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Acute Lymphoblastic Leukemia (ALL) | A Pilot Study of Allopurinol As A Modifier of 6-MP Metabolism in Pediatric ALL

Acute Lymphoblastic Leukemia (ALL) research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Acute Lymphoblastic Leukemia (ALL)

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:AllopurinolAt week 1, patients will begin allopurinol daily (100 mg for weight >30 kg, 50 mg for weight ≤30 kg) and will restart 6-MP and methotrexate at 50 percent of the most recent dose. Patients will continue taking allopurinol in combination with 6-MP and methotrexate for the duration of the study (total of 8 weeks).

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

AllopurinolPatients will stop taking their 6-MP and methotrexate at week 0. One week later (week 1), patients will begin allopurinol daily (100 mg for weight >30 kg, 50 mg for weight ≤30 kg) and will restart 6-MP and methotrexate at 50 percent of the most recent dose. Patients will continue taking allopurinol in combination with 6-MP and methotrexate for the duration of the study (total of 8 weeks). Dose adjustments of 6-MP and methotrexate will be directed by the guidelines outlined in the study protocol.

Study Status

Recruiting

Start Date: January 2014

Completed Date: September 2021

Phase: Early Phase 1

Type: Interventional

Design:

Primary Outcome: Absolute neutrophil count

Secondary Outcome: Feasibility of the addition of allopurinol to ALL maintenance therapy

Study sponsors, principal investigator, and references

Principal Investigator: Stacy Cooper, MD

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborator:

More information:https://clinicaltrials.gov/show/NCT02046694

Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006 Jan 12;354(2):166-78. Review.

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