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

Phase 2

Active, not recruiting

• Conditions: Diffuse Large B Cell Lymphoma; Lymphoma, Non-Hodgkin; Follicular Lymphoma

• Registration Number: NCT04089215
• Lead Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.

Brief Summary

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.

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 Timeline

• Study Start: 2019-06-11
• Study First Submitted: 2019-09-10
• Study First Submitted QC: 2019-09-11
• Study First Posted: 2019-09-13
• Primary Completion: 2021-09-10
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-24
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 82

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Overall survival	3 to 5 years after JWCAR029 infusion
Time to complete response (TTCR)	up to 24 months after JWCAR029 infusion	Time from JWCAR029 infusion to first documentation of CR
Pharmacokinetic (PK)- AUC of JWCAR029	up to 1 year after JWCAR029 infusion	Area under the concentration vs time curve of JWCAR029
Quality of Life C30 questionnaire (EORTC-QLQ-C30)	up to 2 year after JWCAR029 infusion	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
Complete response rate (CRR) in cohort A of LBCL subjects	3 months
Duration of response (DOR)	up to 24 months after JWCAR029 infusion	Time from first response(PR or CR) to disease progression or death from any cause.
Duration of complete remission (DoCR)	up to 24 months after JWCAR029 infusion	Time from complete response (CR) to disease progression or death from any cause.
Duration of partial remission (DoPR)	up to 24 months after JWCAR029 infusion	Time from partial response (PR) to disease progression or death from any cause.
Time to response (TTR)	up to 24 months after JWCAR029 infusion	Time from JWCAR029 infusion to first documentation of CR or PR
Pharmacokinetic (PK)- Tmax of JWCAR029	up to 1 year after JWCAR029 infusion	Time to maximum concentration of JWCAR029 in the peripheral blood
CD19 expression in tumor biopsy samples	up to 2 year after JWCAR029 infusion
Anti-therapeutic JWCAR029 antibody	up to 2 year after JWCAR029 infusion
Changes of inflammation biomarkers-serum ferritin	up to 1 year after JWCAR029 infusion
European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L)	up to 2 year after JWCAR029 infusion	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)
ICU and non-ICU hospitalization days	up to 2 year after JWCAR029 infusion
Changes of T cell counts, subgroups and serum cytokines	up to 2 year after JWCAR029 infusion
Objective response rate (ORR) in cohort B of FL subjects	3 months
Progression-free survival (PFS)	3 to 5 years after JWCAR029 infusion
ICU and non-ICU hospitalization reasons	up to 2 year after JWCAR029 infusion
Changes of inflammation biomarkers-CRP	up to 1 year after JWCAR029 infusion
Pharmacokinetic (PK)- Cmax of JWCAR029	up to 1 year after JWCAR029 infusion	Maximum observed concentration of JWCAR029 in peripheral blood
Adverse events (AEs)	up to 24 months after JWCAR029 infusion	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.

Trial Locations

Locations (10)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Beijing Hospital; 🇨🇳 Beijing, Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

Guangdong General Hospital; 🇨🇳 Guangzhou, Guangdong, China

The First Affiliated Hospital of Zhenzhou Universtity; 🇨🇳 Zhenzhou, Henan, China

Jiangsu Cancer Hospital; 🇨🇳 Nanjing, Jiangsu, China

Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai, China

Institute of Hematology&Hospital of Blood Disease CAMS; 🇨🇳 Tianjin, Tianjin, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China