Pharmacogenomic Analysis in Pediatric Acute Lymphoblastic Leukemia

NCT04770922 | Completed

• 1 other identifier: C04-001
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a retrospective biobank study evaluating the impact of novel genetic variants in a population of 6-mercaptopurine treated pediatric acute lymphoblastic leukemia patients.

Conditions

Acute Lymphoblastic Leukemia, Pediatric; Adverse Drug Event

Keywords

adverse drug event; acute lymphoblastic leukemia; mercaptopurine; pharmacogenomics

Outcome Measures

Primary Outcomes (1)

• Novel genetic variants impact on 6-mercaptopurine adverse drug reactions

  Objective is to clinically validate the presence of novel genetic variants and its impact on adverse drug reactions in a population of pediatric ALL patients treated with 6-MP

  1 year

Secondary Outcomes (1)

• Evaluating relationship of genetic variants to ancestry

  1 year

Study Arms (2)

Pediatric ALL patients on 6-mercaptopurine

Pediatric ALL patients treated with 6-mercaptopurine who did not experience neutropenia.

Pediatric ALL patients on 6-mercaptopurine with neutropenia

Pediatric ALL patients treated with 6-mercaptopurine who experienced neutropenia.

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study population are pediatric patients, under 21 years of age, diagnosed with acute lymphoblastic leukemia patients between April 20, 2012 to August 6, 2020, and received 6-mercaptopurine for therapeutic purposes. All patients were recruited by the investigators at Stanford University Lucile Packard Children's Hospital.

You may qualify if:

• Pediatric acute lymphoblastic leukemia (ALL) subjects
• Received 6-mercaptopurine
• Available biobank (bone marrow or blood) sample(s) from which deoxyribonucleic acid (DNA) can be extracted
• White blood cell (WBC) levels

You may not qualify if:

• Pediatric ALL subjects who did NOT receive 6-mercaptopurine
• No biobank sample
• No WBC level

Sponsors & Collaborators

• Cipherome, Inc.: lead
• Stanford University: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94304, United States

Location

Related Publications (5)

• Bhatia S, Landier W, Hageman L, Chen Y, Kim H, Sun CL, Kornegay N, Evans WE, Angiolillo AL, Bostrom B, Casillas J, Lew G, Maloney KW, Mascarenhas L, Ritchey AK, Termuhlen AM, Carroll WL, Wong FL, Relling MV. Systemic Exposure to Thiopurines and Risk of Relapse in Children With Acute Lymphoblastic Leukemia: A Children's Oncology Group Study. JAMA Oncol. 2015 Jun;1(3):287-95. doi: 10.1001/jamaoncol.2015.0245.

  PMID: 26181173 BACKGROUND

• Park Y, Kim H, Choi JY, Yun S, Min BJ, Seo ME, Im HJ, Kang HJ, Kim JH. Star Allele-Based Haplotyping versus Gene-Wise Variant Burden Scoring for Predicting 6-Mercaptopurine Intolerance in Pediatric Acute Lymphoblastic Leukemia Patients. Front Pharmacol. 2019 Jun 11;10:654. doi: 10.3389/fphar.2019.00654. eCollection 2019.

  PMID: 31244663 BACKGROUND

• Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011 Mar;89(3):387-91. doi: 10.1038/clpt.2010.320. Epub 2011 Jan 26.

  PMID: 21270794 RESULT

• Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay N, Wong FL, Evans WE, Pui CH, Bhatia S, Relling MV. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol. 2015 Apr 10;33(11):1235-42. doi: 10.1200/JCO.2014.59.4671. Epub 2015 Jan 26.

  PMID: 25624441 RESULT

• Lennard L. Implementation of TPMT testing. Br J Clin Pharmacol. 2014 Apr;77(4):704-14. doi: 10.1111/bcp.12226.

  PMID: 23962279 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Observational study of previously collected biobank specimens

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chemically-Induced Disorders

Study Officials

• Kathleen M Sakamoto, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Stephanie M Smith, MD

  Stanford University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 25, 2021
• Study Start: February 23, 2021
• Primary Completion: August 30, 2021
• Study Completion: November 10, 2021
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

US (1)