Back to resultsCD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma
Primary Purpose
Diffuse Large B Cell Lymphoma
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
JWCAR029 (CD19-targeted Chimeric Antigen Receptor Cells)
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring Primary refractory
Eligibility Criteria
Inclusion Criteria:
- ≥ 18 years old;
- Sign on the informed consent;
- Subject must have histologically confirmed diffuse large B lymphoma and primary refractory with first-line therapy;
- 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:
- Subjects who have received second-line treatment or above
- CD19 negative
- 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
- Ruijin hospitalRecruiting
- Zhejiang university school of medicine first affiliated hospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
JWCAR029
Arm Description
The safety and efficacy of JWCAR029 will be evaluated in 1 x 10^8 CAR+T cells dose level
Outcomes
Primary Outcome Measures
Types, frequency, and severity of adverse events and laboratory anomalies
Physiological parameter
Secondary Outcome Measures
Complete response rate (CRR) in primary refractory DLBCL subjects
Investigator evaluated CRR in 1 month
Objective response rate (ORR) in primary refractory DLBCL subjects
Investigator evaluated ORR in 1 month
Best objective response rate (BORR)
The best response from the onset of treatment to the onset of disease progression/recurrence or to the onset of another anticancer treatment
Investigator evaluated CRR
Complete response rate (CRR)
Investigator evaluated ORR (ORR=CR+PR)
Complete response (CR) + partial response（PR）
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
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)
Progression-free survival
Overall survival (OS)
Overall survival
Changes of CRP and serum ferritin
Changes of inflammation biomarkers-CRP and serum ferritin
Anti-therapeutic JWCAR029 antibody
The level of anti-therapeutic JWCAR029 antibody after JWCAR029 infusion
The concentration of Car-T cell
The concentration of Car-T cells
The proportion of Car-T cell subgroups
The proportion of Car-T cell subgroups after infusion
The concentration of CD19 in tumor biopsy samples
The concentration of CD19 in tumor biopsy samples
The change of serum cytokines concentration
The change of serum cytokines concentration after JWCAR029 infusion
Full Information
NCT ID
NCT04812691
First Posted
January 18, 2021
Last Updated
March 22, 2021
Sponsor
Shanghai Ming Ju Biotechnology Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04812691
Brief Title
CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma
Official Title
CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma, Phase Ⅰ,Open-label,Single-arm,Muticenter Study
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
July 10, 2020 (Actual)
Primary Completion Date
June 30, 2021 (Anticipated)
Study Completion Date
March 31, 2023 (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 I, open-label, single-arm, multicenter study to assess the safety and efficacy of JWCAR029 in adult primary refractory DLBCL subjects in China
Detailed Description
This is a phase I, open-label, single-arm, multicenter study conducted in adult subjects with primary refractory DLBCL in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and collect immune response after JWCAR029 treatment.
One dose level of 1.0 x 10^8 CAR+ T cells is adopted in this study. All sujects will be followed for 2 years after JWCAR029 infusion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma
Keywords
Primary refractory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
JWCAR029
Arm Type
Experimental
Arm Description
The safety and efficacy of JWCAR029 will be evaluated in 1 x 10^8 CAR+T cells dose level
Intervention Type
Biological
Intervention Name(s)
JWCAR029 (CD19-targeted Chimeric Antigen Receptor Cells)
Intervention Description
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWCAR029. During JWCAR029 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive 1 x 10^8 CAR+T cells (JWCAR029) treatment by intravenous (IV) injection.
Primary Outcome Measure Information:
Title
Types, frequency, and severity of adverse events and laboratory anomalies
Description
Physiological parameter
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Complete response rate (CRR) in primary refractory DLBCL subjects
Description
Investigator evaluated CRR in 1 month
Time Frame
1 month
Title
Objective response rate (ORR) in primary refractory DLBCL subjects
Description
Investigator evaluated ORR in 1 month
Time Frame
1 month
Title
Best objective response rate (BORR)
Description
The best response from the onset of treatment to the onset of disease progression/recurrence or to the onset of another anticancer treatment
Time Frame
2 years
Title
Investigator evaluated CRR
Description
Complete response rate (CRR)
Time Frame
3 months
Title
Investigator evaluated ORR (ORR=CR+PR)
Description
Complete response (CR) + partial response（PR）
Time Frame
3 months
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
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)
Description
Progression-free survival
Time Frame
up to 2 year after JWCAR029 infusion
Title
Overall survival (OS)
Description
Overall survival
Time Frame
up to 2 year after JWCAR029 infusion
Title
Changes of CRP and serum ferritin
Description
Changes of inflammation biomarkers-CRP and serum ferritin
Time Frame
1 year after JWCAR029 infusion
Title
Anti-therapeutic JWCAR029 antibody
Description
The level of anti-therapeutic JWCAR029 antibody after JWCAR029 infusion
Time Frame
up to 2 year after JWCAR029 infusion
Title
The concentration of Car-T cell
Description
The concentration of Car-T cells
Time Frame
up to 2 year after JWCAR029 infusion
Title
The proportion of Car-T cell subgroups
Description
The proportion of Car-T cell subgroups after infusion
Time Frame
up to 2 year after JWCAR029 infusion
Title
The concentration of CD19 in tumor biopsy samples
Description
The concentration of CD19 in tumor biopsy samples
Time Frame
up to 2 year after JWCAR029 infusion
Title
The change of serum cytokines concentration
Description
The change of serum cytokines concentration after JWCAR029 infusion
Time Frame
up to 2 year after JWCAR029 infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 years old;
Sign on the informed consent;
Subject must have histologically confirmed diffuse large B lymphoma and primary refractory with first-line therapy;
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:
Subjects who have received second-line treatment or above
CD19 negative
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 Shanghai Ming Ju Biotechnology Co., Ltd
Phone
+86 21 50464201
Email
JWCAR029Medical@jwtherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weili Zhao
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruijin hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weili Zhao
Facility Name
Zhejiang university school of medicine first affiliated hospital
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
He Huang
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma
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