Acute Myeloid Leukemia
Conditions
Keywords
acute myeloid leukemia, AML, chemotherapy, exercise, quality of life, cancer-related fatigue, elderly, physical fitness, muscular strength, Feasibility, Efficacy, Safety
Brief summary
Fatigue, reduced quality of life and declines in physical function are common in patients undergoing chemotherapy for acute myeloid leukaemia (AML). Studies in other cancer patients undergoing treatment have shown that exercise improves these symptoms, but there are limited studies in AML. This study of a hospital-based exercise program will help determine if exercise is both feasible and helpful in improving symptoms among for AML patients undergoing chemotherapy.
Detailed description
Background: Acute myeloid leukaemia (AML) is a life-threatening haematological malignancy. Initial treatment with induction chemotherapy requires 4-5 weeks of hospitalization, with a risk of physical deconditioning, declines in quality of life (QOL), and significant fatigue. Four pilot exercise studies have demonstrated improved fitness, strength, QOL, and fatigue in patients undergoing induction, but are limited by small sample sizes, recruitment of mostly younger adults, inconsistent endpoints, and design issues. Prior to conducting a large multi-centre randomized controlled trial (RCT), important pilot work first needs to be done to demonstrate feasibility of a randomized trial of an exercise program in AML patients undergoing induction chemotherapy; to ensure safety; and to provide effect estimates of the intervention on fitness and QOL/fatigue endpoints. Objectives: Primary objectives are: (1) to determine feasibility of recruitment and retention of adult AML patients to a randomized trial of supervised exercise and ability of patients to perform an exercise intervention in hospital; (2) to provide estimates of the effect of exercise on fitness parameters. Secondary objectives are: (1) to determine effects of exercise on QOL and fatigue; (2) to understand the impact of exercise on AML treatment tolerability; (3) to examine safety of the exercise intervention. Methods: Thirty-five patients age 18 or older with newly diagnosed or relapsed AML who are undergoing induction chemotherapy will be recruited at Princess Margaret Hospital. Participants will perform 30-45 minutes of supervised aerobic and resistance exercises 4-5 days per week. Primary outcomes are recruitment rate, exercise adherence rate, and impact on fitness measures (peak aerobic capacity (VO2peak), grip strength, leg strength, 6-minute walk test). QOL will be measured with the European Organization for the Research and Treatment of Cancer (EORTC) core 30-item questionnaire (QLQ-C30). Fatigue will be measured using the Functional Assessment of Cancer Therapy fatigue subscale (FACT-Fatigue). Treatment tolerability outcomes include length of stay, intensive care unit admission, and the development of sepsis. Outcomes over time will be assessed using mixed effects regression models. Significance: Exercise is a promising intervention for improving fitness, QOL and treatment tolerability in AML patients undergoing induction chemotherapy. This pilot RCT will establish feasibility and safety, as well as provide efficacy estimates that will be vital to the design and conduct of a definitive multi-centre RCT of exercise in this patient population.
Interventions
OTHERExercise
After obtaining daily medical clearance, patients will be approached 4-5 days per week to perform 30-45 minutes of supervised exercise with a Canadian Society for Exercise Physiology (CSEP) - Certified Exercise Physiologist. All exercise sessions will be as tolerated, based on patient symptoms.
Sponsors
Toronto Rehabilitation Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* at least 18 years old * newly diagnosed AML, or relapsed AML after having been in complete remission for at least 6 months * initiating induction chemotherapy * ambulatory without need for human assistance * has consented to study * is medically cleared for participation by attending physician
Exclusion criteria
* has another active malignancy * has life expectancy \< 1 month, physician determined * has significant comorbidity * has uncontrolled pain * has haemodynamic instability * lacks fluency in reading and writing English and there is no translator available for each visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Program Adherence. | Baseline, Post-induction (weeks 4-6) | Adherence to supervised exercise program assessed as a percentage of exercise sessions completed(number of days of supervised exercise performed/the number of days that patients were approached to participate). |
| 6-minute Walk Test | Baseline, Post-induction (4-6 weeks) | Measure of functional endurance assessed by the walking distance covered in a 6-minute period. Participants walk a pre-established course for a total of 6 minutes. The distance covered in that time is recorded as the 6-minute walk test score. |
| Timed 10-chair Stands | Baseline, Post-induction (weeks 4-6) | Measure of lower-body strength completed by standing from a seated position 10 times as quickly as possible. |
| Grip Strength | Baseline, Post-induction (weeks 4-6) | Measure of upper-body strength using a Jamar hand dynamometer. Participants were asked to hold and squeeze (the dynamometer) with maximal force. Three trials were completed with each hand, alternating between the right and left to minimize fatigue. The highest recorded value of the dominant hand was used in the analysis. |
| Recruitment Rate | Baseline | Ratio of patients who consented to participate out of all eligible patients expressed as a percentage (eligible patients who consented to participation/eligible patients who declined participation). |
| Retention | Baseline, Post-induction (weeks 4-6) | Percentage of participants who remained in the study (did not withdraw voluntarily). |
| Peak Aerobic Capacity (VO2peak) | Baseline, Post-induction (weeks 4-6) | The modified Bruce protocol is a walking-based treadmill test used to assess peak aerobic capacity. As the test progresses the intensity of each 3-minute work load increases. The test concludes when the participant reaches his maximal heart rate or volitional fatigue. The value attained on this test is measured in metabolic equivalents (METS). METS are a measure of exercise intensity and reflect the physical demands of an activity. In this context, a higher value achieved on the treadmill test (in METS) indicates work at a higher intensity and therefore a higher aerobic capacity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue | Baseline, Post-induction (weeks 4-6) | Fatigue will be assessed using the Functional Assessment of Cancer Therapy fatigue subscale (FACT-Fatigue). The FACT-Fatigue consists of 13 questions and has excellent psychometric characteristics. Fatigue scores derived from this questionnaire range from 0-52 with a higher score reflecting lower fatigue. |
| Length of Stay | Post-induction (weeks 4-6) | Length of stay (date of admission to hospital to date of discharge). |
| Intensive Care Unit (ICU) Admission | Post-induction (weeks 4-6) | Intensive care unit (ICU) admission (percentage of participants admitted to ICU during induction chemotherapy course). |
| Development of Sepsis | Post-induction (weeks 4-6) | Development of sepsis (percentage of participants who developed sepsis during induction chemotherapy course). |
| Global Quality of Life | Baseline, Post-induction (weeks 4-6) | Global quality of life (QOL) will be measured by the European Organization for the Research and Treatment of Cancer (EORTC) core 30-item questionnaire (QLQ-C30). The EORTC QLQ-C30 is a widely used, self-reported, psychometrically sound cancer QOL instrument. QOL scores derived from this questionnaire range from 0-100 with a higher score reflecting a higher QOL. |
Countries
Canada
Participant flow
Recruitment details
This non-randomized phase II study recruited patients between June 2010 and February 2011. All participants were recruited from Princess Margaret Hospital (PMH) in Toronto, Canada.
Participants by arm
| Arm | Count |
|---|---|
| Exercise All study participants were part of the exercise group as this was a non-randomized study. Participants were approached 4-5 times per week to participate in supervised, individualized exercise sessions that incorporated a combination of aerobic, resistance and flexibility exercises. Exercise was light to moderate in intensity and each exercise session was 30-45 minutes in length. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Refused | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Exercise |
|---|---|
| Age, Customized <60 years | 18 years |
| Age, Customized >=60 years | 17 years |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
6-minute Walk Test
Measure of functional endurance assessed by the walking distance covered in a 6-minute period. Participants walk a pre-established course for a total of 6 minutes. The distance covered in that time is recorded as the 6-minute walk test score.
Time frame: Baseline, Post-induction (4-6 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | 6-minute Walk Test | Baseline | 962.5 feet | Standard Deviation 286.3 |
| Exercise | 6-minute Walk Test | Post-induction (weeks 4-6) | 1176.2 feet | Standard Deviation 360.6 |
Primary
Grip Strength
Measure of upper-body strength using a Jamar hand dynamometer. Participants were asked to hold and squeeze (the dynamometer) with maximal force. Three trials were completed with each hand, alternating between the right and left to minimize fatigue. The highest recorded value of the dominant hand was used in the analysis.
Time frame: Baseline, Post-induction (weeks 4-6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | Grip Strength | Post-induction (weeks 4-6) | 21.6 kilograms | Standard Deviation 11 |
| Exercise | Grip Strength | Baseline | 23.9 kilograms | Standard Deviation 11 |
Primary
Peak Aerobic Capacity (VO2peak)
The modified Bruce protocol is a walking-based treadmill test used to assess peak aerobic capacity. As the test progresses the intensity of each 3-minute work load increases. The test concludes when the participant reaches his maximal heart rate or volitional fatigue. The value attained on this test is measured in metabolic equivalents (METS). METS are a measure of exercise intensity and reflect the physical demands of an activity. In this context, a higher value achieved on the treadmill test (in METS) indicates work at a higher intensity and therefore a higher aerobic capacity.
Time frame: Baseline, Post-induction (weeks 4-6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | Peak Aerobic Capacity (VO2peak) | Baseline | 6.9 metabolic equivalent (METS) | Standard Deviation 1.8 |
| Exercise | Peak Aerobic Capacity (VO2peak) | Post-induction (weeks 4-6) | 7.4 metabolic equivalent (METS) | Standard Deviation 1.7 |
Primary
Program Adherence.
Adherence to supervised exercise program assessed as a percentage of exercise sessions completed(number of days of supervised exercise performed/the number of days that patients were approached to participate).
Time frame: Baseline, Post-induction (weeks 4-6)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exercise | Program Adherence. | 45.8 percentage of exercise days completed |
Primary
Recruitment Rate
Ratio of patients who consented to participate out of all eligible patients expressed as a percentage (eligible patients who consented to participation/eligible patients who declined participation).
Time frame: Baseline
Population: For this outcome measure we analyzed 52 participants (rather than 35). Fifty-two participants met the study eligibility criteria. Thirty-five out of 52 consented to participate which is how we derived our recruitment rate of 67% (35/52).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exercise | Recruitment Rate | 67 percentage of patients |
Primary
Retention
Percentage of participants who remained in the study (did not withdraw voluntarily).
Time frame: Baseline, Post-induction (weeks 4-6)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exercise | Retention | 97 percentage of participants |
Primary
Timed 10-chair Stands
Measure of lower-body strength completed by standing from a seated position 10 times as quickly as possible.
Time frame: Baseline, Post-induction (weeks 4-6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | Timed 10-chair Stands | Baseline | 33.0 seconds | Standard Deviation 26 |
| Exercise | Timed 10-chair Stands | Post-induction (weeks 4-6) | 31.1 seconds | Standard Deviation 11.2 |
Secondary
Development of Sepsis
Development of sepsis (percentage of participants who developed sepsis during induction chemotherapy course).
Time frame: Post-induction (weeks 4-6)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exercise | Development of Sepsis | 26.5 percentage of participants |
Secondary
Fatigue
Fatigue will be assessed using the Functional Assessment of Cancer Therapy fatigue subscale (FACT-Fatigue). The FACT-Fatigue consists of 13 questions and has excellent psychometric characteristics. Fatigue scores derived from this questionnaire range from 0-52 with a higher score reflecting lower fatigue.
Time frame: Baseline, Post-induction (weeks 4-6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | Fatigue | Post-induction (weeks 4-6) | 33.9 units on a scale | Standard Deviation 11.7 |
| Exercise | Fatigue | Baseline | 31.5 units on a scale | Standard Deviation 13.1 |
Secondary
Global Quality of Life
Global quality of life (QOL) will be measured by the European Organization for the Research and Treatment of Cancer (EORTC) core 30-item questionnaire (QLQ-C30). The EORTC QLQ-C30 is a widely used, self-reported, psychometrically sound cancer QOL instrument. QOL scores derived from this questionnaire range from 0-100 with a higher score reflecting a higher QOL.
Time frame: Baseline, Post-induction (weeks 4-6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | Global Quality of Life | Baseline | 45.1 units on a scale | Standard Deviation 26.6 |
| Exercise | Global Quality of Life | Post-induction (weeks 4-6) | 51.4 units on a scale | Standard Deviation 21.4 |
Secondary
Intensive Care Unit (ICU) Admission
Intensive care unit (ICU) admission (percentage of participants admitted to ICU during induction chemotherapy course).
Time frame: Post-induction (weeks 4-6)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exercise | Intensive Care Unit (ICU) Admission | 11.5 percentage of participants |
Secondary
Length of Stay
Length of stay (date of admission to hospital to date of discharge).
Time frame: Post-induction (weeks 4-6)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise | Length of Stay | 37.2 days | Standard Deviation 10.6 |