Clinical trial NCT04089215: CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Non-Hodgkins 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) Non-Hodgkins Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
Diffuse Large B Cell Lymphoma
Follicular Lymphoma
Keywords: JWCAR029
B-Cell Malignancies
non-Hodgkin lymphoma
CAR T cells
Chimeric antigen receptor
Relapsed/Refractory
Lead sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-09-13
Enrollment: 82
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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR) in LBCL subjects in cohort A;
timeFrame: 3 months
measure: Complete response rate (CRR) in FL subjects in cohort B
timeFrame: 3 months
Secondary outcomes:
measure: Complete response rate (CRR) in cohort A of LBCL subjects
timeFrame: 3 months
measure: Objective response rate (ORR) in cohort B of FL subjects
timeFrame: 3 months
measure: Adverse events (AEs)
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: Pharmacokinetic (PK)- Cmax of JWCAR029
timeFrame: up to 1 year after JWCAR029 infusion
measure: Pharmacokinetic (PK)- Tmax of JWCAR029
timeFrame: up to 1 year after JWCAR029 infusion
measure: Pharmacokinetic (PK)- AUC of JWCAR029
timeFrame: up to 1 year after JWCAR029 infusion
measure: Progression-free survival (PFS)
timeFrame: 3 to 5 years after JWCAR029 infusion
measure: Overall survival
timeFrame: 3 to 5 years after JWCAR029 infusion
measure: Quality of Life C30 questionnaire (EORTC-QLQ-C30)
timeFrame: up to 2 year after JWCAR029 infusion
measure: European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L)
timeFrame: up to 2 year after JWCAR029 infusion
measure: ICU and non-ICU hospitalization days
timeFrame: up to 2 year after JWCAR029 infusion
measure: ICU and non-ICU hospitalization reasons
timeFrame: up to 2 year after JWCAR029 infusion
measure: Anti-therapeutic JWCAR029 antibody
timeFrame: up to 2 year after JWCAR029 infusion
measure: Changes of T cell counts, subgroups and 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 of inflammation biomarkers-CRP
timeFrame: up to 1 year after JWCAR029 infusion
measure: Changes of inflammation biomarkers-serum ferritin
timeFrame: up to 1 year after JWCAR029 infusion
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Zhenzhou
country: China
facility: The First Affiliated Hospital of Zhenzhou Universtity
state: Henan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Tianjin
country: China
facility: Institute of Hematology&Hospital of Blood Disease CAMS
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Yuqin Song
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.