Fitness in Allogeneic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation Clinical Trial

— FAST  

Official title:

Fitness in Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02564458
• Other study ID #: 15-1705
• Secondary ID: 1R21CA192127-01A
• Status: Completed
• Phase: N/A
• Start date: September 2015
• Est. completion date: June 2018

Study information

• Verified date: July 2018
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose: The primary hypothesis of this study is that the combination of interval exercise training (IET) as well as motivational accelerometry (MA) delivered both as a 5-12 week intervention that will improve cardiorespiratory fitness in patients preparing to undergo allogeneic hematopoietic cell transplantation (alloHCT). MA is not an established term, but in respect to this study, MA refers to the use of wearable accelerometry paired with regular intervals of physical activity coaching from members of the study staff during the IET training. The study will also look at several secondary endpoints including the association of the intervention with changes in cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 (p16INK4a), and the association of the intervention with changes in symptoms and quality of life before and after transplant.

Participants: 60 patients will be randomized into two groups, 30 in the intervention group consisting of both IET and MA, and 30 in the control group applying usual care and use of wearable accelerometry without motivational physical activity coaching.

Procedures (methods): Results of this study will inform a randomized, multi-site study of a pre-transplant exercise intervention.

Description:

The investigator team for the current protocol has recently completed a single-arm pilot protocol (LCCC 1311) of a 6-week home-based unsupervised IET program (goal of three IET sessions per week, 65%-95% Max Heart Rate [MHR]) in patients planning to undergo alloHCT. In our study, participants preparing to undergo alloHCT experienced an average 3.8ml/kg*min improvement in peak volume of oxygen consumed (VO2peak) from pre to post-intervention. Patients in LCCC 1311 wore FitBit accelerometers throughout the study period.

The primary purpose of the current randomized controlled trial is to determine, in patients preparing to undergo alloHCT, whether an intervention comprised of interval exercise training and motivational accelerometry (IET/MA) will improve cardiorespiratory fitness more than the control group who receives usual care and an accelerometer without motivational physical activity coaching. The study will also look at several secondary endpoints including the association of the intervention with changes in p16INK4a, and the association of the intervention with changes in symptoms and quality of life before and after transplant.

This randomized controlled trial will include 60 patients preparing to undergo alloHCT (30 in the intervention group, 30 in the control group). We plan to analyze the effect of IET/MA on VO2peak. Subjects will be recruited after their transplant teams have determined that they will undergo alloHCT within the subsequent 5-12 weeks. Following recruitment, patients will undergo baseline fitness assessments consisting of cardiorespiratory exercise testing using indirect calorimetry on a cycle ergometry (for the assessment of VO2peak), 6 minute walk distance testing, and baseline physical activity, symptom and quality of life questionnaires. Participants randomized to the IET/MA group will then receive an individualized IET/MA prescription for a duration of at least 5 weeks, up until the time of admission for alloHCT or 12 weeks from the initiation of IET/MA, whichever occurs first. The mode of exercise can be walking, jogging, running, cycling, elliptical, stair climbing, or a combination of these, and will be performed unsupervised at home. For the first week, participants will be asked to engage in 30 minutes of aerobic exercise at any intensity for 3-4 days. For weeks two and beyond, participants will undergo 3-4 sessions of IET, consisting of a 5 minute warm-up and five 2-minute intervals, with the goal of reaching 80% MHR, separated by 3 minutes of recovery/light activity in between each interval. Each exercise session is a total of 30 minutes. Fitness assessments will be completed at the end of the intervention period, at the time of admission for alloHCT. Based on the improvement in VO2peak seen in the pre-alloHCT patient population in LCCC 1311, the current study is powered to detect a 3.8ml/kg*min VO2peak improvement in the intervention group relative to the control group.

All participants in both groups will be provided with a FitBit Surge accelerometer. Participants in the intervention group will also receive weekly motivation from a study team member to achieve a 10% week over week improvement in average steps/day. Participants in the control group will not receive this physical activity coaching. Participants will continue to wear the accelerometers after the intervention and until 1 year following alloHCT. Participants in both groups will have blood drawn for p16INK4a levels before and after the IET intervention. Participants in both groups will also complete symptom and quality of life questionnaires before the intervention and periodically throughout the year following alloHCT (please see study plan and time and events tables).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18 to 75 years of age, inclusive

• Verification of a functioning email address and access to electronic device(s) with the ability to charge and sync the FitBit Surge

• Planned allogeneic stem cell transplant with schedule that accommodates at least a 5 week exercise intervention, but not greater than 12 weeks

• Ability to understand and communicate in English

• Ability to understand and comply with study procedures for the entire length of the study

• Willing and able to provide written informed consent

Exclusion Criteria:

• Dementia, altered mental status, or psychiatric condition that would prohibit the understanding or rendering of informed consent

• Co-morbid illness that would contraindicate maximal effort exercise testing or participation in regular exercise programming as determined by the treating physician or exercise physiologist

• Concurrent radiation, chemotherapeutic, or investigational therapy other than transplant related therapy

• Concurrent enrollment in LCCC 1404

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplantation

Intervention

Behavioral:
• Interval Exercise Training/Motivational Accelerometry
During the 5-12 weeks before allogeneic stem cell transplant, the patient will participate in an at home, interval exercise training (IET) program, as well as wear a physical activity tracker, the FitBit Surge, combined with a weekly motivational call, termed Motivational Accelerometry (MA). The combined intervention is referred to as (IET/MA). The first week of the IET program consists of the participants being asked to engage in 30 minutes of aerobic exercise at any intensity for 3-4 days. For weeks two and beyond, patients be asked to undergo 3-4 sessions of IET, consisting of a 5 minute warm-up and five 2-minute intervals, with the goal of reaching 80% MHR, separated by 3 minutes of recovery/light activity in between each interval. Each exercise session is a total of 30 minutes. In addition, each week prior to transplant, the patient will receive a weekly check-in/motivational call from the study staff in order to track progress and motivate the patient to continue participation.

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (21)

Angadi SS, Mookadam F, Lee CD, Tucker WJ, Haykowsky MJ, Gaesser GA. High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study. J Appl Physiol (1985). 2015 Sep 15;119(6):753-8. doi: 10.1152/japplphysiol.00518.2014. Epub 2014 Sep 4. — View Citation

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Bevans M. Health-related quality of life following allogeneic hematopoietic stem cell transplantation. Hematology Am Soc Hematol Educ Program. 2010;2010:248-54. doi: 10.1182/asheducation-2010.1.248. Review. — View Citation

Bevans MF, Mitchell SA, Marden S. The symptom experience in the first 100 days following allogeneic hematopoietic stem cell transplantation (HSCT). Support Care Cancer. 2008 Nov;16(11):1243-54. doi: 10.1007/s00520-008-0420-6. Epub 2008 Mar 6. — View Citation

Bravata DM, Smith-Spangler C, Sundaram V, Gienger AL, Lin N, Lewis R, Stave CD, Olkin I, Sirard JR. Using pedometers to increase physical activity and improve health: a systematic review. JAMA. 2007 Nov 21;298(19):2296-304. Review. — View Citation

Guiraud T, Labrunee M, Gaucher-Cazalis K, Despas F, Meyer P, Bosquet L, Gales C, Vaccaro A, Bousquet M, Galinier M, Sénard JM, Pathak A. High-intensity interval exercise improves vagal tone and decreases arrhythmias in chronic heart failure. Med Sci Sports Exerc. 2013 Oct;45(10):1861-7. doi: 10.1249/MSS.0b013e3182967559. — View Citation

Hallal PC, Victora CG. Reliability and validity of the International Physical Activity Questionnaire (IPAQ). Med Sci Sports Exerc. 2004 Mar;36(3):556. — View Citation

Jones LW, Eves ND, Haykowsky M, Joy AA, Douglas PS. Cardiorespiratory exercise testing in clinical oncology research: systematic review and practice recommendations. Lancet Oncol. 2008 Aug;9(8):757-65. doi: 10.1016/S1470-2045(08)70195-5. Review. — View Citation

Khera N, Zeliadt SB, Lee SJ. Economics of hematopoietic cell transplantation. Blood. 2012 Aug 23;120(8):1545-51. doi: 10.1182/blood-2012-05-426783. Epub 2012 Jun 13. — View Citation

Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Ibrahim JG, Thomas NE, Sharpless NE. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell. 2009 Aug;8(4):439-48. doi: 10.1111/j.1474-9726.2009.00489.x. Epub 2009 May 22. — View Citation

Majhail NS, Rizzo JD, Hahn T, Lee SJ, McCarthy PL, Ammi M, Denzen E, Drexler R, Flesch S, James H, Omondi N, Pedersen TL, Murphy E, Pederson K. Pilot study of patient and caregiver out-of-pocket costs of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2013 Jun;48(6):865-71. doi: 10.1038/bmt.2012.248. Epub 2012 Dec 10. — View Citation

Moholdt T, Bekken Vold M, Grimsmo J, Slørdahl SA, Wisløff U. Home-based aerobic interval training improves peak oxygen uptake equal to residential cardiac rehabilitation: a randomized, controlled trial. PLoS One. 2012;7(7):e41199. doi: 10.1371/journal.pone.0041199. Epub 2012 Jul 18. — View Citation

Nybo L, Sundstrup E, Jakobsen MD, Mohr M, Hornstrup T, Simonsen L, Bülow J, Randers MB, Nielsen JJ, Aagaard P, Krustrup P. High-intensity training versus traditional exercise interventions for promoting health. Med Sci Sports Exerc. 2010 Oct;42(10):1951-8. doi: 10.1249/MSS.0b013e3181d99203. — View Citation

Nytrøen K, Rustad LA, Aukrust P, Ueland T, Hallén J, Holm I, Rolid K, Lekva T, Fiane AE, Amlie JP, Aakhus S, Gullestad L. High-intensity interval training improves peak oxygen uptake and muscular exercise capacity in heart transplant recipients. Am J Transplant. 2012 Nov;12(11):3134-42. doi: 10.1111/j.1600-6143.2012.04221.x. Epub 2012 Aug 17. — View Citation

Puhan MA, Büsching G, Schünemann HJ, VanOort E, Zaugg C, Frey M. Interval versus continuous high-intensity exercise in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2006 Dec 5;145(11):816-25. — View Citation

Sanoff HK, Deal AM, Krishnamurthy J, Torrice C, Dillon P, Sorrentino J, Ibrahim JG, Jolly TA, Williams G, Carey LA, Drobish A, Gordon BB, Alston S, Hurria A, Kleinhans K, Rudolph KL, Sharpless NE, Muss HB. Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer. J Natl Cancer Inst. 2014 Apr;106(4):dju057. doi: 10.1093/jnci/dju057. Epub 2014 Mar 28. — View Citation

Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvão DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, Schneider CM, von Gruenigen VE, Schwartz AL; American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010 Jul;42(7):1409-26. doi: 10.1249/MSS.0b013e3181e0c112. Erratum in: Med Sci Sports Exerc. 2011 Jan;43(1):195. — View Citation

Shephard RJ. Tests of maximum oxygen intake. A critical review. Sports Med. 1984 Mar-Apr;1(2):99-124. Review. — View Citation

Wiskemann J, Dreger P, Schwerdtfeger R, Bondong A, Huber G, Kleindienst N, Ulrich CM, Bohus M. Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Blood. 2011 Mar 3;117(9):2604-13. doi: 10.1182/blood-2010-09-306308. Epub 2010 Dec 29. — View Citation

Wiskemann J, Huber G. Physical exercise as adjuvant therapy for patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008 Feb;41(4):321-9. Epub 2007 Nov 19. Review. — View Citation

Wood WA, Deal AM, Bennett AV, Mitchell SA, Abernethy AP, Basch E, Bailey C, Reeve BB. Comparison of seven-day and repeated 24-hour recall of symptoms in the first 100 days after hematopoietic cell transplantation. J Pain Symptom Manage. 2015 Mar;49(3):513-20. doi: 10.1016/j.jpainsymman.2014.06.011. Epub 2014 Aug 13. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Compare average steps per day during a 5-12 week period of time prior to alloHCT in patients receiving IET/MA vs. controls		5-12 weeks
Other	Compare post-alloHCT average steps per day in patients who received pre-alloHCT IET/MA vs controls.		Post-alloHCT refers to Day0 (transplant day) through Day+365
Other	Compare post-alloHCT symptom burden and quality of life in patients who received pre-alloHCT IET/MA vs controls.		Post-alloHCT refers to Day0 (transplant day) through Day+365
Other	Compare post-alloHCT days alive and out of the hospital within the first 100 days post-transplant in patients who received pre-alloHCT IET/MA vs controls.		Post-alloHCT refers to the initial discharge day after allo-HCT through the first 100 days out of the hospital and/or alive, whichever is the shorter duration.
Other	Compare post-alloHCT survival in patients who received pre-alloHCT IET/MA vs controls.		Post-alloHCT refers to Day0 (transplant day) through Day+365
Primary	Compare changes in VO2peak after a 5-12 week period of time prior to alloHCT in patients undergoing interval exercise training (IET) and motivational accelerometry (MA) vs patients receiving usual care (controls).	Patients will undergo a baseline fitness assessment consisting of cardiorespiratory exercise testing using indirect calorimetry on a cycle ergometer (for the assessment of VO2peak).	5-12 weeks
Secondary	Compare changes in 6 minute walk distance (6MWD) after a 5-12 week period of time prior to alloHCT in patients receiving IET/MA vs controls.		5-12 weeks
Secondary	Compare changes in peripheral blood p16INK4a after a 5-12 week period of time prior to alloHCT in patients receiving IET/MA vs controls.		5-12 weeks

External Links

•   National Cancer Institute. Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
•   National Institutes of Health. Patient Reported Outcomes Measurement Information System (PROMIS).
•   Pasquini MC, Wang Z. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides, 2011. Slides 3, 18, 21-40.