A Pilot Study of Allopurinol as a Modifier of 6-MP Metabolism in Pediatric ALL
Johns Hopkins Kimmel Cancer Center in Baltimore
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).
3.1. Inclusion Criteria / 3.1.1. Currently being treated in the maintenance phase of therapy for pediatric ALL / 3.1.2. Age less than 30 years / 3.1.3. 6-MP at greater than 125% of initial dose for greater than 4 weeks / 3.1.4. ANC persistently greater than 1500/mm3 (as measured by 3 CBCs done over 6 weeks 2 successive monthly CBCs) / 3.1.5. Laboratory evidence of hepatotoxicity as evidenced by one of the following: ALT greater than 200 units/L (5x upper limit of normal) AST greater than 185 units/L (5x upper limit of normal Direct Bilirubin greater than 2.0 mg/dL (5x upper limit of normal) / 3.1.6. Karnofsky/Lansky score greater than 3.2. / 3.2.1. Allergy to allopurinol / 3.2.2. Active relapse of ALL / 3.2.3. Currently enrolled on a Children's Oncology Group therapeutic study
Patients will have a baseline physical examination and baseline laboratory studies performed (week 0) that will include a complete blood cell count(CBC) with differential, comprehensive metabolic panel(CMP), direct bilirubin, thiopurine methyltransferase(TPMT) enzyme activity, and TPMT metabolites (6-TGN and 6-MMP). At this visit, patients will also stop taking their current doses of 6-MP and methotrexate. One week later (week 1), patients will follow up in Pediatric Oncology cilinic and will be prescribed allopurinol once daily (100 mg for weight greater than 30 kg, 50 mg for weight less than 30 kg) and will restart 6-MP and methotrexate at 50percent of the most recent dose. Patients will then return for follow up in Pediatric Oncology clinic for physical examination and laboratory evaluation weekly for 2 visits (weeks 2 and 3), including CBC with differential, CMP, direct bilirubin, TPMT enzyme activity (weeks 3 only), and TPMT metabolites (week 3 only). Patients will then follow up every 2 weeks (weeks 5, 7, and 9)for physical examination and laboratory evaluation (CBC with differential , CMP, and direct bilirubin at a minimum; TPMT metabolites and/or TPMT enzyme activity if clinically indicated). All of the laboratory studies are standard of care for children with ALL according to the current Children's Oncology Group recommendations for the evaluation of patients with high ANC despite high doses of 6-MP.
06/25/2016 05:03 AM