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出境医 / 临床实验 / Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for MRD Positive ALL

Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for MRD Positive ALL

Study Description
Brief Summary:
To evaluate the safety and efficacy of CD19/CD22 Bispecific CAR-T for the treatment of MRD-positive B cell acute lymphoblastic leukemia. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells.

Condition or disease Intervention/treatment Phase
MRD-positive Acute Lymphoblastic Leukemia Biological: anti-CD19/CD22 CAR-T cells Drug: Fludarabine Drug: Cyclophosphamide Phase 1

Detailed Description:
Participants with MRD-positive B cell acute lymphoblastic leukemia can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, CT/MRI , and blood draws. Participants receive chemotherapy prior to the infusion of CD19/CD22 CAR+ T cells. After the infusion, participants will be followed for side effects and effect of CD19/CD22 CAR+ T cells. Study procedures may be performed while hospitalized.
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: The Safety and Clinical Efficacy of Human CD19/CD22 Bispecific CAR-T Cell Therapy for Subjects With MRD-positive B Cell Acute Lymphoblastic Leukemia
Actual Study Start Date : March 11, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: anti-CD19/CD22 CAR-T cells
Administration with anti-CD19/ CD22 CAR-T cells in the MRD-positive ALL patients.
 Biological: anti-CD19/CD22 CAR-T cells
Retroviral vector-transduced autologous T cells to express anti-CD19 and anti-CD22 CARs

Drug: Fludarabine
30mg/m2/d

Drug: Cyclophosphamide
300mg/m2/d
Outcome Measures
Primary Outcome Measures :
  1. Safety measured by occurence of study related adverse effects defined by NCI CTCAE5.0 [ Time Frame: 28 days post infusion ]
    Safety measured by occurence of study related adverse effects defined by NCI CTCAE5.0


Secondary Outcome Measures :
  1. MRD clearance [ Time Frame: 3 months post infusion ]
    MRD clearance

  2. Content of CD19 positive B-cells in peripheral blood [ Time Frame: 3 months post infusion ]
    Content of CD19 positive B-cells in peripheral blood

  3. Content of CAR-T related cytokines positive T cells in circulation [ Time Frame: 3 months post infusion ]
    Content of CAR-T related cytokines positive T cells in circulation

  4. Total response rate (ORR) after administration [ Time Frame: 3 months post infusion ]
    Total response rate (ORR) after administration

  5. Duration of remission (DOR) after administration [ Time Frame: 2 years post infusion ]
    Duration of remission (DOR) after administration

  6. Overall Survival (OS)after administration [ Time Frame: 2 years post infusion ]
    Overall Survival (OS)after administration


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • (1) CD19 positive/CD22 positive, or CD19-CD22 positive B-cell acute lymphoblastic leukemia;
  • (2)18 to 70 Years Old, Male and female;
  • (3) Expected survival > 12 weeks;
  • (4) ECOG score 0-2;

  • (5) Bone marrow examination clearly diagnosed as B-cell acute lymphoblastic leukemia and who met one of the following conditions:

    1. Recurrent patients who achieves MRD-positive CR or CRi after standard therapy;
    2. Those who achieves CR, but failed to achieve MRD-negative after at least 2 courses of consolidation therapy;
  • (6) The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators;

  • (7) Liver, kidney and cardiopulmonary functions meet the following requirements:

    1. Creatinine is in the normal range;
    2. Left ventricular ejection fraction >50%;
    3. Baseline oxygen saturation>92%;
    4. Total bilirubin ≤ 2×ULN;
    5. ALT and AST ≤ 2.5×ULN;
  • (8) Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

  • (1) BCR-ABL fusion gene-positive patients;
  • (2) Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;
  • (3) Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive;
  • (4) Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
  • (5) Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
  • (6) Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
  • (7) Received CAR-T treatment or other gene therapies before enrollment;
  • (8) Patients with symptoms of central nervous system;
  • (9) Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
  • (10) The investigators consider other conditions unsuitable for enrollment.
Contacts and Locations

Contacts
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Contact: Xianmin Song, M.D. 021-63240090 shongxm@139.com
Contact: Hongliang Fang, doctor 021-58552006 fanghongliang@dashengbio.com

Locations
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China, Shanghai
Shanghai General Hospital Recruiting
Shanghai, Shanghai, China, 200080
Contact: Xianmin Song, M.D.    86-21-63240090 ext 3172    shongxm@sjtu.edu.cn   
Sponsors and Collaborators
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Investigators
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Principal Investigator: Xianmin Song, M.D. Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Tracking Information
First Submitted Date  ICMJE April 7, 2019
First Posted Date  ICMJE April 18, 2019
Last Update Posted Date April 1, 2021
Actual Study Start Date  ICMJE March 11, 2019
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2019) 		Safety measured by occurence of study related adverse effects defined by NCI CTCAE5.0 [ Time Frame: 28 days post infusion ]
Safety measured by occurence of study related adverse effects defined by NCI CTCAE5.0
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • MRD clearance [ Time Frame: 3 months post infusion ]
    MRD clearance
  • Content of CD19 positive B-cells in peripheral blood [ Time Frame: 3 months post infusion ]
    Content of CD19 positive B-cells in peripheral blood
  • Content of CAR-T related cytokines positive T cells in circulation [ Time Frame: 3 months post infusion ]
    Content of CAR-T related cytokines positive T cells in circulation
  • Total response rate (ORR) after administration [ Time Frame: 3 months post infusion ]
    Total response rate (ORR) after administration
  • Duration of remission (DOR) after administration [ Time Frame: 2 years post infusion ]
    Duration of remission (DOR) after administration
  • Overall Survival (OS)after administration [ Time Frame: 2 years post infusion ]
    Overall Survival (OS)after administration
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-CD19/CD22 Bispecific CAR-T Cell Therapy for MRD Positive ALL
Official Title  ICMJE The Safety and Clinical Efficacy of Human CD19/CD22 Bispecific CAR-T Cell Therapy for Subjects With MRD-positive B Cell Acute Lymphoblastic Leukemia
Brief Summary To evaluate the safety and efficacy of CD19/CD22 Bispecific CAR-T for the treatment of MRD-positive B cell acute lymphoblastic leukemia. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells.
Detailed Description Participants with MRD-positive B cell acute lymphoblastic leukemia can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, CT/MRI , and blood draws. Participants receive chemotherapy prior to the infusion of CD19/CD22 CAR+ T cells. After the infusion, participants will be followed for side effects and effect of CD19/CD22 CAR+ T cells. Study procedures may be performed while hospitalized.
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
  • MRD-positive
  • Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Biological: anti-CD19/CD22 CAR-T cells
    Retroviral vector-transduced autologous T cells to express anti-CD19 and anti-CD22 CARs
  • Drug: Fludarabine
    30mg/m2/d
  • Drug: Cyclophosphamide
    300mg/m2/d
Study Arms  ICMJE Experimental: anti-CD19/CD22 CAR-T cells
Administration with anti-CD19/ CD22 CAR-T cells in the MRD-positive ALL patients.
Interventions:
  • Biological: anti-CD19/CD22 CAR-T cells
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
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: April 15, 2019) 		10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • (1) CD19 positive/CD22 positive, or CD19-CD22 positive B-cell acute lymphoblastic leukemia;
  • (2)18 to 70 Years Old, Male and female;
  • (3) Expected survival > 12 weeks;
  • (4) ECOG score 0-2;

  • (5) Bone marrow examination clearly diagnosed as B-cell acute lymphoblastic leukemia and who met one of the following conditions:

    1. Recurrent patients who achieves MRD-positive CR or CRi after standard therapy;
    2. Those who achieves CR, but failed to achieve MRD-negative after at least 2 courses of consolidation therapy;
  • (6) The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators;

  • (7) Liver, kidney and cardiopulmonary functions meet the following requirements:

    1. Creatinine is in the normal range;
    2. Left ventricular ejection fraction >50%;
    3. Baseline oxygen saturation>92%;
    4. Total bilirubin ≤ 2×ULN;
    5. ALT and AST ≤ 2.5×ULN;
  • (8) Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

  • (1) BCR-ABL fusion gene-positive patients;
  • (2) Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;
  • (3) Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive;
  • (4) Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
  • (5) Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
  • (6) Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
  • (7) Received CAR-T treatment or other gene therapies before enrollment;
  • (8) Patients with symptoms of central nervous system;
  • (9) Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
  • (10) The investigators consider other conditions unsuitable for enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xianmin Song, M.D. 021-63240090 shongxm@139.com
Contact: Hongliang Fang, doctor 021-58552006 fanghongliang@dashengbio.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03919526
Other Study ID Numbers  ICMJE SHSYXY-CAR-T MRD+ALL
Has Data Monitoring Committee Yes
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 Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Study Sponsor  ICMJE Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Xianmin Song, M.D. Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
PRS Account Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Verification Date March 2021

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

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