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

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.