Acute Myeloid Leukaemia (AML) Patients Undergoing Induction Chemotherapy

• Sponsor: Toronto Rehabilitation Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01170598
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arm: 1
• Duration (Months): 9
• Patients Per Site Per Month: 3.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Other: Exercise	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Pilot Exercise RCT for Acute Myeloid Leukaemia (AML) Patients Undergoing Induction Chemotherapy: Pre-randomization Phase
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Exercise

Other: Exercise; 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.; Other Names: Mixed-modality exercise Resistance exercise training Aerobic exercise training

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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).

6. Retention [Baseline, Post-induction (weeks 4-6)]

   Percentage of participants who remained in the study (did not withdraw voluntarily).

7. 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).

Secondary Outcome Measures

1. 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.

2. 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.

3. Length of Stay [Post-induction (weeks 4-6)]

   Length of stay (date of admission to hospital to date of discharge).

4. 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).

5. Development of Sepsis [Post-induction (weeks 4-6)]

   Development of sepsis (percentage of participants who developed sepsis during induction chemotherapy course).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• Toronto Rehabilitation Institute

Investigators

• Principal Investigator: Shabbir MH Alibhai, MD, MSc, University Health Network, Toronto Rehab Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shabbir Alibhai, Staff Physician and Scientist, Toronto Rehabilitation Institute
• ClinicalTrials.gov Identifier: NCT01170598
• Other Study ID Numbers: AML002
• First Posted: Jul 27, 2010
• Last Update Posted: Apr 20, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by Shabbir Alibhai, Staff Physician and Scientist, Toronto Rehabilitation Institute: acute myeloid leukemia; AML; chemotherapy; exercise; quality of life; cancer-related fatigue; elderly; physical fitness; muscular strength; Feasibility; Efficacy; Safety
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Study Results

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.

Arm/Group Title	Exercise
Arm/Group Description	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.
Period Title: Overall Study
STARTED	35
COMPLETED	29
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Exercise
Arm/Group Description	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.
Overall Participants	35
Age, Customized (years) [Number]
<60 years	18
>=60 years	17
Sex: Female, Male (Count of Participants)
Female	19 54.3%
Male	16 45.7%

Outcome Measures

1. Primary Outcome

Title	Peak Aerobic Capacity (VO2peak)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	35
Baseline	6.9 (1.8)
Post-induction (weeks 4-6)	7.4 (1.7)

2. Primary Outcome

Title	6-minute Walk Test
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	35
Baseline	962.5 (286.3)
Post-induction (weeks 4-6)	1176.2 (360.6)

3. Primary Outcome

Title	Timed 10-chair Stands
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	35
Baseline	33.0 (26.0)
Post-induction (weeks 4-6)	31.1 (11.2)

4. Primary Outcome

Title	Grip Strength
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	35
Baseline	23.9 (11.0)
Post-induction (weeks 4-6)	21.6 (11.0)

5. Secondary Outcome

Title	Global Quality of Life
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	34
Baseline	45.1 (26.6)
Post-induction (weeks 4-6)	51.4 (21.4)

6. Secondary Outcome

Title	Fatigue
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	34
Baseline	31.5 (13.1)
Post-induction (weeks 4-6)	33.9 (11.7)

7. Secondary Outcome

Title	Length of Stay
Description	Length of stay (date of admission to hospital to date of discharge).
Time Frame	Post-induction (weeks 4-6)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	34
Mean (Standard Deviation) [days]	37.2 (10.6)

8. Secondary Outcome

Title	Intensive Care Unit (ICU) Admission
Description	Intensive care unit (ICU) admission (percentage of participants admitted to ICU during induction chemotherapy course).
Time Frame	Post-induction (weeks 4-6)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	34
Number [percentage of participants]	11.5 32.9%

9. Secondary Outcome

Title	Development of Sepsis
Description	Development of sepsis (percentage of participants who developed sepsis during induction chemotherapy course).
Time Frame	Post-induction (weeks 4-6)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	34
Number [percentage of participants]	26.5 75.7%

10. Primary Outcome

Title	Recruitment Rate
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	52
Number [percentage of patients]	67

11. Primary Outcome

Title	Retention
Description	Percentage of participants who remained in the study (did not withdraw voluntarily).
Time Frame	Baseline, Post-induction (weeks 4-6)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	35
Number [percentage of participants]	97 277.1%

12. Primary Outcome

Title	Program Adherence.
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exercise
Arm/Group Description	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.
Measure Participants	34
Number [percentage of exercise days completed]	45.8

Adverse Events

Time Frame	Adverse event data were captured over the course of the intervention (9 months).
Adverse Event Reporting Description	Any adverse events were captured using the National Cancer Institute: Cancer Therapy Evaluation Program Common Terminology Criteria version 3.0.
Arm/Group Title	Exercise
Arm/Group Description	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.
All Cause Mortality
	Exercise
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Exercise
	Affected / at Risk (%)	# Events
Total	0/35 (0%)
Other (Not Including Serious) Adverse Events
	Exercise
	Affected / at Risk (%)	# Events
Total	1/35 (2.9%)
Musculoskeletal and connective tissue disorders
Possible grade II musculoskeletal event	1/35 (2.9%)	1

Limitations/Caveats

Although as per study design, limitations include the lack of a control group due to non-randomization, a small sample size and lack of generalizability.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.