Caloric Restriction + Activity for Acute Lymphoblastic Leukemia

(IDEAL2 Trial)

Recruiting at 19 trial locations

Overseen By Ellynore Florendo

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Etan Orgel

Must be taking: Vincristine, Glucocorticoid, Pegaspargase, Daunorubicin

Must not be taking: Anti-CD20 therapy

Disqualifiers: Underweight, Down syndrome, Previous malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a personalized diet and exercise plan, known as the IDEAL2 Intervention, can enhance chemotherapy effectiveness for treating B-cell Acute Lymphoblastic Leukemia (B-ALL) and reduce weight gain during treatment. Participants will either receive standard care or follow a specific diet and exercise routine designed to lower body fat and improve chemotherapy outcomes. The trial seeks participants aged 10 to 25 who have been diagnosed with B-ALL but have not yet started treatment. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the IDEAL2 Intervention is safe for patients with B-cell Acute Lymphoblastic Leukemia?

Research has shown that the IDEAL2 program, which includes a diet and exercise plan during chemotherapy, is safe. In other studies, patients who followed similar diet and exercise guidelines managed the program well. This approach emphasizes eating fewer calories and increasing activity to enhance the effectiveness of chemotherapy for leukemia.

Reports from these studies have not identified any major side effects from the program. Patients generally handle the dietary and exercise changes without significant issues. The goal is to enhance chemotherapy effectiveness and control weight gain during treatment without causing harm. These findings suggest the program may be safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for leukemia?

Unlike the standard of care for acute lymphoblastic leukemia (ALL), which typically involves education on diet and exercise, the IDEAL2 intervention introduces a structured and specific caloric restriction and exercise regimen. Researchers are excited about this approach because it aims for a significant daily calorie deficit, emphasizing a balanced macronutrient intake with low glycemic load carbohydrates and higher protein. This method also incorporates moderate exercise and a progressive step goal to actively reduce sedentary behavior. By integrating precise dietary changes and physical activity, this intervention could enhance the effectiveness of standard treatments, offering a potentially powerful complementary tool in managing ALL.

What evidence suggests that the IDEAL2 Intervention could be effective for B-ALL?

Research has shown that the IDEAL2 program, tested in this trial, includes a personalized diet and exercise plan that might enhance chemotherapy's effectiveness for treating B-cell Acute Lymphoblastic Leukemia (B-ALL). Participants may receive the IDEAL2 intervention, which involves caloric restriction and increased activity. Studies have found that eating fewer calories and being more active can reduce the number of cancer cells remaining after treatment, known as minimal residual disease (MRD). This suggests the program could make leukemia cells more responsive to chemotherapy. Additionally, this approach aims to prevent the weight gain often seen during the first month of chemotherapy. Overall, combining diet and exercise is being studied to boost chemotherapy's effectiveness and improve patient outcomes. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for young people aged 10 to less than 26 with B-cell Acute Lymphoblastic Leukemia (B-ALL) who are starting their first treatment. They must be able to perform moderate exercise and follow a diet plan, have a body mass index above the 5th percentile but not underweight, and cannot be pregnant or have had previous cancer treatments.

Inclusion Criteria

My leukemia has a high number of blasts in my marrow or blood.

I am between 10 and 25 years old.

I have been diagnosed with B-cell Acute Lymphoblastic Leukemia for the first time.

Exclusion Criteria

I am currently receiving anti-CD20 monoclonal antibody therapy.

I am not on a SJCRH-style 'Total Therapy' regimen.

Patient will be excluded if they are pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive standard B-ALL chemotherapy with the IDEAL2 intervention for caloric restriction and increased physical activity

5 weeks

Weekly visits for monitoring and intervention adjustments

Follow-up

Participants are monitored for safety and effectiveness after induction treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IDEAL2 Intervention

Trial Overview The IDEAL2 Intervention is being tested to see if caloric restriction through personalized nutrition and exercise can make leukemia cells more sensitive to chemotherapy. The study aims to reduce body fat gained during treatment and improve the effectiveness of chemotherapy.

How Is the Trial Designed?

Group I: IDEAL2 intervention Experimental Treatment 1 Intervention

Focused and short-term intervention of diet and exercise during induction. Calorie goal is \>=15% daily deficit as determined by each subject's estimated energy requirement. Fat intake will make up \<25% of daily calories. Carbohydrate will make up \<55% of daily calories consisting of "low" glycemic load foods (\<100/2,000 kcal adjusted for daily calories). Protein will make up \>=20% of daily calories. Subjects will also perform moderate exercise 5 days per week for 30 minutes/session (total = 150 minutes per week). Subjects will have a step goal to decrease sedentary behavior, with a starting goal of \>=1000 steps/day and increasing by at least 1000 steps/day each week.

Group II: Control - Standard of Care Active Control 1 Intervention

One-time education of diet and exercise, which is the standard of care for ALL patients during induction.

Who Is Running the Clinical Trial?

Etan Orgel

Lead Sponsor

Trials

2

Recruited

240+

Therapeutic Advances in Childhood Leukemia Consortium

Collaborator

Trials

21

Recruited

680+

Published Research Related to This Trial

In a study of 762 newly diagnosed pediatric patients with acute lymphoblastic leukemia, being underweight at diagnosis was linked to a higher risk of relapse, although overall survival rates were similar to those of normal or overweight patients.

A decrease in body mass index during the first 32 weeks of treatment was associated with decreased overall survival, primarily due to a loss of lean body mass, highlighting the importance of maintaining body composition during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia. den Hoed, MA., Pluijm, SM., de Groot-Kruseman, HA., et al.[2021]

The IDEAL trial, involving 40 patients aged 10 to 21 with newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL), showed that a diet and exercise intervention did not significantly reduce overall fat mass gain but effectively reduced fat gain in overweight/obese patients by 8.2% (from +9.7% to +1.5%).

The intervention also significantly decreased the risk of minimal residual disease (MRD) after chemotherapy, with an odds ratio of 0.30, suggesting that caloric restriction through diet and exercise may enhance chemotherapy efficacy in B-ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caloric and nutrient restriction to augment chemotherapy efficacy for acute lymphoblastic leukemia: the IDEAL trial. Orgel, E., Framson, C., Buxton, R., et al.[2022]

A 12-week remote lifestyle intervention for 15 children with pediatric acute lymphoblastic leukemia (ALL) showed promising results, with 86.7% of families completing the program.

The intervention led to positive dietary changes, such as increased milk and protein intake and reduced consumption of potatoes, although it did not significantly affect physical activity levels, BMI, or waist circumference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Lifestyle Intervention for Obesity Prevention in Pediatric Survivors of Acute Lymphoblastic Leukemia. Zhang, FF., Kelly, M., Du, M., et al.[2020]

In a study of 15 children with newly diagnosed acute lymphocytic leukemia (ALL), researchers found that both protein synthesis and breakdown rates were significantly higher compared to healthy controls, indicating altered protein metabolism in these patients.

The study revealed a strong correlation between basal metabolic rate (BMR) and protein synthesis, suggesting that the increased energy requirements in ALL patients are closely linked to their elevated protein synthesis rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Close association of accelerated rates of whole body protein turnover (synthesis and breakdown) and energy expenditure in children with newly diagnosed acute lymphocytic leukemia. Kien, CL., Camitta, BM.[2017]

Survivors of acute lymphoblastic leukemia (ALL) showed a significant reduction in total daily energy expenditure (TDEE) compared to survivors of other cancers and healthy controls, which may contribute to obesity in this group.

The decrease in TDEE was primarily due to lower physical activity levels (PAL) in the ALL group, suggesting that reduced activity may be a key factor in the development of obesity among these survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily energy expenditure and physical activity in survivors of childhood malignancy. Warner, JT., Bell, W., Webb, DK., et al.[2008]

A 6-month dietary intervention focusing on a low glycemic diet was successfully implemented in 23 participants with childhood acute lymphoblastic leukemia (ALL), showing significant reductions in sugar intake and increases in vegetable consumption.

The intervention effectively prevented weight gain during the initial treatment phase for ALL, with no increase in body mass index z-scores observed, suggesting it is a feasible approach to manage obesity risks in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A bilingual dietary intervention early in treatment is feasible and prevents weight gain in childhood acute lymphoblastic leukemia. Walters, M., Mowbray, C., Jubelirer, T., et al.[2021]

A pilot study involving 17 children aged 5 to 10 years with acute lymphoblastic leukemia showed that a 6-month home-based exercise intervention was feasible, with 71% of participants completing the program.

The exercise intervention led to significant improvements in physical abilities, including strength and flexibility, with 67% of participants showing enhanced knee strength and 83% improving ankle flexibility, indicating potential benefits for children undergoing cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia. Esbenshade, AJ., Friedman, DL., Smith, WA., et al.[2022]

A 3-visit nutrition intervention for pediatric patients with acute lymphoblastic leukemia (ALL) significantly controlled weight gain during maintenance therapy, as shown in a study of 67 patients (33 intervention, 34 control).

The intervention was particularly effective in managing weight gain trends, even after accounting for factors like initial BMI and weight changes during intensive therapy, indicating its potential as a modifiable strategy to combat obesity in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Nutrition Intervention Attenuates Weight Gain for Pediatric Acute Lymphoblastic Leukemia Patients in Maintenance Therapy. Hill, R., Hamby, T., Bashore, L., et al.[2019]

In a study of 640 children with acute lymphoblastic leukemia (ALL), 27% were found to be overweight or obese, highlighting a significant concern for nutrition-related health issues during and after therapy.

The majority of participants (up to 79%) exceeded the dietary reference intake for total calories and other nutrients, with notable differences in micronutrient intake between standard-risk and high-risk ALL patients, suggesting a need for targeted dietary interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary intake and childhood leukemia: The Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) cohort study. Ladas, EJ., Orjuela, M., Stevenson, K., et al.[2018]

Children treated for acute lymphoblastic leukaemia (ALL) are at risk of excessive weight gain due to significantly lower total energy expenditure compared to healthy peers, primarily caused by reduced habitual physical activity.

The study found that these children also had lower resting energy expenditure and energy intake, suggesting that interventions to prevent obesity should focus on increasing physical activity and monitoring dietary intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced energy expenditure in preobese children treated for acute lymphoblastic leukemia. Reilly, JJ., Ventham, JC., Ralston, JM., et al.[2017]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2828.1/528975/Trial-in-Progress-Update-on-the-TACL-T2020-003

Update on the TACL T2020-003 Randomized Phase 2 Trial to ... The IDEAL-1 intervention consisted of a 10% caloric dietary deficit via a low carbohydrate, low glycemic load, low-fat, and high protein dietary ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05082519

NCT05082519 | Caloric Restriction and Activity to Reduce ... 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 ...

3. tacl.chla.usc.edu tacl.chla.usc.edu/Tacl/Uploaded/T2020-003_IDEAL2%20Protocol%20Amendment%20%231%20(final)_redline_9-1-22.pdf

A PHASE 2 RANDOMIZED TRIAL OF CALORIC ... 1.1.1 To examine efficacy of the IDEAL2 (Improving Diet and Exercise in ALL) caloric restriction and activity intervention integrated into HR B-ALL induction to ...

4. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/T2020-003-01923

T2020-003: Caloric Restriction and Activity to Reduce ... 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 ...

5. withpower.com withpower.com/trial/phase-3-leukemia-9-2021-82b2d

Caloric Restriction + Activity for Acute Lymphoblastic ... The IDEAL trial showed that caloric restriction and increased activity reduced the risk of minimal residual disease (a measure of cancer cells remaining after ...