A Pilot Study of Allopurinol As A Modifier of 6-MP Metabolism in Pediatric ALL
Information source: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Lymphoblastic Leukemia (ALL)
Intervention: Allopurinol (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Sidney Kimmel Comprehensive Cancer Center Official(s) and/or principal investigator(s): Colleen Annesley, MD, Principal Investigator, Affiliation: Johns Hopkins University
Overall contact: Colleen Annesley, MD, Phone: 410-502-9960, Email: cannesl1@jhmi.edu
Summary
This research is being done to determine if allopurinol can change the metabolism of the
oral chemotherapeutic medication 6-mercaptopurine (6-MP) in children with acute
lymphoblastic leukemia (ALL). 6-MP is originally started at a standard dose in children with
ALL, but the dose is adjusted according to the absolute neutrophil count (ANC).
Occasionally, 6-MP doses need to be increased in order to get the ANC into a specific target
range. Also, increasing the 6-MP dose can lead to unwanted side effects, such as
inflammation of the liver as shown by increases in laboratory values (ALT, aspartate
aminotransferase (AST), bilirubin), nausea, and abdominal discomfort. Previous studies in
children with inflammatory bowel disease has shown that combining allopurinol with 6-MP can
decrease side effects associated with high doses of 6-MP and also increase the efficacy of
6-MP. Allopurinol is approved by the Food and Drug Administration for the treatment of tumor
lysis syndrome in ALL. Through this research study, we hope to show that the combination of
allopurinol and 6-MP will be safe, tolerable, and effective in children with ALL.
Clinical Details
Official title: A Pilot Study of Allopurinol As A Modifier of 6-MP Metabolism in Pediatric ALL
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Absolute neutrophil count
Secondary outcome: Feasibility of the addition of allopurinol to ALL maintenance therapySafety of the addition of allopurinol to ALL maintenance therapy Effects of allopurinol on liver function tests Alteration of 6-MP metabolism through the addition of allopurinol
Detailed description:
- Patients will have several visits to the Pediatric Oncology outpatient clinic. Each
visit will consist of a physical examination and laboratory evaluation. Each laboratory
evaluation will consist of taking approximately 10 to 15 milliliters of blood (or
approximately three teaspoons). These clinic visits may actually coincide with clinic
visits that were previously scheduled according to the patient's treatment protocol.
- At the first study visit, patients will have a physical examination and laboratory
evaluation. At that visit, patients will be asked to stop taking 6-MP and methotrexate.
- At the second study visit, which is one week later, patients will again have a physical
examination and laboratory evaluation. We will prescribe allopurinol and restart 6-MP
and methotrexate at half of the patient's previous doses.
- Clinic visits for physical examination and laboratory evaluation will be scheduled
every 1-2 weeks for a total of 5 more visits. Doses of allopurinol, 6-MP, and
methotrexate may be adjusted at these visits based on laboratory values or clinical
symptoms.
Eligibility
Minimum age: N/A.
Maximum age: 30 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Currently being treated in the maintenance phase of therapy for pediatric ALL
- Age ≤30 years
- 6-MP at ≥125% of initial dose for ≥4 weeks
- ANC persistently ≥1500/mm3 (as measured by 3 complete blood cell counts (CBCs) done
over 6 weeks or 2 successive monthly CBCs)
- Laboratory evidence of hepatotoxicity as evidenced by one of the following: ALT ≥200
units/L (5x upper limit of normal), AST ≥185 units/L (5x upper limit of normal),
direct bilirubin ≥2. 0 mg/dL (5x upper limit of normal)
Exclusion Criteria:
- Allergy to allopurinol
- Active relapse of ALL
- Currently enrolled on any therapeutic research study for the treatment of ALL
Locations and Contacts
Colleen Annesley, MD, Phone: 410-502-9960, Email: cannesl1@jhmi.edu
Johns Hopkins Hospital, Baltimore, Maryland 21287, United States; Recruiting Colleen Annesley, MD, Principal Investigator Patrick A Brown, MD, Sub-Investigator
Additional Information
Starting date: January 2014
Last updated: March 31, 2015
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