CAR-T CD19 for Acute Myelogenous Leukemia With t 8:21 and CD19 Expression

Study Overview
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Brief Summary
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Chimeric antigen receptor (CAR-T) engineered T cells against the CD19 protein have been shown to be effective against acute lymphoma and lymphocytic leukemia and are approved by the US (FDA), European (EMA) and Health Basel. However, little information exists on using CD19CAR for treatment of recurrent or irresponsible to previous treatment acute myeloid leukemia. The proposed study will include patients with recurrent disease or those with disease irresponsible to common treatments and they will be treated with CAR-T CD19.

Official Title
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Giving CAR-T CD19 Transgenic T Cells for Acute Myeloid Leukemia Patients (AML) With t 8:21 and CD19 Expression

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: CAR-T CD19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with recurrent acute myeloid leukemia (AML) including those after bone marrow transplantation or not responding to previous therapy, who have exhausted other approved relevant therapies such as chemotherapy protocols that are ineffective and with high toxicity, or FLT3 inhibitors in patients with FLT3 . Exclusion Criteria: Heart disease including severe heart failure (NYHA III-IV), recent MI or CABG surgery (in previous six months), severe ventricular rhythm abnormalities, non ischemic heart disease, LVEF less than 45% Active involvement of CNS Active infection Pregnancy or lactation Graft versus host disease III-IV grade - Stroke or seizure in the last six months before treatment A positive result for the HIV infection (serum) Active hepatitis infection Life-threatening allergies to cyclophosphamide or fludarabine No informed consent signed by candidate Candidate enrolled in other study

Ages Eligible for Study
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Minimum Age: 18 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: Cyclophosphamide, Flodarabine,CAR-T cells<br>The appropriate participants will undergo lymhopheresis to collect lymphocytes from PBMC peripheral blood. CAR T CD19 cells will be produced. The participants will receive cyclophosphamide 300 mg / m² and flodarabine 30 mg / m² lymphodeplition intravenously daily for 3 days. The CAR-T CD19 cells will be given on the 5 to 7 day post lymphodeplition . | Biological: CAR-T CD19<br>* The CAR-T infusion will be given in IV infusion. The target dose is 1 X 106 positive CAR / kg T cells (range: 0.5-1.5X 106 CAR / kg positive T cells).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the peripheral blood counts and differential | Will be evaluated by Coulter counter | Within two years from the introduction of the CAR-T CD19 | 
| The change in the antigen expression on the leukemic blasts | Will be evaluated by FACS | Within two years from the introduction of the CAR-T CD19 | 
| The change in the measurable residual disease | Will be evaluated by PCR | Within two years from the introduction of the CAR-T CD19 | 
| The change in the chromosomal translocations and aberrations | Will be evaluated by cytogenetics and FISH | Within two years from the introduction of the CAR-T CD19 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chimeric antigen receptors; Mixed phenotype acute leukemia; T cells.