R01CA248439

Predictors of Systemic Exposure to Oral 6MP During Maintenance in Adolescents and Young Adults with Acute Lymphoblastic Leukemia - Project Summary / Abstract

Patients diagnosed with cancer between the ages of 15-39 have not seen the same improvement in survival when compared with patients diagnosed as children (<15). These patients have received special designation by the NCI as Adolescents and Young Adults (AYA), accompanied by a mandate to address these outcome disparities.

Acute Lymphoblastic Leukemia (ALL) epitomizes this phenomenon, where survival rates in AYA continue to lag behind children (5-year overall survival: 1-14 years: 86%; 15-21: 56%; 22-29: 42%; 30-39: 35%). Across pediatric-inspired and adult-style therapy regimens, ALL therapy includes a prolonged (~2 years) maintenance phase of chemotherapy requiring daily oral 6-mercaptopurine (6MP).

A large investigation recently confirmed that inadequate systemic exposure to 6MP is associated with an increased risk of relapse. To measure systemic 6MP exposure, this comprehensive approach assessed the levels of a 6MP metabolite (thioguanine nucleotide [TG]) incorporated into DNA (DNA-TG).

Several AYA-specific factors likely contribute to systemic 6MP exposure and have not been examined systematically. These factors are likely related to both the AYA patient (6MP adherence) and healthcare (disease management, reflected by the provider-prescribed 6MP dose intensity [DI]), as well as the barriers and facilitators within these domains.

We hypothesize that systemic exposure to 6MP will correlate with both 6MP adherence (in the patient domain) and disease management, as represented by provider-prescribed 6MP DI (in the healthcare domain). We will examine these associations between DNA-TG levels and both 6MP adherence and 6MP DI, adjusting for pharmacogenetics.

We will then identify barriers/facilitators to both 6MP adherence and disease management, using a mixed methods convergent parallel study design, both quantitatively determining the predictors of adherence and 6MP DI, and qualitatively describing the perspectives of both the patients and healthcare providers.

We will conduct this study using a prospective cohort of AYA patients in ALL maintenance therapy across a national 14-site consortium of multiple types of facilities and oncology practices. For 6 months per patient, 6MP adherence will be monitored electronically and monthly DNA-TG levels will be followed (peripheral blood). Patient questionnaires will capture self-reported barriers and facilitators of adherence as well as sociodemographics; institution-level questionnaires will capture healthcare factors.

Findings from this study have the potential to identify both patient-related and healthcare-related targets amenable to interventions with the potential to mitigate AYA outcome disparities in AYA patients with ALL. Furthermore, this study establishes the infrastructure to continue to follow this cohort for relapse and conduct intervention(s) informed by this proposed trial within a novel AYA-focused consortium.

University Of Alabama At Birmingham

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS; (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION; (3) EPIDEMIOLOGY; (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS; (5) IMMUNOLOGY AND VACCINES; (6) FIELD STUDIES AND STATISTICS; (7) CANCER CHEMOPREVENTION AND INTERCEPTION; (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT; (9) ORGAN SITE STUDIES AND CLINICAL TRIALS; (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES; AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM; TO STIMULATE TECHNICAL INNOVATION; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Birmingham, Alabama 352331711 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the End Date has been extended from 02/28/26 to 02/28/27 and the total obligations have increased 495% from $569,545 to $3,388,567.