Back to resultsCD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Non-Hodgkins Lymphoma
Primary Purpose
Lymphoma, Non-Hodgkin, Diffuse Large B Cell Lymphoma, Follicular Lymphoma
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
CD19-targeted Chimeric Antigen Receptor (CAR) T Cells
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring JWCAR029, B-Cell Malignancies, non-Hodgkin lymphoma, CAR T cells, Chimeric antigen receptor, Relapsed/Refractory
Eligibility Criteria
Inclusion Criteria:
Subjects must meet all of the following criteria to participate in the study:
- ≥ 18 years old;
- Sign on the informed consent;
- Subject must have histologically confirmed large B lymphoma or follicular lymphoma;
- 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;
- 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, corticisteriod, experiment agents, GVHD therapies, radiation, allo-HSCT or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
- 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.
Sites / Locations
- Beijing Cancer HospitalRecruiting
- Beijing Friendship Hospital, Capital Medical UniversityRecruiting
- Beijing HospitalRecruiting
- Peking Union Medical College HospitalRecruiting
- Guangdong General HospitalRecruiting
- The First Affiliated Hospital of Zhenzhou UniverstityRecruiting
- Jiangsu Cancer HospitalRecruiting
- Shanghai East HospitalRecruiting
- Institute of Hematology&Hospital of Blood Disease CAMSRecruiting
- Zhejiang Cancer HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
JWCAR029 treatment
Arm Description
JWCAR029 be administrated in two dose level
Outcomes
Primary Outcome Measures
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；
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
Secondary Outcome Measures
Complete response rate (CRR) in cohort A of LBCL subjects
Objective response rate (ORR) in cohort B of FL subjects
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.
Duration of response (DOR)
Time from first response(PR or CR) to disease progression or death from any cause.
Duration of complete remission (DoCR)
Time from complete response (CR) to disease progression or death from any cause.
Duration of partial remission (DoPR)
Time from partial response (PR) to disease progression or death from any cause.
Time to response (TTR)
Time from JWCAR029 infusion to first documentation of CR or PR
Time to complete response (TTCR)
Time from JWCAR029 infusion to first documentation of CR
Pharmacokinetic (PK)- Cmax of JWCAR029
Maximum observed concentration of JWCAR029 in peripheral blood
Pharmacokinetic (PK)- Tmax of JWCAR029
Time to maximum concentration of JWCAR029 in the peripheral blood
Pharmacokinetic (PK)- AUC of JWCAR029
Area under the concentration vs time curve of JWCAR029
Progression-free survival (PFS)
Overall survival
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
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)
ICU and non-ICU hospitalization days
ICU and non-ICU hospitalization reasons
Anti-therapeutic JWCAR029 antibody
Changes of T cell counts, subgroups and serum cytokines
CD19 expression in tumor biopsy samples
Changes of inflammation biomarkers-CRP
Changes of inflammation biomarkers-serum ferritin
Full Information
NCT ID
NCT04089215
First Posted
September 10, 2019
Last Updated
January 17, 2021
Sponsor
Shanghai Ming Ju Biotechnology Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04089215
Brief Title
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
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Recruiting
Study Start Date
June 11, 2019 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Ming Ju Biotechnology Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
JWCAR029 treatment
Arm Type
Experimental
Arm Description
JWCAR029 be administrated in two dose level
Intervention Type
Biological
Intervention Name(s)
CD19-targeted Chimeric Antigen Receptor (CAR) T Cells
Intervention Description
JWCAR029 be administered at dose level: 1 x 10^8 CAR+T cells and 1.5 x 10^8 CAR+T cells
Primary Outcome Measure Information:
Title
Objective response rate (ORR) in LBCL subjects in cohort A;
Description
Objective response rate (ORR) in 3 month in cohort A of large B cell lymphoma (LBCL) subjects；
Time Frame
3 months
Title
Complete response rate (CRR) in FL subjects in cohort B
Description
Complete response rate (CRR) in 3 month in cohort B of follicular lymphoma (FL) subjects
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Complete response rate (CRR) in cohort A of LBCL subjects
Time Frame
3 months
Title
Objective response rate (ORR) in cohort B of FL subjects
Time Frame
3 months
Title
Adverse events (AEs)
Description
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.
Time Frame
up to 24 months after JWCAR029 infusion
Title
Duration of response (DOR)
Description
Time from first response(PR or CR) to disease progression or death from any cause.
Time Frame
up to 24 months after JWCAR029 infusion
Title
Duration of complete remission (DoCR)
Description
Time from complete response (CR) to disease progression or death from any cause.
Time Frame
up to 24 months after JWCAR029 infusion
Title
Duration of partial remission (DoPR)
Description
Time from partial response (PR) to disease progression or death from any cause.
Time Frame
up to 24 months after JWCAR029 infusion
Title
Time to response (TTR)
Description
Time from JWCAR029 infusion to first documentation of CR or PR
Time Frame
up to 24 months after JWCAR029 infusion
Title
Time to complete response (TTCR)
Description
Time from JWCAR029 infusion to first documentation of CR
Time Frame
up to 24 months after JWCAR029 infusion
Title
Pharmacokinetic (PK)- Cmax of JWCAR029
Description
Maximum observed concentration of JWCAR029 in peripheral blood
Time Frame
up to 1 year after JWCAR029 infusion
Title
Pharmacokinetic (PK)- Tmax of JWCAR029
Description
Time to maximum concentration of JWCAR029 in the peripheral blood
Time Frame
up to 1 year after JWCAR029 infusion
Title
Pharmacokinetic (PK)- AUC of JWCAR029
Description
Area under the concentration vs time curve of JWCAR029
Time Frame
up to 1 year after JWCAR029 infusion
Title
Progression-free survival (PFS)
Time Frame
up to 2 year after JWCAR029 infusion
Title
Overall survival
Time Frame
up to 2 year after JWCAR029 infusion
Title
Quality of Life C30 questionnaire (EORTC-QLQ-C30)
Description
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
Time Frame
up to 2 year after JWCAR029 infusion
Title
European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L)
Description
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)
Time Frame
up to 2 year after JWCAR029 infusion
Title
ICU and non-ICU hospitalization days
Time Frame
up to 2 year after JWCAR029 infusion
Title
ICU and non-ICU hospitalization reasons
Time Frame
up to 2 year after JWCAR029 infusion
Title
Anti-therapeutic JWCAR029 antibody
Time Frame
up to 2 year after JWCAR029 infusion
Title
Changes of T cell counts, subgroups and serum cytokines
Time Frame
up to 2 year after JWCAR029 infusion
Title
CD19 expression in tumor biopsy samples
Time Frame
up to 2 year after JWCAR029 infusion
Title
Changes of inflammation biomarkers-CRP
Time Frame
up to 1 year after JWCAR029 infusion
Title
Changes of inflammation biomarkers-serum ferritin
Time Frame
up to 1 year after JWCAR029 infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must meet all of the following criteria to participate in the study:
≥ 18 years old;
Sign on the informed consent;
Subject must have histologically confirmed large B lymphoma or follicular lymphoma;
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;
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, corticisteriod, experiment agents, GVHD therapies, radiation, allo-HSCT or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
JWCAR029Medical
Phone
+86 21 50464201
Email
JWCAR029Medical@jwtherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuqin Song
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Name
Beijing Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Name
Guangdong General Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Zhenzhou Universtity
City
Zhenzhou
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Name
Jiangsu Cancer Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Name
Shanghai East Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Name
Institute of Hematology&Hospital of Blood Disease CAMS
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33382529
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.
Results Reference
result
Learn more about this trial
CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Non-Hodgkins Lymphoma
We'll reach out to this number within 24 hrs