Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL

Obesity Clinical Trial

— IDEAL2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05082519
• Other study ID #: T2020-003
• Status: Recruiting
• Phase: Phase 2
• Start date: March 12, 2022
• Est. completion date: October 15, 2031

Study information

• Verified date: October 2023
• Source: Therapeutic Advances in Childhood Leukemia Consortium
• Contact: Ellynore Florendo
• Phone: 323-361-3022
• Email: eflorendo[@]chla.usc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: October 15, 2031
• Est. primary completion date: October 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Obesity
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Behavioral:
• IDEAL2 Intervention
Intervention of diet and exercise to improve outcomes for ALL patients

Locations

Country	Name	City	State
United States	C.S. Mott University of Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia
United States	Johns Hopkins / Sydney Kimmel Cancer Center	Baltimore	Maryland
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas, Southwestern	Dallas	Texas
United States	Colorado Children's Hospital	Denver	Colorado
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Baylor Texas Children's Hospital	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	UCSF School of Medicine	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Etan Orgel	Therapeutic Advances in Childhood Leukemia Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EOI MRD positivity >= 0.01%	To compare the rate of MRD >=0.01% at end of induction between experimental arm and control arm	Prior to day 5 until end of induction (~day 35 from start of chemotherapy)
Primary	Change in fat mass	To compare the % change in fat mass from baseline to end of induction between the experimental arm and control arm	Prior to day 5 until end of induction (~day 35 from start of chemotherapy)
Secondary	Proportion of patients with >=75% adherence to diet intervention	To assess the self-reported adherence to the diet component of the IDEAL2 intervention	Prior to day 5 until end of induction (~day 35 from start of chemotherapy)
Secondary	Proportion of patients with >=75% adherence to exercise intervention	To assess the self-reported adherence to the exercise component of the IDEAL2 intervention	Prior to day 5 until end of induction (~day 35 from start of chemotherapy)