Haploidentical Stem Cell Transplantation With CD3/CD19 Depletion and Reduced Intensity Conditioning in Patients With Acute Leukemia

Study Overview
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Brief Summary
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Feasibility and toxicity of haploidentical allogeneic HCT after a reduced intensity conditioning regimen with CD3/CD19 depleted grafts. This study enrolls patients with acute leukemia in complete remission with an indication for allogeneic HCT but without a suitable HLA-identical donor

Official Title
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Multicenter Phase II Study of Haploidentical Hematopoietic Cell Transplantation With CD3/CD19 Depleted Grafts After a Reduced Intensity Conditioning Regimen for Adult Patients With Acute Leukemia

Conditions
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Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Fludarabine, Thiotepa, Melphalan, Thymoglobuline (ATG)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with either ALL or AML in CR with an indication for allogeneic HCT according to the following criteria: AML: high risk patients with one or more of the following risk factors: FLT-3 mutation Complex cytogenetics abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p) Late CR > induction I Age >60 Patients in 2.CR Secondary AML Relapse after a preceding allogeneic HCT from an HLA-identical donor ALL: high risk patients with one or more of the following risk factors: Pro-B-ALL Initial WBC >30.000/µL CR after day 46 after Induction II Complex cytogenetics, t(9,22), t(4,11) Early or mature T-ALL Initially refractory patients with late CR Rising MRD level Patients in 2. CR Relapse after a preceding allogeneic HCT from an HLA-identical donor No HLA-identical donor (not more than 1 antigen mismatch (9/10-Match) or more than 2 allelic mismatches by high-resolution typing). Critical cases should be discussed with the PI. Age <=65, >=18 years Karnofsky Index >60% Exclusion Criteria: Patients with >5% blasts in BM at the time of transplantation Less than 3 months after preceding HCT CNS involvement with disease History of neurologic impairment such as: seizures, severe peripheral neuropathy, signs of leukoencephalopathy, CNS infection, multiple intrathecal chemotherapies, CNS irradiation. In case of heavy pretreatment with irradiation or intrathecal chemotherapy pretransplant CNS MRI and neurological consultation are mandatory Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month. Liver function abnormalities with bilirubin >2 mg/dL and elevation of transaminases higher 2x upper limit of normal. Chronic active viral hepatitis Ejection fraction <40 % on echocardiography Patients with > grade II hypertension by CTC criteria Creatinine clearance <50 ml/min Respiratory failure necessitating supplemental oxygen or DLCO <30% Allergy against murine antibodies HIV-Infection Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control during study treatment and for at least 12 months thereafter. (Women of childbearing potential must have a negative serum pregnancy test at study entry) Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study Patients with a history of psychiatric illness or condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction) Patients unwilling or unable to comply with the protocol Unable to give informed consent Enrollment in an other trial interfering with the endpoints of this study

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Drug: Fludarabine, Thiotepa, Melphalan, Thymoglobuline (ATG)|Conditioning with Fludarabine 30 mg/m2/24h day-8 to -4, Thiotepa 2x5 mg/kg day -3, Melphalan 60 mg/m2 day -2 to -1 and Thymoglobuline (ATG)1.5mg/kg/day day -9 to -6. PBSC depleted of CD3 and CD19 cells by immunomagnetic depletion on CliniMACS.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of treatment related mortality after haploidentical HCT | Cumulative Incidence of treatment related mortality | 1 year after HCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | by Kaplan-Meier | 1, 2 and 5 years after inclusion | 
| Evaluate Engraftment |  | One year after HCT | 
| Evaluate Toxicity |  | One year after HCT | 
| Evaluate Disease Free Survival |  | 1, 2 and 5 years after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haploidentical Transplantation, CD3/CD19 Depletion, AML, ALL, Reduced Intensity Conditioning