Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Zhejiang University | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Genotype-guided Dosing Group | Experimental | All participants will receive 6-MP maintenance therapy with dosage adjustments based on their NUDT15 and TPMT genotype status. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NUDT15/TPMT genotype-guided 6-MP dosing | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Incidence of Grade 3 or Higher Neutropenia | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Severe Infection and Febrile Neutropenia (FN) | 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 |
Not provided
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.
-
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| tian xia, MD | Contact | +86 15267035696 | xiatiansky2013@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Tian Xia, MD | The Children's Hospital of Zhejiang University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital of Zhejiang University School of Medicine | Hangzhou | Zhejiang | China |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Relative Dose Intensity (RDI) of 6-Mercaptopurine (6-MP) | 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 |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |