Clinical trial NCT04718883: CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Mantle Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: JWCAR029
B-Cell Malignancies
Non-Hodgkin lymphoma
CAR T cells
Chimeric antigen receptor
Relapsed/Refractory
Mantle Cell Lymphoma
Lead sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-01-22
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 5 years following JWCAR029 infusion.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 3 months
Secondary outcomes:
measure: Complete response rate (CRR)
timeFrame: 3 months
measure: The best objective response rate
timeFrame: 3 months
measure: The best complete response rate
timeFrame: 3 months
measure: Number of participants with adverse events (AEs)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Type of adverse events (AEs)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Severity of adverse events(AEs)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Number of participants with laboratory abnormalities
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Type of laboratory abnormalities
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Severity of laboratory abnormalities
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Duration of response (DOR)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Duration of complete remission (DoCR)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Duration of partial remission (DoPR)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Time to response (TTR)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Time to complete response (TTCR)
timeFrame: Up to 24 months after JWCAR029 infusion
measure: Cmax of JWCAR029
timeFrame: Up to 1 year after JWCAR029 infusion
measure: Tmax of JWCAR029:
timeFrame: Up to 1 year after JWCAR029 infusion
measure: AUC of JWCAR029:
timeFrame: Up to 1 year after JWCAR029 infusion
measure: Progression-free survival (PFS)
timeFrame: Up to 2 year after JWCAR029 infusion
measure: Overall survival (OS)
timeFrame: Up to 5 year after JWCAR029 infusion
measure: Anti-therapeutic JWCAR029 antibody
timeFrame: Up to 2 year after JWCAR029 infusion
measure: Changes of T cell counts
timeFrame: Up to 2 year after JWCAR029 infusion
measure: Changes of Subgroups of T cell
timeFrame: Up to 2 year after JWCAR029 infusion
measure: Changes of serum cytokines
timeFrame: Up to 2 year after JWCAR029 infusion
measure: CD19 expression in tumor biopsy samples
timeFrame: Up to 2 year after JWCAR029 infusion
measure: Changes in inflammatory biomarkers such as CRP
timeFrame: Up to 2 year after JWCAR029 infusion
measure: Changes in inflammatory biomarkers such as ferritin
timeFrame: Up to 2 year after JWCAR029 infusion
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Consonancy Hospital
state: Fujiang
city: Guanzhou
country: China
facility: Guangdong Province people hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Province Cancer Hospital
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province People Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital affiliated to Fudan University
state: Shanghai
city: Tianjin
country: China
facility: Institute of Hematology, Chinese Academy of Medical Sciences
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang province Cancer Hospital
state: Zhejiang
Study officials:
References: