Clinical Trial to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a open-label to assess the efficacy and safety of IM19 CAR-T cells in R/R B-cell Acute Lymphoblastic Leukemia.

Official Title
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Clinical Trial to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Biological: IM19 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory B-ALL, defined as：1）Not chieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia. 2）Any relapse after HSCT and must be ≥ 6 months from HSCT at the time of IM19 CAR-T cells infusion. 3）Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen. Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI ± chemotherapy ；Ph + all patients with T315I mutation are not required to receive at least two TKI ± chemotherapy in the absence of effective TKI therapy. Morphological evidence of disease in bone marrow (at least 5% blasts). Aged 3 to 70 years. Estimated life expectancy >3 months. ECOG performance status of 0 or 1(age ≥ 16 years) or Lansky (age < 16 years). Women of childbearing age who had a negative blood pregnancy test before the start of the trial and agreed to take effective contraceptive measures during the trial period until the last follow-up; male subjects with fertility partners agreed to take effective contraceptive measures during the trial period until the last follow-up. Adequate organ function. Volunteer to participate in this trial and sign on the informed consent. Exclusion Criteria: Subjects with lsolated extramedullary disease relapse. Subjects with Burkitt's lymphoma. Subjects has obvious symptoms of central nervous system invasion and needs targeted treatment. Subjects has previously received gene product therapy. Subjects has graft-versus-host response（GVHD） and need to use immunosuppressants or GVHD ≥ grade 2 or being treated with anti GVHD or suffering from autoimmune diseases. Subjects has received chemotherapy or radiotherapy within 3 days before leukapheresis. Subjects received systemic steroids within 5 days prior to leukapheresis. Subjects received drugs that stimulated the production of hematopoietic cells in the bone marrow for 5 days prior to leucapheresis. Subjects has participated in other clinical studies within 1 month before screening or plan to participate in other drug clinical trials during this study. Subjects received allogeneic cell therapy within 6 weeks before leukapheresis. Subjects with History or presence of CNS disorder. Subjects with HBV, HCV, HIV ,EBV,ECV or syphilis infection at the time of screening. Pregnant or lactating, or planning pregnancy within 180 days after the end of CAR-T cells infusion, or male patients whose partners plan pregnancy 180 days after their CAR-T cell infusion. Subjects with other tumors in the past 5 years. Within 14 days before enrollment, there were active or uncontrollable infections requiring systemic treatment.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IM19 CAR-T cells<br> | Biological: IM19 CAR-T cells<br>* IM19 CAR-T cells administrated in a dosage to be selected by physician from a specific range.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 28 days after CAR-T cell infusion | 
| Persistence of CAR-T cells (cell counts and cell percentage in peripheral blood and bone marrow ) |  | Up to 24 weeks after CAR-T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) |  | Up to 24 weeks after CAR-T cell infusion | 
| Relapse free surviva（PFS） |  | Up to 24 weeks after CAR-T cell infusion | 
| Duration of Response (DOR) |  | Up to 24 weeks after CAR-T cell infusion | 
| Overall survival (OS) |  | Up to 24 weeks after CAR-T cell infusion | 
| Minimal residual disease（MRD） |  | Up to 24 weeks after CAR-T cell infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T, B-cell Acute Lymphoblastic Leukemia