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

March 5, 2026 updated by: xiatian, The Children's Hospital of Zhejiang University School of Medicine

A Prospective Study of NUDT15/TPMT Multi-gene Combined Guidance on 6-MP Dosage During Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

110

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • The Children's Hospital of Zhejiang University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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.

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Genotype-guided Dosing Group
All participants will receive 6-MP maintenance therapy with dosage adjustments based on their NUDT15 and TPMT genotype status.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative Incidence of Grade 3 or Higher Neutropenia
Time Frame: 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.
From the start of maintenance therapy up to Month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Severe Infection and Febrile Neutropenia (FN)
Time Frame: 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.
Up to 12 months from the start of maintenance therapy
Relative Dose Intensity (RDI) of 6-Mercaptopurine (6-MP)
Time Frame: 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.
Up to 12 months from the start of maintenance therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Children's Hospital of Zhejiang University School of Medicine

Collaborators

Zhejiang University

Investigators

  • Principal Investigator: Tian Xia, MD, Children's Hospital, Zhejiang University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 20, 2026

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

March 2, 2026

First Submitted That Met QC Criteria

March 5, 2026

First Posted (Actual)

March 10, 2026

Study Record Updates

Last Update Posted (Actual)

March 10, 2026

Last Update Submitted That Met QC Criteria

March 5, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-IRB-0015-P-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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