Tirzepatide plus guided resistance exercise for weight loss in adult survivors of childhood ALL

Resistance Exercise and Incretin Mimetic for Cardiometabolic Health in Survivors of ALL With Obesity

This 28-week program will try once-weekly tirzepatide together with remote, supervised resistance training to help adult survivors of childhood ALL who have obesity or overweight with a related health condition lose weight.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Memphis, Tennessee)
• Trial ID: NCT07228741 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label phase II trial testing a combined intervention of weekly tirzepatide and remote, tailored resistance exercise three times per week over 28 weeks in adult survivors of childhood acute lymphoblastic leukemia (ALL). Eligible participants are adults treated with chemotherapy only, at least two years off therapy, with BMI ≥30 kg/m2 or BMI ≥27 kg/m2 plus a weight-related comorbidity. The primary outcome is the proportion of participants achieving at least 5% weight loss from baseline to week 28, with secondary measures including adherence, body composition, cardiometabolic markers, and aging biomarkers. The goal is to determine whether adding structured resistance training can support meaningful weight loss while monitoring lean mass and metabolic health.

Who should consider this trial

Good fit: Adults (≥18 years) who are survivors of childhood ALL treated with chemotherapy only, at least two years off therapy, and who have obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity are ideal candidates.

Not a fit: People who are currently on cancer therapy, pregnant, have contraindications to tirzepatide or supervised resistance exercise, or who do not meet the BMI/comorbidity criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combined approach could produce clinically meaningful weight loss and improve cardiometabolic health while helping preserve muscle mass in ALL survivors with obesity.

How similar studies have performed: Tirzepatide has produced substantial weight loss in general adult populations and resistance training is effective at preserving lean mass, but combining tirzepatide with structured resistance programs specifically in ALL survivors is relatively novel with limited direct evidence.

Eligibility criteria

Inclusion Criteria:

* ≥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)

Exclusion Criteria:

* Participant has known diabetes or is found at baseline to have laboratory evidence of diabetes including HbA1c ≥ 6.5%
* Participant is using or has used weight management medication in the past 3 months or had recent significant weight loss \> 5kg in the last 3 months Severe renal dysfunction (eGFR \<30 mL/min/1.73 m²)

  * Saxenda® (liraglutide 3.0 mg)
  * Xenical®/Alli® (orlistat)
  * Meridia® (sibutramine)
  * Acutrim® (phenylpropanolamine)
  * Sanorex® (mazindol)
  * Adipex® (phentermine)
  * BELVIQ® (lorcaserin)
  * Qsymia® (phentermine/topiramate combination)
  * Contrave® (naltrexone/bupropion)
  * Compounded or generic incretin mimetic (GLP-1) medication

Note: Use of metformin or any other glucose-lowering medication, whether prescribed for polycystic ovary syndrome or diabetes prevention is not permitted.

* Participant has Multiple Endocrine Neoplasia Type 2 (MEN2) or family history of medullary thyroid cancer
* Participant has severe renal dysfunction (renal-eGFR \<30 mL/min/1.73)
* Participant has history of major cardiovascular event in past 3 months (e.g. acute myocardial infarction, cerebrovascular accident, unstable angina, hospitalization due to congestive heart failure or currently NYHA class IV heart failure symptoms)
* Participant has uncontrolled hypertension during clinic assessment (SBP ≥160 mmHg or DBP ≥100 mmHg) ▪ Participant has known acute or chronic hepatitis or signs and symptoms of other liver disease determined by alanine aminotransferase test (ALT) \> 3 times the upper normal limit
* Participant has known chronic pancreatitis or recent acute pancreatitis (in the past 1 year)
* Participant is pregnant, or within 3 months post-partum, or nursing, or planning to become pregnant
* Participant has clinically significant gastric emptying abnormality or chronically takes medications that affect GI motility (does not include Proton pump inhibitor (PPI) or histamine 2 blockade)
* Participant has a transplanted organ or awaiting a transplant
* Participant has current active cancer or undergoing treatment for active cancer
* Participant has untreated hypothyroidism with thyroid-stimulating hormone (TSH) \> 10 uIU/mL or symptomatic
* Participant has severe mental health disorder (e.g.major depressive disorder, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) or a history of suicide attempt
* Participant has a patient health questionnaire-8 (PHQ-8) score of 15 or more at screening
* Participant has a history of known drug or alcohol use disorder that in the opinion of the investigator may preclude the participant from following and completing the protocol
* Participant has history of self-reported marijuana use in the past 3 months and unwilling to abstain during the trial.
* Participant is unwilling or unable to perform self-injections of study drug (visually impaired or physically limited) and does not have assistance of a sighted individual/support person who is trained
* Participant has cognitive impairment that, in the opinion of the investigator, would preclude the ability to participate in the intervention including self-injections and virtual study visits
* Participant is Non-English speaking
* Participant has no access to a smartphone with Bluetooth for accelerometer and WiFi availability for exercise sessions
* Participant lives in a state that we cannot ship medication per current St. Jude Pharmacy restrictions

Where this trial is running

Memphis, Tennessee

• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Stephanie B Dixon, MD, MPH — St. Jude Children's Research Hospital
• Study coordinator: Stephanie B Dixon, MD, MPH

Conditions Acute Lymphoblastic Leukemia; Obesity; ALL; ALL Survivors