Resistance Exercise and Incretin Mimetic for Cardiometabolic Health in Survivors of ALL With Obesity
This is a 28-week, single-arm, open-label phase II clinical trial evaluating the combination of Tirzepatide and remote, supervised, tailored resistance exercise training to achieve weight loss in adult survivors of childhood acute lymphoblastic leukemia (ALL) living with obesity or overweight with comorbidity. Primary Objective(s): • To evaluate the effectiveness for weight loss of the combined intervention using once weekly Tirzepatide plus remote, supervised, tailored resistance exercise (three sessions per week) in adult survivors of childhood ALL with obesity or overweight (BMI ≥27 kg/m2) with ≥1 weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease). The effectiveness will be estimated as the proportion of evaluable participants who achieve at least 5% weight loss from baseline to week 28. The study will target a proportion of participants achieving 5% weight loss of 70% and consider fewer than 40% achieving 5% weight loss as unacceptable. Secondary Objective(s): * Estimate the proportion of participants who adhere to the 28-week combined intervention. Adherence to Tirzepatide will be defined as receiving at least 70% of prescribed doses. Adherence to resistance exercise will be defined as attending at least 50% of prescribed exercise sessions. Adherence to the combined intervention will be considered if participants complete the study and meet both the Tirzepatide and exercise adherence endpoint. The adherence to each component of the intervention will also be reported. * Estimate the average percentage weight loss from week 0 to 28 for participants completing the combined 28-week intervention. The study will target a mean weight reduction of 10% and consider \<5% unacceptable.
• ≥5 years from diagnosis of acute lymphoblastic leukemia (ALL) treated with chemotherapy only
• ≥2 years from completion of therapy
• Participant has a negative (urine or blood) pregnancy test (if female)
∙ Consistent with the FDA-approval for marketing of Tirzepatide for the treatment of obesity:
• Age ≥18 years at the time of enrollment
• Participant has obesity (BMI \> 30kg/m2) or overweight (BMI \> 27kg/m2) with ≥1 weight related co-morbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease)
‣ hypertension: treated or with systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg
⁃ dyslipidemia: treated or with low-density lipoprotein (LDL) ≥160 mg/dL (4.1 mmol/L) or triglycerides ≥150 mg/dL (1.7 mmol/L), or high-density lipoprotein (HDL) \<40 mg/dL (1.0 mmol/L) for men or HDL\<50 mg/dL (1.3 mmol/L) for women
⁃ obstructive sleep apnea
⁃ cardiovascular disease (for example, ischemic cardiovascular disease, New York Heart Association (NYHA) Functional Class I-III heart failure)