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 phase I/II, open-label, multicenter study 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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A Phase 1-2 Study 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: Not chieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia. Any relapse after HSCT and must be ≥ 6 months from HSCT at the time of IM19 CAR-T cells infusion. 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 25 years, either sex; Estimated life expectancy >3 months; ECOG performance status of 0 or 1(age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50; 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: Isolated extramedullary disease relapse； Burkitt's lymphoma； Patient has obvious symptoms of central nervous system invasion and needs targeted treatment; Patient has previously received gene product therapy; Patients have 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; Patient received chemotherapy or radiotherapy within 3 days before leukapheresis Patient used systemic steroids within 5 days before leucapheresis, except those who were recently or currently using inhaled steroids; Patients who used drugs to stimulate the production of bone marrow hematopoietic cells within 5 days before leucapheresis; Patients have participated in other clinical studies within 1 month before screening or plan to participate in other drug clinical trials during this study; Patient received allogeneic cell therapy within 6 weeks before CAR-T cell infusion, such as donor lymphocyte infusion(DLI)； History or presence of CNS disorder, such as epilepsy, epileptic seizures, cerebrovascular disease (ischemia / hemorrhage / cerebral infarction), brain edema, reversible posterior white matter encephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, cerebral organic syndrome or mental disease; Patients has 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; Patients 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: 25 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: Sequential 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 will be administered at dose level:5 x 10^4 CAR+ T cells/kg,1x 10^5 CAR+ T cells/kg,3 x 10^5 CAR+ T cells/kg,1 x 10^6 CAR+ T cells/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Related 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) | The persistence over time of CAR T cells in the peripheral blood as determined by flow cytometry and qPCR. | Up to 24 weeks after CAR-T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) |  | At 28 days, 3 months and 6 months after CAR-T cell infusion | 
| Anti-therapeutic IM19 CAR-T cells antibody |  | 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