Clinical trial NCT04770922: Pharmacogenomic Analysis in Pediatric Acute Lymphoblastic Leukemia
Official title: Pharmacogenomic Analysis of 6-mercaptopurine in Pediatric Acute Lymphoblastic Leukemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Lymphoblastic Leukemia, Pediatric
Adverse Drug Event
Keywords: adverse drug event
acute lymphoblastic leukemia
mercaptopurine
pharmacogenomics
Lead sponsor: Cipherome, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Stanford University
First posted: 2021-02-25
Enrollment: 80
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

Detailed description: The study objective is to clinically validate that the presence of recently discovered novel genetic variation adversely affects a population of 6-mercaptopurine treated pediatric acute lymphoblastic leukemia patients using biobank samples.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: Novel genetic variants impact on 6-mercaptopurine adverse drug reactions
timeFrame: 1 year
Secondary outcomes:
measure: Evaluating relationship of genetic variants to ancestry
timeFrame: 1 year
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Kathleen M Sakamoto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Stephanie M Smith, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Lennard L. Implementation of TPMT testing. Br J Clin Pharmacol. 2014 Apr;77(4):704-14. doi: 10.1111/bcp.12226.