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出境医 / 临床实验 / Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies

Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies

Study Description
Brief Summary:
This is a single arm, open-label study to evaluate the safety and efficacy of humanized anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia B Cell Lymphoma Genetic: Second generation humanized CAR-T cells Phase 1

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. To improve the efficacy and safety, the researchers designed a second-generation humanized CAR, consisting of humanized CD19 single chain variable fragment (scFv) and CD137 costimulatory domain. This study aims to evaluate the safety and effectiveness of humanized anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Relapsed or Refractory B-cell Malignancies by Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells
Actual Study Start Date : May 27, 2019
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : December 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Second generation humanized CAR-T cells
Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.
 Genetic: Second generation humanized CAR-T cells
Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.
Outcome Measures
Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: 5 years ]
    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 :
  1. One-month remission rate [ Time Frame: 1 month ]
    Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).

  2. Overall survival [ Time Frame: 5 years ]
    OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).

  3. Event-free survival [ Time Frame: 5 years ]
    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).

  4. Relapse-free survival [ Time Frame: 5 years ]
    RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).

  5. Rate of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 5 years ]
    In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.

  6. Quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 5 years ]
    In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.

  7. Quantity of anti-CD19 CAR copies in bone marrow cells and peripheral blood cells [ Time Frame: 5 years ]
    In vivo (bone marrow and peripheral blood) quantity of anti-CD19 CAR copies were determined by means of qPCR.


Eligibility Criteria
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Ages Eligible for Study:   14 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy; or relapsed after auto-HSCT/allo-HSCT; or patients voluntarily choose CD19 CAR-T cells as a first treatment;

  2. B cell hematological malignancies include the following three categories:

    A. B-cell acute lymphocytic leukemia (B-ALL);

    B. Indolent B-cell lymphoma (CLL, FL, MZL, LPL);

    C. Aggressive B-cell lymphoma (DLBCL, BL, MCL);

  3. Aged from 14 to 70 years old;
  4. Expected survival time > 6 months;
  5. Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
  6. Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.

Exclusion Criteria:

  1. With a history of epilepsy or other central nervous system diseases;
  2. Having graft-versus-host reaction, requires the use of immunosuppressants;
  3. 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);
  4. Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
  5. Not curable active infection;
  6. Patients with active hepatitis B or hepatitis C virus infection;
  7. Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
  8. Using product of gene therapy before;
  9. 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);
  10. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
  11. Patients with HIV-infection;
  12. Any situation that may increase the risk of patients or interfere with test results.
Contacts and Locations

Contacts
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Contact: Yu Hu, M.D., Ph.D 86-13986183871 dr_huyu@126.com
Contact: Heng Mei, M.D., Ph.D 86-13886160811 hmei@hust.edu.cn

Locations
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China, Hubei
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430022
Contact: Yu Hu, M.D., Ph.D    86-13986183871    dr_huyu@126.com   
Contact: Heng Mei, M.D., Ph.D    86-13886160811    hmei@hust.edu.cn   
Sponsors and Collaborators
Wuhan Sian Medical Technology Co., Ltd
Wuhan Union Hospital, China
Jingzhou Central Hospital
Xiangyang Central Hospital
People Hospital Of Yichang
Investigators
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Principal Investigator: Heng Mei, M.D., Ph.D Wuhan Union Hospital, China
Tracking Information
First Submitted Date  ICMJE July 1, 2019
First Posted Date  ICMJE July 5, 2019
Last Update Posted Date August 7, 2019
Actual Study Start Date  ICMJE May 27, 2019
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2019) 		Number of participants with adverse events [ Time Frame: 5 years ]
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • One-month remission rate [ Time Frame: 1 month ]
    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 [ Time Frame: 5 years ]
    OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
  • Event-free survival [ Time Frame: 5 years ]
    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 [ Time Frame: 5 years ]
    RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
  • Rate of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 5 years ]
    In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.
  • Quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 5 years ]
    In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.
  • Quantity of anti-CD19 CAR copies in bone marrow cells and peripheral blood cells [ Time Frame: 5 years ]
    In vivo (bone marrow and peripheral blood) quantity of anti-CD19 CAR copies were determined by means of qPCR.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies
Official Title  ICMJE Treatment of Relapsed or Refractory B-cell Malignancies by Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells
Brief Summary This is a single arm, open-label study to evaluate the safety and efficacy of humanized 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. To improve the efficacy and safety, the researchers designed a second-generation humanized CAR, consisting of humanized CD19 single chain variable fragment (scFv) and CD137 costimulatory domain. This study aims to evaluate the safety and effectiveness of humanized anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • B Cell Lymphoma
Intervention  ICMJE Genetic: Second generation humanized CAR-T cells
Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.
Study Arms  ICMJE Experimental: Second generation humanized CAR-T cells
Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.
Intervention: Genetic: Second generation humanized CAR-T cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2019) 		10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy; or relapsed after auto-HSCT/allo-HSCT; or patients voluntarily choose CD19 CAR-T cells as a first treatment;

  2. B cell hematological malignancies include the following three categories:

    A. B-cell acute lymphocytic leukemia (B-ALL);

    B. Indolent B-cell lymphoma (CLL, FL, MZL, LPL);

    C. Aggressive B-cell lymphoma (DLBCL, BL, MCL);

  3. Aged from 14 to 70 years old;
  4. Expected survival time > 6 months;
  5. Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
  6. Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.

Exclusion Criteria:

  1. With a history of epilepsy or other central nervous system diseases;
  2. Having graft-versus-host reaction, requires the use of immunosuppressants;
  3. 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);
  4. Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
  5. Not curable active infection;
  6. Patients with active hepatitis B or hepatitis C virus infection;
  7. Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
  8. Using product of gene therapy before;
  9. 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);
  10. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
  11. Patients with HIV-infection;
  12. Any situation that may increase the risk of patients or interfere with test results.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 14 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yu Hu, M.D., Ph.D 86-13986183871 dr_huyu@126.com
Contact: Heng Mei, M.D., Ph.D 86-13886160811 hmei@hust.edu.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04008251
Other Study ID Numbers  ICMJE CART-huCD19-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Wuhan Sian Medical Technology Co., Ltd
Study Sponsor  ICMJE Wuhan Sian Medical Technology Co., Ltd
Collaborators  ICMJE
  • Wuhan Union Hospital, China
  • Jingzhou Central Hospital
  • Xiangyang Central Hospital
  • People Hospital Of Yichang
Investigators  ICMJE
Principal Investigator: Heng Mei, M.D., Ph.D Wuhan Union Hospital, China
PRS Account Wuhan Sian Medical Technology Co., Ltd
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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