Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

Study Overview
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Brief Summary
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The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multi-CAR T cell therapy targeting different AML surface antigens in patients with relapsed or refractory acute myeloid leukemia (AML). Another goal of the study is to learn more about the function of the multi-CAR T cells and their persistency in the patients.

Detailed Description
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Acute myeloid leukemia (AML) is a malignant disease characterized by the rapid growth of myeloblasts that build up in the bone marrow and interfere with the production of normal blood cells. In this study, the patients' own T cells will be genetically modified with lentiviral vectors expressing chimeric antigen receptors. The multi-CAR T cells recognize specific molecules such as CD33, CD38, CD123, CD56, MucI, and CLL1, which are often found expressed on the surface of AML cells. The engineered CAR T cells will be infused into patients. The purpose of this clinical study is to assess the feasibility, safety and efficacy of the multi-CAR T cell therapy against AML. Another goal of the study is to learn more about the function of the multi-CAR T cells and their persistency in the patients.

Official Title
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Multi-center Phase I/II Clinical Trial of Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age older than 2 years. CD33, CD38, CD56, CD123, MucI, and CLL1 expression can be identified in the malignant cells by immuno-histochemical staining or flow cytometry. Karnofsky performance status (KPS) score is higher than 80 and life expectancy > 2 months. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL. Hgb≥80g/L. No cell separation contraindications. Abilities to understand and the willingness to provide written informed consent. Exclusion Criteria: Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection. Active bacterial, fungal or viral infection not controlled by adequate treatment. Known HIV or hepatitis B virus (HBV) infection. Pregnant or nursing women may not participate. History of glucocorticoid for systemic therapy within the week prior to entering the test. Previously treatment with any gene therapy products. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 75 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: Single arm<br>CAR T cells to treat AML | Biological: Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells<br>* Infusion of Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients with treatment related adverse effect | percentage of participants with treatment-related adverse events, as assessed by physical exam, vital signs, standard clinical labs and so on. | a year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti tumor activity of fourth generation CAR-T cells in patients with relapsed or refractory AML | scale of CAR copies and leukemic cell burden (for efficacy) | a year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, CAR T, Muc1,CLL1, CD33, CD38, CD56, and/or CD123