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

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

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

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 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.