Clinical trial NCT04786002: Target Busulfan Exposure in Children With HSCT in China
Official title: The Therapeutic Window of Busulfan in Children With Haemopoietic Stem Cell Transplantation：A Multicenter Study in China
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hematopoietic Stem Cell Transplantation
Keywords: HSCT
busulfan
PPK
EFS
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Soochow University
name: Children's Hospital of Fudan University
name: Fujian Medical University Union Hospital
name: Guangzhou Women and Children's Medical Center
name: West China Second University Hospital
name: Beijing Children's Hospital
name: Shenzhen Children's Hospital
name: The First Affiliated Hospital of Zhengzhou University
First posted: 2021-03-08
Enrollment: 500
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: event-free survival (EFS)
timeFrame: 2 years after administration of busulfan
measure: overall survival (OS)
timeFrame: 2 years after administration of busulfan
Secondary outcomes:
measure: transplantation-related mortality (TRM)
timeFrame: 2 years after administration of busulfan
measure: acute toxicity
timeFrame: 2 years after administration of busulfan
measure: chronic GvHD
timeFrame: 2 years after administration of busulfan
Other outcomes:
Locations:
city: Suzhou
country: China
facility: the First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Liyan Miao, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Soochow University
name: Shaoyan Hu, MD
role: PRINCIPAL_INVESTIGATOR
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