CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia

Evaluation of Safety and Efficacy of CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia Concomitant With Infusion of CD19+T Cells as Feeding Cells

This is a single arm, open-label, single-center, phase I/II study to determine the safety and efficacy of CD19 CAR-T( ssCART-19) combined with feeding T cells (FTCs) as consolidation therapy in patients diagnosed with de novo Philadelphia chromosome positive CD19+ B-ALL. The study will contain the following sequential phases: screening, lymphocyte apheresis, induction and consolidation chemotherapies combined with tyrosine kinase inhibitors. Once in complete response, patients will receive four cycles of ssCART-19s, namely one cycle of ssCART-19 infusion followed by another three cycles of ssCART-19 and FTC infusion. The role of FTCs is to mimic leukemia cells. Therefore, they are expected to stimulate in vivo expansion and persistence of ssCART-19. Considering the limited number of lymphocytes obtained by a single apheresis from patients and cost-efficacy, in addition to safety, we will explore the range of biologically active doses of FTCs in a phase I study. Based on preclinical data, FTCs stimulation of ssCART-19 at a ratio of 1:1 could achieve the best activation response, so 5×106/kg dosage of FTCs was set as the initial dosage in the study, and lower dose was also evaluated. In this study, FTCs will be administered at the dose of 5×106/kg, 3.25×106/kg or 2×106/kg two hours after ssCART-19 infusion on day 1 and once again administered at the same dose on day 8. After ssCART-19 and FTCs infusion, efficacy will be assessed by detecting molecular response for 6 months, PFS and OS will be followed up for 2 years. In phase II, we will expand the study at optimal biological doses of FTCs, and further evaluate the efficacy and safety of the innovative combination therapy of CD19 CAR-T and FTCs.

Phase1 study Optimal biological doses of feeding T cells identification CAR-T cells infusion combined with FTCs will be given in Philadelphia chromosome positive B-ALL patients with remission. FTCs will be administered at the dose of 5×106/kg, 3.25×106/kg or 2×106/kg two hours after ssCART-19 infusion on day 1 and once again administered at the same dose on day 8. Phase 2 Expansion Study CAR-T cells infusion combined with FTCs at optimal biological dosage determined in Phase 1 study will be given in expanded Philadelphia chromosome positive B-ALL patients with remission. Bayesian optimal design is applied in this Phase 2 study to monitor the toxicity and efficacy at the specified interim analyses. The total expected sample sizes are 40.

Phase 2 Molecular response after CD19 CAR-T consolidation therapy for acute Lymphoblastic Leukemia concomitant with infusion of feeding Cells.

Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.

Phase 1 Molecular response after CD19 CAR-T consolidation therapy for acute Lymphoblastic Leukemia concomitant with infusion of feeding Cells.

Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.

The range of biologically active doses and optimal biological doses of feeding T cells will be determined.

It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.

It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined.

It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.

It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined.

Inclusion Criteria: Ph+ acute B-lymphoblastic leukemia patients having received once CD19 CAR-T therapy continuously taking TKI medications no chance to receive allogeneic hematopoietic stem cell transplantation no severe complications ECOG score less than 3 Exclusion Criteria: Detection of mutations on abl gene resistance to TKI medications