Study of IFN-α Combined With CAR-T Cell Therapy in Relapsed and Refractory Acute Lymphoblastic Leukemia（R/R-ALL）

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of IFN-α combined with CAR-T cell therapy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL).

Detailed Description
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This is a phase 2, single-center study. The patients will receive IFN-α combined with infusion of CAR T-cells in R/R B-ALL patients. The study participation will be 5 years including treatment and follow-up periods.

Official Title
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An Open-label, Phase 2, Single-Center Study to Assess the Efficacy and Safety of Interferon-α Combined With Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With Relapsed and Refractory Acute Lymphoblastic Leukemia（R/R-ALL)

Conditions
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B-cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Combination Product: IFN-α combined with CAR-T cell therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed refractory and relapsed acute B-lymphoblastic leukemia. Age 12-65. Eastern Cooperative Oncology Group (ECOG) score 0-2. Target on leukemia is >20% positive detected with flowcytometry. Patients with left ventricular ejection fraction ≥ 0.5 by echocardiography or grade I/II cardiovascular dysfunction according to the New York Heart Association Classification. 5.Patients with aspartate aminotransferase or glutamic-pyruvic transaminase > 3x upper limit of normal or bilirubin > 2.0 mg/dL. 6.No other immunotherapy was received within 3 months. Exclusion Criteria: Patients are pregnant or lactating. Patients with congenital immunodeficiency. Patients with central nervous system leukemia. Patients with uncontrolled active infection. Patients with active hepatitis B or hepatitis C infection. Patients with HIV infection. Patients with atrial or venous thrombosis or embolism. Patients with myo-infarction or severe arrythmia in the recent 6 months. Other comorbidities that investigators considered not suitable for this study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>IFN-α combined with CAR T-cells therapy | Combination Product: IFN-α combined with CAR-T cell therapy<br>* Adults: 14 daily intramuscular injections 300 million IU of Interferon-α for a 28-day cycle. Children: 14 daily intramuscular injections 200mg/m^2 of Interferon-α for a 28-day cycle. CAR T cell: (1-2)×10^7/kg, intravenously infusion.<br>* Other names: CAR-T cell therapy;|
| No Intervention: Control group<br>CAR T-cells therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | ORR includes CR, CRi, MLFS and PR. Complete remission (CR)：Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0x 10^9/L; platelet count >100x10^9/L. CR with incomplete hematologic recovery (CRi)：All CR criteria except for residual neutropenia (<1.0x10^9/L) or thrombocytopenia (<100x10^9/L). Morphologic leukemia-free state (MLFS): Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. Partial remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | time from enrollment to the date of death from any cause | 2 years | 
| Leukemia-free survival (LFS) | time from enrollment to the date of primary refractory disease, or relapse from CR, or death from any cause | 2 years | 
| Cumulative incidence of relapse(CIR) | time from the date of achievement of a remission until the date of relapse | 2 years | 
| the duration of CAR-T cells in patients | the time of CAR-T cells' persistence in blood and the copies of CAR-T cells | 2 years | 
| Number of adverse events | adverse events are evaluated with CTCAE V5.0 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IFN-α, CAR-T