Humanized CD7 CAR T-cell Therapy for r/r CD7+ Acute Leukemia

Study Overview
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Brief Summary
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This is a prospective,open-label, single center and single arm phase 1/2 study to evaluate the efficacy and safety of T cells expressing humanized CD7 chimeric antigen receptors treatment for patients with refractory/relapsed CD7 positive acute leukemia.

Detailed Description
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The patients will receive infusion of CAR T-cells targeting CD7 to confirm the safety and efficacy of CD7 CAR T-Cells in CD7+ relapsed or refractory acute leukemia.

Official Title
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Humanized Chimeric Antigen Receptor T Cells Against CD7 for Refractory/Relapsed CD7+ Acute Leukemia

Conditions
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T Lymphoblastic Leukemia/Lymphoma, Mixed Phenotype Acute Leukemia, Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: Humanized CD7 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed CD7 positive relapsed/refractory acute leukemia. Age 12-65 years. Eastern Cooperative Oncology Group (ECOG) score 0-2. CD7 on leukemia is >30% positive detected with flow cytometry. Patients with left ventricular ejection fraction ≥ 0.5 by echocardiography or grade I/II cardiovascular dysfunction according to the New York Heart Association Classification. Patients with aspartate aminotransferase or glutamic-pyruvic transaminase > 3x upper limit of normal or bilirubin > 2.0 mg/dL. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD38 positive relapsed or refractory acute leukemia<br>Biological/Vaccine: Humanized CD7 CAR-T cells Split intravenous infusion of CD7 CAR-T cells [dose escalating infusion of (0.5- 10)x10^6 CD7 CAR-T cells/kg | Biological: Humanized CD7 CAR-T cells<br>* Split intravenous infusion of CD7 CAR-T cells [dose escalating infusion of (0.5-10)x10^6 CD7 CAR-T cells/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Adverse events are evaluated with CTCAE V5.0 | 12 months | 

Secondary 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 | 
| 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 vivo | the time of CAR-T cells' persistence in blood and the copies of CAR-T cells | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD7 Positive, CAR-T