An Open-Label Intervention Trial to Reduce Senescence and Improve Frailty in Adult Survivors of Childhood Cancer
Frailty, Childhood Cancer
About this trial
This is an interventional treatment trial for Frailty
Eligibility Criteria
Inclusion Criteria:
- Participant in SJLIFE and > 5 years from diagnosis
- ≥18 years of age
- Frail (3 of 5 Fried criteria, including abnormal walking speed; muscle strength; activity level; muscle mass and exhaustion/fatigue scale).
- CD3+ T lymphocytes: p16^INK4A detected at <33 cycles by RT PCR
- Agrees to use contraception as Dasatinib is teratogenic
- Participant has a negative pregnancy test
- QTc <450 milliseconds in electrocardiogram
- Participant has hematocrit of >34 for females and >35 for males
- Participant has hemoglobin of >11 for females and >12 for males
- Able to take oral medications
Exclusion Criteria:
- Currently has HIV, Hepatitis B/C, invasive fungal infection
- Anemia
- Hypersensitivity to study drugs
- New/active malignancy/taking chemotherapy and/or radiation except non-melanoma skin cancers
- Medications that inhibit or induce CYP3A4 or that are sensitive to substrates or substrates with a narrow therapeutic range for CYP2C8, CYP2C9, or CYP2D6
- Taking anticoagulants or antimicrobial agents
- Currently taking Quercetin or Fisetin
- Pregnant or nursing at time of enrollment/during the study
- Impaired cognition or motor performance due to congenital defects
- Currently participating in another research intervention to aid walking speed or other measures of frailty including muscle strength; low activity; muscle mass or exhaustion/fatigue
- Participant is a Non-English Speaker
- Uncontrolled pleural/pericardial effusion or ascites
- Subjects on antiplatelet agents (Clopidogrel [Plavix]; Dipyridamole + Aspirin [Aggrenox]; Ticagrelor [Brilintal]; Prasugrel [Effient]; Ticlopidine [Ticlid]; or other) who are unable or unwilling to reduce or hold therapy prior to and during the 2-day drug dosing. Subjects may continue their previous regimen on Day 3.
Sites / Locations
- St. Jude Children's Research HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Dasatinib plus Quercetin
Fisetin
Day 0 (30 per arm, randomization stratified by sex and age) At the visit on day 7, blood CD3+ T lymphocyte p16^INK4A mRNA and other markers of inflammation and senescence will be accessed to verify that senescent cells have been cleared by the intervention. Post-treatment follow-up will occur on days 60 for (primary endpoints) and day 150 for secondary evaluation. Day 150 will assess the permanence of change after completion of the trial.
Day 0 (30 per arm, randomization stratified by sex and age) At the visit on day 7, blood CD3+ T lymphocyte p16INK4A mRNA and other markers of inflammation and senescence will be accessed to verify that senescent cells have been cleared by the intervention. Post-treatment follow-up will occur on days 60 for (primary endpoints) and day 150 for secondary evaluation. Day 150 to will assess the permanence of change after completion of the trial.