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 2

Not yet recruiting

• Conditions: Acute Leukemia; Mielodysplasic Syndrome; Myeloproliferative Neoplasm
• Interventions: Drug: Busulfan Injection

• Registration Number: NCT04451200
• Lead Sponsor: Institut Paoli-Calmettes

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-03
• Study First Submitted QC: 2020-06-29
• Study First Posted: 2020-06-30
• Status Verified: 2020-10
• Study Start: 2020-11
• Last Update Submitted: 2020-11-16
• Last Update Posted: 2020-11-17
• Primary Completion: 2023-11
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 82

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
busulfan treatment	Busulfan Injection	Personalized BU administration

Primary Outcome Measures

Name	Time	Method
non-relapse mortality evaluation	100 days post graft	non-relapse mortality evaluation

Secondary Outcome Measures

Name	Time	Method
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 60 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	5 years	incidence of acute GVH
the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH	1 year	incidence of chronic GVH
anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival	5 years	overall 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