Hematopoietic Stem Cell TransplantationBuGenes01NCT04822532
Precision Dosing of Busulfan in Children Undergoing HSCT
A study testing GSTA1 genotyping in people with Hematopoietic Stem Cell Transplantation and Allogeneic Hematopoietic Stem Cell Transplantation, run by University Hospital, Geneva at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation, Autologous Hematopoietic Stem Cell Transplantation
- What is being tested?
- GSTA1 genotyping
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 Jun 2021to Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Hôpitaux Universitaires de Genève
Geneva
NAVA Tiago
About this study
Official title: Implementing Pharmacogenetics in the Busulfan Dosing Method for Children Undergoing Hematopoietic Stem-cell Transplantation: a Prospective, Multicentric, Randomized Clinical Trial
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.
Read the 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:
- the most performing method based on age and weight - McCune's model (control arm)
- 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).
- Conditions
- Hematopoietic Stem Cell Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation, Autologous Hematopoietic Stem Cell Transplantation
- Being tested
- GSTA1 genotyping
- Keywords
- Precision dosing, Pharmacogenetics, Children, Adolescent, Busulfan, HSCT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSTA1 genotypingGenetic
Diplotype determination based on 4 single-nucleotide polymorphisms (SNPs) occurring in the promoter region of the GSTA1 gene
| Study group | Role | What they receive |
|---|---|---|
| Pharmacogenetic based-model (GSTA1) | Experimental | Not described Receives: Genetic: GSTA1 genotyping |
| The most performing method based on age and weight - McCune's model | Active comparator | Not described Receives: Genetic: GSTA1 genotyping |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 month
Accuracy of the Bu Clearance prediction
Absolute prediction error between the predicted and measured Bu clearance of the first dose
Measured: 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
Measured: 1 month
Secondary outcomes (7)
Time to deliver the personalized dose
Proportion of personalized doses delivered within the optimal delivery time (to be determined during the first year of the trial)
Measured: 1 week
Incidence of treatment-related toxicities (TRTs)
Measured: 12 months
Incidence and severity of sinusoidal obstruction syndrome (SOS)
Measured: 12 months
Incidence of primary and secondary graft failure
Measured: 12 months
Incidence and severity of acute graft-versus-host disease (aGVHD)
Measured: 12 months
Overall survival
Measured: 12 months
Event-free survival
Considering as event aGVHD, SOS, relapse and death
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2021
- Study start15 Jun 2021
- Primary completionJun 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marc Ansari, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04822532
- Sponsor's protocol ID
- BuGenes 01
- Acronym
- BuGenes01
- Status last verified
- Mar 2021
- First submitted
- 12 Mar 2021
- Last updated
- 2 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24218510Nava 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.
PubMed 29469189Hassine KB, Nava T et al. 2021 (manuscript submitted).
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implementing Pharmacogenetics in the Busulfan Dosing Method for Children Undergoing Hematopoietic Stem-cell Transplantation: a Prospective, Multicentric, Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04822532
- Acronym / sponsor ID
- BuGenes01 / BuGenes 01
- Conditions
- Hematopoietic Stem Cell Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation, Autologous Hematopoietic Stem Cell Transplantation
- Keywords
- Precision dosing, Pharmacogenetics, Children, Adolescent, Busulfan, HSCT
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 260 participants (estimated)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Study start
- 15 Jun 2021 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 30 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- the most performing method based on age and weight - McCune's model (control arm)
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSTA1 genotypingDiplotype determination based on 4 single-nucleotide polymorphisms (SNPs) occurring in the promoter region of the GSTA1 gene | Genetic | Pharmacogenetic based-model (GSTA1), The most performing method based on age and weight - McCune's model |
Primary outcome
Accuracy of the first-dose Bu area under the curve (AUC) prediction
Time frame: 1 month
Proportion of the first doses which result in AUCs within the therapeutic target range defined by the prescriber
Accuracy of the Bu Clearance prediction
Time frame: 1 month
Absolute prediction error between the predicted and measured Bu clearance of the first dose
Dose adjustment requirement
Time frame: 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
7 secondary outcomes
Time to deliver the personalized dose
Time frame: 1 week
Incidence of treatment-related toxicities (TRTs)
Time frame: 12 months
Incidence and severity of sinusoidal obstruction syndrome (SOS)
Time frame: 12 months
Incidence of primary and secondary graft failure
Time frame: 12 months
Incidence and severity of acute graft-versus-host disease (aGVHD)
Time frame: 12 months
Overall survival
Time frame: 12 months
Event-free survival
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2021.
- Background: PubMed 24218510McCune 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.
- Background: PubMed 29469189Nava 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.
- BackgroundHassine KB, Nava T et al. 2021 (manuscript submitted).
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GSTA1 genotyping in people with Hematopoietic Stem Cell Transplantation and Allogeneic Hematopoietic Stem Cell Transplantation, run by University Hospital, Geneva at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marc Ansari, MD Prof (+41795536100, research@cansearch.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy of the first-dose Bu area under the curve (AUC) prediction (time frame: 1 month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04822532, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2021.