Trial in progress: nutrition and exercise to optimize muscle and adiposity in adolescents and young adults with B-cell acute lymphocytic leukemia: The neoma ALL trial Free

Background and Significance:

In 2021-2023, 40% of adults in the United States were obese (Emmerich, NCHS Data Brief, 2024). Obesity is associated with poor survival in adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL) (Stock, Blood, 2019) (Shimony, Blood Advances, 2023). Poorer survival among patients with obesity is multifactorial. Obese patients experience increased treatment toxicities (hepatotoxicity, hyperglycemia, and thromboembolic events) translating into higher non-relapse mortality. Additionally, ALL treatment resistance during induction and maintenance phases, leading to primary induction failures and higher MRD detection rates in those who attain a remission, is seen in those with obesity. The biological basis of these clinical findings has been well described. Adipocytes (1) donate metabolic fuel in the form of asparagine, glutamine, and free fatty acids; (2) reduce chemotherapy-induced oxidative stress; and (3) spur proliferation. Additionally, adipocytes have been shown to protect lymphoblasts from anthracyclines and asparaginase.

The Improve Diet and Exercise in ALL (IDEAL) Trial (Orgel, Blood Advances, 2022) showed that a caloric deficit, accomplished jointly by nutritional and exercise interventions with the end goal of minimizing fat mass gain and muscle loss, was feasible and may improve chemotherapy efficacy during induction in pediatric B-ALL patients. This trial, Nutrition and Exercise to Optimize Muscle and Adiposity in Adults with B-ALL (NEOMA, NCT06785324), aims to bring this therapeutic modality to the AYA ALL population.

Study Design and Methods: NEOMA is a pilot interventional trial of nutrition and exercise in 15 AYA patients with B-ALL. Patients must be age>18 years-50 years, have Philadelphia chromosome negative (Ph (-)) ALL, and receive a pediatric-inspired induction regimen. Ineligibility criteria include BMI<18.5 kg/m². The nutrition intervention targets a 10% caloric deficit calculated from each patient's Basal Metabolic Rate (WHO/Schofield) utilizing a high protein (>25%), low fat (<25%), low glycemic index/high fiber (45-55%) diet. The study dietician meets with the patient on day of enrollment to go over the “menu” of dietary options, provide education, and re-assesses the patient every two days for adherence. The exercise intervention targets 200 minutes of moderate intensity physical activity weekly, as defined by Metabolic Equivalents (METs) of 3-6, made up of aerobic and resistance training activities tailored to the patient's preference by working with the study physical therapist (PT). 200 minutes of moderate intensity physical activity achieves an additional 10% caloric deficit weekly. The 3-week NEOMA intervention is in the inpatient setting.

The primary aim is to establish feasibility, adherence, and usability. NEOMA will be deemed feasible if >70% of patients eligible for enrollment consent to NEOMA. The dietary intervention will be deemed of acceptable adherence if >75% of patients are categorized as “adherent”, defined as >75% of the patient's dietary assessments consistent with the prescribed diet. The exercise intervention will be deemed of acceptable adherence if >50% of patients are able to meet the exercise goal (200 minutes of 3-6 METs physical activity=600 MET-minutes minimum weekly goal) in 2 out of 3 weeks of induction therapy. Secondary outcomes include body composition and metabolomic changes, end of induction MRD status as assessed by ClonoSEQ® assay, and treatment toxicities. Metabolomics assessments are done on daily serum samples and pre- and post-intervention bone marrow aspirate utilizing a modified folch extraction to measure both lipids and polar metabolites on a dedicated LC-MS system. Changes in visceral adiposity and skeletal muscle are evaluated at the 1^st lumbar spinal level from CT scans using the Data Analysis Facilitation Suite, version 3.6.0 (Voronoi Health Analytics Inc) to obtain automated body composition measurements.

Current Progress: NEOMA opened on 5/12/2025 with an anticipated enrollment over 1 year. 2 patients have been approached for consent with 1 patient enrolling and 1 screen failure (Ph+). This is the first interventional study in AYAs with ALL aimed to decrease adiposity and improve muscle mass during induction therapy. If the NEOMA intervention is shown to be feasible, useable, and effective, the study would provide preliminary data to inform a randomized clinical trial of the intervention.