CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Lymphoblastic Leukemia, Adult B-Cell

Intervention / Treatment
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* Biological: CD19 CAR-T cells infusion combined with feeding T cells (FTCs)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: CAR-T cells infusion combined with feeding T cells (FTCs)<br> | Biological: CD19 CAR-T cells infusion combined with feeding T cells (FTCs)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase1 Incidence of adverse events (AEs) and abnormal laboratory test results | AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0). | 6 months after CD19 CAR-T consolidation therapy termination | 
| 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%. | 3 months after CD19 CAR-T consolidation therapy termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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%. | 3 months after CD19 CAR-T consolidation therapy termination | 
| Phase 1 The range of biologically active doses and optimal biological doses of feeding T cells. | The range of biologically active doses and optimal biological doses of feeding T cells will be determined. | 6 months after CD19 CAR-T consolidation therapy termination | 
| Phase 1 Overall survial (OS) | 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. | 2 years | 
| Phase 1 Relapse free survival（RFS） | 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. | 2 years | 
| Phase 2 Incidence of adverse events (AEs) and abnormal laboratory test results | AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0). | 6 months after CD19 CAR-T consolidation therapy termination | 
| Phase 2 Overall survial (OS) | 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. | 2 years | 
| Phase 2 Relapse free survival（RFS） | 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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feeding T cell, CD19 CAR-T therapy