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

Primary Purpose

Acute Lymphoblastic Leukemia, Pediatric

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
6-mercaptopurine
Standard treatment
Individualized treatment
Sponsored by
Wei Zhao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia, Pediatric focused on measuring acute lymphoblastic leukemia, 6-mercaptopurine, children, individualized treatment

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • 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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard treatment regimen

Individualized treatment regimen

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

hepatotoxicity
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.
Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design.
6-methylmercaptopurine nucleotides (6-MMPN) concentrations in erythrocytes.
Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design.

Full Information

First Posted
January 9, 2020
Last Updated
January 10, 2020
Sponsor
Wei Zhao
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT04228393
Brief Title
The Individualized Treatment of 6-mercaptopurine in Children With Acute Lymphoblastic Leukemia in China
Official Title
The Individualized Treatment of 6-mercaptopurine in Children With Acute Lymphoblastic Leukemia in China
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2020 (Anticipated)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Wei Zhao
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
Detailed Description
To inflict minimal pain on the child contributing blood samples, opportunistic sampling design was chosen to collect pharmacokinetic samples.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Pediatric
Keywords
acute lymphoblastic leukemia, 6-mercaptopurine, children, individualized treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard treatment regimen
Arm Type
Active Comparator
Arm Description
6-mercaptopurine was administered according to the Chinese Children Cancer Group (CCCG) protocol-ALL 2015.
Arm Title
Individualized treatment regimen
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
6-mercaptopurine
Other Intervention Name(s)
6-MP
Intervention Description
6-mercaptopurine was administered orally to patients once daily.
Intervention Type
Procedure
Intervention Name(s)
Standard treatment
Intervention Description
The initial dose is 50mg/m2. The dose was adjusted according to white blood cells.
Intervention Type
Procedure
Intervention Name(s)
Individualized treatment
Intervention Description
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.
Primary Outcome Measure Information:
Title
leukopenia
Description
Leukopenia was graded by common toxicity criteria as follows: Grade 3, 1.0-2.0 × 109/L, and Grade 4, < 1.0 × 109/L.
Time Frame
6 weeks
Title
thiopurine-induced leukopenia
Description
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.
Time Frame
6-weeks
Secondary Outcome Measure Information:
Title
hepatotoxicity
Description
Hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine transaminase (ALT) levels 2-fold above the upper limit without cytolysis.
Time Frame
6 weeks
Title
6-thioguanine nucleotides (6-TGN) concentrations in erythrocytes.
Description
Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design.
Time Frame
3 months
Title
6-methylmercaptopurine nucleotides (6-MMPN) concentrations in erythrocytes.
Description
Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Zhao, Ph.D
Phone
86053188383308
Email
zhao4wei2@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yan H Shi, Ph.D
Phone
86053188383308
Email
zhao4wei2@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Zhao, Ph.D
Organizational Affiliation
Shandong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
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
City
Tanjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China

12. IPD Sharing Statement

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

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