Determinants of Mercaptopurine Toxicity in Paediatric Acute Lymphoblastic Leukemia Maintenance Therapy

Determinants of Mercaptopurine Toxicity in Paediatric Acute Lymphoblastic

The present study was conducted to assess the population pharmacokinetics of 6-mercaptopurine (6-MP) in Pediatric Acute Lymphoblastic Leukemia (ALL) and genetic polymorphisms

Study Overview

• Status: Unknown
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Mercaptopurine

Detailed Description

The investigators' purpose was to identify genetic factors and metabolite concentrations associated with both hematological toxicity in patients with ALL maintained on 6-MP in Chinese.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients have been diagnosed with Acute Lymphoblastic Leukemia
• Childhood patients who were undergoing chemotherapy or continuous follow-up after completion of chemotherapy
• Patients received the phase of maintenance therapy that included oral 6-MP (>4 weeks) and completion of ≥ 6 months according to the CCLG (Chinese Children's Leukemia Group) protocol-ALL 2015

Exclusion Criteria:

• Patients with high-risk ALL (presence of higher-risk features: MRD ≥ 1% at 46 day, or age < 6 month and white blood cell (WBC) count ≥ 300×109/L with translocations t(9;22) (q34;q11) [BCR-ABL], t(4;11) (q21;q23) [AF4/MLL], t(1;19) (q23;p13) [E2A-PBX1] or other MLL-rearrangements) were removed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antitumor drugs; Mercaptopurine administered at standard dose for children with hematological neoplasms.	Drug: Mercaptopurine; Dose of mercaptopurine was adjusted to maintain a target white blood cells (WBC) between 2.0-3.0 × 109/L.; Other Names: Purinethol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red blood cells (RBC) concentration of 6-mercaptopurine (6-MP)	To detect of RBC 6-MP metabolite concentrations and evaluate the association of metabolite concentrations and side effects	at second day after oral administration
Genetic polymorphisms in Chinese patients with ALL	To detect the frequencies of genetic polymorphisms of Chinese patients receiving 6-MP for treatment of ALL	at second day after oral administration

Collaborators and Investigators

• Sponsor: Shandong University
• Investigators: Principal Investigator: Wei Zhao, Ph.D, Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 19, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Mercaptopurine
• Other Study ID Numbers: 2018Mercaptopurine001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No