Target Busulfan Exposure in Children With HSCT in China

NCT ID: NCT04786002

Last Updated: 2021-03-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-01

Study Completion Date

2023-06-01

Brief Summary

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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

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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

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Hematopoietic Stem Cell Transplantation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Busulfan

The BU administration regimen was four times a day (Q6h), continuous intravenous infusion for 2 hours, 3 or 4 days in a row.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. The subjects or their legal guardians voluntarily sign the informed consent, and can complete the study in accordance with the requirements of the program;
2. No age or gender restriction;
3. Patients with blood disease confirmed by histopathology or cytology;
4. 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.

Exclusion Criteria

1. Patients with difficulty in vein blood sampling (if there is a needle, blood history);
2. BU TDM was not performed during the treatment;
3. Subjects who are considered unfit to participate in the trail by the investigator.
Minimum Eligible Age

0 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Hospital of Soochow University

OTHER

Sponsor Role collaborator

Children's Hospital of Fudan University

OTHER

Sponsor Role collaborator

Fujian Medical University Union Hospital

OTHER

Sponsor Role collaborator

Guangzhou Women and Children's Medical Center

OTHER

Sponsor Role collaborator

West China Second University Hospital

OTHER

Sponsor Role collaborator

Beijing Children's Hospital

OTHER

Sponsor Role collaborator

Shenzhen Children's Hospital

OTHER_GOV

Sponsor Role collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Liyan Miao, PhD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Soochow University

Shaoyan Hu, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Soochow University

Locations

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the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Chenrong Huang, PhD

Role: CONTACT

86-512-67972699 ext. 8651267972699

Xiaohuan Du, MS

Role: CONTACT

86-512-80692268

Facility Contacts

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Chenrong Huang, PhD

Role: primary

8651267972699 ext. 8651267972699

Xiaohuan Du, MS

Role: backup

8651280692268 ext. 8651280692268

References

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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.

Reference Type BACKGROUND
PMID: 8640171 (View on PubMed)

Bartelink 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.

Reference Type BACKGROUND
PMID: 19167683 (View on PubMed)

Palmer 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.

Reference Type BACKGROUND
PMID: 27481448 (View on PubMed)

Bartelink 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.

Reference Type BACKGROUND
PMID: 27746112 (View on PubMed)

Ansari 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.

Reference Type BACKGROUND
PMID: 24061446 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29469189 (View on PubMed)

Other Identifiers

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2019-KY-BXA-01

Identifier Type: -

Identifier Source: org_study_id

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