Chronic Lymphocytic Leukemia Clinical Trial

Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL

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.

View Full Description

Full 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.

View Eligibility Criteria

Eligibility Criteria

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 patients 10-19 years, BMI <18.5 in 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 is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

240

Study ID:

NCT05082519

Recruitment Status:

Recruiting

Sponsor:

Etan Orgel

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 16 Locations for this study

See Locations Near You

Children's Hospital Los Angeles
Los Angeles California, 90027, United States More Info
Etan Orgel, MD
Principal Investigator
Children's Hospital Orange County
Orange California, 92868, United States More Info
Van Huynh, MD
Principal Investigator
UCSF School of Medicine
San Francisco California, 94158, United States More Info
Michelle Hermiston, MD
Principal Investigator
Children's Healthcare of Atlanta at Egleston
Atlanta Georgia, 30322, United States More Info
Melinda Pauly, MD
Principal Investigator
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago Illinois, 60611, United States More Info
Jenna Rossoff, MD
Principal Investigator
Johns Hopkins / Sydney Kimmel Cancer Center
Baltimore Maryland, 21231, United States More Info
Patrick Brown, MD
Principal Investigator
Children's Hospitals and Clinics of Minnesota
Minneapolis Minnesota, 55404, United States More Info
Nathan Gossai, MD
Principal Investigator
Columbia University Medical Center
New York New York, 10032, United States More Info
Nobuko Hijiya, MD
Contact
Levine Children's Hospital
Charlotte North Carolina, 28203, United States More Info
Joel Kaplan, DO
Principal Investigator
Cincinnati Children's Hospital Medical Center
Cincinnati Ohio, 45229, United States More Info
Robin Norris, MD
Contact
Nationwide Children's Hospital
Columbus Ohio, 43205, United States More Info
Susan Vear-Colace, MD
Principal Investigator
Oregon Health & Science University
Portland Oregon, 97239, United States More Info
Bill Chang, MD
Principal Investigator
Children's Hospital of Philadelphia
Philadelphia Pennsylvania, 19104, United States More Info
Susan Rheingold, MD
Principal Investigator
University of Texas, Southwestern
Dallas Texas, 75235, United States More Info
Tamra Slone, MD
Contact
Cook Children's Medical Center
Fort Worth Texas, 76104, United States More Info
Kenneth Heym, MD
Principal Investigator
Children's Hospital of Wisconsin
Milwaukee Wisconsin, 53226, United States More Info
Michael Burke, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

240

Study ID:

NCT05082519

Recruitment Status:

Recruiting

Sponsor:


Etan Orgel

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.