CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia
- Conditions
- Acute Lymphoblastic Leukemia, Adult B-Cell
- Interventions
- Biological: CD19 CAR-T cells infusion combined with feeding T cells (FTCs)
- Registration Number
- NCT03984968
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 27
- Ph+ acute B-lymphoblastic leukemia patients
- continuously taking TKI medications
- no chance to receive allogeneic hematopoietic stem cell transplantation
- no severe complications
- ECOG score less than 3
- Detection of mutations on abl gene
- resistance to TKI medications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CAR-T cells infusion combined with feeding T cells (FTCs) CD19 CAR-T cells infusion combined with feeding T cells (FTCs) -
- Primary Outcome Measures
Name Time Method Phase1 Incidence of adverse events (AEs) and abnormal laboratory test results 6 months after CD19 CAR-T consolidation therapy termination AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0).
Phase 2 Molecular response after CD19 CAR-T consolidation therapy for acute Lymphoblastic Leukemia concomitant with infusion of feeding Cells. 3 months after CD19 CAR-T consolidation therapy termination Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.
- Secondary Outcome Measures
Name Time Method Phase 1 Overall survial (OS) 2 years 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.
Phase 2 Incidence of adverse events (AEs) and abnormal laboratory test results 6 months after CD19 CAR-T consolidation therapy termination AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0).
Phase 2 Overall survial (OS) 2 years 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.
Phase 1 Molecular response after CD19 CAR-T consolidation therapy for acute Lymphoblastic Leukemia concomitant with infusion of feeding Cells. 3 months after CD19 CAR-T consolidation therapy termination Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.
Phase 1 The range of biologically active doses and optimal biological doses of feeding T cells. 6 months after CD19 CAR-T consolidation therapy termination The range of biologically active doses and optimal biological doses of feeding T cells will be determined.
Phase 1 Relapse free survival（RFS） 2 years 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.
Phase 2 Relapse free survival（RFS） 2 years 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.
Trial Locations
- Locations (1)
The First Affliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China