B Precursor Type Acute Leukemia
Conditions
Brief summary
This study tests the ability of a focused dietary, exercise, and activity intervention to reduce fat gain during induction therapy for childhood acute lymphoblastic leukemia to improve disease response and reduce toxicity.
Detailed description
In our previous study, we have observed that: 1) nearly half ALL patients are overweight or obese at diagnosis, 2) all patients, regardless of starting weight, gain significant fat mass over the first month of therapy (on average 20-30%), and 3) obesity at the time of diagnosis is associated with a higher likelihood of poor response to chemotherapy as evidenced by persistent leukemia (minimal residual disease) after induction therapy. Together, these data show that body fat is a significant risk factor for ALL treatment failure, and that its negative effects are evident within the first month of treatment. Recent laboratory and clinical data illustrates the ability of diet restriction and physical activity to improve chemotherapy efficacy, reduce treatment-related toxicities and better overall quality of life. Given the importance of successful induction therapy for ALL in predicting long term survival and the negative role of obesity on treatment success, this study tests a complete personalized dietary and exercise intervention for pre-adolescents, adolescents, and young adults newly diagnosed with B-precursor ALL (pre-B ALL) that aims to reduce fat gained during induction therapy and thereby improve treatment response, toxicity rates, and quality of life.
Interventions
BEHAVIORALDietary Intervention
Beginning at time of diagnosis, the dietary component of the intervention uses a personalized menu to implement high protein, moderate fat, and low glycemic index/high fiber diet to achieve a minimum net -10% daily caloric deficit during the induction phase of chemotherapy.
BEHAVIORALActivity and Exercise Intervention
Beginning at the time of diagnosis, the exercise and activity component uses an activity menu to implement a target level of 200 minutes per week of moderate exercise activity (as estimated by metabolic equivalents) during the induction phase of chemotherapy.
Sponsors
Gabrielle's Angel Foundation
Children's Hospital Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Greater than or equal to 10 years of age and less than or equal to 21 years of age at time of diagnosis * Have a new diagnosis of untreated NCI/Rome High Risk B-precursor ALL (HR-ALL) * Are beginning treatment on- or as per- a Children's Cancer Group/Children's Oncology Group (CCG-COG) protocol with a 4-drug Induction including vincristine, daunorubicin (or doxorubicin), asparaginase, and at least 14 days of glucocorticoid steroids
Exclusion criteria
* Have a diagnosis of Down syndrome (Trisomy 21) or any genetic disease associated with abnormal body composition * Be underweight or at risk for underweight with moderate weight loss, defined as a starting Body Mass Index (BMI) \<10th percentile for age and sex (for those \>20 years of age, defined as an absolute BMI \< 18.5) * Have pre-existing abnormal intestinal function (e.g. protein-wasting enteropathy, fat malabsorption) * Be unable to comply with the recommended diet or activity interventions (as determined by study or treatment team) * Have a history of prior chemotherapy or radiation for other cancers * Be unable to complete the necessary radiology examinations with fully interpretable data (e.g. hip replacement and metal prostheses preclude evaluation by DXA) * Be pregnant (to be confirmed by urine or serum pregnancy test as per institutional routine care for chemotherapy and radiology exams)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fat Mass | Diagnosis and 28-35 days | Assessment of change in fat before and after the induction chemotherapy phase (first 28 days of chemotherapy) as measured dual-energy x-ray absorptiometry (DXA) in comparison to fat gain in a recent historical cohort. Calculated as (Day 28 Fat Mass - Diagnosis Fat Mass)/Diagnosis Fat Mass |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Minimal Residual Disease >=0.01% | 28-35 days from diagnosis | Compare the rate of minimal residual disease positivity (defined as \>=0.01%) in the bone marrow by flow cytometry after the induction phase of chemotherapy as compared to a recent historical cohort |
| Percentage of Successfully Completed Visits With Study Dietitian and Study Physiotherapist | 28 days | Assess feasibility of incorporating the intervention into induction chemotherapy as defined by \>80% of overall scheduled study visits successfully completed. The expected number of overall visits is equal to the sum of total visits scheduled with the physiotherapist (PT) or the registered dietitian (RD). The measure was calculated as the total # expected visits/completed visits. |
| Percentage of Overall Adherence to the IDEAL Intervention | 28 days | Overall adherence to the study intervention was calculated as the mean of dietary adherence (average of percent consumed calories/prescribed calories for each food group) and activity (self-reported % adherence to prescribed days). |
Countries
United States
Participant flow
Pre-assignment details
A non-prospective, historical cohort was used as a comparison group for this single-arm study.
Participants by arm
| Arm | Count |
|---|---|
| Obesity Intervention Personalized 28-day Dietary Intervention and Activity and Exercise Intervention with the goal to reduce fat gain and lean muscle loss while inducing an overall negative energy balance.
Dietary Intervention: Beginning at time of diagnosis, the dietary component of the intervention uses a personalized menu to implement high protein, moderate fat, and low glycemic index/high fiber diet to achieve a minimum net -10% daily caloric deficit during the induction phase of chemotherapy.
Activity and Exercise Intervention: Beginning at the time of diagnosis, the exercise and activity component uses an activity menu to implement a target level of 200 minutes per week of moderate exercise activity (as estimated by metabolic equivalents) during the induction phase of chemotherapy. | 40 |
| Historical Control Historical control assembled from previous, unselected, consecutive patients treated for B-ALL matching eligibility criteria. | 80 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | No MRD and no imaging available | 0 | 1 |
| Overall Study | Regimen change | 1 | 0 |
Baseline characteristics
| Characteristic | Historical Control | Total | Obesity Intervention |
|---|---|---|---|
| Age, Continuous | 14.7 years STANDARD_DEVIATION 2.5 | 14.80 years STANDARD_DEVIATION 2.69 | 15.0 years STANDARD_DEVIATION 3 |
| BMI Category Lean | 45 Participants | 59 Participants | 14 Participants |
| BMI Category Obese | 26 Participants | 46 Participants | 20 Participants |
| BMI Category Overweight | 9 Participants | 15 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 66 Participants | 92 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 22 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United States | 80 participants | 120 participants | 40 participants |
| Sex: Female, Male Female | 37 Participants | 53 Participants | 16 Participants |
| Sex: Female, Male Male | 43 Participants | 67 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 40 | 2 / 80 |
| other Total, other adverse events | 0 / 40 | 0 / 80 |
| serious Total, serious adverse events | 0 / 40 | 0 / 80 |
Outcome results
Primary
Fat Mass
Assessment of change in fat before and after the induction chemotherapy phase (first 28 days of chemotherapy) as measured dual-energy x-ray absorptiometry (DXA) in comparison to fat gain in a recent historical cohort. Calculated as (Day 28 Fat Mass - Diagnosis Fat Mass)/Diagnosis Fat Mass
Time frame: Diagnosis and 28-35 days
Population: Includes enrolled (or from historical control) with imaging information via DXA scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Obesity Intervention | Fat Mass | 5.1 percent change in fat mass |
| Historical Control | Fat Mass | 10.7 percent change in fat mass |
Secondary
Percentage of Overall Adherence to the IDEAL Intervention
Overall adherence to the study intervention was calculated as the mean of dietary adherence (average of percent consumed calories/prescribed calories for each food group) and activity (self-reported % adherence to prescribed days).
Time frame: 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Obesity Intervention | Percentage of Overall Adherence to the IDEAL Intervention | 82.1 % adherence |
Secondary
Percentage of Participants With Minimal Residual Disease >=0.01%
Compare the rate of minimal residual disease positivity (defined as \>=0.01%) in the bone marrow by flow cytometry after the induction phase of chemotherapy as compared to a recent historical cohort
Time frame: 28-35 days from diagnosis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Obesity Intervention | Percentage of Participants With Minimal Residual Disease >=0.01% | 12 Participants |
| Historical Control | Percentage of Participants With Minimal Residual Disease >=0.01% | 30 Participants |
p-value: 0.0295% CI: [0.09, 0.92]Regression, Logistic
Secondary
Percentage of Successfully Completed Visits With Study Dietitian and Study Physiotherapist
Assess feasibility of incorporating the intervention into induction chemotherapy as defined by \>80% of overall scheduled study visits successfully completed. The expected number of overall visits is equal to the sum of total visits scheduled with the physiotherapist (PT) or the registered dietitian (RD). The measure was calculated as the total # expected visits/completed visits.
Time frame: 28 days
Population: A total of 392 visits with the PT or RD were expected to be completed as part of the the study intervention.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Obesity Intervention | Percentage of Successfully Completed Visits With Study Dietitian and Study Physiotherapist | 339 Visits |