Anti-CLL1 CAR T-cell Therapy in CLL1 Positive Relapsed/Refractory Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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This is a single center, open-label phase 1/2 study to evaluate the safety and efficacy of anti-CLL1 chimeric antigen receptor engineered T cell immunotherapy (CART) in the treatment of CLL1 positive relapsed or refractory acute myeloid leukemia.

Detailed Description
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The patients will receive infusion of anti-CLL1 CAR T-cells to confirm the safety and efficacy of anti-CLL1 CAR T-cells in relapsed or refractory acute myeloid leukemia.

Official Title
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Pilot Study of the Safety and Efficacy of Anti-CLL1 Chimeric Antigen Receptor Engineered T-Cells in the Treatment of CLL1 Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: anti-CLL1 CART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CLL1 positive relapsed/refractory acute myeloid leukemia Age 6-65 years Left ventricular ejection fractions ≥ 0.5 by echocardiography Creatinine < 1.6 mg/dL Aspartate aminotransferase/aspartate aminotransferase < 3x upper limit of normal Total bilirubin <2.0 mg/dL Karnofsky performance status ≥ 60 Expected survival time ≥ 3 months (according to investigator's judgement) Exclusion Criteria: Patients are pregnant or lactating Uncontrolled active infection Class III/IV cardiovascular disability according to the New York Heart Association Classification Active hepatitis B or hepatitis C infection Patients with HIV infection Patients with history of seizure Active central nervous system leukemia

Ages Eligible for Study
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Minimum Age: 6 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: CLL1 positive relapsed or refractory acute myeloid leukemia<br> | Biological: anti-CLL1 CART<br>* Split intravenous infusion of anti-CLL1 CAR T cells [dose escalating infusion of (5-20)x10^6 anti-CLL1 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 | 
| overall survival (OS) | The date of enrollment to the date of death from any cause | 2 years | 
| Event-free survival (EFS) | Time from enrollment to the date of primary refractory disease, or relapse from CR or CRi, or death from any cause | 2 years | 
| Cumulative incidence of relapse(CIR) | Time from the date of achievement of a remission to the date of relapse | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL1, CART, AML