Fitness in Allogeneic Stem Cell Transplantation

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).

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