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NCT00268528 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
Not reported
Status at capture
COMPLETED
Registry last update
2020-07-07

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
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"
healthy Volunteers
false
maximum Age
21 Years
sampling Method
NON_PROBABILITY_SAMPLE
sex
ALL
std Ages
  1. CHILD
  2. ADULT
study Population
Children with ALL from four different ethnic and racial groups (Caucasians, African-Americans, Hispanics, and Asians) receiving maintenance/continuation chemotherapy.
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Behavioral: Compliance Monitoring
    2. Other: Laboratory Biomarker Analysis
    3. Drug: Mercaptopurine
    4. Drug: Methotrexate
    5. Other: Questionnaire Administration
    6. Other: Study of Socioeconomic and Demographic Variables
    label
    Health service research (electronic pill monitoring system)
interventions
  1. arm Group Labels
    1. Health service research (electronic pill monitoring system)
    description
    Receive an electronic pill monitoring system comprising an empty MEMS medication bottle with TrackCap
    name
    Compliance Monitoring
    type
    BEHAVIORAL
  2. arm Group Labels
    1. Health service research (electronic pill monitoring system)
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  3. arm Group Labels
    1. Health service research (electronic pill monitoring system)
    description
    Given PO
    name
    Mercaptopurine
    other Names
    1. 3H-Purine-6-thiol
    2. 6 MP
    3. 6 Thiohypoxanthine
    4. 6 Thiopurine
    5. 6-Mercaptopurine
    6. 6-Mercaptopurine Monohydrate
    7. 6-MP
    8. 6-Purinethiol
    9. 6-Thiopurine
    10. 6-Thioxopurine
    11. 6H-Purine-6-thione, 1,7-dihydro- (9CI)
    12. 7-Mercapto-1,3,4,6-tetrazaindene
    type
    DRUG
  4. arm Group Labels
    1. Health service research (electronic pill monitoring system)
    description
    Given PO
    name
    Methotrexate
    other Names
    1. Abitrexate
    2. Alpha-Methopterin
    3. Amethopterin
    4. Brimexate
    5. CL 14377
    6. CL-14377
    7. Emtexate
    8. Emthexat
    9. Emthexate
    10. Farmitrexat
    11. Fauldexato
    12. Folex
    type
    DRUG
  5. arm Group Labels
    1. Health service research (electronic pill monitoring system)
    description
    Ancillary studies
    name
    Questionnaire Administration
    type
    OTHER
  6. arm Group Labels
    1. Health service research (electronic pill monitoring system)
    description
    Receive an electronic pill monitoring system comprising an empty MEMS medication bottle with TrackCap
    name
    Study of Socioeconomic and Demographic Variables
    type
    OTHER
Study design
observational Model
COHORT
time Perspective
PROSPECTIVE
Enrollment
count
720
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Adherence to 6-MP as measured by 6TGN and MethylTIMP levels
    time Frame
    169 days
  2. description
    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.
    measure
    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
    time Frame
    Up to 169 days
  3. description
    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.
    measure
    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
    time Frame
    169 days
  4. description
    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.
    measure
    EFS
    time Frame
    Up to 10 years
  5. description
    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.
    measure
    Critical level of adherence (measured independently by 6TGN/MethylTIMP, MEMS?, self-report) that has a significant impact on EFS
    time Frame
    Up to 10 years
  6. description
    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).
    measure
    Prevalence of adherence to 6-MP by ethnicity (measured independently by 6TGN/MethylTIMP, MEMS?, Self-report) that has a significant impact on EFS
    time Frame
    Up to 10 years
  7. description
    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).
    measure
    Behavioral, socio-demographic predictors of adherence using the questionnaire data
    time Frame
    Up to 10 years
  8. description
    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.
    measure
    Pill-taking practices using the MEMS? data
    time Frame
    Up to 169 days
  9. description
    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.
    measure
    Impact of adherence (measured independently by 6TGN/MethylTIMP, MEMS, self-report) on ethnic/racial differences in EFS
    time Frame
    Up to 10 years
secondary Outcomes
  1. description
    Correlations between mean dosage- and TPMT-normalized serial red cell 6-MP metabolites and mean adherence by electronic pill monitoring system and self-report will be assessed for statistical significance by Spearman's rank correlation coefficient.
    measure
    Concordance among red cell thiopurine metabolite levels, electronic pill monitoring, and self-reported adherence among the ethnic/racial groups
    time Frame
    Up to 168 days
Full study description
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.
detailed Description
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.
Source references
references
  1. citation
    Bidoli C, Yang W, Karol SE, Lucafo M, Stocco G, Yang JJ. Unraveling Novel Genetic Determinants of Thiopurine Response Via TWAS. Clin Pharmacol Ther. 2026 Jan;119(1):84-88. doi: 10.1002/cpt.70053. Epub 2025 Sep 5.
    pmid
    40908865
    type
    DERIVED
  2. citation
    Wadhwa A, Chen Y, Hageman L, Hoppmann A, Angiolillo A, Dickens DS, Neglia JP, Ravindranath Y, Ritchey AK, Termuhlen A, Wong FL, Landier W, Bhatia S. Poverty and relapse risk in children with acute lymphoblastic leukemia: a Children's Oncology Group study AALL03N1 report. Blood. 2023 Jul 20;142(3):221-229. doi: 10.1182/blood.2023019631.
    pmid
    37070673
    type
    DERIVED
  3. citation
    Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay N, Wong FL, Evans WE, Pui CH, Bhatia S, Relling MV. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol. 2015 Apr 10;33(11):1235-42. doi: 10.1200/JCO.2014.59.4671. Epub 2015 Jan 26.
    pmid
    25624441
    type
    DERIVED
  4. citation
    Bhatia S, Landier W, Hageman L, Kim H, Chen Y, Crews KR, Evans WE, Bostrom B, Casillas J, Dickens DS, Maloney KW, Neglia JP, Ravindranath Y, Ritchey AK, Wong FL, Relling MV. 6MP adherence in a multiracial cohort of children with acute lymphoblastic leukemia: a Children's Oncology Group study. Blood. 2014 Oct 9;124(15):2345-53. doi: 10.1182/blood-2014-01-552166. Epub 2014 May 14.
    pmid
    24829202
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        <p id="_1480" tabindex="-1">Evidence (adherence to treatment):</p> <div class="pdq-content-list"><ol id="_1481"><li>The COG <a href="/clinicaltrials/NCT00268528">AALL03N1 (NCT00268528)</a> trial studied the impact of nonadherence to mercaptopurine during maintenance therapy in 327 children and adolescents (169 Hispanic
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        ="-1">Evidence (adherence to treatment):</p> <div class="pdq-content-list"><ol id="_1481"><li>The COG <a href="/clinicaltrials/NCT00268528">AALL03N1 (NCT00268528)</a> trial studied the impact of nonadherence to mercaptopurine during maintenance therapy in 327 children and adolescents (169 Hispanic patients and 158 non-H
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      source update dates
      1. context
        Updated: April 21, 2025
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        April 21, 2025

    Preserved source evidence · Not medical advice