Acute Lymphoblastic Leukemia, Pediatric
Conditions
Keywords
acute lymphoblastic leukemia, 6-mercaptopurine, children, individualized treatment
Brief summary
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
To inflict minimal pain on the child contributing blood samples, opportunistic sampling design was chosen to collect pharmacokinetic samples.
Interventions
DRUG6-mercaptopurine
6-mercaptopurine was administered orally to patients once daily.
PROCEDUREStandard treatment
The initial dose is 50mg/m2. The dose was adjusted according to white blood cells.
PROCEDUREIndividualized treatment
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.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Qianfoshan Hospital
Qilu Hospital of Shandong University
Children's Hospital of Hebei Province
The Affiliated Hospital of Qingdao University
Wei Zhao
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of acute lymphoblastic leukemia; 2. Age 1-18y at time of initial diagnosis; 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 4. Informed consent signed by the patients parents or guardians before initiation of the study.
Exclusion criteria
1. Ph-positive ALL, matrue B-cell ALL, BC-CML; 2. Secondary to immunodeficiency, second cancer； 3. Abnormal liver and kidney function; 4. Patients divided into intermediate or high risk groups according to the risk grouping criteria of the Chinese Children Cancer Group (CCCG) protocol-ALL 2015; 5. Patients who enrolled in another clinical trial; 6. Expected survival time less than the treatment cycle; 7. Patients with other factors that researcher considers unsuitable for inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| leukopenia | 6 weeks | Leukopenia was graded by common toxicity criteria as follows: Grade 3, 1.0-2.0 × 109/L, and Grade 4, \< 1.0 × 109/L. |
| thiopurine-induced leukopenia | 6-weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| hepatotoxicity | 6 weeks | Hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine transaminase (ALT) levels 2-fold above the upper limit without cytolysis. |
| 6-thioguanine nucleotides (6-TGN) concentrations in erythrocytes. | 3 months | Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design. |
| 6-methylmercaptopurine nucleotides (6-MMPN) concentrations in erythrocytes. | 3 months | Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design. |
Countries
China
Contacts
Primary ContactWei Zhao, Ph.D
Backup ContactYan H Shi, Ph.D
Outcome results
None listed