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

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ClinicalTrials.gov Identifier: NCT03919526
Recruitment Status : Recruiting
First Posted : April 18, 2019
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
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 : December 2020
Estimated Study Completion Date : June 2021


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




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



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03919526


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

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Responsible Party: Xianmin Song, MD, principal investigator, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT03919526     History of Changes
Other Study ID Numbers: SHSYXY-CAR-T MRD+ALL
First Posted: April 18, 2019    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine:
CD19/CD22
Bispecific CAR-T
leukemia
MRD-positive
B-ALL

Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists