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

Phase 2Not Yet RecruitingNCT04451200

Institut Paoli-Calmettes82 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Leukemia Mielodysplasic Syndrome Myeloproliferative Neoplasm

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

non-relapse mortality evaluation

Time frame: 100 days post graft

Secondary Outcomes

incidence of grade 3 or 4 toxicities

To evaluate toxicities linked to sequential bususlfan administration

Time frame: 1 month

graft taking after sequential busulfan conditioning

incidence of hematological reconstituation

Time frame: day 30 and day 100 post graft

incidence of transfusion needs for red blood cells

number of transfusions after graft

Time frame: day 30 post graft

incidence of transfusion needs for red blood cells

number of transfusions after graft

Time frame: day 60 post graft

incidence in graft taking after sequential busulfan conditioning

Lymphocyte chimerism

Time frame: day 100 post graft

anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH

incidence of acute GVH

Time frame: 1 year

anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH

incidence of acute GVH

Time frame: 5 years

the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH

incidence of chronic GVH

Time frame: 1 and 5 years

the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH

incidence of chronic GVH

Time frame: 1 year

anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival

progression-free survival

Time frame: 5 years

anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival

overall survival

Time frame: 1 year

anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival

overall survival

Time frame: 5 years

anti-tumoral efficacy of sequential busulfan conditioning: Incidence of relapse

Incidence of relapse

Time frame: 1 year

Differences between the theoretical target AUC and the measured a posteriori

To study the pharmacokinetics of the sequential administration of busulfan

Time frame: 1 month

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts