CAR-T-19 Cells for Patients With CD19+ Relapse/Refractory B-ALL

Study Overview
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Brief Summary
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This is a single-arm, open-label phase I study to determine the safety, tolerability, and recommended dose (RD) of CAR-T-19 cells for patients with CD19+ relapse/refractory B-ALL under the age of 25.

Detailed Description
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B-cell acute lymphoblastic leukemia (B-ALL) accounting for 85% of all ALL cases, is a common hematological malignancy in children and adults. CD19 is a widely expressed antigen in both normal B cells and B cells-derived leukemia and lymphomas. This is a single-arm, open-label phase I study of CAR-T-19 (anti CD19 scFv chimeric antigen receptor T) cells for patients with CD19-positive relapse/refractory B-ALL under the age of 25. Primary endpoint is to determine the safety, tolerability, and recommended dose (RD) of CAR-T-19. Secondary endpoints measure ORR, OS and others.

Official Title
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A Single-arm, Open-label Phase I Study of CAR-T-19 (Anti CD19 scFv Chimeric Antigen Receptor T) Cells for Patients With CD19-positive Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia Under The Age of 25

Conditions
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CD19+ Relapse/Refractory B-ALL

Intervention / Treatment
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* Biological: CAR-T-19 Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapse/refractory B-ALL. Tumor cells from bone marrow or peripheral blood are measured CD19+ with 3 months before enrollment. Karnofsky Score ≥ 70 or Lansky Score ≥ 50. Patients who have a life expectancy of at least 12 weeks. Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures. Exclusion Criteria: Patients with extramedullary relapse (EMR). Patients with genetic diseases, Burkitt lymphoma and leukemia or other malignancies. Patients positive for any of the following: HbsAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA. Patients with other uncontrolled infection. Patients who received anti-CD19 / anti-CD3 therapy, or any other anti-CD19 therapy. Patients with active Grade II-IV GVHD within 3 months prior to screening. Tumor cells are detected in cerebrospinal fluid. Patients who received HSCT within 3 months prior to screening. Anticipated other clinical trials within 4 weeks before this trial Pregnant or lactating women. Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.

Ages Eligible for Study
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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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T-19 Cells<br>The patients with CD19+ relapse or refractory B-ALL will receive a single infusion of autologous CAR-T-19 cells, with the escalated dose ranging from 0.5×10^6/kg to 5.0×10^6/kg CAR+ cells. | Biological: CAR-T-19 Cells<br>* T cells were isolated from the PBMC of patients, transduced with lentivirus, expanded in vitro, and infused into patients. The escalated doses include 0.5×10^6/kg,1.5×10^6/kg, 5.0×10^6/kg CAR+ cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | DLT within 28 days (±3 days) after CAR-T-19 infusion. | up to 2 years | 
| Maximum tolerated dose (MTD) | The maximum dose of DLT occurred in ≤1/6 of the subjects within 28 days (±3 days) after CAR-T-19 infusion. | up to 2 years | 
| Adverse events | Percentage of subjects with adverse events. | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall recovery rate (ORR) | Percentage of subjects who achieved complete response (CR) and incomplete hematologic recovery (CRi) for the first time at Day 28 and Day 90 after CAR-T-19 infusion. | up to 2 years | 
| MRD-Negative Rate | Percentage of subjects with MRD-negative CR and incomplete blood and MRD-negative CRi for the first time at Day 28 and Day 90 after CAR-T-19 infusion. | up to 2 years | 
| Duration of Response (DOR) | The time from achieving CR and CRi for the first time to recurrence or death from any cause | up to 2 years | 
| Progression-free Survival (PFS) | The time from CAR-T-19 infusion to recurrence, progression or death from any cause, whichever occurs first. | up to 2 years | 
| Overall survival (OS) | The time from CAR-T-19 infusion to death from any cause. | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-ALL, CAR-T