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

Launched by ST. JUDE CHILDREN'S RESEARCH HOSPITAL · Jan 28, 2021

Keywords

ClinConnect Summary

This clinical trial is looking at ways to help adult survivors of childhood cancer who are experiencing frailty, which means they may have difficulty walking, low muscle strength, or low activity levels. The researchers are testing two treatment combinations, one that includes two drugs called Dasatinib and Quercetin, and another that uses Fisetin alone. The main goal is to see if these treatments can improve walking speed and reduce certain old cells in the body that are linked to aging, which might help the participants feel stronger and more active.

To join the study, participants must be at least 18 years old and have been diagnosed with childhood cancer over five years ago. They should also show signs of frailty based on specific criteria. Throughout the trial, participants will take the study drugs for a short period, and researchers will monitor their walking speed and health markers at the beginning and after 60 days. They will also check in again at 150 days to see if the improvements last. It’s important to note that there are certain health conditions and medications that could prevent someone from participating, so interested individuals should discuss this with their doctor to see if they qualify.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Participant in SJLIFE and \> 5 years from diagnosis.
• • ≥18 years of age.
• • Frail (2 of 4 objectively measured Fried criteria adapted,(excluding self-reported fatigue as a criteria), including abnormal walking speed; muscle strength; activity level; and muscle mass). See Section 5 for details.
• • CD3+ T lymphocytes: p16INK4A detected at \<34 cycles by RT PCR.
• • Agrees to use contraception as Dasatinib is teratogenic.
• • Female participant has a negative pregnancy test.
• • QTc \<450 milliseconds in electrocardiogram.
• • Able to take oral medications.
• 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