Hematopoietic Stem Cell TransplantationNCT04786002
Target Busulfan Exposure in Children With HSCT in China
An observational study of Hematopoietic Stem Cell Transplantation, run by The First Affiliated Hospital of Soochow University at 1 site in China.
Trial summary
Objectives To evaluate the correlation between BU exposure and post-transplant clinical results (efficacy and safety) to establish the optimal BU treatment window for myeloablative conditioning in Chinese pediatrics, provide theoretical basis and the new strategy for BU individualized dosage, further optimize… Read more about this study
- Who is it for?
- Ages 0 to 18 years
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation
- What is being tested?
- Busulfan
- Type of treatment
- Injection or infusion
- How many people
- 500 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2020to 1 Jun 2023
- Phase
- Observational
- 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 0 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: 500 participants of any sex between the age of 0.1 and 18 years. Patients receiving the BU-based myeloablative conditioning before transplantation.
Who may be able to join
- The subjects or their legal guardians voluntarily sign the informed consent, and can complete the study in accordance with the requirements of the program;
- No age or gender restriction;
- Patients with blood disease confirmed by histopathology or cytology;
- BU-based regimen will be adopted. The BU administration regimen was four times a day (Q6h), continuous intravenous infusion for 2 hours, 3 or 4 days in a row.
Who cannot join
- Patients with difficulty in vein blood sampling (if there is a needle, blood history);
- BU TDM was not performed during the treatment;
- Subjects who are considered unfit to participate in the trail by the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
the First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
Chenrong Huang, PhD, 8651267972699 ext. 8651267972699, chrishuangcr@163.com
Xiaohuan Du, MS, 8651280692268 ext. 8651280692268, dxhszet@163.com
About this study
Official title: The Therapeutic Window of Busulfan in Children With Haemopoietic Stem Cell Transplantation：A Multicenter Study in China
Objectives To evaluate the correlation between BU exposure and post-transplant clinical results (efficacy and safety) to establish the optimal BU treatment window for myeloablative conditioning in Chinese pediatrics, provide theoretical basis and the new strategy for BU individualized dosage, further optimize transplant treatment and reduce drug-related toxicity.
Population 500 participants of any sex between the age of 0.1 and 18 years. Patients receiving the BU-based myeloablative conditioning before transplantation.
Read more
Endpoint primary To establish BU pop-PK model and analyze the association between BU AUC and event-free survival (EFS)or overall survival (OS) after transplantation in Chinese pediatrics.
Secondary The investigators are also interested in transplantation-related mortality (TRM), acute toxicity and chronic GvHD.
Read the detailed description
Objectives To evaluate the influence factors of BU metabolism in children and the correlation between BU exposure and post-transplant clinical results (efficacy and safety) to establish the optimal BU treatment window for myeloablative conditioning in Chinese pediatrics, provide theoretical basis and the new strategy for BU individualized dosage, further optimize transplant treatment and reduce drug-related toxicity.
Endpoint primary The main study endpoints are event-free survival (EFS) and overall survival (OS). EFS is calculated from the time of transplant until death, relapse of disease, or graft failure (defined as non-engraftment or rejection), whichever occurred first. OS is the time between transplantation and death of any cause. All surviving patients are censored at day of last contact. Duration of follow-up is the time from transplant to the last assessment for surviving patients or death.
Secondary The investigators are also interested in transplantation-related mortality (TRM), acute toxicity and chronic GvHD. TRM is defined as death unrelated to underlying disease. Acute toxicities are defined as VOD (diagnosed according to modified Seattle criteria), acute GvHD grade II-IV (diagnosed and graded according to Mount Sinai Acute GvHD International Consortium (MAGIC) criteria, oral mucositis (grade II-IV) and hemorrhagic cystitis (grade II-IV). Two of the most commonly utilised scales for oral mucositis are the WHO and NCI-CTCAE scales. Chronic GvHD should be graded as mild, moderate or severe according to the National Institutes of Health (NIH) consensus criteria.
- Conditions
- Hematopoietic Stem Cell Transplantation
- Being tested
- Busulfan
- Keywords
- HSCT, busulfan, PPK, EFS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
The BU administration regimen was four times a day (Q6h), continuous intravenous infusion for 2 hours, 3 or 4 days in a row.
What is being measured
The primary outcome is the main question the study is designed to answer.
event-free survival (EFS)
EFS is calculated from the time of transplant until death, relapse of disease, or graft failure (defined as non-engraftment or rejection), whichever occurred first.
Measured: 2 years after administration of busulfan
overall survival (OS)
OS is the time between transplantation and death of any cause.
Measured: 2 years after administration of busulfan
Secondary outcomes (3)
transplantation-related mortality (TRM)
TRM is defined as death unrelated to underlying disease.
Measured: 2 years after administration of busulfan
acute toxicity
Acute toxicities are defined as VOD (diagnosed according to modified Seattle criteria),, acute GvHD grade II-IV (diagnosed and graded according to Mount Sinai Acute GvHD International Consortium (MAGIC) criteria, oral mucositis (grade II-IV) and hemorrhagic cystitis (grade II-IV). Two of the most commonly utilised scales for oral mucositis are the WHO and NCI-CTCAE scales.
Measured: 2 years after administration of busulfan
chronic GvHD
Chronic GvHD should be graded as mild, moderate or severe according to the National Institutes of Health (NIH) consensus criteria
Measured: 2 years after administration of busulfan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2021
- Study start1 Nov 2020
- Primary completion1 Dec 2022 (estimated)
- Study completion1 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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 The First Affiliated Hospital of Soochow UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Soochow University, Children's Hospital of Fudan University, Fujian Medical University Union Hospital, Guangzhou Women and Children's Medical Center, West China Second University Hospital, Beijing Children's Hospital, Shenzhen Children's Hospital, The First Affiliated Hospital of Zhengzhou University
- Responsible party
- Sponsor
- Investigators
- Liyan Miao, PhD, Principal investigator, The First Affiliated Hospital of Soochow UniversityShaoyan Hu, MD, Principal investigator, Children's Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04786002
- Sponsor's protocol ID
- 2019-KY-BXA-01
- Status last verified
- Mar 2021
- First submitted
- 3 Mar 2021
- Last updated
- 10 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Dix SP, Wingard JR, Mullins RE, Jerkunica I, Davidson TG, Gilmore CE, York RC, Lin LS, Devine SM, Geller RB, Heffner LT, Hillyer CD, Holland HK, Winton EF, Saral R. Association of busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant. 1996 Feb;17(2):225-30.
PubMed 8640171Bartelink IH, Bredius RG, Belitser SV, Suttorp MM, Bierings M, Knibbe CA, Egeler M, Lankester AC, Egberts AC, Zwaveling J, Boelens JJ. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. Biol Blood Marrow Transplant. 2009 Feb;15(2):231-41. doi: 10.1016/j.bbmt.2008.11.022.
PubMed 19167683Palmer J, McCune JS, Perales MA, Marks D, Bubalo J, Mohty M, Wingard JR, Paci A, Hassan M, Bredeson C, Pidala J, Shah N, Shaughnessy P, Majhail N, Schriber J, Savani BN, Carpenter PA. Personalizing Busulfan-Based Conditioning: Considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee. Biol Blood Marrow Transplant. 2016 Nov;22(11):1915-1925. doi: 10.1016/j.bbmt.2016.07.013. Epub 2016 Jul 29.
PubMed 27481448Bartelink IH, Lalmohamed A, van Reij EM, Dvorak CC, Savic RM, Zwaveling J, Bredius RG, Egberts AC, Bierings M, Kletzel M, Shaw PJ, Nath CE, Hempel G, Ansari M, Krajinovic M, Theoret Y, Duval M, Keizer RJ, Bittencourt H, Hassan M, Gungor T, Wynn RF, Veys P, Cuvelier GD, Marktel S, Chiesa R, Cowan MJ, Slatter MA, Stricherz MK, Jennissen C, Long-Boyle JR, Boelens JJ. Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet Haematol. 2016 Nov;3(11):e526-e536. doi: 10.1016/S2352-3026(16)30114-4. Epub 2016 Oct 13.
PubMed 27746112Ansari M, Theoret Y, Rezgui MA, Peters C, Mezziani S, Desjean C, Vachon MF, Champagne MA, Duval M, Krajinovic M, Bittencourt H; Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematopoietic stem cell transplantation. Ther Drug Monit. 2014 Feb;36(1):93-9. doi: 10.1097/FTD.0b013e3182a04fc7.
PubMed 24061446Nava 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 29469189
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Therapeutic Window of Busulfan in Children With Haemopoietic Stem Cell Transplantation：A Multicenter Study in China
- ClinicalTrials.gov ID
- NCT04786002
- Acronym / sponsor ID
- 2019-KY-BXA-01
- Conditions
- Hematopoietic Stem Cell Transplantation
- Keywords
- HSCT, busulfan, PPK, EFS
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Collaborators
- Children's Hospital of Soochow University, Children's Hospital of Fudan University, Fujian Medical University Union Hospital, Guangzhou Women and Children's Medical Center, West China Second University Hospital, Beijing Children's Hospital, Shenzhen Children's Hospital, The First Affiliated Hospital of Zhengzhou University
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 1 Dec 2022 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 8 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.
Objectives To evaluate the correlation between BU exposure and post-transplant clinical results (efficacy and safety) to establish the optimal BU treatment window for myeloablative conditioning in Chinese pediatrics, provide theoretical basis and the new strategy for BU individualized dosage, further optimize transplant treatment and reduce drug-related toxicity.
Population 500 participants of any sex between the age of 0.1 and 18 years. Patients receiving the BU-based myeloablative conditioning before transplantation.
Endpoint primary To establish BU pop-PK model and analyze the association between BU AUC and event-free survival (EFS)or overall survival (OS) after transplantation in Chinese pediatrics.
Secondary The investigators are also interested in transplantation-related mortality (TRM), acute toxicity and chronic GvHD.
Detailed description
Objectives To evaluate the influence factors of BU metabolism in children and the correlation between BU exposure and post-transplant clinical results (efficacy and safety) to establish the optimal BU treatment window for myeloablative conditioning in Chinese pediatrics, provide theoretical basis and the new strategy for BU individualized dosage, further optimize transplant treatment and reduce drug-related toxicity.
Endpoint primary The main study endpoints are event-free survival (EFS) and overall survival (OS). EFS is calculated from the time of transplant until death, relapse of disease, or graft failure (defined as non-engraftment or rejection), whichever occurred first. OS is the time between transplantation and death of any cause. All surviving patients are censored at day of last contact. Duration of follow-up is the time from transplant to the last assessment for surviving patients or death.
Secondary The investigators are also interested in transplantation-related mortality (TRM), acute toxicity and chronic GvHD. TRM is defined as death unrelated to underlying disease. Acute toxicities are defined as VOD (diagnosed according to modified Seattle criteria), acute GvHD grade II-IV (diagnosed and graded according to Mount Sinai Acute GvHD International Consortium (MAGIC) criteria, oral mucositis (grade II-IV) and hemorrhagic cystitis (grade II-IV). Two of the most commonly utilised scales for oral mucositis are the WHO and NCI-CTCAE scales. Chronic GvHD should be graded as mild, moderate or severe according to the National Institutes of Health (NIH) consensus criteria.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- 500 participants of any sex between the age of 0.1 and 18 years. Patients receiving the BU-based myeloablative conditioning before transplantation.
Key inclusion criteria (4 listed)
- The subjects or their legal guardians voluntarily sign the informed consent, and can complete the study in accordance with the requirements of the program;
- No age or gender restriction;
- Patients with blood disease confirmed by histopathology or cytology;
- BU-based regimen will be adopted. The BU administration regimen was four times a day (Q6h), continuous intravenous infusion for 2 hours, 3 or 4 days in a row.
Key exclusion criteria (3 listed)
- Patients with difficulty in vein blood sampling (if there is a needle, blood history);
- BU TDM was not performed during the treatment;
- Subjects who are considered unfit to participate in the trail by the investigator.
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 |
|---|---|---|
| BusulfanThe BU administration regimen was four times a day (Q6h), continuous intravenous infusion for 2 hours, 3 or 4 days in a row. | Drug | – |
Primary outcome
event-free survival (EFS)
Time frame: 2 years after administration of busulfan
EFS is calculated from the time of transplant until death, relapse of disease, or graft failure (defined as non-engraftment or rejection), whichever occurred first.
overall survival (OS)
Time frame: 2 years after administration of busulfan
OS is the time between transplantation and death of any cause.
3 secondary outcomes
transplantation-related mortality (TRM)
Time frame: 2 years after administration of busulfan
acute toxicity
Time frame: 2 years after administration of busulfan
chronic GvHD
Time frame: 2 years after administration of busulfan
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2021.
- Background: PubMed 8640171Dix SP, Wingard JR, Mullins RE, Jerkunica I, Davidson TG, Gilmore CE, York RC, Lin LS, Devine SM, Geller RB, Heffner LT, Hillyer CD, Holland HK, Winton EF, Saral R. Association of busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant. 1996 Feb;17(2):225-30.
- Background: PubMed 19167683Bartelink IH, Bredius RG, Belitser SV, Suttorp MM, Bierings M, Knibbe CA, Egeler M, Lankester AC, Egberts AC, Zwaveling J, Boelens JJ. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. Biol Blood Marrow Transplant. 2009 Feb;15(2):231-41. doi: 10.1016/j.bbmt.2008.11.022.
- Background: PubMed 27481448Palmer J, McCune JS, Perales MA, Marks D, Bubalo J, Mohty M, Wingard JR, Paci A, Hassan M, Bredeson C, Pidala J, Shah N, Shaughnessy P, Majhail N, Schriber J, Savani BN, Carpenter PA. Personalizing Busulfan-Based Conditioning: Considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee. Biol Blood Marrow Transplant. 2016 Nov;22(11):1915-1925. doi: 10.1016/j.bbmt.2016.07.013. Epub 2016 Jul 29.
- Background: PubMed 27746112Bartelink IH, Lalmohamed A, van Reij EM, Dvorak CC, Savic RM, Zwaveling J, Bredius RG, Egberts AC, Bierings M, Kletzel M, Shaw PJ, Nath CE, Hempel G, Ansari M, Krajinovic M, Theoret Y, Duval M, Keizer RJ, Bittencourt H, Hassan M, Gungor T, Wynn RF, Veys P, Cuvelier GD, Marktel S, Chiesa R, Cowan MJ, Slatter MA, Stricherz MK, Jennissen C, Long-Boyle JR, Boelens JJ. Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet Haematol. 2016 Nov;3(11):e526-e536. doi: 10.1016/S2352-3026(16)30114-4. Epub 2016 Oct 13.
- Background: PubMed 24061446Ansari M, Theoret Y, Rezgui MA, Peters C, Mezziani S, Desjean C, Vachon MF, Champagne MA, Duval M, Krajinovic M, Bittencourt H; Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematopoietic stem cell transplantation. Ther Drug Monit. 2014 Feb;36(1):93-9. doi: 10.1097/FTD.0b013e3182a04fc7.
- 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.
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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.
Liyan Miao, PhD principal investigator
The First Affiliated Hospital of Soochow University
Shaoyan Hu, MD principal investigator
Children's Hospital of Soochow University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hematopoietic Stem Cell Transplantation, run by The First Affiliated Hospital of Soochow University at 1 site in China.
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 4 inclusion and 3 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 10 Mar 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 China. 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 Chenrong Huang, PhD (86-512-67972699 ext. 8651267972699, chrishuangcr@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
event-free survival (EFS) (time frame: 2 years after administration of busulfan). The study lists 2 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 NCT04786002, which also lists 6 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 10 Mar 2021.