NCT05082519

Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL

A Phase 2 Randomized Trial of Caloric Restriction and Activity to Reduce Chemoresistance in B-cell Acute Lymphoblastic Leukemia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: Etan Orgel · Academic / Other
• Sex: All
• Age: 10 Years – 25 Years
• Healthy volunteers: Not accepted

Summary

This study is for older children, adolescents, and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL). Higher amounts of body fat is associated with resistance to chemotherapy in patients with B-ALL. Chemotherapy during the first month causes large gains in body fat in most people, even those who start chemotherapy at a healthy weight. This study is being done to find out if caloric restriction achieved by a personalized nutritional menu and exercise plan during routine chemotherapy can make the patient's ALL more sensitive to chemotherapy and also reduce the amount of body fat gained during treatment. The goals of this study are to help make chemotherapy more effective in treating the patient's leukemia as demonstrated by fewer patients with leukemia minimal residual disease (MRD) while also trying to reduce the amount of body fat that chemotherapy causes the patient to gain in the first month.

Detailed description

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.

Conditions

• B-cell Acute Lymphoblastic Leukemia
• Obesity

Interventions

Type	Name	Description
BEHAVIORAL	IDEAL2 Intervention	Intervention of diet and exercise to improve outcomes for ALL patients

Timeline

• Start date: 2022-03-12
• Primary completion: 2026-10-15
• Completion: 2031-10-15
• First posted: 2021-10-19
• Last updated: 2023-10-26

Locations

20 sites across 1 country: United States