Study to Assess Compliance With Long-Term Mercaptopurine Treatment in Young Patients With Acute Lymphoblastic Leukemia in Remission

PRIMARY OBJECTIVES:

I. To determine and compare adherence to maintenance mercaptopurine (6-MP) in a cohort of
children with acute lymphoblastic leukemia (ALL) from four different ethnic and racial groups
(Caucasians, African-Americans, Hispanics, and Asians) receiving maintenance/continuation
chemotherapy, using the following assessments: serial red cell 6-MP metabolites
(6-thioguanine [6TGN] and methyl thioinosine monophosphate [TIMP]); frequency of 6-MP dosing
using an electronic pill monitoring system (Microelectromechanical Systems [MEMS]?);
self-report of adherence to 6-MP by questionnaire.

II. To determine the impact of adherence to 6-MP (measured using 6TGN, methyl [Me]TIMP, MEMS?
and self-report data independently) on event-free-survival (EFS) in the entire cohort, after
adjusting for known predictors of disease outcome.

III. Define a critical level of adherence (measured independently by 6TGN, MeTIMP, MEMS?,
self-report) that has a significant impact on EFS for the entire cohort.

IV. Describe prevalence of adherence to 6-MP by ethnicity (6TGN, MeTIMP, MEMS?, Self-report).

V. Describe behavioral and socio-demographic predictors of adherence using the questionnaire
data.

VI. Describe the pill-taking practices in this cohort using the MEMS? data. VII. To evaluate
the impact of adherence on ethnic/racial difference in EFS.

SECONDARY OBJECTIVES:

I. To assess the concordance among 6TGN and MeTIMP levels, electronic pill monitoring, and
self-reported adherence in the ethnic/racial groups.

OUTLINE:

Patients receive an electronic pill monitoring system comprising an empty MEMS? medication
bottle with TrackCap? child resistant (CR). The mercaptopurine prescription is filled using
this system. Beginning on day 1 of the third or later course of maintenance therapy, patients
take all doses of mercaptopurine from the MEMS? medication bottle with TrackCap? CR for at
least 169 days. The MEMS? TrackCap? CR is mailed to the Coordinating Center at the end of
study. Patients also receive methotrexate orally (PO) as indicated by their individual
chemotherapy regimen.

NOTE: *Study closed to accrual for Caucasian and Hispanic patients as of 8/14/2009.

After completion of study, patients are followed up every 6 months for 5 years and then
annually for up to 10 years.

Inclusion Criteria:

- Diagnosis of ALL in first remission, irrespective of risk stratification; enrollment
on a Children's Oncology Group (COG) therapeutic study for ALL is not required, but
the treatment plan must meet the criteria in this protocol

- Belongs to one of the four following ethnic/racial categories: African-American,
Asian, Caucasian, or Hispanic; below please find definitions for these categories

- African-American: includes patients who are African-American or of sub-Saharan
black African ancestry

- Asian: patients of Asian ancestry, including the following: Asian Indian
(subcontinent), Chinese, Japanese, Korean, Native Hawaiian, Guamanian or
Chamorro, Pacific Islander, Filipino, Vietnamese, Samoan, Hmong, Cambodian, Thai,
Laotian, or Other Asian races

- Caucasian: includes White or light-skinned patients of European, North African,
or Middle Eastern ancestry

- Hispanic: patients of Hispanic ethnicity, including the following: Mexican,
Mexican American, Chicano, Cuban, Puerto Rican, or Other Spanish/Hispanic/Latino
ethnicity

- Receiving self- or parent/caregiver-administered oral anti-metabolite chemotherapy
during the maintenance/continuation phase of therapy; patients are eligible if their
treatment plan calls for the following doses of 6-MP and methotrexate (MTX) during the
maintenance/continuation phase: 6-MP ? 75 mg/m^2/day orally; MTX 20 mg/m^2/week
orally;** (modification of 6-MP or MTX dosing based on laboratory or clinical
parameters is acceptable)

- For guidance regarding if and when a patient being treated on or according to a
specific COG (or legacy group) protocol is eligible, please refer to ?AALL03N1
Eligibility by Protocol Tool,? available in the study data forms packet on the
COG website

- Has completed at least 24 weeks of maintenance/continuation chemotherapy, and is
scheduled to receive at least 24 more weeks of maintenance/continuation chemotherapy**

- For guidance regarding if and when a patient being treated on or according to a
specific COG (or legacy group) protocol is eligible, please refer to ?AALL03N1
Eligibility by Protocol Tool,? available in the study data forms packet on the
COG website

- Written informed consent from the patient and/or the patient?s legally authorized
guardian, obtained prior to registration and any study-related procedures, and in
accordance with institutional policies approved by the United States (U.S) Department
of Health and Human Services

Exclusion Criteria:

- Patients of multi-ethnic/multi-racial backgrounds are not eligible for this study;
while patients of multi-ethnic/multi-racial ancestry (e.g., Caucasian/Japanese,
Hawaiian/Puerto Rican) are not eligible, patients of mixed ancestry within a
race/ethnicity (e.g., Japanese/Chinese = Asian or Korean/Japanese/Hawaiian = Asian or
Mexican/Puerto Rican = Hispanic) may participate as long as they fall under the
general classification of "African-American," "Asian," "Caucasian," or "Hispanic"