RecruitingInterventionalPhase 2

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

NCT ID: NCT05082519Sponsor: Etan OrgelLast updated: 2023-10-26

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.

Arms & interventions

BehavioralIDEAL2 Intervention
Intervention of diet and exercise to improve outcomes for ALL patients

Outcome measures

Primary

EOI MRD positivity >= 0.01%
To compare the rate of MRD \>=0.01% at end of induction between experimental arm and control arm
Time frame: Prior to day 5 until end of induction (~day 35 from start of chemotherapy)
Change in fat mass
To compare the % change in fat mass from baseline to end of induction between the experimental arm and control arm
Time frame: Prior to day 5 until end of induction (~day 35 from start of chemotherapy)

Secondary

Proportion of patients with >=75% adherence to diet intervention
Time frame: Prior to day 5 until end of induction (~day 35 from start of chemotherapy)
Proportion of patients with >=75% adherence to exercise intervention
Time frame: Prior to day 5 until end of induction (~day 35 from start of chemotherapy)

Eligibility criteria

Sex: AllAge: 10 Years to 25 YearsHealthy volunteers: No

Inclusion Criteria: * Patients must be ≥ 10.0 and \<26.0 years of age. * Patients must have a diagnosis of de novo B-ALL * Patients must have a M3 marrow (\>25% blasts by morphology) or at least 1,000/µL circulating leukemia cells in PB confirmed by Flow Cytometry (or other convincing evidence of a B-ALL diagnosis not meeting above criteria following central review by the Study Hematopathologist and Study Chair or Vice-Chair). * The treatment regimen must be the first treatment attempt for B-ALL- * Must be a multi-agent induction regimen inclusive of vincristine, glucocorticoid, pegaspargase/calaspargase, and daunorubicin or doxorubicin and with a planned duration \<35 days. * Organ function must meet that required for initiation of chemotherapy * Patients at diagnosis must meet Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age (or be expected to recover prior to Day 8) . * If the patient is a female of childbearing potential, a negative urine or serum pregnancy test is required within two weeks prior to enrollment. Exclusion Criteria: * Patient will be excluded if they are underweight at time of enrollment (BMI% \<5th percentile for age for patients age 10-19 years, BMI \<18.5 in patients 20-29 years). * Patients with Down syndrome or a DNA fragility syndrome (such as Fanconi anemia, Bloom syndrome) will be excluded. * Patient receiving a SJCRH-style "Total Therapy" regimen will be excluded. * Patients receiving anti-CD20 monoclonal antibody therapy during induction therapy. * Patients will be excluded if they received treatment for a previous malignancy. * Patient will be excluded if they are pregnant. * Patient will be excluded if they have a pre-diagnosis requirement for enteral or parenteral supplementation . * Patient will be excluded due to inability to perform the intervention (e.g., specific nutritional needs, severe developmental delay, paraplegia) * Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results

Study locations (20)

Children's Hospital Los Angeles

Los Angeles, California, 90027

Recruiting

Etan Orgel, MD · Principal Investigator

Children's Hospital Orange County

Orange, California, 92868

Recruiting

Van Huynh, MD · Principal Investigator

UCSF School of Medicine

San Francisco, California, 94158

Recruiting

Michelle Hermiston, MD · Principal Investigator

Colorado Children's Hospital

Denver, Colorado, 80045

Recruiting

Lisa Hartman, M.D. · Contact

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322

Not Yet Recruiting

Melinda Pauly, MD · Principal Investigator

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611

Recruiting

Jenna Rossoff, MD · Principal Investigator

Johns Hopkins / Sydney Kimmel Cancer Center

Baltimore, Maryland, 21231

Not Yet Recruiting

Patrick Brown, MD · Principal Investigator

C.S. Mott University of Michigan

Ann Arbor, Michigan, 48109

Recruiting

Jennifer Agrusa, M.D. · Contact

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404

Recruiting

Nathan Gossai, MD · Principal Investigator

Columbia University Medical Center

New York, New York, 10032

Not Yet Recruiting

Nobuko Hijiya, MD · Contact

Levine Children's Hospital

Charlotte, North Carolina, 28203

Recruiting

Joel Kaplan, DO · Principal Investigator

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

Not Yet Recruiting

Robin Norris, MD · Contact

Nationwide Children's Hospital

Columbus, Ohio, 43205

Not Yet Recruiting

Susan Vear-Colace, MD · Principal Investigator

Oregon Health & Science University

Portland, Oregon, 97239

Not Yet Recruiting

Bill Chang, MD · Principal Investigator

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

Recruiting

Susan Rheingold, MD · Principal Investigator

University of Texas, Southwestern

Dallas, Texas, 75235

Recruiting

Tamra Slone, MD · Contact

Cook Children's Medical Center

Fort Worth, Texas, 76104

Not Yet Recruiting

Kenneth Heym, MD · Principal Investigator

Baylor Texas Children's Hospital

Houston, Texas, 77030

Recruiting

Karen Rabin, M.D. · Contact

Primary Children's Hospital

Salt Lake City, Utah, 84113

Recruiting

Mallorie Heneghan, M.D. · Contact

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226

Not Yet Recruiting

Michael Burke, MD · Principal Investigator