Acute Leukemia, Mielodysplasic Syndrome, Myeloproliferative Neoplasm
Conditions
Brief summary
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.
Interventions
injections doses will be personalized by PK at days -7 and -4
Sponsors
Institut Paoli-Calmettes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| non-relapse mortality evaluation | 100 days post graft | non-relapse mortality evaluation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| incidence of grade 3 or 4 toxicities | 1 month | To evaluate toxicities linked to sequential bususlfan administration |
| graft taking after sequential busulfan conditioning | day 30 and day 100 post graft | incidence of hematological reconstituation |
| incidence of transfusion needs for red blood cells | day 30 post graft | number of transfusions after graft |
| incidence in graft taking after sequential busulfan conditioning | day 100 post graft | Lymphocyte chimerism |
| anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH | 1 year | incidence of acute GVH |
| the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH | 1 and 5 years | incidence of chronic GVH |
| anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival | 5 years | progression-free survival |
| anti-tumoral efficacy of sequential busulfan conditioning: Incidence of relapse | 1 year | Incidence of relapse |
| Differences between the theoretical target AUC and the measured a posteriori | 1 month | To study the pharmacokinetics of the sequential administration of busulfan |
Contacts
Primary ContactDominique Genre, MD
Outcome results
None listed