CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Non-Hodgkins 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) Non-Hodgkins Lymphoma

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

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, Non-Hodgkin; Follicular Lymphoma; Diffuse Large B 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 R/R Non-Hodgkins Lymphoma in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and collect the patient reported quality of life changes and immune response after JWCAR029 treatment.

There will be two cohorts of cohort A and cohort B. Large B cell lymphoma (LBCL) patients will be enrolled in cohort A and follicular lymphoma patients will be enrolled in cohort B. Two dose levels of 1.0 x 10^8 CAR+ T cells and 1.5 x 10^8 CAR+ T cells are adopted in this study in both cohorts, subjects will be randomly assigned into the two dose levels with a 1:1 ratio. All sujects will be followed for 2 years following JWCAR029 infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: JWCAR029Medical; Phone Number: +86 21 50464201; Email: JWCAR029Medical@jwtherapeutics.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Hospital
    • Beijing, Beijing, China
      • Recruiting
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangdong General Hospital
  • Henan
    • Zhenzhou, Henan, China
      • Recruiting
      • The First Affiliated Hospital of Zhenzhou Universtity
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai East Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Institute of Hematology&Hospital of Blood Disease CAMS
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang 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:

• Subjects must meet all of the following criteria to participate in the study:

  1. ≥ 18 years old;
  2. Sign on the informed consent;
  3. Subject must have histologically confirmed large B lymphoma or follicular lymphoma;
  4. Subjects have accessible PET-positive lesion and have measurable CT-positive lesion according to Lugano Classification;
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
  6. Adequate organ function;
  7. Adequate vascular access for leukapheresis procedure;
  8. Subjects who have previously received CD19 targeted therapy must confirm that lymphoma lesions still express CD19;
  9. Women of childbearing potential must agree to use highly effective methods of contraception for 1 year after the last dose of JWCAR029;
  10. 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:

1. Central nervous system (CNS) only involvement by malignancy or primary CNS lymphoma;
2. History of another primary malignancy that has not been in remission for at least 2 years;
3. Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
4. Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
5. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
6. Presence of acute or chronic graft-versus-host disease (GVHD);
7. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
8. Pregnant or nursing women;
9. Subjects using of any chemotherapy, corticisteriod, experiment agents, GVHD therapies, radiation, allo-HSCT or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
10. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
11. 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 in two dose level	Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells; JWCAR029 be administered at dose level: 1 x 10^8 CAR+T cells and 1.5 x 10^8 CAR+T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) in LBCL subjects in cohort A;	Objective response rate (ORR) in 3 month in cohort A of large B cell lymphoma (LBCL) subjects；	3 months
Complete response rate (CRR) in FL subjects in cohort B	Complete response rate (CRR) in 3 month in cohort B of follicular lymphoma (FL) subjects	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response (TTR)	Time from JWCAR029 infusion to first documentation of CR or PR	up to 24 months after JWCAR029 infusion
Time to complete response (TTCR)	Time from JWCAR029 infusion to first documentation of CR	up to 24 months after JWCAR029 infusion
Pharmacokinetic (PK)- Cmax of JWCAR029	Maximum observed concentration of JWCAR029 in peripheral blood	up to 1 year after JWCAR029 infusion
Pharmacokinetic (PK)- Tmax of JWCAR029	Time to maximum concentration of JWCAR029 in the peripheral blood	up to 1 year after JWCAR029 infusion
Pharmacokinetic (PK)- AUC of JWCAR029	Area under the concentration vs time curve of JWCAR029	up to 1 year after JWCAR029 infusion
Complete response rate (CRR) in cohort A of LBCL subjects		3 months
Objective response rate (ORR) in cohort B of FL subjects		3 months
Adverse events (AEs)	Number of participants with adverse events, type of adverse events, severity of adverse events, and number of participants with laboratory abnormalities, type of laboratory abnormalities and 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
Progression-free survival (PFS)		up to 2 year after JWCAR029 infusion
Overall survival		up to 2 year after JWCAR029 infusion
Quality of Life C30 questionnaire (EORTC-QLQ-C30)	EORTC-QLQ-C30 is composed of both multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/health-related quality of life (HRQoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale	up to 2 year after JWCAR029 infusion
European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L)	The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems)	up to 2 year after JWCAR029 infusion
ICU and non-ICU hospitalization days		up to 2 year after JWCAR029 infusion
ICU and non-ICU hospitalization reasons		up to 2 year after JWCAR029 infusion
Anti-therapeutic JWCAR029 antibody		up to 2 year after JWCAR029 infusion
Changes of T cell counts, subgroups and serum cytokines		up to 2 year after JWCAR029 infusion
CD19 expression in tumor biopsy samples		up to 2 year after JWCAR029 infusion
Changes of inflammation biomarkers-CRP		up to 1 year after JWCAR029 infusion
Changes of inflammation biomarkers-serum ferritin		up to 1 year after JWCAR029 infusion

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Ying Z, Yang H, Guo Y, Li W, Zou D, Zhou D, Wang Z, Zhang M, Wu J, Liu H, Zhang P, Yang S, Zhou Z, Zheng H, Song Y, Zhu J. Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China. Cancer Med. 2021 Feb;10(3):999-1011. doi: 10.1002/cam4.3686. Epub 2020 Dec 31.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 11, 2019
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): September 30, 2024

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (ACTUAL): September 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 17, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: non-Hodgkin lymphoma; Chimeric antigen receptor; Relapsed/Refractory; 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, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: JWCAR029-002

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