Back to resultsCompetitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma (MatchCART)
Primary Purpose
Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
anti-CD19 CAR-T
Fludarabine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Hematopoietic/Lymphoid Cancer
Eligibility Criteria
Inclusion Criteria:
- 5 Years to 70 Years, Male and female;
- Expected survival > 12 weeks;
- Performance score 0-2;
Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions;
- Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
- Disease recurrence after stem cell transplantation;
- Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
- Creatinine < 2.5 mg/dl;
- ALT/AST < 3x normal;
- Bilirubin < 2.0 mg/dl;
- Adequate venous access for apheresis, and no other contraindications for leukapheresis;
- Take contraceptive measures before recruit to this trial;
- Written voluntary informed consent is given.
Exclusion Criteria:
- Patients with symptoms of central nervous system
- Accompanied by other malignant tumor
- Active hepatitis B or C, HIV infection
- Any other diseases could affect the outcome of this trial
- Suffering severe cardiovascular or respiratory disease
- Poorly controlled hypertension
- A history of mental illness and poorly controlled
- Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
- Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
- Reaching a steady dose if receiving anticoagulant therapy before assignment
- Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- Pregnant or lactating women
- Subject suffering disease affects the understanding of informed consent or comply with study protocol.
Sites / Locations
- Henan Province of TCMRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Mixed CD19CAR transfer
Arm Description
All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number
Outcomes
Primary Outcome Measures
Safety (incidence of adverse events defined as dose-limited toxicity)
Secondary Outcome Measures
Overall complete remission rate
Survival of CAR T cells in circulation measured by flow cytometry and PCR
Duration of remission
Overall survival
Full Information
NCT ID
NCT02685670
First Posted
February 14, 2016
Last Updated
March 14, 2017
Sponsor
The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Collaborators
Xinqiao Hospital of Chongqing, Xuzhou Medical University
1. Study Identification
Unique Protocol Identification Number
NCT02685670
Brief Title
Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma
Acronym
MatchCART
Official Title
A Phase I/II Study of Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 Chimeric Antigen Receptor T-Cells in Patients With Refractory CD19+ B-lineage Leukemia/Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Unknown status
Study Start Date
February 2016 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Collaborators
Xinqiao Hospital of Chongqing, Xuzhou Medical University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single-arm open-label phase I/II study to determine the relative superiority of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. In this trial, all subjects will be competitively infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number to test a hypothesis that CD137-costimulation can promote the persistence and engraftment of CAR-T cells and this superiority can lead to improved progression-free survival.
Detailed Description
Primary objectives
1. To determine the safety and feasibility of adoptive transfer of T cells modified to express CD19-specific chimeric antigen receptor (CD19CAR) for treatment of leukemia and lymphoma
Secondary objectives
To measure the efficacy of anti-tumor responses after CD19CAR T cell infusion
To determine if CD19CAR T cells engineered with 4-1BB signaling domain is superior to that with CD28 signaling domain for their homing and persistence after CD19CAR T cell infusion
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Refractory Chronic Lymphocytic Leukemia, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Chronic Lymphocytic Leukemia, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mixed CD19CAR transfer
Arm Type
Experimental
Arm Description
All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number
Intervention Type
Biological
Intervention Name(s)
anti-CD19 CAR-T
Intervention Description
Ex vivo-expanded autologous T cells modified to express CD19 CAR
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Primary Outcome Measure Information:
Title
Safety (incidence of adverse events defined as dose-limited toxicity)
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Overall complete remission rate
Time Frame
8 weeks
Title
Survival of CAR T cells in circulation measured by flow cytometry and PCR
Time Frame
1 year
Title
Duration of remission
Time Frame
1 year
Title
Overall survival
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
5 Years to 70 Years, Male and female;
Expected survival > 12 weeks;
Performance score 0-2;
Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions;
Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
Disease recurrence after stem cell transplantation;
Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
Creatinine < 2.5 mg/dl;
ALT/AST < 3x normal;
Bilirubin < 2.0 mg/dl;
Adequate venous access for apheresis, and no other contraindications for leukapheresis;
Take contraceptive measures before recruit to this trial;
Written voluntary informed consent is given.
Exclusion Criteria:
Patients with symptoms of central nervous system
Accompanied by other malignant tumor
Active hepatitis B or C, HIV infection
Any other diseases could affect the outcome of this trial
Suffering severe cardiovascular or respiratory disease
Poorly controlled hypertension
A history of mental illness and poorly controlled
Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
Reaching a steady dose if receiving anticoagulant therapy before assignment
Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
Pregnant or lactating women
Subject suffering disease affects the understanding of informed consent or comply with study protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhi Cheng, M.D.
Phone
+(86)-139-3852-6995
Email
clinicaltrials.chengzhi@outlook.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhi Cheng, M.D.
Organizational Affiliation
The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henan Province of TCM
City
Zhengzhou
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhi Cheng, M.D.
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma
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