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

Mantle Cell 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) Mantle Cell Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04718883
• Other study ID #: JWCAR029-005
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 13, 2021
• Est. completion date: August 7, 2028

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 assess the efficacy and safety of JWCAR029 in adult R/R Mantle Cell Lymphoma subjects in China.

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 5 years following JWCAR029 infusion.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: August 7, 2028
• Est. primary completion date: October 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Biological:
• CD19-targeted Chimeric Antigen Receptor (CAR) T Cells
JWCAR029 will be administered at dose level: 1 x 10^8 CAR+T cells

Locations

Country	Name	City	State
China	Peking University Cancer Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Fujian Medical University Consonancy Hospital	Fuzhou	Fujiang
China	Guangdong Province people hospital	Guanzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang province Cancer Hospital	Hangzhou	Zhejiang
China	Jiangsu Province People Hospital	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Zhongshan Hospital affiliated to Fudan University	Shanghai	Shanghai
China	Institute of Hematology, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Henan Province Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete response rate (CRR)	Complete response rate (CRR) in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects	3 months
Secondary	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
Secondary	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
Secondary	Number of participants with adverse events (AEs)	Number of participants with adverse events	Up to 24 months after JWCAR029 infusion
Secondary	Type of adverse events (AEs)	Type of adverse events	Up to 24 months after JWCAR029 infusion
Secondary	Severity of adverse events(AEs)	Severity of adverse events	Up to 24 months after JWCAR029 infusion
Secondary	Number of participants with laboratory abnormalities	Number of participants with laboratory abnormalities	Up to 24 months after JWCAR029 infusion
Secondary	Type of laboratory abnormalities	Type of laboratory abnormalities	Up to 24 months after JWCAR029 infusion
Secondary	Severity of laboratory abnormalities	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 complete response (CR) or partial response (PR)	Up to 24 months after JWCAR029 infusion
Secondary	Time to complete response (TTCR)	Time from JWCAR029 infusion to first documentation of complete response (CR)	Up to 24 months after JWCAR029 infusion
Secondary	Cmax of JWCAR029	Maximum observed concentration of JWCAR029 in peripheral blood	Up to 1 year after JWCAR029 infusion
Secondary	Tmax of JWCAR029:	Time to maximum concentration of JWCAR029 in the peripheral blood	Up to 1 year after JWCAR029 infusion
Secondary	AUC of JWCAR029:	Area under the concentration vs time curve of JWCAR029 in the peripheral blood	Up to 1 year after JWCAR029 infusion
Secondary	Progression-free survival (PFS)	Progression-free survival	Up to 2 year after JWCAR029 infusion
Secondary	Overall survival (OS)	Overall survival	Up to 5 year after JWCAR029 infusion
Secondary	Anti-therapeutic JWCAR029 antibody	Anti-therapeutic JWCAR029 antibody	Up to 2 year after JWCAR029 infusion
Secondary	Changes of T cell counts	Changes of T cell counts	Up to 2 year after JWCAR029 infusion
Secondary	Changes of Subgroups of T cell	Changes of Subgroups of T cell	Up to 2 year after JWCAR029 infusion
Secondary	Changes of serum cytokines	Changes of serum cytokines	Up to 2 year after JWCAR029 infusion
Secondary	CD19 expression in tumor biopsy samples	CD19 expression in tumor biopsy samples	Up to 2 year after JWCAR029 infusion
Secondary	Changes in inflammatory biomarkers such as CRP	Changes in inflammatory biomarkers such as CRP	Up to 2 year after JWCAR029 infusion
Secondary	Changes in inflammatory biomarkers such as ferritin	Changes in inflammatory biomarkers such as CRP	Up to 2 year after JWCAR029 infusion