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A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies

NCT03050190

Description:

The study will evaluate safety and efficacy of a 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • B-Cell Lymphoblastic Leukemia/Lymphoma
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
  • Official Title: A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies

Clinical Trial IDs

  • ORG STUDY ID: GIMI-IRB-16001
  • NCT ID: NCT03050190

Conditions

  • B-cell Malignancies

Purpose

The study will evaluate safety and efficacy of a 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.

Detailed Description

      Background:

      T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in
      different clinical settings. Recent successes suggest that increased costimulatory signaling
      in the CAR design is critical for long term efficacy. Activation of T cell response from
      large tumor burden may induce a severe response. To increase safety, a novel design using an
      inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR
      lentiviral vector (4SCAR) carrying T cell costimulatory signals for CD28/CD27 plus an
      inducible apoptotic caspase 9 gene has been established. The study aims to evaluate the
      activities of a new CAR gene-modified T cells targeting CD19-positive tumors based on a
      CD19-specific single chain gene constructed 4SCAR (4SCAR19).

      Objective:

      To evaluate safety and efficacy of administrating 4SCAR19 T cells to patients with CD19
      positive B cell malignancies following a cyclophosphamide/fludarabine based conditioning
      regimen.

      Eligibility:

      Patients older than 6-month-old with CD19 positive B cells malignancies that have recurred
      after or refractory to standard therapy and is deemed incurable using standard treatment.

      Design:

      Participants will be screened based on cancer cell phenotype analyzed using flow cytometry or
      immunohistochemical staining methods.

      Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis, and T cells
      will be activated and modified to express the 4SCAR19 gene.

      On Day -5 to -7, PBMC will be activated and enriched for T cells, which will be followed by
      4SCAR19 lentiviral transduction. The total cell preparation time is approximately 5-7 days.

      Participants will receive a preparative conditioning regimen comprising
      cyclophosphamide/fludarabine to prepare their immune system to accommodate the modified CAR T
      cells. The preparative regimen will be based on patient immune condition and consistent with
      standard chemotherapy conditioning regimen.

      Participants will receive an infusion of the modified 4SCAR19 T cells and closely followed up
      for treatment-related responses.

      Participants will be continuously monitored for CAR T cells and clinical responses at present
      timeline.
    

Trial Arms

NameTypeDescriptionInterventions
Therapeutic 4SCAR19 cellsExperimentalPatients who have relapsed and refractory B cell leukemia after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. aged more than 6 months.
    
              2. malignant B cell surface expression CD19 molecules.
    
              3. the KPS score over 80 points, and survival time is more than 3 months.
    
              4. greater Hgb 80 g/L.
    
              5. no contraindications to solid and cell separation
    
            Exclusion Criteria:
    
              1. accompanied with other active diseases, the treatment is difficult to correct.
    
              2. bacteria, fungus, or virus infection, unable to control.
    
              3. people living with HIV.
    
              4. active HBV and HCV infection.
    
              5. of pregnancy and nursing mothers.
    
              6. before entering the test of the use of glucocorticoid systemic treatment within a
                 week.
    
              7. confirmed before used CAR - but invalid
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:6 Months
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events
    Time Frame:24 weeks
    Safety Issue:
    Description:physiological parameter (for safety, measuring cytokine response, fever, symptoms)

    Secondary Outcome Measures

    Measure:Anti tumor activity of fourth generation anti CD19 CAR-T cells in patients with relapsed or refractory B cell malignancies
    Time Frame:1 year
    Safety Issue:
    Description:scale of CAR copies and leukemic cell burden (for efficacy)

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Shenzhen Geno-Immune Medical Institute

    Trial Keywords

    • CART therapy
    • 4SCAR19
    • CD19
    • B cell leukemia
    • B-ALL

    Last Updated

    September 18, 2019