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

Follicular Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04089215
• Other study ID #: JWCAR029-002
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 11, 2019
• Est. completion date: September 30, 2024

Study information

• Verified date: November 2023
• Source: Shanghai Ming Ju Biotechnology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 82
• Est. completion date: September 30, 2024
• Est. primary completion date: September 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

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

Locations

Country	Name	City	State
China	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	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Shanghai East Hospital	Shanghai	Shanghai
China	Institute of Hematology&Hospital of Blood Disease CAMS	Tianjin	Tianjin
China	The First Affiliated Hospital of Zhenzhou Universtity	Zhenzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Ming Ju Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (1)

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 lymphom — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Complete response rate (CRR) in cohort A of LBCL subjects		3 months
Secondary	Objective response rate (ORR) in cohort B of FL subjects		3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to response (TTR)	Time from JWCAR029 infusion to first documentation of CR or PR	up to 24 months after JWCAR029 infusion
Secondary	Time to complete response (TTCR)	Time from JWCAR029 infusion to first documentation of CR	up to 24 months after JWCAR029 infusion
Secondary	Pharmacokinetic (PK)- Cmax of JWCAR029	Maximum observed concentration of JWCAR029 in peripheral blood	up to 1 year after JWCAR029 infusion
Secondary	Pharmacokinetic (PK)- Tmax of JWCAR029	Time to maximum concentration of JWCAR029 in the peripheral blood	up to 1 year after JWCAR029 infusion
Secondary	Pharmacokinetic (PK)- AUC of JWCAR029	Area under the concentration vs time curve of JWCAR029	up to 1 year after JWCAR029 infusion
Secondary	Progression-free survival (PFS)		3 to 5 years after JWCAR029 infusion
Secondary	Overall survival		3 to 5 years after JWCAR029 infusion
Secondary	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
Secondary	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
Secondary	ICU and non-ICU hospitalization days		up to 2 year after JWCAR029 infusion
Secondary	ICU and non-ICU hospitalization reasons		up to 2 year after JWCAR029 infusion
Secondary	Anti-therapeutic JWCAR029 antibody		up to 2 year after JWCAR029 infusion
Secondary	Changes of T cell counts, subgroups and serum cytokines		up to 2 year after JWCAR029 infusion
Secondary	CD19 expression in tumor biopsy samples		up to 2 year after JWCAR029 infusion
Secondary	Changes of inflammation biomarkers-CRP		up to 1 year after JWCAR029 infusion
Secondary	Changes of inflammation biomarkers-serum ferritin		up to 1 year after JWCAR029 infusion