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

Acute Lymphoblastic Leukemia, Pediatric Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04228393
• Other study ID #: 2020-6-mercaptopurine-001
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: February 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: January 2020
• Source: Shandong University
• Contact: Wei Zhao, Ph.D
• Phone: 86053188383308
• Email: zhao4wei2[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 82
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia, Pediatric
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• 6-mercaptopurine
6-mercaptopurine was administered orally to patients once daily.

Procedure:
• Standard treatment
The initial dose is 50mg/m2. The dose was adjusted according to white blood cells.
• Individualized 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.

Locations

Country	Name	City	State
China	State Key Laboratory of Experimental Haematology, Department of Paediatric Haematology, Institute of Haematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College	Tanjin	Tianjin

Sponsors (6)

Lead Sponsor	Collaborator
Wei Zhao	Children's Hospital of Hebei Province, Institute of Hematology & Blood Diseases Hospital, Qianfoshan Hospital, Qilu Hospital of Shandong University, The Affiliated Hospital of Qingdao University

Country where clinical trial is conducted

China, 

Outcome

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