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出境医 / 临床实验 / Anti-CD22 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy for Relapsed Refractory B-cell Malignancies

Anti-CD22 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy for Relapsed Refractory B-cell Malignancies

Study Description
Brief Summary:
This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of anti-CD22 CAR-T cells in patients with relapsed or refractory B-cell Malignancies.

Condition or disease Intervention/treatment Phase
B Cell Lymphoma Acute Lymphoblastic Leukemia Genetic: Third generation 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. CAR consists of single chain variable fragment (scFv) and activation domain of T cell. In preclinical study, the researchers constructed a third generation CAR containing CD137 and CD28 costimulatory domains.

This study aims to evaluate the safety and effectiveness of anti-CD22 CAR-T cells in patients with relapsed or refractory B-cell Malignancies.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Anti-CD22 CAR-T Therapy in Patients With Relapsed/Refractory B-cell Malignancies: a Single-center, Open-label, Single-arm Clinical Study
Actual Study Start Date : August 5, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 30, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Third generation CAR-T cells
Patients receive CD22 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity.
Genetic: Third generation CAR-T cells
Patients receive CD22 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity.

Outcome Measures
Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: 3 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: 3 years ]
    OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).

  3. Event-free survival [ Time Frame: 3 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: 3 years ]
    RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).

  5. Rate of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.

  6. Quantity of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.

  7. Quantity of anti-CD22 CAR copies in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of anti-CD22 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. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
  2. Male or female patients aged 14 to 70 years (including 14 and 70 years old).
  3. Pathological and histological examination confirmed CD22+ B-cell malignancies, and patients met the following criteria for refractory or relapsed B-cell malignancies.

    A.Refractory/relapsed B-cell lymphoblastic leukemia (Meeting one of the following)

    i. Recurrence within 6 months after first remission.

    ii. Primary refractory disease which cannnot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.

    iii. Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.

    iv. Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.

    B.Refractory/relapsed B-cell lymphoma (Meeting 1 of the first 4 items plus item 5)

    i. Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.

    ii. Achieved CR after standard chemotherapy, but relapsed within 6 months.

    iii. 2 or more relapses after CR.

    iv. Not suitable for HSCT, or abandon HSCT due to various restrictions, or relapse after HSCT.

    v. Subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy with anthracyclines.

  4. B-cell malignancies include the following three types

    A. B-cell acute lymphoblastic leukemia (B-ALL)

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

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

  5. Having a measurable or evaluable lesion

    A. Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.

    B. Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.

  6. Patient's main organs functioning well

    A. Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L

    B. Renal function: Creatinine < 220μmol/L.

    C. Pulmonary function: Indoor oxygen saturation≥95%.

    D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%.

  7. The patients did not receive any antitumor treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before enrollment, and the toxicity related to previous treatments had returned to < 1 level at enrollment (except for low grade toxicity such as alopecia).
  8. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
  9. Patient ECOG score≤ 2, estimated survival time≥3 months.

Exclusion Criteria:

  1. Have a history of epilepsy or other central nervous system diseases.
  2. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
  3. Male or female with a pregnancy plan in the next 1 year.
  4. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment.
  5. Uncontrolled infectious disease within 4 weeks prior to enrollment.
  6. Active hepatitis B/C virus infection.
  7. HIV infected patients.
  8. Suffering from a serious autoimmune disease or immunodeficiency disease.
  9. The patient is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
  10. The patient participated in other clinical trials within 6 weeks prior to enrollment.
  11. Systemic use of corticosteroids within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
  12. Suffering from mental diseases.
  13. Patient has drug abuse/addiction.
  14. According to the researcher's judgment, the patient has other unsuitable enrollment conditions.
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 Union Hospital, China
Wuhan Bio-Raid Biotechnology Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Heng Mei, M.D., Ph.D Wuhan Union Hospital, China
Tracking Information
First Submitted Date  ICMJE June 28, 2019
First Posted Date  ICMJE July 5, 2019
Last Update Posted Date August 7, 2019
Actual Study Start Date  ICMJE August 5, 2019
Estimated Primary Completion Date June 30, 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: 3 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: 3 years ]
    OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
  • Event-free survival [ Time Frame: 3 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: 3 years ]
    RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
  • Rate of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.
  • Quantity of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.
  • Quantity of anti-CD22 CAR copies in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of anti-CD22 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 Anti-CD22 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy for Relapsed Refractory B-cell Malignancies
Official Title  ICMJE Efficacy and Safety of Anti-CD22 CAR-T Therapy in Patients With Relapsed/Refractory B-cell Malignancies: a Single-center, Open-label, Single-arm Clinical Study
Brief Summary This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of anti-CD22 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 third generation CAR containing CD137 and CD28 costimulatory domains.

This study aims to evaluate the safety and effectiveness of anti-CD22 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
  • B Cell Lymphoma
  • Acute Lymphoblastic Leukemia
Intervention  ICMJE Genetic: Third generation CAR-T cells
Patients receive CD22 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity.
Study Arms  ICMJE Experimental: Third generation CAR-T cells
Patients receive CD22 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity.
Intervention: Genetic: Third generation 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)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
  2. Male or female patients aged 14 to 70 years (including 14 and 70 years old).
  3. Pathological and histological examination confirmed CD22+ B-cell malignancies, and patients met the following criteria for refractory or relapsed B-cell malignancies.

    A.Refractory/relapsed B-cell lymphoblastic leukemia (Meeting one of the following)

    i. Recurrence within 6 months after first remission.

    ii. Primary refractory disease which cannnot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.

    iii. Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.

    iv. Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.

    B.Refractory/relapsed B-cell lymphoma (Meeting 1 of the first 4 items plus item 5)

    i. Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.

    ii. Achieved CR after standard chemotherapy, but relapsed within 6 months.

    iii. 2 or more relapses after CR.

    iv. Not suitable for HSCT, or abandon HSCT due to various restrictions, or relapse after HSCT.

    v. Subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy with anthracyclines.

  4. B-cell malignancies include the following three types

    A. B-cell acute lymphoblastic leukemia (B-ALL)

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

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

  5. Having a measurable or evaluable lesion

    A. Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.

    B. Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.

  6. Patient's main organs functioning well

    A. Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L

    B. Renal function: Creatinine < 220μmol/L.

    C. Pulmonary function: Indoor oxygen saturation≥95%.

    D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%.

  7. The patients did not receive any antitumor treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before enrollment, and the toxicity related to previous treatments had returned to < 1 level at enrollment (except for low grade toxicity such as alopecia).
  8. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
  9. Patient ECOG score≤ 2, estimated survival time≥3 months.

Exclusion Criteria:

  1. Have a history of epilepsy or other central nervous system diseases.
  2. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
  3. Male or female with a pregnancy plan in the next 1 year.
  4. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment.
  5. Uncontrolled infectious disease within 4 weeks prior to enrollment.
  6. Active hepatitis B/C virus infection.
  7. HIV infected patients.
  8. Suffering from a serious autoimmune disease or immunodeficiency disease.
  9. The patient is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
  10. The patient participated in other clinical trials within 6 weeks prior to enrollment.
  11. Systemic use of corticosteroids within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
  12. Suffering from mental diseases.
  13. Patient has drug abuse/addiction.
  14. According to the researcher's judgment, the patient has other unsuitable enrollment conditions.
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 NCT04007978
Other Study ID Numbers  ICMJE WHUH-CART-CD22-01
Has Data Monitoring Committee Not Provided
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 MEI HENG, Wuhan Union Hospital, China
Study Sponsor  ICMJE Wuhan Union Hospital, China
Collaborators  ICMJE Wuhan Bio-Raid Biotechnology Co., Ltd.
Investigators  ICMJE
Principal Investigator: Heng Mei, M.D., Ph.D Wuhan Union Hospital, China
PRS Account Wuhan Union Hospital, China
Verification Date August 2019

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

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