Study to Examine Outcomes Disparities in Pediatric ALL

BETHESDA, Maryland—Investigators affiliated with the Children's Oncology Group (COG) have launched a multicenter trial aimed at determining why the relapse and survival rates of children with acute lymphoblastic leukemia (ALL) differ among the major racial and ethnic groups living in the United States.

Researchers plan to monitor the disease biology, drug metabolism, and compliance to long-term medication dosing of 720 relapsed ALL patients in hopes of finding clues to the rate disparities. They expect to accrue patients at 107 sites, 99 of which are in the United States, 7 in Canada, and 1 in Australia.

ALL is the most common childhood cancer in the United States, and although once considered universally fatal, it is now curable in approximately 80% of pediatric patients. Children of various racial and ethnic backgrounds have similar remission rates following initial treatment. However, they have different relapse and survival rates. Asian children have the highest survival rate, followed by Caucasians, Hispanics, and African Americans.

"It is very important to understand why these differences exist, so we can initiate interventions to mitigate these differences," said Smita Bhatia, MD, MPH, protocol chair for the trial and director of epidemiology and outcomes research, City of Hope Comprehensive Cancer Center. "If effective interventions can be developed, survival for Hispanic and African-American children could potentially improve by 10% to 15%."

The National Cancer Institute (NCI) will fund most of the costs of the trial, called the Study of Adherence to Long-Term Maintenance Mercaptopurine Therapy in Young Patients with Acute Lymphoblastic Leukemia in First Remission (COG-AALL03N1). The COG study has seven primary objectives. The first is to determine adherence to maintenance mercaptopurine and compare it among the four ethnic/racial groups using a series of assessments. The assessments include serial red cell measurements of the mercaptopurine metabolites 6TGN and methylTIMP, the frequency of mercaptopurine dosing using an electronic pill monitoring system, and self-reported questionnaires filled out by a cohort of younger ALL patients from the four ethnic and racial groups.

The other six objectives seek to determine the impact of adherence to mercaptopurine on event-free survival in the entire cohort, after adjusting for known predictors of disease outcome; define a critical level of adherence that has a significant impact on event-free survival in the entire cohort; assess the prevalence of adherence to the drug by ethnicity; describe behavioral and sociodemographic predictors of adherence; describe the pill-taking practices of the cohort; and evaluate the impact of adherence on ethnic/racial differences in event-free survival. The study's single secondary objective is to assess concordance among 6TGN and methylTIMP levels, electronic pill monitoring, and self-reported adherence in the various ethnic/racial groups.

An electronic pill monitoring system—the Medication Event Monitoring System (MEMS)—serves as a key to determining patient adherence. The system's TrackCap child-resistant (CR) bottle cap records whenever the pill bottle is opened.

Because racial/ethnic differences in drug metabolism may contribute to the dissimilar remission and survival rates, researchers will collect frequent blood samples. Patients or caregivers will complete a demographic questionnaire on day 29, and complete a self-reported adherence questionnaire on days 29, 57, 113, and 141. Patients will be followed periodically after completion of the study.

Eligible Patients

Dr. Bhatia and her colleagues seek to enroll patients who were age 21 years or younger at the time of their diagnosis who are in their first remission and undergoing long-term maintenance therapy for ALL. Participants must belong to one of four ethnic/racial categories, African American, Asian, Caucasian, or Hispanic. Eligible patients must be receiving self- or parent/caregiver-administered oral antimetabolite chemotherapy during the maintenance phase of therapy, have completed at least two courses of maintenance therapy, and be scheduled to receive at least two or more courses.