Evaluation of 3 Different Doses of IV Busulfan

Study Overview
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Brief Summary
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Albeit the safety of the stem cell transplantation procedure has been greatly improved, further refining the intensity of the conditioning is an important issue to explore, especially in patients with poor prognosis, the goal being to maintain the very favorable safety profile and improve the disease control. This is the goal our prospective trial; we aim to prospectively evaluate in a prospective multicenter trial the efficacy of different conditioning regimens in patients with high-risk myeloid malignancies. The study is a phase II trial randomizing patients between a prospective active control arm (BX2) and two experimental arms (BX3 and BX4). A standard group was kept in this clinical trial in order to avoid the limitations induced by the comparison with historical controls in the context of continuously improving practice. Each experimental arm will be conducted in parallel according to a standard phase II trial design. In addition, this trial will associate four ancillary studies to the main clinical objective: 1/ a prospective assessment of the quality of life of the patients over a period of 2 years 2/ an analysis of the cost effectiveness of the procedure, assessed over a period of 2 years 3/ an observational busulfan pharmacokinetic study 4/ a busulfan pharmacogenomic study

Official Title
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Prospective and Multicentre Evaluation of 3 Different Doses of IV Busulfan Associated With Fludarabine and Thymoglobuline in the Conditioning of Allogeneic Stem Cell Transplantation (SCT) From a Matched Related or Unrelated Donor in Patients With Poor Prognosis Myeloid Malignancies

Conditions
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Myelodysplastic Syndrome, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: BX2
* Drug: BX3
* Drug: BX4-Suspended


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with poor prognosis myeloid malignancies: Myelodysplastic syndrome, Acute Myeloid Leukemia (AML) beyond Complete Response (CR1), CR1 AML with poor risk cytogenetics Adult patients: aged ≥ 55 years up to 65 or < 55 years not eligible for myeloablative conditioning regimen based on Total Body Irradiation (TBI) or double alkylating agent combinations. Availability of a HLA identical sibling or matched unrelated donor (10/10) Affiliation to social security Written Informed Consent Exclusion Criteria: History of previous Allo-Hematological Stem Cell Transplantation (HSCT) HIV positivity Signs of chronic active hepatitis B and/or C Evolutive psychiatric disease Concomitant neoplastic disease Pregnant or lactating woman or without contraception (for child bearing potential wom-en) Usual contra-indications for Allo-HSCT

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BX2<br>Fludarabine (Fludara®): 30 mg/m2 on D-6, D-5, D-4, D-3 and D-2 Busulfan IV (Busilvex®) : 3.2 mg/kg/d on D-4 and D-3 Thymoglobuline®: 2.5 mg/kg/d on D-3 and D-2 | Drug: BX2<br> <br> * Other names: Busulfan Intravenous 2 days at 3.2 mg/kg/d;|
| Experimental: BX3<br>Fludarabine (Fludara®): 30 mg/m² on D-6, D-5, D-4, D-3 and D-2 Busulfan IV (Busilvex®) : 3.2 mg/kg/d on D-5, D-4 and D-3 Thymoglobuline® : 2.5 mg/kg/d on D-3 and D-2 | Drug: BX3<br> <br> * Other names: Busulfan Intravenous 3 days;|
| Active Comparator: BX4-Suspended<br>Fludarabine (Fludara®): 30 mg/m²on D-6, D-5, D-4, D-3 and D-2 Busulfan IV (Busilvex®) : 3.2 mg/kg/d on D-6, D-5, D-4 and D-3 Thymoglobuline® : 2.5 mg/kg/d on D-3 and D-2 | Drug: BX4-Suspended<br>* Suspended<br>* Other names: Busulfan intravenous 4 days;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression or death | 2-year progression free survival rates | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to neutrophil>0.5G/l and platelets>50G/l | hematologic recovery | up to 2 months | 
| Graft versus host disease |  | up to 2 years | 
| relapse |  | up to 2 years | 
| Occurrence of grade 3-4 adverse events according the CTC-AE v4.0 scale | safety | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplasic syndrome, Acute Myeloid leukemia