Precision Dosing of Busulfan in Children Undergoing HSCT

NCT04822532 | Unknown

• 1 other identifier: BuGenes 01
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic Stem Cell Transplantation; Allogeneic Hematopoietic Stem Cell Transplantation; Autologous Hematopoietic Stem Cell Transplantation

Keywords

Precision dosing; Pharmacogenetics; Children; Adolescent; Busulfan; HSCT

Outcome Measures

Primary Outcomes (3)

• Accuracy of the first-dose Bu area under the curve (AUC) prediction

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

  1 month

• Accuracy of the Bu Clearance prediction

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

  1 month

• Dose adjustment requirement

  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

  1 month

Secondary Outcomes (7)

• Time to deliver the personalized dose

  1 week

• Incidence of treatment-related toxicities (TRTs)

  12 months

• Incidence and severity of sinusoidal obstruction syndrome (SOS)

  12 months

• Incidence of primary and secondary graft failure

  12 months

• Incidence and severity of acute graft-versus-host disease (aGVHD)

  12 months

Study Arms (2)

Pharmacogenetic based-model (GSTA1)

EXPERIMENTAL

Genetic: GSTA1 genotyping

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

ACTIVE COMPARATOR

Genetic: GSTA1 genotyping

Interventions

GSTA1 genotyping GENETIC

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

Pharmacogenetic based-model (GSTA1); The most performing method based on age and weight - McCune's model

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

Hôpitaux Universitaires de Genève

Geneva, Switzerland

RECRUITING

Related Publications (3)

• McCune JS, Bemer MJ, Barrett JS, Scott Baker K, Gamis AS, Holford NH. Busulfan in infant to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and Bayesian dose personalization. Clin Cancer Res. 2014 Feb 1;20(3):754-63. doi: 10.1158/1078-0432.CCR-13-1960. Epub 2013 Nov 11.

  PMID: 24218510 BACKGROUND

• Nava T, Kassir N, Rezgui MA, Uppugunduri CRS, Huezo-Diaz Curtis P, Duval M, Theoret Y, Daudt LE, Litalien C, Ansari M, Krajinovic M, Bittencourt H. Incorporation of GSTA1 genetic variations into a population pharmacokinetic model for IV busulfan in paediatric hematopoietic stem cell transplantation. Br J Clin Pharmacol. 2018 Jul;84(7):1494-1504. doi: 10.1111/bcp.13566. Epub 2018 Apr 27.

  PMID: 29469189 BACKGROUND

• Hassine KB, Nava T et al. 2021 (manuscript submitted).

  BACKGROUND

Central Study Contacts

Marc Ansari, MD Prof

CONTACT

+41795536100; research@cansearch.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professeur Marc Ansari

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 30, 2021
• Study Start: June 15, 2021
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: August 2, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)