A Study of Different Programs to Help ALL Patients With Taking Maintenance Medicine at Home

Risk-Based 6MP Adherence Enhancement Strategies in Children, Adolescent and Young Adults With ALL - A Pilot Study

This clinical trial tests different programs to help patients with acute lymphoblastic leukemia (ALL) remember to take their medications during maintenance therapy at home. One problem with ALL maintenance treatment is remembering to take medicines at home like patients are supposed to. In maintenance, a medicine called 6-mercaptopurine or "6MP" is taken by mouth every day at home. In this study, 6MP prescriptions are filled into a special medication bottle called MEMS® which is fitted with a special cap called TrackCap™ that electronically records when the medication bottle is opened. Researchers are trying a new program to help patients be better at taking their 6MP like they're supposed to. This new program may help patients to remember to take their 6MP medication.

Study Overview

• Status: Suspended
• Conditions: Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Drug: Mercaptopurine; Other: Media Intervention; Other: Media Intervention; Other: Medical Device Usage and Evaluation; Behavioral: Training and Education; Behavioral: Compliance Monitoring; Other: Health Promotion and Education; Behavioral: Telephone-Based Intervention; Behavioral: Telephone-Based Intervention; Other: Informational Intervention; Behavioral: Compliance Monitoring; Behavioral: Telephone-Based Intervention; Behavioral: Telephone-Based Intervention

Detailed Description

PRIMARY OBJECTIVES:

I. Collect data on the feasibility of a phase 3 adherence-enhancing 2 parallel 2-arm randomized clinical trial.

Ia. Estimate participation rates, refusal reasons, and attrition rates. Ib. Evaluate rates of completeness of all aspects of the study (surveys [rates of missing elements]; MEMS® TrackCap™ return rates; maintenance form return rates from site clinical research assistants [CRAs]; blood samples for pharmacogenetics and deoxyribonucleic acid [DNA]-incorporated thioguanine nucleotide [DNA-TG] levels).

SECONDARY OBJECTIVES:

I. Among baseline non-adherers, estimate the impact of ultra-intensified intervention package (U-iIP) versus (vs.) intervention package (IP) on 6MP adherence.

II. Among baseline adherers, estimate the impact of patient-empowered intervention package (pIP) vs. education alone (EDU) on 6MP adherence.

OUTLINE:

Patients receive the Patient Supply Kit containing an empty MEMS® medication bottle with TrackCap™ with child resistant medication bottles and child resistant standard caps, and written instructions for the patient and pharmacist, along with their 6MP prescription. Beginning on day 1 cycle 1 of Maintenance Therapy, 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. Patients are instructed to return the first MEMS® TrackCap™ to the clinic on day 1 of Maintenance cycle 2. Patients are then assigned to 1 of 2 groups based on baseline adherence rates (adherers [adherence rate >= 95%] and non-adherers [adherence rate < 95%]).

NON-ADHERERS: Patients are randomized to 1 of 2 arms during cycle 2 of Maintenance therapy.

ARM I (IP): Patients receive another Patient Supply Kit and MEMS® TrackCap™ to use on day 1 of Maintenance cycle 3 and for the remaining duration of the study. Patients and their caregiver view the multimedia interactive patient/parent/other adult education (MIPE) program that features video clips of ALL patients and their parents/other adults discussing Maintenance treatment in the clinic on day 1 of cycle 3. A designated parent/other adult is selected and trained briefly in prompting and supervising the patient to take 6MP daily by the CRA on day 1 of Maintenance cycle 3. Patients also receive customized printed medication schedules approximately every 4 weeks (days 1, 29, and 57) during Maintenance cycles 3-5 (during scheduled clinic visits) from their healthcare provider. Patients and/or the parent/other adult receive automated customized electronic reminders delivered via smartphone according to the patient's electronic 6MP schedule. Once the designated parent/other adult receives the customized electronic reminder for 6MP, they are instructed to prompt initiation of the 6MP dose (if necessary), and to supervise the ingestion of the prescribed 6MP (in all instances). If the patient is not present when the dose of 6MP is due, the patient receives a call from the designated parent/other adult to prompt initiation of the dose. Patients and designated parents/other adults will be instructed to electronically indicate when 6MP has been taken (indicative of directly supervised therapy [DST] execution). Additionally, patients undergo blood sample collection on the study.

ARM II (U-iIP): Patients receive another Patient Supply Kit and MEMS® TrackCap™ to use on day 1 of Maintenance cycle 3 and for the remaining duration of the study. Patients and their caregiver view the MIPE program that features video clips of ALL patients and their parents/other adults discussing Maintenance treatment in the clinic on day 1 of cycle 3. A designated parent/other adult is selected and trained briefly in prompting and supervising the patient to take 6MP daily by the CRA on day 1 of Maintenance cycle 3. Patients also receive customized printed medication schedules approximately every 4 weeks (days 1, 29, and 57) during Maintenance cycles 3-5 (during scheduled clinic visits) from their healthcare provider. Patients and/or the parent/other adult receive automated customized electronic reminders delivered via smartphone according to the patient's electronic 6MP schedule. Once the designated parent/other adult receives the reminder for 6MP, they are instructed to prompt initiation of the 6MP dose (if necessary), and to supervise the ingestion of the prescribed 6MP (in all instances). If the patient is not present when the dose of 6MP is due, the patient receives a call from the designated parent/other adult to prompt initiation of the dose. Patients and designated parents/other adults will be instructed to electronically indicate when 6MP has been taken (indicative of DST execution). If there is no response by the designated parent/other adult indicating 6MP ingestion within 1 hour of the scheduled time, additional automated reminders are sent. The Adherence Study Coordinating Center will evaluate electronic responses (indicative of DST execution) every 4 weeks. The DST response rates will be communicated to the COG sites, identifying the patients as low DST responders (response rate: < 85%) or high DST responders (response rate: ≥ 85%), along with instructions to serve as a guideline for communicating these results when reviewing them with their patient. DST response rates will be reviewed with the patient every 4 weeks at the clinic visit by the healthcare provider for all U-iIP patients (irrespective of response rate). Patients (and their designated caregiver) receive booster MIPE videos to view on their smartphone every 4 weeks (Days 1, 29, and 57) during Maintenance cycles 3-5, with content that reinforces the importance of 6MP in treating leukemia, having a daily routine for 6MP ingestion, and executing/confirming directly supervised therapy (DST) with each dose, and review common barriers to 6MP ingestion and DST execution (e.g., patient away from home, change in daily schedule), address additional barriers significantly associated with DST execution, and feature examples of patients/other adults self-identifying barriers (e.g., parent not always home at time of 6MP, lack of organizational skills, etc.), and provide specific steps to overcome the barriers. Additionally, patients undergo blood sample collection on the study.

ADHERERS: Patients are randomized to 1 of 2 arms during cycle 2 of Maintenance therapy.

ARM III (EDU: Patients receive another Patient Supply Kit and MEMS® TrackCap™ to use on day 1 of Maintenance cycle 3 and for the remaining duration of the study. Patients and their caregiver view the MIPE program that features video clips of ALL patients and their parents/other adults discussing Maintenance treatment in the clinic on day 1 of cycle 3. Additionally, patients undergo blood sample collection on the study.

ARM IV (pIP): Patients receive another Patient Supply Kit and MEMS® TrackCap™ to use on day 1 of Maintenance cycle 3 and for the remaining duration of the study. On day 1 of Maintenance cycle 3, patients and their caregiver view the MIPE program that features video clips of ALL patients and their parents/other adults discussing Maintenance treatment in the clinic. On day 1 of Maintenance cycle 3, the patient and a designated parent/other adult are trained to set daily reminders on their smartphones at the time the 6MP is due, and to use the "snooze" function to allow repeated reminders in case the medication cannot be taken when the alarm first goes off. The designated parent/other adult is also trained briefly by the CRA in prompting and supervising the patient to take 6MP daily. Once the designated parent/other adult hears the smartphone alarm for 6MP, they are instructed to prompt initiation of the 6MP dose (if necessary), and to supervise the ingestion of the prescribed 6MP (in all instances). If the patient is not present when the dose of 6MP is due, the patient receives a call from the designated parent/other adult to prompt initiation of the dose. Additionally, patients undergo blood sample collection on the study.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • Arkansas
    • Little Rock, Arkansas, United States, 72202-3591
      • Arkansas Children's Hospital
  • California
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Golisano Children's Hospital of Southwest Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic-Jacksonville
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C S Mott Children's Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • Summerlin Hospital Medical Center
    • Las Vegas, Nevada, United States, 89109
      • Sunrise Hospital and Medical Center
    • Las Vegas, Nevada, United States, 89135
      • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Hospital
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • San Antonio, Texas, United States, 78229
      • Methodist Children's Hospital of South Texas
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: >= 10 years and =< 25 years
• Previously enrolled onto AALL1732
• Consented to the AALL1732 mercaptopurine adherence correlative study
• Maintenance therapy has not yet begun
• English or Spanish-speaking (patient and parent/other adult)
• Planning to receive 6MP (as tablets) during maintenance phase of therapy
• Able and willing to use the MEMS® TrackCap™ (e.g., not using a pillbox or prescribed liquid 6MP)
• Has a designated parent/other adult who is willing to enter into a mutual agreement with the patient to participate in a daily supervised medication administration routine
• Patient/parent/other adult must be willing to use a smartphone to receive medication reminders
• Receiving treatment at a Children's Oncology Group (COG) institution in the United States

Exclusion Criteria:

• Patients who have previously participated in or are currently participating in another intervention clinical trial designed to improve adherence

• Regulatory requirements

  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adherers arm III (EDU); Patients receive another Patient Supply Kit and MEMS® TrackCap™ to use on day 1 of Maintenance cycle 3 and for the remaining duration of the study. Patients and their caregiver view the MIPE program that features video clips of ALL patients and their parents/other adults discussing Maintenance treatment in the clinic on day 1 of cycle 3. Additionally, patients undergo blood sample collection on the study.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: Media Intervention; View MIPE program videos; Other: Media Intervention; Review booster MIPE videos; Other: Medical Device Usage and Evaluation; Use MEMS® with TrackCap™; Behavioral: Training and Education; Undergo training for prompting and supervising 6MP; Other: Informational Intervention; Receive Patient Supply Kit
Experimental: Non-adherers arm I (IP); See Detailed Description.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Mercaptopurine; Given PO; Other Names: 6-MP; Purinethol; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; U-4748; WR-2785; Other: Media Intervention; View MIPE program videos; Other: Media Intervention; Review booster MIPE videos; Other: Medical Device Usage and Evaluation; Use MEMS® with TrackCap™; Behavioral: Training and Education; Undergo training for prompting and supervising 6MP; Behavioral: Compliance Monitoring; Receive DST; Other: Health Promotion and Education; Receive customized printed medication schedules; Behavioral: Telephone-Based Intervention; Receive automated customized electronic reminders via smartphone; Behavioral: Telephone-Based Intervention; Receive electronic reminders with successive alerts (using the "snooze" function); Other: Informational Intervention; Receive Patient Supply Kit; Behavioral: Compliance Monitoring; Healthcare provider reviews DST response rates with the patient and any challenges they are having with 6MP adherence every 4 weeks at clinic visits; Behavioral: Telephone-Based Intervention; Receive additional automated reminders; Behavioral: Telephone-Based Intervention; Manually activate daily smartphone reminders with successive alerts (using the "snooze" function)
Experimental: Adherers arm IV (pIP); See Detailed Description.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Mercaptopurine; Given PO; Other Names: 6-MP; Purinethol; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; U-4748; WR-2785; Other: Media Intervention; View MIPE program videos; Other: Media Intervention; Review booster MIPE videos; Other: Medical Device Usage and Evaluation; Use MEMS® with TrackCap™; Behavioral: Training and Education; Undergo training for prompting and supervising 6MP; Behavioral: Compliance Monitoring; Receive DST; Behavioral: Telephone-Based Intervention; Receive automated customized electronic reminders via smartphone; Behavioral: Telephone-Based Intervention; Receive electronic reminders with successive alerts (using the "snooze" function); Other: Informational Intervention; Receive Patient Supply Kit; Behavioral: Compliance Monitoring; Healthcare provider reviews DST response rates with the patient and any challenges they are having with 6MP adherence every 4 weeks at clinic visits; Behavioral: Telephone-Based Intervention; Receive additional automated reminders; Behavioral: Telephone-Based Intervention; Manually activate daily smartphone reminders with successive alerts (using the "snooze" function)
Experimental: Non-adherers arm II (U-iIP); See Detailed Description.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Mercaptopurine; Given PO; Other Names: 6-MP; Purinethol; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; U-4748; WR-2785; Other: Media Intervention; View MIPE program videos; Other: Media Intervention; Review booster MIPE videos; Other: Medical Device Usage and Evaluation; Use MEMS® with TrackCap™; Behavioral: Training and Education; Undergo training for prompting and supervising 6MP; Behavioral: Compliance Monitoring; Receive DST; Other: Health Promotion and Education; Receive customized printed medication schedules; Behavioral: Telephone-Based Intervention; Receive automated customized electronic reminders via smartphone; Behavioral: Telephone-Based Intervention; Receive electronic reminders with successive alerts (using the "snooze" function); Other: Informational Intervention; Receive Patient Supply Kit; Behavioral: Compliance Monitoring; Healthcare provider reviews DST response rates with the patient and any challenges they are having with 6MP adherence every 4 weeks at clinic visits; Behavioral: Telephone-Based Intervention; Receive additional automated reminders; Behavioral: Telephone-Based Intervention; Manually activate daily smartphone reminders with successive alerts (using the "snooze" function)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participation	Will calculate and report the proportion of patients eligible for the study who participate and will report a corresponding 95% confidence interval.	At baseline (by day 1 of maintenance chemotherapy)
Refusal reasons	A single question in a study case report form prompts refusal reason. For each available reason, will calculate and report the proportion of patients reporting that refusal reason as well as corresponding 95% confidence intervals.	At baseline (by day 1 of maintenance chemotherapy)
Attrition	Will calculate and report the proportion of patients who drop out of the study prior to completion among those eligible and enrolled and will report the corresponding 95% confidence interval.	By 60 weeks from day 1 of maintenance chemotherapy
Completion of study measures	Will calculate and report the proportion of patients who complete the following measures by the end of the study follow-up period: study survey submission, MEMS® TrackCap™ return, maintenance form return, and blood sample submission. Will also report the corresponding 95% confidence intervals.	By 60 weeks from day 1 of maintenance chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-mercaptopurine (6MP) adherence (baseline non-adherers)	Among baseline non-adherers, the proportion of days with protocol defined appropriate medication use during the study follow up period will be captured for each patient using the MEMS cap. Will calculate and report the mean proportion of adherence days by arm and the corresponding 95% confidence interval.	By 60 weeks from day 1 of maintenance chemotherapy
6MP adherence (baseline adherers)	Among baseline adherers, protocol defined appropriate medication use during the study follow up period will be captured for each patient using the MEMS cap. Will calculate and report the proportion with >= 95% adherence over the study follow up period by arm with a corresponding 95% confidence interval.	By 60 weeks from day 1 of maintenance chemotherapy

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Investigators: Principal Investigator: Smita Bhatia, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Estimated): March 3, 2027
• Study Completion (Estimated): March 3, 2027

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: October 10, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Purines; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Socioeconomic Factors; Population Characteristics; Sulfhydryl Compounds; Health Education; Mercaptopurine; Educational Status; Specimen Handling; azathiopurine; Health Promotion
• Other Study ID Numbers: ACCL2433 (Other Identifier: CTEP); UG1CA189955 (U.S. NIH Grant/Contract); NCI-2024-08458 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); COG-ACCL2433 (Other Identifier: DCP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No