Clinical trial NCT04451200: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acute Leukemia
Mielodysplasic Syndrome
Myeloproliferative Neoplasm
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
First posted: 2020-06-30
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: non-relapse mortality evaluation
timeFrame: 100 days post graft
Secondary outcomes:
measure: incidence of grade 3 or 4 toxicities
timeFrame: 1 month
measure: graft taking after sequential busulfan conditioning
timeFrame: day 30 and day 100 post graft
measure: incidence of transfusion needs for red blood cells
timeFrame: day 30 post graft
measure: incidence of transfusion needs for red blood cells
timeFrame: day 60 post graft
measure: incidence in graft taking after sequential busulfan conditioning
timeFrame: day 100 post graft
measure: anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH
timeFrame: 1 year
measure: anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH
timeFrame: 5 years
measure: the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH
timeFrame: 1 and 5 years
measure: the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH
timeFrame: 1 year
measure: anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival
timeFrame: 5 years
measure: anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival
timeFrame: 1 year
measure: anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival
timeFrame: 5 years
measure: anti-tumoral efficacy of sequential busulfan conditioning: Incidence of relapse
timeFrame: 1 year
measure: Differences between the theoretical target AUC and the measured a posteriori
timeFrame: 1 month
Other outcomes:
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