Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission

Study Overview
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Brief Summary
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This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia that has had a decrease in or disappearance of signs and symptoms of cancer (remission). Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the impact of interventions proposed in intervention program (IP) versus (vs.) education alone (EDU) on adherence to oral 6MP (mercaptopurine) in children with acute lymphoblastic leukemia (ALL). Adherence will be measured by: i) Medication Event Monitoring Systems (MEMS) (primary measure of adherence to oral 6MP, providing real-time data; ii) red cell thioguanine nucleotide (TGN) levels (providing data on chronic, systemic 6MP exposure). SECONDARY OBJECTIVES: I. Examine the modifying effect of sociodemographic and psychosocial variables, and the mediating effect of health beliefs/ knowledge on change in adherence with intervention. II. Determine impact of IP vs. EDU on risk of relapse of ALL. OUTLINE: Patients are randomized to 1 of 2 intervention arms. ARM I: Patients receive the Patients Supply Kit containing an electronic pill monitoring system, a MEMS® medication bottle with TrackCap™ with standard resistant cap, and written instructions for the patient and pharmacist. Parents and/or caregivers are also trained to supervise patients' intake of the medication. Beginning on day 1, patients start using the MEMS® medication bottle with TrackCap™. Clinical research assistants contact patients and parents by telephone the next day to confirm that TrackCap™ is being used, to identify any obstacles, and to determine solutions. Beginning on day 29, patients and caregivers view an interactive multimedia educational program on-line or via DVD. Patients also receive a customized electronic mercaptopurine schedule and automated customized text message reminders delivered via cellular phone or web-based interface. Patients and caregivers are instructed to return the MEMS® medication bottle with TrackCap™ to the clinic by day 141. ARM II: Patients receive the usual standard of care and the mercaptopurine from the MEMS® medication bottle with TrackCap™ as patients in arm I. Patients and caregivers also view an interactive multimedia educational program on day 29. After completion of study treatment, patients are followed up every 6 months for 5 years and then annually until 10 years from diagnosis.

Official Title
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A Comprehensive Approach to Improve Medication Adherence in Pediatric ALL

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Behavioral: Behavioral Intervention
* Behavioral: Compliance Monitoring
* Other: Laboratory Biomarker Analysis
* Drug: Mercaptopurine
* Other: Questionnaire Administration
* Procedure: Standard Follow-Up Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ALL, in first remission; enrollment on a Children Oncology Group (COG) therapeutic study for ALL is not required At the time of enrollment, patient must have completed at least 24 weeks of maintenance chemotherapy, and is scheduled to receive at least 24 more weeks of maintenance chemotherapy Receiving continuous oral 6MP during the maintenance phase of therapy for ALL (held only for toxicity or illness), and will be returning to the clinic every 4 weeks for scheduled appointments while enrolled on COG ACCL1033 (between days 1 and 141) Has a designated parent or caregiver who is willing to enter into a mutual agreement with the patient to participate in a daily supervised medication administration routine Able and willing to use the MEMS® TrackCap™ (e.g., not using a pillbox or prescribed liquid 6MP) Parent/caregiver and patient (if 12 years and older) must be willing to use a cellular telephone to receive medication reminders via text messaging during study period Patient and parent/caregiver must speak English or Spanish All patients and/or their parents or legal guardians must sign a written informed consent All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: Patients with Down syndrome Patients who previously participated in or are currently participating in another intervention clinical trial designed to improve adherence

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (intervention program and mercaptopurine)<br>See detailed description. | Behavioral: Behavioral Intervention<br>* Receive intervention program<br>* Other names: Behavioral Treatments;Behavioral: Compliance Monitoring<br>* Correlative studies<br>Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Mercaptopurine<br>* Given orally<br>* Other names: WR-2785;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm II (standard of care and mercaptopurine)<br>Patients receive the usual standard of care and the mercaptopurine from the MEMS® medication bottle with TrackCap™ as patients in arm I. Patients and caregivers also view an interactive multimedia educational program on day 29. | Behavioral: Compliance Monitoring<br>* Correlative studies<br>Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Mercaptopurine<br>* Given orally<br>* Other names: WR-2785;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Standard Follow-Up Care<br>* Receive usual standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with adherence rate greater than or equal to 95% to mercaptopurine as measured by MEMS® | Compared between the IP and EDU groups using logistic regression. Mercaptopurine levels will be modeled as a function of time to examine longitudinal changes to 6TGN levels between the treatment groups using the generalized estimating equation (GEE) method for longitudinal normally distributed data. | 4 months | 
| Proportion of patients with adherence rate greater than or equal to 95% to mercaptopurine as measured by red cell TGN levels | Compared between the IP and EDU groups using logistic regression. Mercaptopurine levels will be modeled as a function of time to examine longitudinal changes to 6TGN levels between the treatment groups using the GEE method for longitudinal normally distributed data. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of adherence patients by sociodemographic and psychosocial variables | Evaluated analytically by logistic regression methods. | 4 months | 
| Mediating effect of health beliefs/ knowledge on change in adherence with intervention | Evaluated analytically by logistic regression methods. | 4 months | 
| Impact of IP vs. EDU on risk of relapse in children with ALL | An intention-to-treat analysis will be used to compare the effectiveness of EDU and IP interventions in decreasing the risk of relapse. Cox proportional hazards regression models will be used to examine the impact of intervention on relapse. Covariates in the analysis will include clinical and sociodemographic predictors, and the intervention arm (IP vs. EDU). | Up to 10 years |