Childhood Acute Lymphoblastic Leukemia
Conditions
Keywords
NUDT15, TPMT, 6-MP, Pharmacogenetics, Maintenance Therapy
Brief summary
This is a prospective, single-center clinical study to evaluate the safety and efficacy of a personalized 6-mercaptopurine (6-MP) dosing strategy guided by NUDT15 and TPMT genotypes in children with Acute Lymphoblastic Leukemia (ALL) during maintenance therapy. The study compares this gene-guided strategy with historical controls to assess if it reduces the incidence of Grade ≥3 neutropenia and infection events.
Interventions
DRUGNUDT15/TPMT genotype-guided 6-MP dosing
Initial dosage of 6-Mercaptopurine (6-MP) is stratified based on NUDT15 and TPMT genotypes: Normal metabolizers: 100% standard dose (50-75 mg/m\^2/d). Intermediate metabolizers: 30-80% of the recommended dose. Poor metabolizers: 10-30% of the recommended dose. Subsequent dosage adjustments are made based on toxicity monitoring and therapeutic drug monitoring (TDM) of 6-TGN and 6-MMP levels.
Sponsors
The Children's Hospital of Zhejiang University School of Medicine
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Diagnosed with ALL and scheduled for maintenance therapy. Plan to receive oral 6-MP. NUDT15 and TPMT genotyping results available. Baseline liver and kidney function within acceptable limits (ALT/AST ≤ 2.5xULN, etc.). Signed informed consent. -
Exclusion criteria
Down syndrome. Relapsed/refractory disease before maintenance. Prior hematopoietic stem cell transplantation. Severe organ dysfunction or uncontrolled infection. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Grade 3 or Higher Neutropenia | From the start of maintenance therapy up to Month 12 | Defined according to NCI CTCAE v5.0 criteria. Grade ≥3 neutropenia is defined as an Absolute Neutrophil Count (ANC) \< 1000/mm³. The measure reports the percentage of participants who experience at least one episode of Grade ≥3 neutropenia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Severe Infection and Febrile Neutropenia (FN) | Up to 12 months from the start of maintenance therapy | The percentage of participants experiencing Grade 3 or higher infections (assessed per NCI CTCAE v5.0) or FN events. FN is defined as a single oral temperature ≥38.3°C or ≥38.0°C sustained for more than 1 hour, combined with an ANC \< 500/mm³. |
| Relative Dose Intensity (RDI) of 6-Mercaptopurine (6-MP) | Up to 12 months from the start of maintenance therapy | RDI is calculated as the ratio of the actual cumulative dose of 6-MP received by the participant to the recommended cumulative dose based on the standard protocol (calculated by body surface area). The result is reported as a percentage. |
Countries
China
Contacts
CONTACTtian xia, MD
PRINCIPAL_INVESTIGATORTian Xia, MD
Children's Hospital, Zhejiang University School of Medicine
Outcome results
None listed