Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL

GOALS AND OBJECTIVES Hypothesis: Caloric restriction with increased physical activity integrated into induction chemotherapy will decrease chemoresistance and reduce minimal residual disease (MRD). In children receiving induction therapy for NCI/Rome high-risk B-cell acute lymphoblastic leukemia (HR B-ALL), 1.1 Primary Objectives * To examine efficacy of the IDEAL2 (Improving Diet and Exercise in ALL) caloric restriction and activity intervention integrated into HR B-ALL induction to reduce incidence of end of induction (EOI) MRD ≥0.01%. * To examine the efficacy of the IDEAL2 intervention to reduce gain in fat mass during induction 1.2 Secondary Objective • To assess self-reported adherence (defined ≥75%) to the diet and activity components of the IDEAL intervention. 1.3 Exploratory Clinical Objectives * To compare rates of continued MRD positivity by end of consolidation (EOC MRD ≥0.01%). * To compare loss of lean mass (LM), physical inactivity, fitness (via two-minute walk test), and motor function (via BOT-2) at EOI and/or at EOC between intervention and control arms * To compare differences in macronutrient and micronutrient intake during induction and at EOC between intervention and control arms * To compare utilization of immunotherapy (CAR, other) and hematopoietic stem cell transplantation (HSCT) between intervention and control arms * To compare event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) between intervention and control arms. * To compare chemotherapy dose-delivery, obesity-associated treatment toxicities (hepatotoxicity, pancreatitis, thrombosis, steroid-induced hyperglycemia, ICU admission, infection) between intervention and control arms * To evaluate the reliability of relative fat mass (RFM) to estimate body fat percentage, FM, and LM as measured by dual-energy X-ray absorptiometry (DXA) * To explore influence of sleep patterns on changes in FM from baseline to EOI and to EOC * To compare patient-reported quality of life (PedsQL scale) between intervention and control arms * To explore the impact of household material hardship (HMH) on dietary intake, activity, and trial primary endpoints of MRD and change in FM 1.4 Exploratory Integrated Biology Objectives * To quantify the effect of the IDEAL2 intervention, obesity, insulin, and adiponectin on PIK3K/AKT, mTOR, MAPK/ERK signaling and NfKB transcription via mass cytometry of ALL cells * To quantify the effect of the IDEAL2 intervention and obesity on differences in adipokines and cytokines circulating in the plasma * To investigate differences in the metabolome in the plasma and bone marrow extra-cellular fluid at diagnosis and at EOI between intervention and control arms * To explore the underlying biology of chemoresistance, obesity, adipocytes, and ALL cells OUTLINE: Patients are randomized to 1 of 2 arms EXPERIMENTAL ARM: Standard of care nutrition education plus the updated "Improving Diet and Exercise in ALL" (IDEAL2) intervention to achieve calorie restriction through a personalized nutritional program and increased activity/exercise. CONTROL ARM: One-time standard of care nutritional education session All patients receive standard of care B-ALL chemotherapy.