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

Acute Leukemia Clinical Trial

— BUSEQ  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04451200
• Other study ID #: BUSEQ-IPC 2020-006
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 2020
• Est. completion date: December 2028

Study information

• Verified date: October 2020
• Source: Institut Paoli-Calmettes
• Contact: Dominique Genre, MD
• Phone: +33491223778
• Email: drci.up[@]ipc.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 82
• Est. completion date: December 2028
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Leukemia
• Mielodysplasic Syndrome
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm

Intervention

Drug:
• Busulfan Injection
injections doses will be personalized by PK at days -7 and -4

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Institut Paoli-Calmettes

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	non-relapse mortality evaluation	non-relapse mortality evaluation	100 days post graft
Secondary	incidence of grade 3 or 4 toxicities	To evaluate toxicities linked to sequential bususlfan administration	1 month
Secondary	graft taking after sequential busulfan conditioning	incidence of hematological reconstituation	day 30 and day 100 post graft
Secondary	incidence of transfusion needs for red blood cells	number of transfusions after graft	day 30 post graft
Secondary	incidence of transfusion needs for red blood cells	number of transfusions after graft	day 60 post graft
Secondary	incidence in graft taking after sequential busulfan conditioning	Lymphocyte chimerism	day 100 post graft
Secondary	anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH	incidence of acute GVH	1 year
Secondary	anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH	incidence of acute GVH	5 years
Secondary	the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH	incidence of chronic GVH	1 and 5 years
Secondary	the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH	incidence of chronic GVH	1 year
Secondary	anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival	progression-free survival	5 years
Secondary	anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival	overall survival	1 year
Secondary	anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival	overall survival	5 years
Secondary	anti-tumoral efficacy of sequential busulfan conditioning: Incidence of relapse	Incidence of relapse	1 year
Secondary	Differences between the theoretical target AUC and the measured a posteriori	To study the pharmacokinetics of the sequential administration of busulfan	1 month