NUDT15/TPMT Multi-gene Guided 6-MP Dosing in Childhood ALL Maintenance Therapy

Condition(s) studied

Investigational drug(s) / intervention(s)

NUDT15/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.

Study 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.

Eligibility

Primary outcome measure(s)

• 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.

Trial sites (1)

More The Children's Hospital of Zhejiang University School of Medicine trials in China