An Open-Label Intervention Trial to Reduce Senescence and Improve Frailty in Adult Survivors of Childhood Cancer

Exclusion Criteria

• •Currently has HIV, Hepatitis B/C, invasive fungal infection
• •Anemia or as per clinical judgement.
• •Hypersensitivity to study drugs
• •New/active malignancy/taking chemotherapy and/or radiation except non-melanoma skin cancers
• •Currently taking 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 anticoagulant or antiplatelet agents (Warfarin, 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 2-3 day drug dosing. Subjects may continue their previous regimen after drug dosing is complete.
• •Cognitive impairment defined by IQ \<80
• •Diagnosis of a psychotic disorder
• •Laboratory tests as indicated or as per clinical judgement
• •Severe hepatic dysfunction with ALT/AST \> 3 times upper limit of normal.
• •Total bilirubin \> 2 times upper limit of normal.
• •eGFR \<25 ml/min/1.73m2 or as per clinical judgement.
• •Hemoglobin \< 7 g/dl; white blood cell count ≤2,000/mm3 (≤2.0 x 109/L) or ≥20,000/mm3 (≥20 x 109/L); platelet count ≤40,000/μL (≤40 x 109/L); absolute neutrophil count ≤1 x 109/L; lymphocyte count \<0.3 x 109/L at screening as a marker of poor nutrition
• •Fasting glucose \>300.
• •Participant is unable to ambulate