NCT00268528|Completed

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

Understanding the Ethnic and Racial Differences in Survival in Children With Acute Lymphoblastic Leukemia

Children's Oncology Group ClinicalTrials.gov

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7 other identifiers

AALL03N1NCI-2009-00305CDR000045974807-462COG-AALL03N1R01CA096670U10CA095861

Study Type

observational

Target

720

Locations

3 countries

Sites

135

Timeline

RegisteredDec 2005

StartedMay 2005

CompletionJun 2020

Brief Summary

This clinical trial is assessing compliance with long-term mercaptopurine treatment in young patients with acute lymphoblastic leukemia in remission. Assessing why young patients who have acute lymphoblastic leukemia may not take their medications as prescribed may help identify ways to assist them in taking their medications more consistently and may improve long-term treatment outcomes.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

720

participants targeted

Target at P75+ for all trials

Timeline

Completed

Started May 2005

Longer than P75 for all trials

Geographic Reach

3 countries

135 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

15.1 years study duration

Study Start

First participant enrolled

May 30, 2005

Completed

7 months until next milestone

First Submitted

Initial submission to the registry

December 20, 2005

Completed

2 days until next milestone

First Posted

Study publicly available on registry

December 22, 2005

Completed

6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 5, 2012

Completed

8.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2020

Completed

Last Updated

July 7, 2020

Status Verified

October 1, 2019

Enrollment Period

6.8 years

First QC Date

December 20, 2005

Last Update Submit

July 1, 2020

Conditions

Childhood Acute Lymphoblastic Leukemia in Remission

Outcome Measures

Primary Outcomes (9)

Adherence to 6-MP as measured by 6TGN and MethylTIMP levels
Will initially perform an exploratory data analysis on distributions across the four groups using side-by-side boxplots, histograms, and summary quantities (mean, median, quartiles, standard deviations, inter-quartile-range, etc.). If central values summarize across-group differences well, then mean and median of the distribution will be compared between 6 pairs of the four ethnic groups using the two-sample t-test and the Mann-Whitney U-test. Will perform these tests adjusting for 6 pairwise multiple comparisons among the four groups using the Bonferroni?s correction method.
169 days
Adherence as measured by frequency of 6-MP dosing as a continuous variable using MEMS? defined as the number of days the MEMS? Cap openings are recorded, taken as a percentage of days doses were prescribed during the study period
Will initially perform an exploratory data analysis on distributions across the four groups using side-by-side boxplots, histograms, and summary quantities (mean, median, quartiles, standard deviations, inter-quartile-range, etc.). If central values summarize across-group differences well, then mean and median of the distribution will be compared between 6 pairs of the four ethnic groups using the two-sample t-test and the Mann-Whitney U-test. Will perform these tests adjusting for 6 pairwise multiple comparisons among the four groups using the Bonferroni?s correction method.
Up to 169 days
Self-report of adherence to 6-MP by questionnaire, defined as the number of days doses of 6-MP are reported to being taken, as a percentage of days doses were prescribed during the study period
Will initially perform an exploratory data analysis on distributions across the four groups using side-by-side boxplots, histograms, and summary quantities (mean, median, quartiles, standard deviations, inter-quartile-range, etc.). If central values summarize across-group differences well, then mean and median of the distribution will be compared between 6 pairs of the four ethnic groups using the two-sample t-test and the Mann-Whitney U-test. Will perform these tests adjusting for 6 pairwise multiple comparisons among the four groups using the Bonferroni?s correction method.
169 days
EFS
For each of the three types of adherence measures, will fit independent Cox?s proportional-hazard models to assess the prognostic significance of the adherence measure on EFS, after adjusting for known predictors of disease outcome, including the National Cancer Institute risk group (based on the age at diagnosis and presenting white cell count) and chromosomal abnormalities.
Up to 10 years
Critical level of adherence (measured independently by 6TGN/MethylTIMP, MEMS?, self-report) that has a significant impact on EFS
Will fit a separate Cox regression model to each of the three adherence measures (i.e., 6TGN, MeTIMP, MEMS, and self-report). Using no more than several knots, the natural spline (a special type of cubic splines) fits a very wide range of smoothly changing adherence effects. The adherence effects on EFS will be visualized graphically. This will be the primary approach for defining the critical level of adherence. To confirm the spline analysis results, will categorize the continuous adherence measures into multiple levels and estimate the effect of each adherence level.
Up to 10 years
Prevalence of adherence to 6-MP by ethnicity (measured independently by 6TGN/MethylTIMP, MEMS?, Self-report) that has a significant impact on EFS
Will describe the prevalence of non-adherence by race/ethnicity and compare the prevalence by using two-tailed chi-squared test (with a Yates' correction).
Up to 10 years
Behavioral, socio-demographic predictors of adherence using the questionnaire data
The reasons for non-adherence will be assessed. The relationship between adherence to 6-MP as reported by the patients/parents and the independent behavioral variables knowledge of medications, understanding of treatment regimen, extent of treatment side effects, length of treatment, and beliefs about the efficacy of the regimen, beliefs and attitudes towards health and medical care will be evaluated descriptively first using standard parametric or non-parametric tests, and then analytically by logistic regression (dichotomous adherence) or linear regression (continuous adherence).
Up to 10 years
Pill-taking practices using the MEMS? data
Using the MEMS? output data, the adherence report will be analyzed for: i) longest and shortest interval between doses in hours; ii) percent prescribed doses taken, and iii) percent prescribed doses taken on schedule.
Up to 169 days
Impact of adherence (measured independently by 6TGN/MethylTIMP, MEMS, self-report) on ethnic/racial differences in EFS
Will fit independent Cox?s proportional-hazard models to assess the impact of adherence measure on EFS, after adjusting for known predictors of disease outcome, including the National Cancer Institute risk group (based on the age at diagnosis and presenting white cell count) and chromosomal abnormalities.
Up to 10 years

Secondary Outcomes (1)

Concordance among red cell thiopurine metabolite levels, electronic pill monitoring, and self-reported adherence among the ethnic/racial groups
Up to 168 days

Study Arms (1)

Health service research (electronic pill monitoring system)

Patients receive an electronic pill monitoring system comprising an empty MEMS\^? medication bottle with TrackCap? 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 PO as indicated by their individual chemotherapy regimen.

Behavioral: Compliance MonitoringOther: Laboratory Biomarker AnalysisDrug: MercaptopurineDrug: MethotrexateOther: Questionnaire AdministrationOther: Study of Socioeconomic and Demographic Variables

Interventions

Compliance MonitoringBEHAVIORAL

Receive an electronic pill monitoring system comprising an empty MEMS medication bottle with TrackCap