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 (BUSEQ)

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

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 Overview

• Status: Not yet recruiting
• Conditions: Acute Leukemia; Myeloproliferative Neoplasm; Mielodysplasic Syndrome
• Intervention / Treatment: Drug: Busulfan Injection

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: busulfan treatment; Personalized BU administration	Drug: Busulfan Injection; injections doses will be personalized by PK at days -7 and -4

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut Paoli-Calmettes

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2020
• Primary Completion (ANTICIPATED): November 1, 2023
• Study Completion (ANTICIPATED): December 1, 2028

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (ACTUAL): June 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Busulfan
• Other Study ID Numbers: BUSEQ-IPC 2020-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No