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

Sponsor

Wei Zhao (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04228393

Collaborator

Institute of Hematology & Blood Diseases Hospital (Other), Qianfoshan Hospital (Other), Qilu Hospital of Shandong University (Other), Children's Hospital of Hebei Province (Other), The Affiliated Hospital of Qingdao University (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia, Pediatric	Drug: 6-mercaptopurine Procedure: Standard treatment Procedure: Individualized treatment	Phase 2/Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

82 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 1, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard treatment regimen 6-mercaptopurine was administered according to the Chinese Children Cancer Group (CCCG) protocol-ALL 2015.	Drug: 6-mercaptopurine 6-mercaptopurine was administered orally to patients once daily. Other Names: 6-MP Procedure: Standard treatment The initial dose is 50mg/m2. The dose was adjusted according to white blood cells.
Experimental: Individualized treatment regimen 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 6-mercaptopurine was administered orally to patients once daily. Other Names: 6-MP Procedure: 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.

Arm

Intervention/Treatment

Active Comparator: Standard treatment regimen

6-mercaptopurine was administered according to the Chinese Children Cancer Group (CCCG) protocol-ALL 2015.

Drug: 6-mercaptopurine

6-mercaptopurine was administered orally to patients once daily.

Other Names:

6-MP

Procedure: Standard treatment

The initial dose is 50mg/m2. The dose was adjusted according to white blood cells.

Experimental: Individualized treatment regimen

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

6-mercaptopurine was administered orally to patients once daily.

Other Names:

6-MP

Procedure: 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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	China	300020