Pharmacogenomics of Asparaginase Induced Hepatotoxicity

Pharmacogenomics of Age-Specific, Asparaginase-Induced Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia

This pilot trial studies the impact of genetic information on developing liver damage caused by asparaginase in participants with newly diagnosed acute lymphoblastic leukemia. Testing saliva samples may help doctors find certain genetic markers that may predict whether participants will tolerate asparaginase, which is given as part of clinical care for acute lymphoblastic leukemia.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Procedure: Biospecimen Collection

Detailed Description

PRIMARY OBJECTIVES:

I. To establish the association between the SOD2 rs4880 genotypes and asparaginase-induced hepatotoxicity in Hispanic patients.

II. To identify novel single nucleotide polymorphisms (SNPs) that are associated with asparaginase induced hepatotoxicity.

OUTLINE:

Participants' SOD2 rs4880 SNP genotype (based on saliva from buccal swabs) will be classified. Participants with the CC genotype will be compared to participants with the CT or TT genotype. Buccal swabs of prospective participants' saliva will be collected when participant achieves complete remission (during regular clinical visit). Retrospective participants will be identified through search of pharmacy records for those who received asparaginase within the last 5 years (2012-2017). Recurrent patients will be consented during their regular clinical visits and samples will be collected.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Christine Duran; Phone Number: 323-865-0371; Email: duran_c@med.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC / Norris Comprehensive Cancer Center
      • Contact: Houda Alachkar, PhD; Phone Number: 323-442-2696; Email: alachkar@usc.edu
      • Principal Investigator: Houda Alachkar, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed with Acute Lymphoblastic Leukemia (ALL) who are seen at USC facilities will be recruited.

Description

Inclusion Criteria:

• Newly diagnosed with acute lymphoblastic leukemia (ALL) - no prior treatment for ALL
• Receiving asparaginase as part of the primary treatment regimen
• Ability to understand and the willingness to sign a written informed consent
• For retrospective recruitment, those who have received asparaginase between 2012 and 2017; and are current patients of University of Southern California (USC)

Exclusion Criteria:

• Patients who are unable to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Biospecimen Collection; Buccal swabs of prospective participants' saliva will be collected when participant achieves complete remission (during regular clinical visit) from their asparaginase treatment.	Procedure: Biospecimen Collection; Undergo collection of saliva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatotoxicity following treatment with asparaginase	Hepatotoxicity per Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) and defined as > or = grade 3 of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT), or > or = grade 3 bilirubin elevation.	Up to 6 months

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Houda Alachkar, Ph.D., University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2018
• Primary Completion (Estimated): May 22, 2025
• Study Completion (Estimated): May 22, 2026

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

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; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: 9L-17-16 (Other Identifier: USC / Norris Comprehensive Cancer Center); P30CA014089 (U.S. NIH Grant/Contract); NCI-2018-00813 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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