Sequential and Personalized PK-guided Busulfan Administration in the Frame of the Conditiong Regimen for Allo-HSCT in Patients With Malignant Hemopathies Ineligible for the Standard Myeloablative Conditioning

Study Overview
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Brief Summary
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Because the anti-leukemic activity of busulfan, this dug is largely used in graft conditioning but in elderly and/or cormobid patienth an excess of toxicity is observed. This study focus on the possibility of significanty reducing this toxicity by customizing the doses of busulfan to individual PK parameters.

Official Title
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Sequential and Personalized Pharmacokinetic-guided Busulfan Administration in the Frame of the Conditiong Regimen for Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Malignant Hemopathies Ineligible for the Standard Myeloablative Conditioning

Conditions
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Acute Leukemia, Mielodysplasic Syndrome, Myeloproliferative Neoplasm

Intervention / Treatment
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* Drug: Busulfan Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient up to 65 years old Acute leukemia, myelodysplastic syndrome or myeloproliferative neoplasia eligible for an allogeneic transplant Chemosensitive disease, in complete or partial or stable remission Allograft from an identical HLA related donor, Haplo-identical or unrelated (HLA compatibility from 8/10 to 10/10 according to HLA-A, -B, -C, -DR, -DQ allelics) Signed consent to participate -. Affiliation to a social security regimen or beneficiary of this regimen Patient not eligible for standard myeloablative conditioning due to age> = 45 years and / or the presence of an HCT-CI comorbidity score> = 3 Exclusion Criteria: Pregnant woman, without effective contraception or breastfeeding Person in emergency situation, patient deprived of liberty or placed under the authority of a tutor, Impossibility of undergoing medical follow-up of the trial for geographic, social or psychological reasons Contraindications to performing an allogeneic transplant Previous allograft Placental blood allograft

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: busulfan treatment<br>Personalized BU administration | Drug: Busulfan Injection<br>* injections doses will be personalized by PK at days -7 and -4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| non-relapse mortality evaluation | non-relapse mortality evaluation | 100 days post graft | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of grade 3 or 4 toxicities | To evaluate toxicities linked to sequential bususlfan administration | 1 month | 
| graft taking after sequential busulfan conditioning | incidence of hematological reconstituation | day 30 and day 100 post graft | 
| incidence of transfusion needs for red blood cells | number of transfusions after graft | day 30 post graft | 
| incidence of transfusion needs for red blood cells | number of transfusions after graft | day 60 post graft | 
| incidence in graft taking after sequential busulfan conditioning | Lymphocyte chimerism | day 100 post graft | 
| anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH | incidence of acute GVH | 1 year | 
| anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH | incidence of acute GVH | 5 years | 
| the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH | incidence of chronic GVH | 1 and 5 years | 
| the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH | incidence of chronic GVH | 1 year | 
| anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival | progression-free survival | 5 years | 
| anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival | overall survival | 1 year | 
| anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival | overall survival | 5 years | 
| anti-tumoral efficacy of sequential busulfan conditioning: Incidence of relapse | Incidence of relapse | 1 year | 
| Differences between the theoretical target AUC and the measured a posteriori | To study the pharmacokinetics of the sequential administration of busulfan | 1 month |