The Individualized Treatment of 6-mercaptopurine in Children With Acute Lymphoblastic Leukemia in China

Study Overview
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Brief Summary
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The purpose of this study was to assess the efficacy and safety of individualized treatment of 6-mercaptopurine (6-MP) in Chinese children with acute lymphoblastic leukemia, and to investigate the dose-concentration-response (DER) relationship between thiopurine metabolites and adverse events. The individualized administration of 6-MP was established in Chinese children with acute lymphoblastic leukemia.

Detailed Description
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To inflict minimal pain on the child contributing blood samples, opportunistic sampling design was chosen to collect pharmacokinetic samples.

Official Title
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The Individualized Treatment of 6-mercaptopurine in Children With Acute Lymphoblastic Leukemia in China

Conditions
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Acute Lymphoblastic Leukemia, Pediatric

Intervention / Treatment
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* Drug: 6-mercaptopurine
* Procedure: Standard treatment
* Procedure: Individualized treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of acute lymphoblastic leukemia; Age 1-18y at time of initial diagnosis; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Informed consent signed by the patients parents or guardians before initiation of the study. Exclusion Criteria: Ph-positive ALL, matrue B-cell ALL, BC-CML; Secondary to immunodeficiency, second cancer； Abnormal liver and kidney function; Patients divided into intermediate or high risk groups according to the risk grouping criteria of the Chinese Children Cancer Group (CCCG) protocol-ALL 2015; Patients who enrolled in another clinical trial; Expected survival time less than the treatment cycle; Patients with other factors that researcher considers unsuitable for inclusion

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard treatment regimen<br>6-mercaptopurine was administered according to the Chinese Children Cancer Group (CCCG) protocol-ALL 2015. | Drug: 6-mercaptopurine<br>* 6-mercaptopurine was administered orally to patients once daily.<br>* Other names: 6-MP;Procedure: Standard treatment<br>* The initial dose is 50mg/m2. The dose was adjusted according to white blood cells.<br>|
| Experimental: Individualized treatment regimen<br>6-mercaptopurine was administered on the basis of Chinese Children Cancer Group (CCCG) protocol-ALL 2015 combined with Clinical Pharmacogenetics Implementation Consortium (CPIC), genotypes and the concentrations of 6-TGN in red blood cells. | Drug: 6-mercaptopurine<br>* 6-mercaptopurine was administered orally to patients once daily.<br>* Other names: 6-MP;Procedure: Individualized treatment<br>* The initial dose is determined according to the genotypes of patients combined with Clinical Pharmacogenetics Implementation Consortium (CPIC). The dose was adjusted according to white blood cells, genotypes and the concentrations of 6-TGN in red blood cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| leukopenia | Leukopenia was graded by common toxicity criteria as follows: Grade 3, 1.0-2.0 × 109/L, and Grade 4, < 1.0 × 109/L. | 6 weeks | 
| thiopurine-induced leukopenia | Resolution of leukopenia was determined after 6-MP dose reduction or discontinuation, both in the absence of other apparent causes for the leukopenia or its disappearance. | 6-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hepatotoxicity | Hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine transaminase (ALT) levels 2-fold above the upper limit without cytolysis. | 6 weeks | 
| 6-thioguanine nucleotides (6-TGN) concentrations in erythrocytes. | Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design. | 3 months | 
| 6-methylmercaptopurine nucleotides (6-MMPN) concentrations in erythrocytes. | Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lymphoblastic leukemia, 6-mercaptopurine, children, individualized treatment