Clofarabine/Ara-C Treatment Combined With Reduced-intensity Conditioning Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Primary Treatment Failure

Study Overview
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Brief Summary
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The present trial will establish a prospective sequential Allogeneic Stem Cell Transplantation (allo-SCT) treatment combining both salvage chemotherapy and Reduced Intensity Conditioning (RIC) for primary treatment failure Acute Myeloid Leukemia (AML), to which future innovative strategies can be compared.

Detailed Description
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Primary Endpoint: To improve the 2 year overall survival in patients with primary treatment failure * Secondary Endpoints: Feasibility of early transplantation within a multicenter trial Leukemia-free survival (LFS) at 2 years from transplantation Leukemia Response rate at day +30, +90 and 6 months Cumulative incidence of relapse, death from leukemia, and non-relapse mortality (NRM) Incidence and severity of acute and chronic Graft-versus-Host disease Feasibility and safety of early discontinuation of immunosuppressive therapy

Official Title
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Clofarabine/Ara-C Treatment Combined With Reduced-intensity Conditioning Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Primary Treatment Failure

Conditions
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AML

Intervention / Treatment
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* Drug: Clofarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of AML in the status of primary induction failure (i.e. persistent leukemia after 2 courses of induction chemotherapy or persisting bone marrow hypoplasia fol-lowing induction chemotherapy +/-minimal residual disease) Age: 18-55 years Availability of an HLA identical family donor OR unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of 1 allele or antigen mismatch OR family donor with maximum 1 allele mismatch. Have adequate renal and hepatic functions as indicated by the following laboratory values: Serum creatinine ≤1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m² as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) Serum bilirubin ≤1.5 mg/dL × upper limit of normal (ULN) Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 × ULN Alkaline phosphatase ≤2.5 × ULN Exclusion Criteria: Documented chloroma Patients having AML M3 Documented leukemic infiltration of CNS/cerebrospinal fluid Karnofsky performance score below < 60% Acute or chronic heart failure HIV infection, chronic viral hepatitis Severe neurological or psychiatric disorders Any circumstances that preclude the use of the drugs used within the protocol Prior allogeneic or autologous stem cell transplantation > 3 courses of prior chemotherapy Denied informed consent Pregnancy or denied of effective contraceptive method

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Clofarabine<br> | Drug: Clofarabine<br>* The present protocol aims to test the strategy of an early Reduced Intensity Conditioning (RIC) allo-SCT; in combination with a sequential preparative regimen for allo-SCT (Clofarabine, Intermediate dose Ara-C chemotherapy, followed by RIC with Cyclophosphamide, IV Busulfan and ATG; and delayed prophylactic infusion of donor lymphocytes (DLI) will be able to improve the outcome of patients with primary treatment failure AML.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the survival rate at 2 years after transplantation |  | at 2 years after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, primary induction failure