A Pilot Study of Allopurinol As A Modifier of 6-MP Metabolism in Pediatric ALL

• Status: Completed
• Trial end date: 2020-04-06
• Target enrollment: 0
• Participant gender: All

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, the investigators hope to show that the combination of allopurinol and 6-MP will be safe, tolerable, and effective in children with ALL.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Treatments: Allopurinol; Methotrexate

Criteria

Inclusion Criteria:

• Currently being treated in the maintenance phase of therapy for pediatric ALL

• Age ≤30 years

• 6-MMP:6-TGN ratio ≥40 within 21 days prior to enrollment

• 6-MMP ≥12,000/8x108 red blood cells (RBC) within 21 days prior to enrollment

• One of the following within 21 days prior to enrollment:

1. ANC persistently ≥1500/mm3 (as measured by 3 CBCs done over 6 weeks or 2 successive monthly complete blood counts (CBCs) despite 6-MP ≥150% of Children's oncology group (COG) dosing OR

2. Evidence of ≥ Grade 3 hepatotoxicity with one of the following:

ALT ≥5x upper limit of normal (based on institutional standards) AST ≥5x upper limit of normal (based on institutional standards) Direct bilirubin ≥5x upper limit of normal (based on institutional standards) OR

3. Evidence of ≥ Grade 2 gastrointestinal toxicity (including, but not limited to:

nausea, vomiting, anorexia, gastrointestinal pain)

Exclusion Criteria:

• Allergy to allopurinol

• Active relapse of ALL or lymphoblastic lymphoma

• Currently enrolled on any therapeutic research study for the treatment of ALL or lymphoblastic lymphoma

• Known history of chronic liver disease (other than Gilbert's syndrome)

• Pregnant or breastfeeding females