Randomized Study of Conditioning of Fludarabine Combined With Single or Dual Alkylating Agents in Myeloid Malignancies

Study Overview
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Brief Summary
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Fludarabine and busulfan becomes standard conditioning regimen for adult patients with acute myeloid leukemia (AML) or myelodysplasia syndrome (MDS). The overall relapse rate is 15 20%. More recently, the investigators demonstrated that conditioning regimen with dual alkylating agents consistent of fludarabine, busulfan and melphalan achieved a low incidence of relapse (<10%). This multiple-center randomize study is aim to compare the transplantation outcome in adult patients with AML/MDS undergoing allo-HSCT with conditioning regimen of Flu-Bu4 vs. FLu-Bu-Mel.

Detailed Description
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Fludarabine and busulfan was considered as myeloablative but reduced toxicity regimen and became as the mainstay of conditioning regimen for adult patients with acute myeloid leukemia (AML) or myelodysplasia syndrome (MDS). The disease relapse remained as major cause of treatment failure. In general, the cumulated incidence of relapse (CIR) is about 15 20% dependent on the risk of patients undergoing allogeneic stem cell transplantation (allo-HSCT). Conditioning regimen with dual alkylating agents such as fludarabine, busulfan and thiotepa (TBF) showed decreased risk of relapse in myeloid malignancies. More recently, the investigators demonstrated that conditioning regimen with dual alkylating agents consistent of fludarabine, busulfan and melphalan could achieve a low incidence of relapse (2 year CIR <10%). In this multiple-center randomize study, the aim is to compare the transplantation outcome in adult patients with AML/MDS undergoing allo-HSCT with conditioning regimen of Flu-Bu vs. Flu-Bu-Mel.

Official Title
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Multiple-center Randomized Study to Compare Fludarabine and Busulfan Versus Fludarabine, Busulfan and Melphalan in Adult Patients With Acute Myeloid Leukemia (AML) and Myelodysplasia Syndrome (MDS)

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Fludarabine, busulfan and melphalan
* Drug: Fludarabine and Busulfan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute myeloid leukemia (acute promyelocytic leukemia excluded) in 1st complete remission myelodysplasia syndrome with bone marrow blast >5% and remaining less than 20% at transplantation patients with HLA matched sibling donor, 9-10 matched unrelated donor or haplo-identical related donors inform consent provided Exclusion Criteria: AML patients with active CNS or extramedullary diseases patients with active viral, bacterial or fungal infection patients with hepatitis B virus >1X103 copy/ml patients with abnormal liver function, renal function, respiratory or cardiac dysfunction patients with uncontrolled mental disorders patients with HIV

Ages Eligible for Study
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Minimum Age: 16 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: study group with fludarabine, busulfan and melphalan regimen versus control group with fludarabine and busulfan
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flu-Bu2-Mel140<br>Patients receive fludarabine, busulfan and melphalan as conditioning regimen | Drug: Fludarabine, busulfan and melphalan<br>* FLudarabine 150mg/m2 + Busulfan 6.4mg.kg + Mel 140mg/m2<br>|
| Active Comparator: Flu-Bu4<br>Patients receive fludarabine and busulfan as conditioning regimen | Drug: Fludarabine and Busulfan<br>* FLudarabine 150mg/m2 + Busulfan 12.8mg.kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | event defined as relapse and death of any causes | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | event defined as death of any causes | 2 year | 
| incidence of relapse | event defined as disease relapse (bone marrow or extra medullary) | 2 year | 
| non relapse mortality | event defined as death without disease relapse | day 100 | 
| non relapse mortality | event defined as death without disease relapse | 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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conditioning regimen, melphalan, busulfan, fludarabine