Target Busulfan Exposure in Children With HSCT in China

NCT04786002 | Unknown DMC

• 1 other identifier: 2019-KY-BXA-01
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Hematopoietic Stem Cell Transplantation

Keywords

HSCT; busulfan; PPK; EFS

Outcome Measures

Primary Outcomes (2)

• 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.

  2 years after administration of busulfan

• overall survival (OS)

  OS is the time between transplantation and death of any cause.

  2 years after administration of busulfan

Secondary Outcomes (3)

• transplantation-related mortality (TRM)

  2 years after administration of busulfan

• acute toxicity

  2 years after administration of busulfan

• chronic GvHD

  2 years after administration of busulfan

Interventions

Busulfan DRUG

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

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead
• Children's Hospital of Soochow University: collaborator
• Children's Hospital of Fudan University: collaborator
• Fujian Medical University Union Hospital: collaborator
• Guangzhou Women and Children's Medical Center: collaborator
• West China Second University Hospital: collaborator
• Beijing Children's Hospital: collaborator
• Shenzhen Children's Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator

Study Sites (1)

the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 8640171 BACKGROUND

• 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.

  PMID: 19167683 BACKGROUND

• 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.

  PMID: 27481448 BACKGROUND

• 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.

  PMID: 27746112 BACKGROUND

• 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.

  PMID: 24061446 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

Biospecimen

Retention: SAMPLES WITH DNA

The genetic variants were determined at the following loci: GSTA1-69C/T (rs3957357); -52G/A(rs3957356); -513A/G (rs11964968); -631T/G (rs4715333); -1142C/G(rs58912740) and GSTP1 313A/G (rs1695). Homozygous deletion of the GSTM1 and GSTT1 genes was also determined.

MeSH Terms

Interventions

Busulfan

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Liyan Miao, PhD

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

• Shaoyan Hu, MD

  Children's Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chenrong Huang, PhD

CONTACT

86-512-67972699; chrishuangcr@163.com

Xiaohuan Du, MS

CONTACT

86-512-80692268; dxhszet@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 8, 2021
• Study Start: November 1, 2020
• Primary Completion: December 1, 2022
• Study Completion: June 1, 2023
• Last Updated: March 10, 2021

Record last verified: 2021-03

Locations

CN (1)