malignancy that has not been in remission for at least 2 years;
• Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
• Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
• Presence of acute or chronic graft-versus-host disease (GVHD);
• History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
• Pregnant or nursing women;
• Subjects using of any chemotherapy, corticosteriod, experiment agents, GVHD therapies, radiation or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
• Received allo-hematopoietic stem cell transplantation therapy previously.
• Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
• Received CAR T-cell or other genetically-modified T-cell therapy previously.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: JWCAR029 treatment; JWCAR029 be administrated at dose level: 1 x 10^8 CAR+T cells	Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells; JWCAR029 will be administered at dose level: 1 x 10^8 CAR+T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate (ORR) in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR)	Complete response rate (CRR) in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects	3 months
The best objective response rate	The best objective response rate in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects	3 months
The best complete response rate	The best complete response rate in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects	3 months
Number of participants with adverse events (AEs)	Number of participants with adverse events	Up to 24 months after JWCAR029 infusion
Type of adverse events (AEs)	Type of adverse events	Up to 24 months after JWCAR029 infusion
Severity of adverse events(AEs)	Severity of adverse events	Up to 24 months after JWCAR029 infusion
Number of participants with laboratory abnormalities	Number of participants with laboratory abnormalities	Up to 24 months after JWCAR029 infusion
Type of laboratory abnormalities	Type of laboratory abnormalities	Up to 24 months after JWCAR029 infusion
Severity of laboratory abnormalities	Severity of laboratory abnormalities	Up to 24 months after JWCAR029 infusion
Duration of response (DOR)	Time from first response(PR or CR) to disease progression or death from any cause	Up to 24 months after JWCAR029 infusion
Duration of complete remission (DoCR)	Time from complete response (CR) to disease progression or death from any cause	Up to 24 months after JWCAR029 infusion
Duration of partial remission (DoPR)	Time from partial response (PR) to disease progression or death from any cause.	Up to 24 months after JWCAR029 infusion
Time to response (TTR)	Time from JWCAR029 infusion to first documentation of complete response (CR) or partial response (PR)	Up to 24 months after JWCAR029 infusion
Time to complete response (TTCR)	Time from JWCAR029 infusion to first documentation of complete response (CR)	Up to 24 months after JWCAR029 infusion
Cmax of JWCAR029	Maximum observed concentration of JWCAR029 in peripheral blood	Up to 1 year after JWCAR029 infusion
Tmax of JWCAR029:	Time to maximum concentration of JWCAR029 in the peripheral blood	Up to 1 year after JWCAR029 infusion
AUC of JWCAR029:	Area under the concentration vs time curve of JWCAR029 in the peripheral blood	Up to 1 year after JWCAR029 infusion
Progression-free survival (PFS)	Progression-free survival	Up to 2 year after JWCAR029 infusion
Overall survival (OS)	Overall survival	Up to 2 year after JWCAR029 infusion
Anti-therapeutic JWCAR029 antibody	Anti-therapeutic JWCAR029 antibody	Up to 2 year after JWCAR029 infusion
Changes of T cell counts	Changes of T cell counts	Up to 2 year after JWCAR029 infusion
Changes of Subgroups of T cell	Changes of Subgroups of T cell	Up to 2 year after JWCAR029 infusion
Changes of serum cytokines	Changes of serum cytokines	Up to 2 year after JWCAR029 infusion
CD19 expression in tumor biopsy samples	CD19 expression in tumor biopsy samples	Up to 2 year after JWCAR029 infusion
Changes in inflammatory biomarkers such as CRP	Changes in inflammatory biomarkers such as CRP	Up to 2 year after JWCAR029 infusion
Changes in inflammatory biomarkers such as ferritin	Changes in inflammatory biomarkers such as CRP	Up to 2 year after JWCAR029 infusion

Collaborators and Investigators

• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 13, 2021
• Primary Completion (ANTICIPATED): June 30, 2023
• Study Completion (ANTICIPATED): June 30, 2025

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: January 17, 2021
• First Posted (ACTUAL): January 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Mantle Cell Lymphoma; Chimeric antigen receptor; Relapsed/Refractory; Non-Hodgkin lymphoma; B-Cell Malignancies; CAR T cells; JWCAR029
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell
• Other Study ID Numbers: JWCAR029-005

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