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

Status:	Recruiting
Conditions:	Blood Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	Any - 30
Updated:	9/13/2018
Start Date:	January 2014
End Date:	September 2021
Contact:	Stacy Cooper, MD
Email:	scoope30@jhmi.edu
Phone:	410-614-5055

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.

- 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. The investigators 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.

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

We found this trial at

sites

Johns Hopkins Hospital

1800 Orleans St.
Baltimore, Maryland 21287

410-955-5000