BuGenes01: Precision Dosing of Busulfan in Children Undergoing HSCT

Sponsor
University Hospital, Geneva (Other)
Overall Status
Recruiting
CT.gov ID
NCT04822532
Collaborator
(none)
260
1
2
47.5
5.5

Study Details

Study Description

Brief Summary

The objective of this clinical trial is to evaluate the personalization the conditioning regimen prior to the hematopoietic stem cell transplant (HSCT) in children and adolescents, to improve HSCT efficacy while reducing conditioning-related toxicities. Namely, we are going to compare the accuracy of two methods for determining the first dose of busulfan, one of the medicines used during the conditioning regimen. First doses will be determined based either only on anthropometric information such as age and weight or by adding a genetic factor that influences the individual ability of busulfan metabolization.

Detailed Description

Participants will be randomly assigned (1:1 ratio, stratified by conditioning regimen - the presence of fludarabine) to receive their first dose of busulfan according to:

  1. the most performing method based on age and weight - McCune's model (control arm)

  2. a method that also considers a pharmacogenetic factor (variants occurring in the promoter region of the GSTA1 gene) in association with the co-administered chemotherapeutic agent fludarabine in the dose personalization (experimental arm)

This is an international study being carried out in five countries (Canada, Italy, Switzerland, France, and Denmark).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
260 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Implementing Pharmacogenetics in the Busulfan Dosing Method for Children Undergoing Hematopoietic Stem-cell Transplantation: a Prospective, Multicentric, Randomized Clinical Trial
Actual Study Start Date :
Jun 15, 2021
Anticipated Primary Completion Date :
Jun 1, 2025
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pharmacogenetic based-model (GSTA1)

Genetic: GSTA1 genotyping
Diplotype determination based on 4 single-nucleotide polymorphisms (SNPs) occurring in the promoter region of the GSTA1 gene

Active Comparator: The most performing method based on age and weight - McCune's model

Genetic: GSTA1 genotyping
Diplotype determination based on 4 single-nucleotide polymorphisms (SNPs) occurring in the promoter region of the GSTA1 gene

Outcome Measures

Primary Outcome Measures

  1. Accuracy of the first-dose Bu area under the curve (AUC) prediction [1 month]

    Proportion of the first doses which result in AUCs within the therapeutic target range defined by the prescriber

  2. Accuracy of the Bu Clearance prediction [1 month]

    Absolute prediction error between the predicted and measured Bu clearance of the first dose

  3. Dose adjustment requirement [1 month]

    Change in percentage between the first dose administered and the next time-wise adjustable dose: 2nd (Bu q24h), 3rd (Bu q12h), or 5th (Bu q6h) doses

Secondary Outcome Measures

  1. Time to deliver the personalized dose [1 week]

    Proportion of personalized doses delivered within the optimal delivery time (to be determined during the first year of the trial)

  2. Incidence of treatment-related toxicities (TRTs) [12 months]

  3. Incidence and severity of sinusoidal obstruction syndrome (SOS) [12 months]

  4. Incidence of primary and secondary graft failure [12 months]

  5. Incidence and severity of acute graft-versus-host disease (aGVHD) [12 months]

  6. Overall survival [12 months]

  7. Event-free survival [12 months]

    Considering as event aGVHD, SOS, relapse and death

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Patients must be aged from 0-18 years old on entry to the study;

  • Clinical indication of allogeneic or autologous hematopoietic stem cell transplantation;

  • The conditioning protocol must include IV Bu formulations, Busulfex® (Otsuka Pharmaceutical), Busilvex® (Pierre Fabre Pharma) or other European Medicines Agency (EMA) or Food and Drugs Administration (FDA) approved generic formulations regardless of the administration schedule (q6h, q12h, or q24h)

  • The expected length of time from recruitment to starting the conditioning regimen must be superior to 10 days;

  • Informed written consent to participate in the study signed by the participant/parent

Exclusion Criteria:

• At least one of the drugs listed below scheduled to be administered in the Bu administration days up to 24h after the last dose of Bu, whenever a washout is not possible:

  • Metronidazol (required washout: 7 days)

  • Nalidixic acid (required washout: 7 days)

  • Phenytoin (required washout: 21 days)

  • Itraconazole (required washout: 14 days)

  • Ketoconazole (required washout: 7 days)

  • Voriconazole (required washout: 7 days)

  • Deferasirox (required washout: 7 days)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hôpitaux Universitaires de Genève Geneva Switzerland

Sponsors and Collaborators

  • University Hospital, Geneva

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Marc Ansari, Professeur Marc Ansari, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT04822532
Other Study ID Numbers:
  • BuGenes 01
First Posted:
Mar 30, 2021
Last Update Posted:
Aug 2, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Keywords provided by Marc Ansari, Professeur Marc Ansari, University Hospital, Geneva

Study Results

No Results Posted as of Aug 2, 2021