Acute Myeloid Leukaemia (AML) Patients Undergoing Induction Chemotherapy

A Pilot Exercise RCT for Acute Myeloid Leukaemia (AML) Patients Undergoing Induction Chemotherapy: Pre-randomization Phase

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Other: Exercise

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 Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Post-induction (weeks 4-6)
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.	Baseline, Post-induction (4-6 weeks)
Timed 10-chair Stands	Measure of lower-body strength completed by standing from a seated position 10 times as quickly as possible.	Baseline, Post-induction (weeks 4-6)
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.	Baseline, Post-induction (weeks 4-6)
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).	Baseline
Retention	Percentage of participants who remained in the study (did not withdraw voluntarily).	Baseline, Post-induction (weeks 4-6)
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).	Baseline, Post-induction (weeks 4-6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Post-induction (weeks 4-6)
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.	Baseline, Post-induction (weeks 4-6)
Length of Stay	Length of stay (date of admission to hospital to date of discharge).	Post-induction (weeks 4-6)
Intensive Care Unit (ICU) Admission	Intensive care unit (ICU) admission (percentage of participants admitted to ICU during induction chemotherapy course).	Post-induction (weeks 4-6)
Development of Sepsis	Development of sepsis (percentage of participants who developed sepsis during induction chemotherapy course).	Post-induction (weeks 4-6)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Alibhai SM, O'Neill S, Fisher-Schlombs K, Breunis H, Brandwein JM, Timilshina N, Tomlinson GA, Klepin HD, Culos-Reed SN. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy. Leuk Res. 2012 Oct;36(10):1255-61. doi: 10.1016/j.leukres.2012.05.016. Epub 2012 Jun 21.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: July 21, 2010
• First Submitted That Met QC Criteria: July 26, 2010
• First Posted (Estimate): July 27, 2010

Study Record Updates

• Last Update Posted (Estimate): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 18, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Safety; Feasibility; chemotherapy; exercise; quality of life; Efficacy; elderly; AML; acute myeloid leukemia; physical fitness; muscular strength; cancer-related fatigue
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: AML002