BUSEQ: 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

Sponsor

Institut Paoli-Calmettes (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04451200

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Leukemia Mielodysplasic Syndrome Myeloproliferative Neoplasm	Drug: Busulfan Injection	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

82 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: busulfan treatment

Personalized BU administration

Drug: Busulfan Injection

injections doses will be personalized by PK at days -7 and -4

Outcome Measures

Primary Outcome Measures

non-relapse mortality evaluation [100 days post graft]
non-relapse mortality evaluation

Secondary Outcome Measures

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 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 [1 year]
incidence of acute GVH
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 and 5 years]
incidence of chronic 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]
progression-free survival
anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival [1 year]
overall survival
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Institut Paoli-Calmettes

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Institut Paoli-Calmettes

ClinicalTrials.gov Identifier:

NCT04451200

Other Study ID Numbers:

BUSEQ-IPC 2020-006

First Posted:

Jun 30, 2020

Last Update Posted:

Nov 17, 2020

Last Verified:

Oct 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Myeloproliferative Disorders

Busulfan

Study Results

No Results Posted as of Nov 17, 2020