CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies
Primary Purpose
Acute Lymphoblastic Leukemia, B Cell Lymphoma
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Second generation CAR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia
Eligibility Criteria
Inclusion Criteria:
- The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT); or patients voluntarily choose CD19 CAR-T cells as a first treatment;
B cell hematological malignancies include the following three categories:
- B-cell acute lymphocytic leukemia (B-ALL);
- Indolent B-cell lymphoma (CLL, FL, MZL, LPL);
- Aggressive B-cell lymphoma (DLBCL, BL, MCL);
- < 70 years old;
- Expected survival time > 6 months;
- Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
- Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.
Exclusion Criteria:
- With a history of epilepsy or other central nervous system diseases;
- Having graft-versus-host reaction, requires the use of immunosuppressants;
- The presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within recent six months, or heart disease with cardiac function in any grade 3 (moderate) or 4 ( severe) (according to the New York Heart Association (NYHA) Functional Classification System);
- Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
- Not curable active infection;
- Patients with active hepatitis B or hepatitis C virus infection;
- Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
- Using product of gene therapy before;
- Creatinine> 2.5 mg / dl (221.0 umol/L); ALT / AST> 3 X the normal amount; Bilirubin> 2.0 mg / dl (34.2 umol/L);
- Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
- Patients with HIV-infection;
- Any situation that may increase the risk of patients or interfere with test results.
Sites / Locations
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Second generation CAR-T cells
Arm Description
Patients receive CD19 CAR-T cells transduced with a lentiviral vector on days 0, 1, and 2 in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Number of participants with adverse events
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)
Secondary Outcome Measures
One-month remission rate
Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).
Overall survival
OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
Event-free survival
EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).
Relapse-free survival
RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
Rate and quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells
In vivo (bone marrow and peripheral blood) rate and quantity of CAR-T cells were determined by means of flow cytometry and qPCR.
Full Information
NCT ID
NCT02965092
First Posted
November 13, 2016
Last Updated
May 8, 2019
Sponsor
Wuhan Sian Medical Technology Co., Ltd
Collaborators
Wuhan Union Hospital, China, Jingzhou Central Hospital, Xiangyang Central Hospital, People Hospital Of Yichang
1. Study Identification
Unique Protocol Identification Number
NCT02965092
Brief Title
CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies
Official Title
Treatment of Relapsed or Refractory B-cell Malignancies by CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 2, 2015 (Actual)
Primary Completion Date
January 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wuhan Sian Medical Technology Co., Ltd
Collaborators
Wuhan Union Hospital, China, Jingzhou Central Hospital, Xiangyang Central Hospital, People Hospital Of Yichang
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a single arm, open-label, phase 1/2 study to evaluate the safety and efficacy of anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.
Detailed Description
Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CAR-T therapy showed great effect on patients with relapsed or refractory B cell malignancies. CAR consists of single chain variable fragment (scFv) and activation domain of T cell. In preclinical study, the researchers constructed a second generation CAR containing CD137 costimulatory domain. This study aims to evaluate the safety and effectiveness of anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, B 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
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Second generation CAR-T cells
Arm Type
Experimental
Arm Description
Patients receive CD19 CAR-T cells transduced with a lentiviral vector on days 0, 1, and 2 in the absence of disease progression or unacceptable toxicity.
Intervention Type
Genetic
Intervention Name(s)
Second generation CAR-T cells
Other Intervention Name(s)
CAR-T cells
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Description
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)
Time Frame
5 years
Secondary Outcome Measure Information:
Title
One-month remission rate
Description
Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).
Time Frame
1 month
Title
Overall survival
Description
OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
Time Frame
5 years
Title
Event-free survival
Description
EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).
Time Frame
5 years
Title
Relapse-free survival
Description
RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
Time Frame
5 years
Title
Rate and quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells
Description
In vivo (bone marrow and peripheral blood) rate and quantity of CAR-T cells were determined by means of flow cytometry and qPCR.
Time Frame
5 years
10. Eligibility
Sex
All
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT); or patients voluntarily choose CD19 CAR-T cells as a first treatment;
B cell hematological malignancies include the following three categories:
B-cell acute lymphocytic leukemia (B-ALL);
Indolent B-cell lymphoma (CLL, FL, MZL, LPL);
Aggressive B-cell lymphoma (DLBCL, BL, MCL);
< 70 years old;
Expected survival time > 6 months;
Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.
Exclusion Criteria:
With a history of epilepsy or other central nervous system diseases;
Having graft-versus-host reaction, requires the use of immunosuppressants;
The presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within recent six months, or heart disease with cardiac function in any grade 3 (moderate) or 4 ( severe) (according to the New York Heart Association (NYHA) Functional Classification System);
Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
Not curable active infection;
Patients with active hepatitis B or hepatitis C virus infection;
Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
Using product of gene therapy before;
Creatinine> 2.5 mg / dl (221.0 umol/L); ALT / AST> 3 X the normal amount; Bilirubin> 2.0 mg / dl (34.2 umol/L);
Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
Patients with HIV-infection;
Any situation that may increase the risk of patients or interfere with test results.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Hu, M.D., Ph.D
Phone
86-13986183871
Email
dr_huyu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Heng Mei, M.D., Ph.D
Phone
86-13886160811
Email
hmei@hust.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yu Hu, M.D., Ph.D
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
027
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Hu, M.D., Ph.D
Phone
86-13986183871
Email
dr_huyu@126.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35799791
Citation
Zhang Y, Zhou F, Wu Z, Li Y, Li C, Du M, Luo W, Kou H, Lu C, Mei H. Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia. Front Immunol. 2022 Jun 21;13:914959. doi: 10.3389/fimmu.2022.914959. eCollection 2022.
Results Reference
derived
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CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies
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