A Phase III Randomized, Multicenter Trial Testing Whether Exercise or Stress Management Improves Functional Status and Symptoms of Autologous and Allogeneic Recipients (BMT CTN #0902)
Phase: NA
Conditions: Physiological Stress
Sponsor: Medical College of Wisconsin

BMT CTN 0902  
A Phase III Randomized, Multicenter Trial Testing 
Whether Exercise or Stress Management Improves 
Functional Status and Symptoms of Autologous 
and Allogeneic Recipients 
NCT01278927 

 
 
A Phase III Randomized, Multicenter Trial  
Testing Whether Exercise or Stress Management Improves  
Functional Status and Symptoms of Autologous and Allogeneic 
Recipients  
 
BMT CTN PROTOCOL 0902 
Version 2.0 
 
 
Study Chairpersons 
Stephanie J. Lee, M.D., M.P.H.1 
Paul B. Jacobsen, Ph.D.2 
 
Smita Bhatia, M.D., M.P.H.3 
Amrin Chowdhury4 
Mary Horowitz, M.D., M.S.5 
Heather Jim, Ph.D.2  
Jennifer Le-Rademacher, PhD.5 
Brent Logan, Ph.D.5 
Navneet Majhail, M.D, M.S.6 
J. Douglas Rizzo, M.D., M.S.5 
Karen L. Syrjala, Ph.D.1 
Galen Switzer, Ph.D.7 
John R. Wingard, M.D.8 
William Wood, M.D. 9 
 
 
Sponsored by the National Institutes of Health 
National Heart, Lung, and Blood Institute 
National Cancer Institute 
 
 
1 Fred Hutchinson Cancer Research Center 
2 H. Lee Moffitt Cancer Center 
3 City of Hope National Medical Center 
4 The EMMES Corporation 
5 CIBMTR, Medical College of Wisconsin 
6 University of Minnesota  
7 University of Pittsburgh  
8 University of Florida 
9  University of North Carolina 
 
 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
i 
 
Core Study Participants: 
Affiliate Study Participants: 
Case Western Reserve University Consortium 
  - Ohio State University 
  - Oregon Health & Science University 
  - University Hospitals of Cleveland 
City of Hope National Medical Center 
Fred Hutchinson Cancer Research Center 
Johns Hopkins University 
University of Florida College of Medicine 
University of Michigan Cancer Center 
University of Minnesota  
University of Nebraska Medical Center 
Fox Chase/Temple University 
H. Lee Moffitt Cancer Center 
Karmanos Cancer Institute 
Medical College of Wisconsin 
Medical University of South Carolina 
Rush University Medical Center 
 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
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PROTOCOL SYNOPSIS – BMT CTN PROTOCOL 0902 
 
A Phase III Randomized, Multicenter Trial  
Testing Whether Exercise or Stress Management Improves  
Functional Status and Symptoms of Autologous and Allogeneic Recipients 
 
 
Principal Investigators: Stephanie J. Lee, M.D., M.P.H. 
 
Paul Jacobsen, Ph.D. 
 
Study Design: 
 
Phase 
III, 
randomized, 
unblinded, 
multicenter, 
prospective 
comparative study of exercise, stress management, the combination 
of exercise and stress management versus standard care to improve 
functional status and symptoms. 
Patients complete baseline measures and are randomized to one of the 
four arms, stratified by center and type of transplant procedure 
(autologous/syngeneic, 
myeloablative 
allogeneic, 
reduced 
intensity/non-ablative allogeneic).  The exercise and stress 
management interventions are designed to be self-administered after 
a brief, 10-15 minute training session.   
Endpoint assessment will occur at 100 days +/- 14 days and 6 months 
+/- one month 
 
Primary Objective:  
To determine whether exercise or stress management improves self-
reported physical and mental functioning compared to standard care 
at 100 days using an intention to treat analysis 
 
Secondary Objectives: 
a) To determine whether exercise or stress management improves 
physical and mental functioning compared to standard care at 100 
days, limiting the analysis to patients who survive and provide a 
Day 100 self-assessment (conditional analysis with main effects) 
 
b) To compare physical and mental functioning among the 4 groups 
using pair-wise comparisons, limiting the analysis population to 
patients who provide a Day 100 self-assessment (pair-wise 
conditional analysis) 
 
c) To compare symptoms (fatigue, pain, sleep, nausea, cancer and 
treatment distress) at 100 days among patients who provide a Day 
100 self-assessment (conditional analysis) 
d) To compare the number of hospital days within the first 100 days 
e) To assess durability of effects by comparing functional status and 
symptoms at 6 months 
f) To compare overall survival at 6 months 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
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Eligibility: 
Inclusions: 
a) 
Age 18 years or older. 
b) 
Able to speak and read English. 
c) 
Able to exercise at low to moderate intensity - adequate 
cardiopulmonary reserve, as judged by self-reported ability to 
walk up one flight of stairs, no requirement for supplemental 
oxygen, and physician judgment. 
d) Willing and able to provide informed consent. 
e) Stated willingness to comply with study procedures and 
reporting requirements. 
f) Planned autologous or allogeneic transplantation within 6 
weeks. 
 
Exclusions: 
a) Orthopedic, neurologic or other problems which prevent safe 
ambulation and protocol adherence. 
b) Participation in another clinical trial with quality of life or 
functional status as a primary endpoint. 
c) Planned anti-cytotoxic therapies, other than TKI, Gleevac or 
Rituximab OR unless pre-approved by the protocol chair, within 
100 days post-transplant. 
d) Planned DLI within 100 days post-transplant. 
e) Planned 
tandem 
transplant 
(autologous/autologous 
or 
autologous/allogeneic). 
 
Treatment Description: Exercise. The goal is to have participants exercise by walking 3 to 5 
times per week for at least 20 to 30 minutes at a maximum intensity 
of 50 to 75% of their estimated heart rate reserve.    
Stress management. The goal is to have participants practice paced 
abdominal breathing, progressive muscle relaxation with guided 
imagery, and use of coping self-statements to decrease stress. 
Standard care will follow institutional guidelines that reflect 
standard practices  
All 4 groups will receive a general informational DVD about 
hematopoietic cell transplantation. 
 
Accrual Objective: 
700 subjects will be randomized approximately 1:1:1:1 across the 
four study arms. 
 
Accrual Period: 
The estimated accrual period is 36 months.  

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
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Study Duration: 
Patients will be followed for 6 months after transplantation.  
 
Statistical issues: 
The primary objectives of the study are to compare physical 
functioning and mental functioning between the groups who do or do 
not receive exercise training and between the groups who do or do 
not receive stress management training (factorial design).  The 
sample size calculation is based upon having 85% power to detect 
differences of 0.5 STD in the primary endpoint between groups 
(exercise vs. no exercise or stress management vs. no stress 
management) after splitting the type I error rate across these 4 
primary comparisons.  This analysis controls for baseline assessment 
and clinical characteristics and accounts for cancelled transplants and 
missing data using an Intention-to-Treat analysis.  Randomization 
will be stratified for balance based on center and type of transplant 
(autologous, myeloablative allogeneic, and non-myeloablative 
allogeneic groups).  
 
 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
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TABLE OF CONTENTS 
 
 
1. 
BACKGROUND AND RATIONALE ................................................................................. 1-1 
1.1. 
Exercise ................................................................................................................................... 1-1 
1.2. 
Stress Management ................................................................................................................ 1-7 
1.3. 
Rationale for Combined Exercise and Stress Management ............................................... 1-9 
2. 
STUDY DESIGN .................................................................................................................... 2-1 
2.1. 
Study Overview ...................................................................................................................... 2-1 
2.2. 
Hypothesis and Study Objectives ......................................................................................... 2-1 
2.2.1. 
Primary Objective .................................................................................................................... 2-1 
2.2.2. 
Secondary Objectives ............................................................................................................... 2-1 
2.3. 
Patient Eligibility for Randomization .................................................................................. 2-2 
2.3.1. 
Patient Inclusion Criteria ......................................................................................................... 2-2 
2.3.2. 
Patient Exclusion Criteria ........................................................................................................ 2-2 
2.4. 
Interventions .......................................................................................................................... 2-2 
2.4.1. 
Exercise .................................................................................................................................... 2-3 
2.4.2. 
Stress Management .................................................................................................................. 2-3 
2.4.3. 
Combination Exercise and Stress Management ....................................................................... 2-4 
2.4.4. 
Standard Care Only (informational DVD) ............................................................................... 2-5 
2.4.5. 
Training of Interventionist ....................................................................................................... 2-5 
2.4.6. 
Quality Control of Intervention Delivery ................................................................................. 2-6 
2.5. 
Stem Cell Transplantation .................................................................................................... 2-6 
2.6. 
Design Rationale .................................................................................................................... 2-6 
2.7. 
Study Risks ............................................................................................................................. 2-8 
2.8. 
Study Benefits ........................................................................................................................ 2-8 
2.9. 
Study Withdrawal .................................................................................................................. 2-8 
3. 
STUDY ENDPOINTS ............................................................................................................ 3-1 
3.1. 
Primary Endpoint .................................................................................................................. 3-1 
3.1.1. 
Functional Status ...................................................................................................................... 3-1 
3.2. 
Secondary Endpoints ............................................................................................................. 3-1 
3.2.1. 
Symptoms ................................................................................................................................ 3-1 
3.2.2. 
Days of Hospitalization ............................................................................................................ 3-2 
3.2.3. 
Late Outcomes (6 months) ....................................................................................................... 3-2 
3.2.4. 
Survival (6 months) .................................................................................................................. 3-2 
3.3. 
Additional Clinical Factors ................................................................................................... 3-2 
3.3.1. 
Demographic, Clinical and Transplant Characteristics ............................................................ 3-2 
3.3.2. 
Intervention Credibility ............................................................................................................ 3-2 
3.3.3. 
Exercise Activity ...................................................................................................................... 3-2 
3.3.4. 
Stress Reduction Activity ........................................................................................................ 3-3 
4. 
PATIENT REGISTRATION, ENROLLMENT AND RANDOMIZATION ................... 4-1 
4.1. 
Approaching Patients, Eligibility Screening and Obtaining Consent ............................... 4-1 
4.2. 
Study Registration and Randomization ............................................................................... 4-1 
4.3. 
Training and Reinforcement in Intervention Use ............................................................... 4-1 
4.4. 
Patient Assessment................................................................................................................. 4-2 
4.4.1. 
Endpoint Assessment ............................................................................................................... 4-2 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
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4.4.2. 
Use of Intervention .................................................................................................................. 4-2 
4.5. 
Study Monitoring ................................................................................................................... 4-2 
4.5.1. 
Case Report Forms ................................................................................................................... 4-3 
4.5.2. 
Reporting Patient Deaths ......................................................................................................... 4-3 
4.5.3. 
Reporting Serious Adverse Events .......................................................................................... 4-3 
4.5.3.1. 
Patient SAEs ............................................................................................................................. 4-3 
4.5.4. 
CIBMTR Data Reporting ......................................................................................................... 4-3 
4.6. 
Quality Control ...................................................................................................................... 4-4 
5. 
STATISTICAL CONSIDERATIONS ................................................................................. 5-1 
5.1. 
Study Design ........................................................................................................................... 5-1 
5.1.1. 
Accrual ..................................................................................................................................... 5-1 
5.1.2. 
Randomization ......................................................................................................................... 5-1 
5.1.3. 
Primary Endpoint ..................................................................................................................... 5-1 
5.2. 
Sample Size and Power Calculations ................................................................................... 5-2 
5.2.1. 
Power Calculation for Primary Intention-to-Treat Analysis .................................................... 5-2 
5.2.2. 
Power Calculation for Key Secondary Analysis of Main Effects in Survivors who Complete 
Day 100 Assessments ............................................................................................................. 5-3 
5.2.3. 
Power Calculation for Key Secondary Analysis Comparing all Four Treatment Combinations 
in Survivors who Complete Day 100 Assessments ................................................................ 5-3 
5.3. 
Interim Analysis Plan ............................................................................................................ 5-3 
5.3.1. 
Interim Analysis for Efficacy ................................................................................................... 5-3 
5.3.2. 
Interim Analysis for Futility .................................................................................................... 5-3 
5.4. 
Demographics and Baseline Characteristics ....................................................................... 5-4 
5.5. 
Analysis Plan .......................................................................................................................... 5-4 
5.5.1. 
Analysis of Primary Endpoints ................................................................................................ 5-4 
5.5.2. 
Analysis of Secondary Endpoints ............................................................................................ 5-4 
5.5.3. 
Analysis of Additional Clinical Factors ................................................................................... 5-6 
5.6. 
Safety Analysis ....................................................................................................................... 5-6 
 
 
LIST OF APPENDICES 
 
APPENDIX A – HUMAN SUBJECTS 
APPENDIX B – INFORMED CONSENTS 
APPENDIX C – REFERENCES 
 
 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
1-1 
CHAPTER 1 
 
 
1. BACKGROUND AND RATIONALE 
 
The adverse effects of hematopoietic cell transplantation (HCT) on short and long term quality of 
life are well documented (reviewed in Pidala1).  Patients experience numerous aversive 
symptoms (e.g., nausea, fatigue, and sleep disturbance) that are accompanied by declines in 
physical and mental well-being.  Although most longitudinal studies show return to baseline 
functioning for the majority of patients, it may take 6 to 12 months or longer to reach this goal.2,3  
 
Clinical trials have shown that training in stress management techniques and participation in 
formal exercise programs each offered in isolation are effective in improving quality of life in 
patients receiving standard-dose chemotherapy and HCT.  Review of these studies suggests that 
stress management interventions primarily improve mental health outcomes and nausea.  The 
impact of exercise training interventions is more variable; most studies report physical health 
benefits, with some studies also reporting mental health benefits.  Small studies suggest that 
combining stress management training and exercise are feasible and well-tolerated, but whether 
the combination provides an additive or synergistic impact on quality of life outcomes has not 
been directly investigated.   
 
The purpose of this study is to test whether exercise or stress management training delivered to 
autologous and allogeneic HCT patients prior to transplantation can improve functional status 
and the transplant experience.  
 
1.1. 
Exercise 
 
A 2008 review found 15 published studies of exercise in the context of HCT up through May 
2007.  A total of 609 patients were included in the review, with no study reporting any 
unexpected or negative effects.4-19  Study size ranged from 12-100 participants with 
approximately half autologous and half allogeneic patients.  Most involved isolated aerobic 
exercise programs such as walking, recumbent biking or treadmills and occurred during or after 
the transplantation process; strength training and combined strategies were evaluated less often.  
Significant benefits were reported for physical performance, quality of life, and fatigue.20  A 
variety of biological, psychological, and social mechanisms have been proposed to account for 
the beneficial effects of exercise on quality of life in people with cancer.21 
 
The University of Minnesota conducted a randomized trial of a structured walking regimen on a 
treadmill at a dosage of 15 minutes twice daily while in the hospital followed by 30 minutes of 
walking daily after discharge.  Results in 122 patients showed a smaller decline in Karnofsky 
performance status in the exercise group compared to control patients which was not statistically 
significant in the whole group but was statistically significant in the subset of older and less fit 
patients receiving non-ablative conditioning (p=0.04).  Compliance was excellent with 93% in 
the exercise arm exercising during hospitalization compared to 58% in the control arm.  There 
were no differences in length of hospitalization or survival, but all trends favored the exercise 
group.19 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
1-2 
Thus, self-administered exercise in the context of HCT, even during acute hospitalization, is 
feasible and small studies suggest significant benefits over standard care. Table 1.1 summarizes 
relevant studies. 
 
 
TABLE 1.1 – SUMMARY OF EXERCISE TRIALS IN ADULT HCT 
 
Author 
Year 
N 
Study 
Characteristics 
Intervention 
Endpoints 
Summary of Results 
Cunningham 
BA, Morris 
G, Cheney 
CL, et al1 
1986 
30 
RCT, allogeneic 
HCT 
3 groups: Control, 
physical therapy 
3x/week, physical 
therapy 5x/week 
Muscle protein 
status measured 
by nitrogen 
balance, 
creatinine, 3 
methylhistidine 
excretion 
Results favored a muscle 
protein-sparing effect of 
exercise but patient 
heterogeneity problematic 
Decker WA, 
Turner-
McGlade J, 
Fehir KM2 
1989 
5 
Single arm 
Individualized 
endurance 
training/exercise 
prescription (30 
min 3x/week) 
 
Results not significant 
Dimeo F, 
Bertz H, 
Finke J, et 
al3 
1996 
20 
Single arm, 17 
allogeneic and 3 
autologous HCT, 
started 30 days 
post allogeneic 
HCT 
Professionally 
administered rehab 
program, treadmill 
walking 5x/week 
for 6 weeks 
Training speed, 
distance walked, 
maximal METs, 
heart rate, lactate 
concentration 
Statistically significant 
(p<0.001) improvements 
in all measures pre-post in 
completers (n=14) 
Dimeo FC, 
Tilmann 
MHM, Bertz 
H, et al. 4 
1997 
36 
Concurrent 
controls (n=18) 
and treated group 
(n=18) based on 
distance to 
hospital, 
autologous HCT 
Professionally 
administered rehab 
program, treadmill 
walking 5x/week 
for 6 weeks 
Maximal 
performance, 
maximum heart 
rates, 
hemoglobin, 
interviews at 7 
weeks 
Statistically significant 
improvement in 
maximum performance in 
the exercise group 
compared with controls 
(p=0.04), higher 
hemoglobin than controls 
(p=0.04), no difference in 
heart rates. Fatigue and 
limitations with usual 
daily activities reported 
by 25% of control 
patients, 0% of 
intervention patients in 
completers (n=36) 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
1-3 
Author 
Year 
N 
Study 
Characteristics 
Intervention 
Endpoints 
Summary of Results 
Dimeo F, 
Fetscher S, 
Lange W, et 
al5 
1997 
70 
RCT, autologous 
HCT 
Professionally 
administered 
exercise regimen of 
biking on a supine 
ergometer 30 min 
daily, goal to reach 
50% of cardiac 
reserve, during 
hospitalization 
Maximal speed 
on the treadmill 
test at discharge 
Exercise group with less 
decrement in performance 
(p=0.05), higher maximal 
physical performance 
(p=0.04), shorter duration 
of neutropenia (p=0.01) 
and thrombocytopenia 
(p=0.06), severity of 
diarrhea (p=0.04), 
severity of pain (p=0.01) 
and duration of 
hospitalization (p=0.03) 
among completers (n=60). 
Similar results in 
multivariate regression 
Dimeo FC, 
Stieglitz RD, 
Novelli-
Fischer U, et 
al6 
1999 
59 
RCT according 
to week 
recruited, 
autologous HCT 
Professionally 
administered 
exercise regimen of 
biking on a supine 
ergometer 30 min 
daily, goal to reach 
50% of cardiac 
reserve, during 
hospitalization 
Patient-reported 
outcomes: 
POMS, SCL-90 
Control group had 
increased fatigue and 
somatic complaints 
(p<0.01) and decreased 
vigor (p=0.05) but not in 
the exercise group. 
Exercise group had 
improvement in 
obsessive-compulsive 
traits, fear, interpersonal 
sensitivity, and phobic 
anxiety (p<0.05) 
Dimeo F, 
Schwartz S, 
Fietz T, et 
al7 
2003 
66 
Single arm, 
conventional 
chemo (n=45) or 
autologous HCT 
(n=21) 
Professionally 
administered rehab 
program, treadmill 
walking 5x/week, 
during 
hospitalization 
Walking speed, 
perceived effort 
at 80% maximum 
heart rate 
No significant change 
over time, which was 
viewed as positive by the 
authors given the 
anticipated decline 
without exercise 
Courneya 
KS, Keats 
MR, Turner 
AR. 8 
2000 
25 
Single arm, 
autologous HCT 
Self-administered 
supine ergometer 
during 
hospitalization 
Patient-reported 
outcomes: FACT-
BMT, Bradburn 
Affect Balance 
Scale, SWLS 
(satisfaction with 
life scale), CES-
D, STAI 
40% reported no cycling 
at all, 24% reported no 
cycling or walking, mean 
combined cycling/walking 
was < 8 min/day. Exercise 
during hospitalization 
correlated with all Quality 
of Life (QOL) and PRO 
indices including 
depression, anxiety and 
days hospitalized except 
emotional and social well-
being 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
1-4 
Author 
Year 
N 
Study 
Characteristics 
Intervention 
Endpoints 
Summary of Results 
Mello M, 
Tanaka C, 
Dulley FL. 9  
2003 
18 
RCT, allogeneic 
HCT 
Control vs. 6 week 
exercise program 
of active exercise, 
muscle stretching, 
treadmill walking 
for 40 min, 
5x/week 
Muscle strength 
Control group had 
decreased strength, less 
change in exercise group; 
intergroup comparison not 
significant 
Hayes SC, et 
al10-13 
2003 
2003 
2004 
2004 
12 
RCT and 
matching, 
autologous HCT 
Professionally 
administered, 
control/stretching 
group vs. aerobic, 
treadmill, 3x/week 
20-40 min at 70-
90% of maximum 
heart rate and 
resistance exercise, 
2x/week x 3 
months 
Lymphocyte 
number and 
function, total 
energy 
expenditure, body 
weight, body 
composition, 
patient-reported 
outcomes 
(CARES), peak 
aerobic capacity 
and muscular 
strength 
No difference in 
immunologic parameters. 
Exercise group had gains 
in fat-free mass (p<0.01), 
decreased % body fat 
(p<0.05), improved QOL 
(global QOL, physical 
and psychosocial QOL, 
fewer and less severe 
problems), peak aerobic 
capacity (p=0.05) and 
upper and lower body 
strength (p<0.01) 
compared to controls 
Coleman 
EA, Coon S, 
Hall-Barrow 
J et al. 14 
2003 
24 
RCT, autologous 
HCT 
Control with 
encouragement to 
be active vs. 
Home-based 
exercise therapy 
with walking and 
strength resistance 
training with 
stretch bands 
Fatigue, mood 
disturbance, 
sleep, lean body 
weight 
Statistical improvement in 
lean body weight (8 
completers) 
Kim SD, 
Kim HS15 
2006 
35 
RCT, allogeneic 
HCT 
Control vs. bed 
exercise 30 min 
every day, 
relaxation 
breathing for 6 
weeks 
Lymphocyte 
count 
Decrease in lymphocyte 
in the control group but 
not in the exercise group. 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
1-5 
Author 
Year 
N 
Study 
Characteristics 
Intervention 
Endpoints 
Summary of Results 
Wilson RW, 
Jacobsen 
PB, Fields 
KK16 
2005 
17 
Single arm, > 6 
months after 
either autologous 
(n=13) or 
allogeneic (n=4) 
HCT 
Home based 
exercise, 20-40 min 
at 40-60% of 
predicted heart rate 
reserve, 3-5 x week 
for 12 weeks 
Patient-reported 
outcomes: SF36, 
fatigue symptom 
inventory; 
ventilatory 
threshold (aerobic 
fitness) 
Aerobic fitness, fatigue 
severity, physical well-
being improved (p<0.05) 
(completers=13) 
Carlson LE, 
Smith D, 
Russell J, et 
al17 
2006 
12 
Single arm, > 6 
months after 
allogeneic HCT 
Individualized mild 
aerobic exercise 
program using 
ergometers, 15-30 
minues, 3x week x 
12 weeks 
Patient reported 
outcomes: FACT-
F, Brief Fatigue 
Inventory, CES-
D, POMS; SCID; 
physiological 
measures (VT2, 
changes in stroke 
volume, heart 
rate, lactate level, 
perceived 
exertion) 
Significant improvements 
in fatigue (BFI, FACT-F), 
vigor (p<0.001), VT2, 
stroke volume, and 
significant decrease in 
heart rate, lactate level 
and perceived exertion. 
The effect size for fatigue 
was 1.82 STD 
DeFor TE, 
Burns LJ, 
Gold EMA, 
et al18 
2007 
100 
RCT, allogeneic 
HCT 
Control vs. 
structured walking 
program, treadmill 
walking 2x/day x 
15 minutes while in 
hospital, 30 
minutes daily as 
outpatients 
Karnofsky 
performance 
status, self-
reported well 
being, length of 
hospital stay, 
survival 
Decline in KPS less in the 
exercise group than 
control group, but not 
statistically significant 
(p=0.2). In subset 
analyses, older and less fit 
patients receiving reduced 
intensity had less KPS 
decline than controls 
(p=0.04). Better physical 
well-being  at hospital 
discharge in overall group 
(p<0.01) and better 
physical and emotional 
well being at discharge in 
non-myeloablative 
exercise group compared 
with control 
Coleman 
EA, Coon 
SK, 
Kennedy RL 
et al19 
2008 
120 
RCT, autologous 
HCT, myeloma 
Control vs. Home-
based 
individualized 
program, walking, 
stretching, strength 
resistance training 
5x week 
Number of RBC 
and platelet 
transfusions and 
total number of 
stem cell 
collection days 
Exercise group had 
significantly fewer RBC 
transfusions and attempts 
at stem cell collection 
than controls; note that 
although randomized, 
exercise group had greater 
exercise capacity before 
HCT 

BMT CLINICAL TRIALS NETWORK 
 
Exercise and Stress Reduction– Protocol 0902 
Version 2.0 dated March 30, 2011 
 
 
1-6 
Author 
Year 
N 
Study 
Characteristics 
Intervention 
Endpoints 
Summary of Results 
Jarden M, 
Baadsgaard 
MT, 
Hovgaard 
DJ et al20-22 
2007 
2009 
2009 
42 
RCT, allogeneic 
HCT 
Control vs. 
Supervised, 1 hr 5x 
week of cycling, 
stretching, 
resistance training, 
progressive muscle 
relaxation and 
cognitive 
behavioral therapy 
Aerobic capacity, 
muscle strength, 
functional 
performance, 
physical activity 
level, clinical 
outcomes, 
patient-reported 
outcomes 
(EORTC, FACT-
An, HADS, Mimi 
Mac) 
Intervention group had 
better physical capacity 
(p<0.0001), muscle 
strength, functional 
performance, less diarrhea 
(p=0.01), fewer days TPN 
(p=0.02). Longitudinal 
changes in QOL, fatigue 
and psychological well 
being showed a trend to 
better outcomes with 
intervention but not 
statistically significant. 
Separate paper reports 
less symptom intensity 
 
1 Cunningham BA, Morris G, Cheney CL, et al: Effects of resistive exercise on skeletal muscle in marrow transplant recipients 
receiving total parenteral nutrition. JPEN J Parenter Enteral Nutr 10:558-63, 1986 
2 Decker WA, Turner-McGlade J, Fehir KM: Psychosocial aspects and the physiological effects of a cardiopulmonary exercise 
program in patients undergoing bone marrow transplantation (BMT) for acute leukemia (AL). Transplant Proc 21:3068-9, 
1989 
3 Dimeo F, Bertz H, Finke J, et al: An aerobic exercise program for patients with haematological malignancies after bone marrow 
transplantation. Bone Marrow Transplant 18:1157-60., 1996 
4 Dimeo FC, Tilmann MH, Bertz H, et al: Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy 
and autologous peripheral stem cell transplantation. Cancer 79:1717-22, 1997 
5 Dimeo F, Fetscher S, Lange W, et al: Effects of aerobic exercise on the physical performance and incidence of treatment-related 
complications after high-dose chemotherapy. Blood 90:3390-4., 1997 
6 Dimeo FC, Stieglitz RD, Novelli-Fischer U, et al: Effects of physical activity on the fatigue and psychologic status of cancer 
patients during chemotherapy. Cancer 85:2273-7, 1999 
7 Dimeo F, Schwartz S, Fietz T, et al: Effects of endurance training on the physical performance of patients with hematological 
malignancies during chemotherapy. Support Care Cancer 11:623-8, 2003 
8 Courneya KS, Keats MR, Turner AR: Physical exercise and quality of life in cancer patients following high dose chemotherapy 
and autologous bone marrow transplantation. Psychooncology 2000; 9:127-36 
9 Mello M, Tanaka C, Dulley FL: Effects of an exercise program on muscle performance in patients undergoing allogeneic bone 
marrow transplantation. Bone Marrow Transplant 32:723-8, 2003 
10 Hayes S, Davies PS, Parker T, et al: Total energy expenditure and body composition changes following peripheral blood stem 
cell transplantation and participation in an exercise programme. Bone Marrow Transplant 31: 331-8, 2003 
11 Hayes SC, Rowbottom D, Davies PS, et al: Immunological changes after cancer treatment and participation in an exercise 
program. Med Sci Sports Exerc 35: 2-9, 2003. 
12 Hayes S, Davies PS, Parker T, et al: Quality of life changes following peripheral blood stem cell transplantation and 
participation in a mixed-type, moderate-intensity, exercise program. Bone Marrow Transplant 33:553-8, 2004 
13 Hayes SC, Davies PS, Parker TW, et al: Role of a mixed type, moderate intensity exercise programme after peripheral blood 
stem cell transplantation. Br J Sports Med 38:304-9; discussion 309, 2004 
14 Coleman EA, Coon S, Hall-Barrow J, et al: Feasibility of exercise during treatment for multiple myeloma. Cancer Nurs 
26:410-9, 2003 
15 Kim SD, Kim HS: A series of bed exercises to improve lymphocyte count in allogeneic bone marrow transplantation patients. 
Eur J Cancer Care (Engl) 15:453-7, 2006 
16 Wilson RW, Jacobsen PB, Fields KK: Pilot study of a home-based aerobic exercise program for sedentary cancer survivors 
treated with hematopoietic stem cell transplantation. Bone Marrow Transplant 35:721-7, 2005 
17 Carlson LE, Smith D, Russell J, et al: Individualized exercise program for the treatment of severe fatigue in patients after 
allogeneic hematopoietic stem-cell transplant: a pilot study. Bone Marrow Transplant 37:945-54, 2006 
18 DeFor TE, Burns LJ, Gold EM, et al: A randomized trial of the effect of a walking regimen on the functional status of 100 
adult allogeneic donor hematopoietic cell transplant patients. Biol Blood Marrow Transplant 13:948-55, 2007 
19 Coleman EA, Coon SK, Kennedy RL, et al: Effects of exercise in combination with epoetin alfa during high-dose 
chemotherapy and autologous peripheral blood stem cell transplantation for multiple myeloma. Oncology Nurs Forum 2008; 
35: E53-E61 

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20 Jarden M, Hovgaard D, Boesen E, et al: Pilot study of a multimodeal intervention: mixed-type exercise and psychoeducation in 
patients undergoing allogeneic stem cell transplantation. BMT 2007; 40: 793-800  
21 Jarden M, Baadsgaard MT, Hovgaard DJ, et al: A randomized trial on the effect of a multimodal intervention on physical 
capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT. BMT 2009; 43: 725-737  
22 Jarden M, Nelausen K, Hovgaard D, et al: The effect of a multimodal intervention on treatment-related symptoms in patients 
undergoing hematopoietic stem cell transplantation: a randomized controlled trial. J Pain Symptom Manage 2009; 38: 174-
190.  
 
1.2. 
Stress Management 
Many studies suggest that professionally administered stress management training including 
progressive muscle relaxation training with guided imagery22 and hypnosis23 are effective in 
relieving nausea, vomiting and emotional distress in the period just before chemotherapy 
administration.  A systematic review24 identified two possible mechanisms for the effects of 
stress management: physiological relaxation and enhanced perceptions of self-efficacy and 
mastery. Both effects would seem highly beneficial to patients undergoing HCT.  However, very 
few studies of stress management training have been performed in the HCT population. 
 
Stress management does not have to be professionally directed.  An important study compared 
professionally delivered stress management to self-administered training.25  The training was 
similar to the proposed intervention in our trial, including instruction in three techniques 
(abdominal breathing, progressive muscle relaxation training with guided imagery, and coping 
self-statements) found to be effective in improving quality of life in a variety of clinical 
populations.26-28  In the professionally administered form, training was provided during a 60-
minute session conducted by a mental health professional.  In the patient self-administered form, 
training was provided via materials distributed by a mental health professional.  Only the self-
administered form was superior to usual care in improving quality of life.  Moreover, costs of 
this intervention were 68% less than average costs of other professionally administered stress 
management interventions for chemotherapy patients.  Table 1.2 summarizes the relevant 
studies. 
 
 
TABLE 1.2 – SUMMARY OF STRESS MANAGEMENT TRIALS IN ADULT HCT,  
PLUS SELECTED OTHER RELEVANT TRIALS 
 
Author 
Year 
N 
Sample 
Characteristics 
Intervention 
Endpoints 
Summary of results 
Syrjala KL, 
Cummings 
C, 
Donaldson 
GW, et al1 
1992 
67 
RCT, allogeneic 
HCT 
4 groups: hypnosis 
training, cognitive 
behavioral coping, 
therapist contact control, 
standard treatment. Two 
90 minute sessions pre 
transplant, 10 in-hospital 
booster sessions 
Pain, 
nausea, 
emesis, 
opioid use 
Hypnosis training 
reduced pain. 
Nausea, emesis and 
opioid use did not 
differ among 
treatment groups 

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Author 
Year 
N 
Sample 
Characteristics 
Intervention 
Endpoints 
Summary of results 
Syrjala KL, 
Donaldson 
GW, Davis 
MW, et al2 
1995 
94 
RCT, allogeneic 
HCT 
4 groups: Usual care; 
therapist support; 
relaxation and imagery 
training; and relaxation 
and imagery plus 
cognitive-behavioral 
coping skills. Pre-HCT 
training, seen twice a 
week for 20-40 min 
sessions.  
Pain, nausea 
Relaxation and 
imagery training 
decreased reported 
pain compared to 
standard care and 
therapist support; 
adding cognitive-
behavioral training 
did not have an 
additive effect 
Gaston-
Johansson F, 
Fall-Dickson 
J, Nanda J, 
et al3 
2000 
110 
RCT, auto HCT, 
breast cancer 
2 groups: Comprehensive 
Coping Strategy Program 
(CCSP) of preparatory 
information, cognitive 
restructuring, relaxation 
with guided imagery; 
standard care. Training 2 
weeks before HCT, 
audiotape provided. 
Reinforced 3 times during 
hospitalization. 
Pain, 
fatigue, 
anxiety, 
depression, 
nausea 
CCSP experienced 
decreased nausea 
and fatigue 
compared to 
controls. Anxiety 
was mild in the 
SSCP group and 
moderate in the 
controls. 
Jacobsen 
PB, Meade 
CD, Stein 
KD, et al4 
2002 
411 
RCT, outpatients 
receiving 
chemotherapy 
3 groups: Usual 
psychosocial care; 
Professionally 
administered form of 
stress management 
training (60 minutes); or 
patient self-administered 
form of stress 
management training (10 
minutes) prior to 
chemotherapy.  
Functional 
status 
(SF36), 
depression, 
anxiety 
Compared with 
patients who 
received usual care 
only, patients 
receiving the self-
administered 
intervention reported 
significantly better 
physical functioning, 
greater vitality, 
fewer role 
limitations because 
of emotional 
problems, and better 
mental health. No 
difference in QOL 
between the control 
group and the 
Professionally 
administered 
training group. The 
cost of the self-
administered 
training was 68% 
less than the 
professionally 
administered 
training. 

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Author 
Year 
N 
Sample 
Characteristics 
Intervention 
Endpoints 
Summary of results 
Wilson RW, 
Taliaferro 
LA, 
Jacobsen 
PB5 
2006 
39 
Pilot feasibility 
study, 
outpatients 
receiving 
chemotherapy 
5-10 minute training, goal 
to exercise 20-40 min at 
50-75% estimated heart 
rate reserve 3-5 times/wk 
and stress management 
techniques, reinforced 
before each chemotherapy 
cycle 
Functional 
status 
(SF36) 
24 completed the 
study (10 became 
ineligible due to 
death, chemotherapy 
stopped etc; 5 chose 
not to complete the 
study). Paired t tests 
showed 
improvements since 
baseline in bodily 
pain and mental 
health 
1. Syrjala KL, Cummings C, Donaldson GW. Hypnosis or cognititve behavioral training for the reduction of pain and nausea during cancer treatment: a controlled clinical 
trial. Pain 1992; 48: 137-146. 
2.  Syrjala KL, Donaldson GW, Davis MW, et al: Relaxation and imagery and cognitive-behavioral training reduce pain during cancer treatment: a controlled clinical trial. 
Pain 63:189-98., 1995 
3. Gaston-Johansson F, Fall-Dickson J, Nanda J et al. The effectiveness of the Comprehensive Coping Strategy Program on clincal outcomes in breast cancer autologous 
bone marrow transplantation. Cancer Nurs 2000; 23: 277-285. 
4.  Jacobsen PB, Meade CD, Stein KD, et al: Efficacy and costs of two forms of stress management training for cancer patients undergoing chemotherapy. J Clin Oncol 
20:2851-62, 2002 
5.  Wilson RW, Taliaferro LA, Jacobsen PB. Pilot study of a self-administered stress management and exercise intervention during chemotherapy for cancer. Support Care 
Cancer 2006; 14: 928-935. 
 
 
1.3. 
Rationale for Combined Exercise and Stress Management  
 
This trial includes a group that receives training in both stress management and exercise training, 
based on the hypothesis that the combined intervention may yield greater improvements in a 
broader array of quality of life outcomes than either form of training alone.  That is, it may be 
possible to combine the anticipated mental health benefits with stress management training with 
the physical health benefits hypothesized with exercise training to achieve synergistic results.  
Most studies suggest that there are some mental health benefits attainable with exercise and 
conversely, some physical and symptom benefits associated with stress management.  There is 
no evidence to suggest that exercise has negative mental health benefits or that stress 
management has negative physical benefits.  The protocol team acknowledges the theoretical 
negative interaction between the interventions based on overwhelming patients with too many 
instructions and expectations however the balance of the evidence suggests that assuming 
additive effects is reasonable. 
 
Exercise research suggests several ways in which exercise training might increase the potency of 
stress management training.  First, exercise training may serve as an effective distractor during 
periods of acute stress.  Second, cardiorespiratory benefits of exercise training may enhance 
physiologic responses to progressive muscle relaxation and deep breathing.  Third, engaging in 
exercise training may improve mood29,30 and enhance perceptions of self-efficacy and mastery.  
Similarly, research on stress management training31,32 suggests at least two ways in which stress 
management training might increase the potency of exercise training.  First, by promoting active 
problem solving, stress management training may reduce barriers to engaging in exercise 
training.  Second, by reducing physiologic reactions to stress, stress management training may 
increase capacity to engage in exercise training.   
 

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Potential synergy between the stress management and exercise training is an important secondary 
analysis that will use pairwise analytic techniques. 
 

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CHAPTER 2 
 
 
2. STUDY DESIGN 
 
2.1. 
Study Overview 
 
Phase III, randomized, unblinded, multicenter, prospective comparative study of exercise or 
stress management versus standard care to improve functional status and symptoms. 
 
2.2. 
Hypothesis and Study Objectives 
 
The primary hypothesis of this trial is that use of self-administered exercise or stress 
management techniques by hematopoietic cell transplant recipients will improve their transplant 
experience and post-transplant functioning.  Specifically, we hypothesize that the exercise 
intervention will primarily improve physical functioning, and the stress management intervention 
will primarily improve mental functioning.  Secondary analyses will test whether the 
combination of both interventions will have additive or synergistic effects on these endpoints.  
Symptoms may be improved and days of hospitalization may be decreased by the interventions. 
 
2.2.1. Primary Objective 
 
To determine whether exercise or stress management improves self-reported physical and mental 
functioning compared to standard care at 100 days after transplantation. 
 
2.2.2. Secondary Objectives 
 
To compare several secondary measures of an improved transplant experience.  Specifically, 
secondary analyses will determine whether physical and mental functioning differs among the 
groups in patients surviving 100 days and providing self-reported data.  We will also explore 
whether the combination of both interventions has an additive or synergistic effect on these 
endpoints.  Secondary analyses will also test whether symptoms (fatigue, pain, sleep, nausea, 
cancer and treatment distress) are less at 100 days and number of hospital days within the first 
100 days is decreased by the interventions.  We will also test whether benefits are durable by 
comparing functional status and symptoms at six months between the intervention groups and 
the control arm. Survival at 6 months will be compared. 
 

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2.3. 
Patient Eligibility for Randomization 
 
2.3.1. Patient Inclusion Criteria 
 
Patients may be included in this trial if they meet all of the following criteria: 
 
1. Age 18 years or older – the interventions and assessment tools have not been validated 
for children. 
2. Able to speak and read English – interaction with the interventionist trainer and endpoint 
measurement must occur in English.  If the interventions are proven effective, then 
additional studies to create and validate a culturally appropriate intervention will be 
required. 
3. Able to exercise at low to moderate intensity – current participation in a supervised or 
unsupervised exercise program is allowed. 
4. Adequate cardiopulmonary reserve, as judged by self-reported ability to walk up one 
flight of stairs, no need for supplemental oxygen, and physician judgment. 
5. Willing and able to provide informed consent. 
6. Stated willingness to comply with study procedures and reporting requirements. 
7. Planned autologous or allogeneic transplantation within 6 weeks. 
 
2.3.2. Patient Exclusion Criteria 
 
Patients will be excluded from this trial if they meet any of the following criteria: 
1. Orthopedic, neurologic or other problems which prevent safe ambulation and protocol 
adherence. 
2. Participation in another clinical trial with quality of life or functional status as a primary 
endpoint. 
3. Planned anti-cytotoxic therapies, other than TKI, Gleevac or Rituximab OR unless pre-
approved by the Protocol Chair, within 100 days post-transplant. 
4. Planned DLI within 100 days post-transplant.  
5. Planned tandem transplant (autologous/autologous or autologous/allogeneic). 
 
2.4. 
Interventions 
 
All intervention groups require that participants have access to a DVD player to watch the video 
materials.  For those few patients without such access, we will ensure that they are able to view 
the DVD in the clinic.  The stress management group requires a CD player.  Almost all 
participants are expected to own such equipment or have ready access to it.  Descriptions of the 
interventions are in section 2.4.1-2.4.4 below. Additional details are found in section 4.3. All 
“Day +X” refer to “days post transplant,” for example, “Day 30 +/- 7 days” refers to 30 +/- 7 
days after graft infusion. 

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2.4.1. Exercise 
 
Participants assigned to the Exercise arm will receive a packet of materials from the study 
interventionist, along with a brief (10 minute) personalized introduction to the home-based 
exercise intervention.  The packet of materials will consist of a videotape (or DVD if preferred), 
a brochure, a workbook, and an electronic step counter (Digi-Walker Model #SW-651-04).  
Participants will be instructed to view the 15 minute videotape and directions in the brochure for 
exercise training before admission for transplantation.  The videotape and brochure discuss the 
rationale and potential benefits of engaging in regular exercise.  The emphasis is on walking, as 
previous research has demonstrated relatively high rates of adherence and quality of life benefits 
with such programs,33 and most transplant units can accommodate this form of exercise.  The 
videotape and brochure provide information about the importance and practice of warming up 
and cooling down, pulse monitoring during exercise, proper attire and footwear, 
recommendations regarding hydration, suggestions about when and where to exercise, 
precautions and advice about when not to exercise, cautions regarding overtraining, advice on 
addressing perceived barriers to exercise, and instructions on how to operate the electronic step 
counter.  Interspersed throughout the videotape and brochure are testimonials provided by 
patients about the benefits of exercise training.  The goal is to have participants exercise at least 
3 to 5 times per week for at least 20 to 30 minutes at a maximum intensity of 50 to 75% of their 
estimated heart rate reserve.  This goal is consistent with guidelines for exercise in cancer 
patients developed by Courneya et al. and published by the ACSM.34  Although the exercise 
instructions are not tailored to the level of prior exercise, the exercise goal is based on target 
heart rate.  Because attained heart rate with any particular level of exercise varies according to 
prior physical conditioning and current health status, the use of the target heart rate automatically 
adjusts for past and current strength and conditioning.  This intervention is expected to exert 
beneficial effects on quality of life by improving cardiorespiratory fitness35 and perceived control 
of the symptom experience.  Participants will be provided with log forms that they can use to 
record their exercise schedules.  However, these logs are for their use and will not be analyzed 
for research purposes.   
 
On Day 30 +/- 7 days participants will meet briefly with the same interventionist whenever 
possible.  The purpose of this meeting is to answer any questions about the intervention and 
promote adherence to exercise recommendations.  This meeting will also be used to monitor for 
contraindications to continuation of moderate intensity exercise.  To minimize contamination 
across intervention conditions, participants randomized to Exercise will be provided with only 
general advice regarding stress management (i.e., to continue using any techniques they currently 
use to manage stress).  The interventionist will meet with the patient again in person or by phone 
at approximately 60 +/- 7 days post transplant.  Whenever possible, this should be the same 
interventionist who previously met with the patient. 
 
2.4.2. Stress Management 
 
The Stress Management intervention to be used is the same intervention used in prior studies of 
patients receiving chemotherapy.25  Participants will receive a packet of materials from the study 
interventionist, along with a brief (10 minute) standardized introduction to the self-administered 

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intervention.  The packet of materials will consist of a videotape (or DVD if preferred), 
audiotape (or CD if preferred), brochure, and workbook.  Participants will be instructed to first 
view the 15 minute videotape and then follow brochure directions about further training, 
practice, and use of stress management techniques.  The videotape and brochure discuss sources 
and manifestations of stress during treatment and potential benefits of using stress management 
techniques.  They also provide brief instruction in paced abdominal breathing, progressive 
muscle relaxation with guided imagery, and use of coping self-statements, as well as 
recommendations for practicing these techniques.  Testimonials about the benefits of stress 
management training provided by patients are interspersed throughout the videotape and 
brochure.  The paced breathing exercise follows a format similar to that developed by Turk et 
al.36  The relaxation and guided imagery exercise uses a format similar to that developed by 
Burish et al.22  The use of coping self-statements is adapted from Meichenbaum’s stress 
inoculation training.37  Selection of these intervention components was guided by a cognitive-
behavioral model of symptom management.36  Consistent with this model, this intervention is 
expected to exert beneficial effects by reducing appraisals of stress, increasing perceived self-
efficacy in managing stress, and increasing perceived control of the symptom experience.  
Participants will be provided with log forms with which to record practice of the three stress 
management techniques.  However, these logs are for their use and will not be analyzed for 
research purposes.   
 
On Day 30 +/- 7 days the same interventionist will meet with the participant briefly to answer 
any questions about the intervention, encourage the continued use of stress management 
techniques as recommended, and monitor for any adverse reactions to use of the techniques.  To 
minimize contamination across intervention conditions, participants randomized to Stress 
Management will be provided with only general feedback about fitness testing and only general 
advice about exercise during transplant (i.e., to maintain any usual patterns of exercise to the 
extent possible).  The interventionist will meet with the patient again in person or by phone at 
approximately 60 +/- 7 days post transplant.  Whenever possible, the interventionist meeting 
with the patient at 30 and 60 days should be the same interventionist who previously met with 
the patient.    
 
2.4.3. Combination Exercise and Stress Management 
 
The combined Exercise and Stress Management intervention will combine the major elements of 
the interventions described above.  Participants will receive a packet of materials from the study 
interventionist, along with a brief (15 minute) personalized introduction to the interventions.  
The packet of materials will consist of a videotape (or DVD if preferred), an audiotape (or CD if 
preferred) of progressive muscle relaxation and guided imagery, a brochure about exercise and 
stress management, and an electronic step counter.  Instructions and information regarding stress 
management and exercise will be identical to those included in the other videotapes.  The 
videotape will include footage not appearing in the other two videotapes explaining the benefits 
of engaging in both stress management and exercise during treatment and is approximately 25 
minutes in length.  Selected patient testimonials from the other videotapes will also be included.  
A brochure combining the major elements of the other two brochures will also be produced.  The 
introduction to the combination intervention provided by the study interventionist will combine 
the elements described above for the Exercise and Stress Management interventions.  

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Participants in this intervention condition will be provided with log forms to record practice of 
stress management techniques and completion of recommended exercise training.  However, 
these logs are for their use and will not be analyzed for research purposes.   
 
On Day 30 +/- 7 days the same interventionist will meet with the participant briefly to answer 
any questions about the interventions, encourage the continued use of the interventions as 
recommended, and monitor for any adverse reactions.  The interventionist will meet with the 
patient again in person or by phone at approximately 60 +/- 7 days post transplant.  Whenever 
possible, the interventionist meeting with the patient at 30 and 60 days should be the same 
interventionist who previously met with the patient.      
 
2.4.4. Standard Care Only (informational DVD) 
 
Patients randomized to standard care only will receive usual psychosocial care and a general 
transplant DVD produced by the National Marrow Donor Program entitled, “Words of 
Experience. Stories of Hope” which covers a variety of pre and post-transplant topics.  The DVD 
is approximately 45 minutes long organized into a series of chapters, is appropriate for both 
autologous and allogeneic patients, and does not provide any instruction in exercise or stress 
management techniques.  
 
Patients randomized to standard care only will be informed of their assigned condition and 
receive the DVD.  The interventionist will briefly discuss the topics of the DVD and elicit 
questions.  To minimize contamination across intervention conditions, participants randomized 
to the control group will be provided with only general advice about exercise and stress 
management during treatment (i.e., to maintain any usual patterns of exercise to the extent 
possible and to continue using any techniques they currently use to manage stress).  
 
All groups (exercise, stress management, combined exercise and stress management, and 
control) will receive the same general transplant DVD. 
 
2.4.5. Training of Interventionist 
 
It is anticipated that designated interventionists will be research personnel trained as physicians, 
nurses or nurse practitioners, physician assistants, social workers, research assistants, data 
managers or other persons familiar with HCT.  A center must designate two individuals who will 
be trained to provide instructions about the intervention to study participants.  The requirement 
for two trained interventionists per center is to ensure availability throughout the enrollment 
period, and also to allow one interventionist to deliver the patient training and the other to collect 
outcome measures if necessary.  Ideally, each center will designate a third person, uninvolved 
with intervention delivery, to collect patient-reported outcomes.  
 
Prior to enrollment of the first participant, the interventionists will undergo extensive training 
under the supervision of Protocol Team members that includes instruction in how to implement 
protocols for introducing each intervention, explaining intervention materials, identifying a 
recommended duration and intensity of exercise, and answering questions during the initial 
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contacts with participants.  A key element of the training will be instruction in how to avoid 
contamination among the intervention conditions.  Interventionists will only be recorded with 
subjects enrolled in the study.   
 
2.4.6. Quality Control of Intervention Delivery 
 
Some intervention sessions will be audio taped during the study for quality control to verify the 
intervention is delivered properly.  Sites will be informed of the selection process for selecting 
the interventions to audio tape.  The Protocol Team Member, who will evaluate the 
interventions, will provide feedback to the interventionists at sites.  Interventionists at participating 
centers should adhere to the “BMT CTN 0902 Evaluation of Intervention Delivery SOP” for guidelines 
regarding selection process of the interventions to be taped and feedback from the evaluator.  In addition, 
the two trained interventionists at each center should use the Fidelity Checklists to ensure all the 
requirements of an intervention are met, as explained in the SOP.   
 
2.5. 
Stem Cell Transplantation 
 
Patients may receive any type of transplant conditioning, any type of stem cell source and donors 
may be HLA-matched or mismatched.  Prior transplantation is allowed.  Syngeneic donors are 
allowed and will be included in the stratum of autologous procedures.  Graft-versus-host disease 
prophylaxis, graft engineering, monitoring for and treatment of complications and supportive 
care will be per institutional standards.  Definitions of myeloablative and reduced 
intensity/nonmyeloablative conditioning regimens for the purposes of stratification and 
randomization will be per Center for International Blood and Marrow Transplant Research 
definitions. 
 
2.6. 
Design Rationale 
 
In planning the current study, several alternative methodological approaches were considered 
but not adopted.   
• 
Dose intensity of the exercise intervention: The most successful exercise interventions 
generally involve a more intensive exercise program including personal trainers, 
personal exercise equipment, strength plus aerobic training and increased contact with 
boosters.  However, these approaches are not currently feasible within the personnel and 
financial constraints of transplant centers, so the intervention could not be widely 
disseminated.  We envision the current study as a test of dissemination.  Despite the 
strong preliminary evidence that formal exercise programs are beneficial and the fact 
that most centers encourage their patients to exercise during HCT, almost none provide 
formal exercise training or use home-based exercise programs.  
• 
Delivery of the intervention: The Protocol Team opted for interventions that are self-
administered after a brief training session based on two considerations.  First, as noted 
above for exercise, an intensive delivery system in not feasible within current center 
resources.  Second, two randomized studies, one testing an exercise intervention33 and 
one evaluating stress management training,25 found greater effects with the self-
administered interventions than supervised programs. 

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• 
Delay of intervention delivery: Many quality of life intervention programs target a 
period later after transplantation, both for practical as well as scientific reasons.  
Favoring delayed study is the fact that the period of greatest toxicity is likely to be 
immediately post-transplant, interfering with participants’ ability to use the interventions 
effectively.  Acute toxicity and early mortality may make it difficult to discern any 
intervention benefits.  Differences in early mortality and complication rates among 
patient subpopulations may add unwanted noise.  Arguments for early delivery include 
that other exercise and stress management studies have detected benefits of interventions 
applied early during the transplant process.  From a practical perspective, it is easier to 
enroll patients prior to transplant and train them in use of the interventions.  It is also 
possible that use of the intervention prior to admission could increase the efficacy of the 
intervention once transplant commences. 
• 
Objective measures of intervention use: The use of objective measures of intervention 
use rather than subjective self-report use of interventions was considered.  Although 
wrist-worn actigraphs which measure actual activity could be used for this purpose, we 
were concerned about the feasibility and expense of outfitting study participants with 
this equipment.  Previous studies of cancer patients employing actigraphs have been 
characterized by relatively small sample sizes.38,39  Daily patient diaries were considered 
but deemed too burdensome in this population.  As this is primarily an effectiveness trial 
of dissemination based on solid preliminary studies, we felt that the extra costs and 
logistical difficulties did not justify the information to be learned. 
• 
Objective endpoint measures: The use of objective measures of physical and mental 
functioning was considered.  Physiologic testing through exercise stress tests require 
special equipment and personnel, and are time consuming and costly.  We considered 
measurement of a 2 or 6 minute walk40,41 test, but this would add burden to the 
participants and sites, and may not be feasible in busy clinical areas.  
• 
Timing of endpoint assessment: The primary endpoint could be assessed earlier or later 
than 100 days. An earlier assessment time might increase the number of evaluable 
participants but would increase the heterogeneity of symptoms due to different 
conditioning agents and intensity.  A later assessment time might dilute the effect of the 
intervention due to treatment-related mortality, relapse, loss to follow up and other 
events.  
• 
Analytic design: An intention-to-treat analysis which assigns functional scores to 
patients who either die before endpoint assessment or who fail to provide 100 day self-
reported data was selected as the primary analysis in order to provide the most 
conservative estimate of the interventions’ effectiveness.  Because of the large number of 
anticipated deaths and missing Day 100 data severely inflates the target sample size, the 
primary analysis will exploit the factorial design and collapse groups according to the 
intervention being tested (stress management vs. no stress management, exercise vs. no 
exercise).  A critical secondary analysis will address the clinical question of whether one 
or more of the intervention arms improve functional status and symptoms among 
patients who survive using pairwise comparisons. 
• 
Exclusion of children: We designed the study for adults since the interventions and 
many of the instruments are only validated in adults.  It is possible, perhaps likely, that 

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adolescents may need a different approach to stress management and exercise than these 
self-directed interventions, and we were reluctant to extrapolate from adult to 
adolescents without appropriate validation studies. 
 
2.7. 
Study Risks 
 
Medical risks of study participation are expected to be low but could conceivably be due to 
exercise participation such as an exercise-related musculoskeletal injury.  Adverse events due to 
exercise participation will be reported.  There is a very low risk that the patient-reported 
measures or practice of stress management techniques might actually increase patient distress.  
If a member of the study team becomes aware of psychosocial distress, they will notify the 
patient’s clinical provider who will assess the patient and make appropriate referrals according 
to standard institutional practice.  Increased psychosocial distress due to study participation will 
be considered a severe adverse event and will be reportable; distress incidentally noted will not 
be reported to research entities.  For example, a participant reporting distress but not attributing 
it to study participation will be considered “incidentally noted distress.”  If distress is attributed 
to study participation by the patient, then it will be considered a severe adverse event. 
 
We do not expect the biobehavioral interventions under study to be related to engraftment, graft-
vs-host disease, infections, relapse or organ complications such as pulmonary, hepatic, 
neurologic etc.  These complications are seen after allogeneic and autologous HCT and are very 
unlikely to be biologically associated with study participation.  These types of transplant-related 
complications will be considered expected events for the purposes of this study.  In addition, 
exercise or stress management complications, as described above such as musculoskeletal injury 
or increased awareness of stress, are considered expected.  
 
Unexpected severe adverse events are events related to participation in exercise or stress 
management that are plausibly related to study participation.  For example, development of an 
arrhythmia during exercise or falling and breaking a hip during exercise are considered 
unexpected severe adverse events. 
 
2.8. 
Study Benefits 
 
It is unknown whether study participants will experience any benefits.  We hope that functional 
status will be improved and symptoms will be lessened by these interventions.  
 
2.9. 
Study Withdrawal 
 
Subjects may be withdrawn from study participation if the treating physician believes it is in the 
patient’s best interest to cease collection of patient-reported outcomes.  Temporary or permanent 
discontinuation of exercise or stress management techniques is NOT a reason for subject 
withdrawal, since the analysis is on an intent-to-treat basis and patients are evaluable even if 
they never use any of the techniques.  
 

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CHAPTER 3 
 
 
3. STUDY ENDPOINTS 
 
3.1. 
Primary Endpoint 
 
3.1.1. Functional Status 
 
The Physical Component Score (PCS) and Mental Component Score (MCS) of the SF-36 will be 
the primary endpoint measures of functional status.  
 
The Acute (past week) Version of the MOS 36-Item Short Form (SF-36), a widely used self-
report measure designed to assess perceived health and functioning, contains eight scales: 
Physical Functioning (PF), Role-Physical (R-P); Bodily Pain (BP); General Health (GH); 
Vitality (VT); Social Functioning (SF); Mental Health (MH); and Role-Emotional (R-E).42,43 
Scales are comprised of different numbers of items and use a variety of rating formats.  Raw 
scores are converted to a standard metric (0-100), with higher scores being indicative of a better 
health state.  The SF-36 also yields two summary scores reflecting the underlying two-
dimensional factor structure: Physical Component Summary (PCS) scale and Mental Component 
Summary (MCS) scale.  These summary scores are derived by multiplying the z-score for each 
scale by its respective physical or mental factor score coefficient and summing the products.  
Resulting scores are then transformed into T-scores (mean=50; standard deviation=10). Factor 
analysis has shown that the PF, R-P, and BP scales have stronger loadings on the “physical” 
component than the “mental” component, with the reverse being true for the MH, R-E, and SF 
scales.42  The GH and VT scales have noteworthy loadings on both the physical and mental 
components.  The validity and reliability of the SF-36 has been established in a number of 
clinical populations, including cancer patients43 The SF-36 has been used in several BMT CTN 
trials including BMT CTN 0102 (Auto/Auto vs. Auto/Allo HCT for Multiple Myeloma) and 
BMT CTN 0202 (Autologous vs. Allogeneic HCT for follicular lymphoma). 
 
3.2. 
Secondary Endpoints 
 
3.2.1. Symptoms 
 
The SF-36 provides measures of pain and fatigue.  Two questions using a similar format as the 
SF-36 will be added to measure nausea.  Cancer and treatment distress will be measured by the 
acute version of the Cancer and Treatment Distress (CTXD) scale, a 27 item validated measure 
of distress with domains of Uncertainty, Health Burden, Family Strain, Identity and Managing 
the Medical System used extensively in HCT studies.3,44 Sleep.  The Pittsburgh Sleep Quality 
Index (PSQI)45 is a widely used seven item self-report measure of sleep patterns and difficulties.  
A modified version will be used to obtain self-reports of the following for the past week: sleep 
quality, sleep latency, sleep efficiency, and use of sleeping medications.46  The reliability and 
validity of the PSQI has been demonstrated in a variety of clinical populations, including cancer 
patients.45,47   
 

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3.2.2. Days of Hospitalization 
 
The number of hospital days within the first 100 days after graft infusion will be collected for 
patients surviving at least 100 days.   
 
3.2.3. Late Outcomes (6 months) 
 
The SF-36, CTXD and Pittsburgh Sleep Quality Index will be collected from participants at six 
months. 
 
3.2.4. Survival (6 months) 
 
Overall survival is defined as the interval between transplantation and death or last follow-up.  
Patients alive when the study closes or lost to follow up are censored at the date of last contact.  
Both survival at 6 months and overall survival at last follow-up will be reported. 
 
3.3. 
Additional Clinical Factors 
 
3.3.1. Demographic, Clinical and Transplant Characteristics 
 
As in our previous research,25 we will assess the following via chart review or self-report: age, 
race/ethnicity, marital status, education, occupation, employment status, income, co-morbid 
medical conditions.48-51  In addition, we will collect information on use of prescription and 
nonprescription medications, alcohol, tobacco.  Height and weight will be used to calculate body 
mass (wt[kg]/ht[m2]).  Standard patient and transplant factors will be collected such as disease 
type, disease stage, prior chemotherapy treatment, conditioning regimen, graft source, graft-
versus-host disease prophylaxis, transplant complications, relapse and survival.  
 
3.3.2. Intervention Credibility 
 
Intervention credibility will be assessed using self-report measures adapted from our previous 
research.25  The use of three identical items across intervention conditions will allow for 
personnel collecting these forms to remain blinded to intervention assignment.  Participants will 
be asked to rate the following on 7-point scales (0=not at all to 6=extremely) after meeting with 
the interventionist: anticipated effectiveness of the assigned intervention in improving quality of 
life, skill and competency of the interventionist, and perceived importance of making the 
assigned intervention available to other patients.  These data will be used to confirm the 
equivalence of the three intervention conditions with regard to credibility. 
 
3.3.3. Exercise Activity 
 
Exercise activity will be assessed using the Leisure Score Index (LSI) of the Godin Leisure-Time 
Exercise Questionnaire52 and a one item version of the Stages of Change Form for Exercise 
(SOC-E).53  The LSI consists of 18 questions that assess the average frequency of mild, 
moderate, and strenuous exercise in a typical week.  As in our current research, the LSI will be 
modified to include assessment of average duration of exercise and perceived exertion.54  We 

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will rely on standard scoring to compute a total score.52  The reliability and validity of the LSI 
has been found to compare favorably with other self-report measures of exercise in terms of test-
retest scores and correlations with objective activity monitors and objective fitness indices.55  
The LSI will be collected at baseline, 30 days, 60 days, 100 days and 6 months.  The SOC-E 
consists of a 5-choice response format that can be used to classify respondents’ stages of change 
for adoption of regular exercise (i.e., precontemplation, contemplation, preparation, action, or 
maintenance).  The typical 6-month anchoring has been modified to three months for the current 
study to reflect the interval between assessments.  Information will be used to confirm expected 
differences in exercise between participants randomized to the different groups.  In addition, 
these data will be used to explore “dose-response” relationships between amount of exercise and 
magnitude of changes in quality of life outcomes. 
 
3.3.4. Stress Reduction Activity 
 
Stress reduction activity will be assessed in all participants using the 5-item Stress Reduction 
Checklist (SRC).25  The methods assessed are those that comprise the Stress Management 
intervention.  Each method is listed by the term used to describe it in the intervention as well as 
by an operational definition.  Thus, participants can complete it regardless of whether they 
received instruction in stress management.  All assessments (baseline, 30 days, 60 days, 100 
days, and 6 months) will be keyed to the past week.  In previous research, we found that SRC 
scores documented expected differences in use of stress management techniques between 
subjects who did and did not receive instruction in stress management.25  SRC data will be used 
to confirm expected differences in use of stress management techniques between participants 
randomized to different groups and explore possible differences in use of stress management 
techniques between participants randomized to Stress Management along versus Combined 
Exercise and Stress Management. 
 
 

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TABLE 3.3: PATIENT-REPORTED MEASURES 
 
 
#  
Items 
Enroll-
ment 
30 days 
+/-  
7 days 
60 days 
+/-  
7 days 
100 days 
+/-  
14 days 
6 months 
+/-  
1 month 
Primary and Secondary Endpoints 
 
 
 
 
 
 
• 
SF-36 (SF-36) + 2 nausea items 
38 
X 
Ψ 
Ψ 
X 
X 
• 
BMT Distress Scale (CTX-D) 
27 
X 
 
 
X 
X 
• 
Pittsburgh Sleep Quality Index (PSQI) 
7 
X 
 
 
X 
X 
Exercise Measures 
 
 
 
 
 
 
• 
Leisure Score Index (LSI) 
18 
X 
X 
X 
X 
X 
• 
Stages of Change for Exercise (SOC-E) 
1 
X 
X 
X 
X 
X 
Stress Management Measures 
 
 
 
 
 
 
• 
Stress Reduction Checklist (SRC) 
5 
X 
X 
X 
X 
X 
Sociodemographic, Habits and Beliefs 
 
 
 
 
 
 
• 
Age, Sex, Race, Ethnicity, Education, 
Marital Status 
9 
X 
 
 
 
 
• 
Smoking, Alcohol 
6 
X 
 
 
 
 
• 
Intervention Credibility 
3 
X* 
 
 
 
 
 
 
 
 
 
 
 
Total # of Items  
(Estimated Time) 
114 
114 
(20 min) 
25  
(5 min) 
25  
(5 min) 
88 
(15 min) 
88  
(15 min) 
* after meeting with the interventionist 
Ψ Single item general health question from the SF-36 1 (SF-1) 
 

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CHAPTER 4 
 
 
4. PATIENT REGISTRATION, ENROLLMENT AND RANDOMIZATION 
 
4.1. 
Approaching Patients, Eligibility Screening and Obtaining Consent 
 
Subjects may be approached for enrollment on this protocol once they are scheduled for 
transplantation as long as the planned transplant date is within six weeks.  Transplant physicians 
or other center staff will evaluate patient eligibility for enrollment onto this protocol.  Eligibility 
criteria will be verified and ineligible patients will proceed off study and no further study 
procedures will be conducted.  Eligible patients willing to potentially participate in the trial will 
have a thorough discussion about the protocol with an investigator, a sub-investigator, clinical 
research nurse, or research coordinator.  If necessary, this discussion may take place by 
telephone.  During the discussion, the purpose of the study and study procedures will be 
presented as objectively as possible, and the potential benefits and risks of participation will be 
explained.  The patient will be given a copy of the entire signed consent document to keep.  The 
last page of the consent document must be signed by the patient and by the clinician who 
discussed the protocol.  Transplant center personnel will record the documentation of patient 
consent in EMMES AdvantageEDCSM (Electronic Data Capture, an Internet-based data entry 
system) and patients will be registered through AdvantageEDC.  
 
4.2. 
Study Registration and Randomization 
 
Once the subject is deemed eligible, has given written informed consent, completed the baseline 
assessment, and the transplant center has confirmed patient eligibility and necessary 
stratification variables, randomization occurs.  A subject may be randomized on to one of four 
arms: exercise, stress management, combined exercise and stress management, or standard care.  
If a patient consents but discontinues trial participation prior to randomization, they will be 
replaced.  
 
4.3. 
Training and Reinforcement in Intervention Use 
 
Once a patient is randomized, the intervention must be delivered before the day of graft infusion 
(Day 0).  Thus, subjects will meet with the interventionist for 10-15 minutes to receive their self-
administered materials and brief training.  Subjects randomized to standard care will meet with 
the interventionist to discuss the information in the pamphlet. 
 
If transplantation occurs more than two weeks after the training session, the interventionist will 
briefly contact the patient within seven days of graft infusion (Day 0 +/- 7 days) to reinforce use 
of the intervention.  In addition, the interventionist will meet with patients from all four groups at 
Day 30 +/- 7 days in person or by phone, to briefly reinforce use of the assigned intervention if 
applicable and to remind the patient about endpoint assessment at Day 100 and six months.  A 
similar contact will occur at approximately Day 60 +/- 7 days for all groups. 
 

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ENROLL     RANDOMIZE   TRAIN    DAY 0
Boost30   Boost60   DAY 90             6 MO
Baseline
Assessment
(up to 6 wks
pre HCT)
1˚Physical/mental status
2˚Symptoms
1:1:1:1
Stratified by:
• Center
• HCT type
Train before day 0
ENROLL     RANDOMIZE   TRAIN    DAY 0
Boost30   Boost60   DAY 90             6 MO
Baseline
Assessment
(up to 6 wks
pre HCT)
1˚Physical/mental status
2˚Symptoms
1:1:1:1
Stratified by:
• Center
• HCT type
Train before day 0
4.4. 
Patient Assessment 
 
4.4.1. Endpoint Assessment 
 
Patient self-reported information relevant to endpoint assessment will be collected at baseline 
(before randomization), at 100 days +/- 14 days, and at six months +/- one month.  Patients may 
complete these assessments on paper forms or by responding to questions read verbatim by the 
assessor.  The optimal method of self-reported data collection is via self-administered paper 
surveys.  Study staff will carefully review all self-completed paper forms for ambiguous 
responses and missing data, and clarify these with the participant. Reasons for inability to 
complete the assessments will be recorded.  If a patient is not able to complete self-administered 
instruments or prefers interviewer-administered assessments, data will be collected via this 
mechanism, either in person or over the phone.  The method of data collection will be recorded.   
 
4.4.2. Use of Intervention 
 
At the time of the Day 30 and Day 60 reinforcements and again at the Day 100 and six month 
assessments, self-reported use of the interventions and one item about general health will be 
recorded.  In order to decrease social desirability bias, these forms will be given to the patient to 
complete later and return via self-addressed, stamped envelope.  If the information must be 
collected by interview, the other interventionist or other study personnel will contact the patient. 
 
See Table 3.3 for a summary of patient assessments. 
 
 
 
4.5. 
Study Monitoring 
 
As the primary concerns about trial participation will be distress with the self-assessments and 
injuries related to exercise, monitoring will be focused on these issues.  Patients will be 
monitored clinically with laboratory assessments, physical exams, restaging studies and other 
testing deemed to be standard practice and appropriate by the treating physician and the 
transplant center.  
 

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4.5.1. Case Report Forms 
 
A description of the forms, the procedures required for forms completion and timeliness of 
submission can be found in the Data Management Handbook and User’s Guide. Forms that are 
not received within the specified time are considered delinquent.  Transplant centers can view 
submitted past due, and expected forms via AdvantageEDC.  A missing form will continue to be 
requested either until the form is reported, or until an exception is granted. 
 
4.5.2. Reporting Patient Deaths 
 
Death of subject information must be reported to the BMT CTN Data Coordinating Center 
(DCC) within one business day of the event notification to the transplant center.  If the cause of 
death is unknown, it need not be recorded at the time of the initial reporting.  However, once the 
cause of death is known, the form must be updated.  
 
4.5.3. Reporting Serious Adverse Events 
 
4.5.3.1. 
Patient SAEs 
 
Reporting of patient serious adverse events (SAE) will be consistent with standard BMT CTN 
procedures but be limited to events which are possibly, probably or definitely associated with 
participation in this study since this protocol does not involve any pharmacologic treatment or 
invasive procedures.  Unexpected, grades 3-5 adverse events (AEs) will be reported through an 
expedited AE reporting system via the web-based electronic data capture system, 
AdvantageEDC. Unexpected, grades 4-5 AEs must be reported within 24 hours of the event.  
Unexpected, grade 3 AEs must be reported within three business days of knowledge of the event.  
Other SAEs will be tracked periodically as defined in the Form Submission Schedule, staged 
according to NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.  
The Data and Safety Monitoring Board will receive summary reports of all adverse experiences 
on at least an annual basis. Please see section 2.7 for definitions and examples of expected and 
unexpected SAEs. 
 
4.5.4. CIBMTR Data Reporting 
 
Centers participating in BMT CTN trials must register and provide transplant outcome data on 
all consecutive hematopoietic stem cell transplants done at their institution during their time of 
BMT CTN participation to the Center for International Blood and Marrow Transplant Research 
(CIBMTR).  Registration is done using procedure and forms developed by CIBMTR for the 
Stem Cell Transplant Outcomes Database (SCTOD).  (Note: Federal legislation requires 
submission of these forms for all US allogenic transplant recipients.)  
 
Patients enrolled in this trial will remain on pre selected form submission track (Transplant 
Essential Data track also known as “TED” track or Comprehensive Report From track also 
known as “CRF” track) that was originally assigned by the CIBMTR algorithm.  CIBMTR forms 
will be submitted directly to the CIBMTR at the times specified on the Form Submission 
Schedule. 

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4.6. 
Quality Control 
 
Because of this protocol relies on patient-reported outcomes for the primary analyses, collection 
of these data are critical.  We anticipate up to a 15% inability to collect Day 100 data from 
surviving patients based on logistic problems and patient refusal.  However, center compliance 
will be monitored every three months.  If a center falls below 75% for its cumulative compliance 
with Day 100 data collection, procedures will be instituted to evaluate whether continued 
participation in the trial is warranted.  This evaluation will result in either corrective actions or 
suspension of participation. 
 
At least two interventionists at each participating center must complete interventionist training 
and be certified by a protocol team member before the center can begin enrollment on the trial, 
similar to other studies in which a center personnel needs to demonstrate competence in 
investigational cell processing techniques before they can enroll protocol patients.  Centers 
should adhere to guidelines outlined in the BMT CTN 0902 SOP.  
 

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CHAPTER 5 
 
 
5. STATISTICAL CONSIDERATIONS 
 
5.1. 
Study Design 
 
The protocol is designed as a factorial trial with two interventions, exercise and stress 
management, which results in four treatment arms: standard care, exercise only, stress 
management only and the combination of exercise and stress management. The primary 
objective of this randomized phase III trial is to test the ability of exercise training or stress 
management training to improve physical and mental functioning at Day 100.  
 
5.1.1. Accrual 
 
It is estimated that three years of accrual will be necessary to enroll the targeted sample size of 
700 patients, based on a survey sent to centers.  Both Core and Affiliate Centers will enroll 
patients on this study.  Accrual will be reported by race, ethnicity, and sex.  
 
5.1.2. Randomization 
 
All patients will be randomized in a 1:1:1:1 ratio using random block sizes for the four arms.  
Randomization will be stratified by transplant center and type of transplant procedure 
(autologous/syngeneic, myeloablative allogeneic, or reduced intensity/non-myeloablative 
allogeneic).  
 
5.1.3. Primary Endpoint 
 
The co-primary endpoints are physical functioning and mental functioning at Day 100 as 
measured by the SF-36, which will be scored according to the instructions of the developer.  The 
primary analysis will be performed using the intent-to-treat principle so that all randomized 
patients will be included in the analysis, classified according to their randomized treatment 
assignment.  Patients who have missing data due to death will be scored as the lowest value, and 
patients who are alive but are missing the Day 100 outcome will be scored as the next lowest 
value.  In the primary analysis, the effect of an intervention (exercise or stress management) on 
an outcome (PCS or MCS) will be determined by collapsing arms with the intervention into the 
treatment group and arms without the intervention into the control group then comparing the 
outcome between control vs. treatment groups.  For example, the effect of exercise on physical 
functioning will be determined by comparing the PCS scores between two groups, one 
comprised of standard care and stress management only arms vs. the other comprised of exercise 
only and combination arms. These comparisons will be done using the Mann-Whitney test.  
Detailed analysis plan including imputation of incomplete data is given in Section 5.5. 
 

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5.2. 
Sample Size and Power Calculations 
 
5.2.1. Power Calculation for Primary Intention-to-Treat Analysis 
 
The primary objective of this study is to determine if training patients to practice exercise or 
stress management during transplantation improves the patient’s experience, as measured by 
physical and mental functioning.  Because of the co-primary endpoints, the allowable Type I 
error rate α = 0.05 is divided in half so that the significance level to be used is 0.05/2 = 0.025 for 
each end point.   
 
To account for the missing data in an intent-to-treat analysis, the sample sizes shown in Table 5.2 
were calculated by Monte Carlo simulations with 10,000 replications based on the following 
assumptions.  First, it is assumed that the functional status scores (MCS or PCS) are normally 
distributed and the detectable difference between two groups is δ SD; values of δ at 0.4 and 0.5 
were considered.  Furthermore, it is assumed that there is no difference in survival and no 
difference in incomplete data collection at Day 100 for surviving patients between groups.  All 
deaths occurring prior to Day 100 regardless of treatment were assigned a functional status score 
which is lower than the lowest observed functional status scores.  All surviving patients missing 
the Day 100 assessment irrespective of treatment were given a functional status score higher than 
deaths and lower than the lowest observed function status. 
 
The completed functional status scores including observed and imputed values were compared 
between groups using a nonparametric Mann-Whitney test.  The power to detect a δ SD 
difference using the ITT analysis with the target sample size of 700 patients is given in Table 5.2 
for various plausible rates for Day 100 mortality and missing data among survivors.  In 
particular, assuming Day 100 mortality rate of 15% in both groups and incomplete assessment in 
15% of the surviving patients, the target sample size of 700 patients will have 85% power to 
detect a 0.5 SD difference in functional status scores between groups.  Other plausible rates for 
mortality and missing data are also included.   
 
TABLE 5.2: POWER TO DETECT VARIOUS EFFECT SIZES IN  
THE PRIMARY ITT ANALYSIS 
 
Effect size δ, in SD 
Day 100 Mortality 
Proportion of Survivors Missing  
Day 100 Forms 
15% 
10% 
0.4 
15% 
67% 
77% 
 
10% 
77% 
87% 
0.5 
15% 
85% 
93% 
 
10% 
92% 
97% 
  

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5.2.2. Power Calculation for Key Secondary Analysis of Main Effects in Survivors who 
Complete Day 100 Assessments 
 
The effect of exercise or stress reduction on mental and physical functioning in survivors who 
completed Day 100 assessments will be determined in a series of secondary analyses.  The power 
calculations for these secondary analyses are based on the same assumptions as in 5.2.1, namely 
15% mortality by day 100 and 15% missing data among survivors at the 100 day follow-up visit.  
PCS and MCS scores will be compared between exercise vs. no exercise groups and stress 
management vs. no stress management groups by collapsing arms as described in the primary 
analysis.  Because of the co-primary endpoints, the allowable Type I error rate is divided in half.  
A sample size of 700 gives 87% power to detect an effect size of 0.3 SD between groups on any 
of the two endpoints using the evaluable patients.  With the same sample size, this analysis 
provides the power to detect a much smaller effect size than in the primary ITT analysis.  
 
5.2.3. Power Calculation for Key Secondary Analysis Comparing all Four Treatment 
Combinations in Survivors who Complete Day 100 Assessments 
 
In another key secondary analysis, PCS and MCS scores will be compared between all pairs of 
treatment combinations.  There are six pair-wise comparisons between four treatment arms.  To 
adjust for multiple comparison, the Type I error rate is divided in six.  The Type I error rate is 
further divided in half due to the co-primary endpoints so that the significance level to be used is 
0.05/12=0.0042.  A sample size of 700 gives 86% power to detect an effect size of 0.5 SD 
between any pair of treatments on any of the two endpoints, using the evaluable patients and 
under the same assumptions about mortality and missing data as in Sections 5.2.1 and 5.2.2.  
 
5.3. 
Interim Analysis Plan 
 
5.3.1. Interim Analysis for Efficacy 
 
No interim analysis for efficacy will be performed for several reasons.  First, because of the short 
anticipated accrual period (3 years) and primary endpoints assessment at 100 days, we will 
almost have completed enrollment before the results of the interim analysis are known.  Second, 
physical risks to participants are likely to be minimal so the risks are low of exposing 
participants to an inferior treatment arm or alternatively, denying participants or other patients 
access to effective interventions.  Third, the use of co-primary endpoints would require that both 
be found significant at an interim analysis in order to stop; otherwise the power to detect 
differences in the other endpoint would be impacted.  This makes it less likely that an interim 
analysis would result in a closure of an arm.  Finally, stopping enrollment to one of the 
intervention arms at an interim analysis would impact the ability to investigate interactions and 
synergism between the two interventions, which is an important secondary analysis.   
 
5.3.2. Interim Analysis for Futility 
 
No interim analysis for futility will be performed.  All intervention arms are considered minimal 
risk to participants.  Dropping one arm at the interim analysis will compromise the ability to 
evaluate secondary endpoints, which are also of considerable interest.  Finally, dropping of either 

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the exercise alone arm or stress management arm alone will compromise the ability to evaluate 
the added impact of the combination arm.  For all these reasons, no interim analysis for futility 
will be performed. 
 
5.4. 
Demographics and Baseline Characteristics 
 
Demographic and baseline characteristics will be summarized for all patients.  Characteristics to 
be examined are: patient characteristics (age, sex, race/ethnicity, performance status, disease and 
disease risk, CMV status, and psychosocial and functional factors); donor characteristics (donor 
type, HLA-match, age, sex, CMV status); graft characteristics (type, CD34+ or total nucleated 
count per kg); and transplant characteristics (type, conditioning, GVHD prophylaxis).  Between 
groups comparisons will be performed for continuous variables via a Kruskal-Wallis test and for 
categorical variables, via the chi-square test. 
 
Before conducting the secondary analyses described below, the distributional properties of study 
variables will be examined to determine if variance stabilizing or normalizing transformations 
should be applied.  Participants who complete the study and are alive at Day 100 will be 
compared to participants who drop out before Day 100 in order to identify predictors of attrition.  
Although participants will be randomly assigned to intervention conditions, significant 
differences may be present among the conditions on demographic, disease, or treatment 
variables.  To identify these potential confounding variables, intervention and control conditions 
will be compared on all baseline demographic and disease variables and on all treatment 
variables measured during the course of study participation.  
 
5.5. 
Analysis Plan 
 
5.5.1. Analysis of Primary Endpoints 
 
The analysis of primary endpoints will include all randomized subjects, classified according to 
their randomized treatment allocation, irrespective of treatment actually received.  Two 
comparisons will be considered in the primary analysis, comparing exercise vs. no exercise 
groups and comparing stress management vs. no stress management groups.  The effect of 
exercise training will be estimated by collapsing arms with exercise versus arms without exercise 
and the effect of stress reduction will be analyzed by collapsing arms with stress reduction vs. 
arms without stress reduction.  The effect of each intervention will be analyzed on both mental 
and functional outcomes.  In this analysis, all patients who die within 100 days post transplant 
will be given MCS and PCS scores lower than the lowest observed scores and all survivors 
missing Day 100 assessment will be given scores higher than patients who died but lower than 
the lowest observed scores.  The completed functional status scores will be compared using a 
Mann-Whitney test with a two-sided significance level of 0.025. 
 
5.5.2. Analysis of Secondary Endpoints 
1. Conditional analysis of functional status in survivors with Day 100 assessments: This 
analysis is limited to the population of survivors who provide Day 100 self-reports.  The 
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arms without exercise and the effect of stress reduction will be analyzed by collapsing 
arms with stress reduction vs. arms with stress reduction.  The effect of each intervention 
will be analyzed on both mental and functional outcomes.  MCS and PCS scores will be 
compared at a two-sided significance level of 0.025. 
2.  Pair-wise conditional analysis of functional status in survivors with Day 100 
assessments: This analysis is limited to the population of survivors who provide Day 100 
self-reports.  MCS and PCS scores will be compared between each pair of treatment arms 
in this analysis.  Four treatment arms result in six pair-wise comparisons.  The two-sided 
significance level to be used in this analysis is 0.0042.  We will also test for an interaction 
between the two interventions, exercise and stress management.  The direction of a 
statistically significant interaction will allow for determination of a synergistic effect, 
where the combined effect is greater than what is expected from the combination of the 
two single interventions vs. an interaction where the combined effect is lower than what 
would be expected from combining the two interventions.  
3. Overall survival: This analysis will include all randomized subjects.  The event is death 
from any cause.  The time to this event is the time from randomization to death, loss to 
follow-up or the end of study, whichever comes first.  Patients alive at the time of last 
follow-up are considered censored.  Survival curves will be estimated separately for each 
treatment groups using the Kaplan Meier product limit estimator.  Overall survival will be 
compared between groups using a log-rank test. 
4. Assessment of missing data: Graphical presentations and logistic regression analysis will 
be performed to understand the missing data mechanism as well as to identify factors 
associated with incomplete data for survivors.  Plots of change in functional status scores 
from baseline to 100 days and 6 months stratified by time of drop-out will be generated 
separately for each group to determine pattern of missingness.  Logistic regression will be 
used to identify baseline and clinical characteristics associated with missing data.  All 
demographics and baseline characteristics listed in Section 5.4 along with the single item 
SF-1 general health information collected at Day 30 and 60 and the baseline functional 
scores measured at enrollment will be included in the logistic model. 
5. Functional status scores with multiple imputation:  In this analysis, incomplete data for 
surviving patients will be replaced by values resulting from multiple imputations where 
the missing values will be estimated by regression models which will include the baseline 
functional scores, the SF-1 measurement at Day 30 and 60 and various combinations of 
factors significantly associated with missing data.  We will then analyze these alternate 
imputation schemes using a Mann-Whitney test on all patients in an ITT analysis (where 
patients who die are scored at the bottom), or using linear mixed models including only 
patients who are alive at Day 100. 
6. Symptoms: Domain and summary scores will be calculated for each instrument 
according to the recommendations of the developers.  These will be compared between 
groups using the Kruskal-Wallis test, adjusting for baseline scores for patients survive to 
Day 100.  

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7. Days of hospitalization: The total number of hospital days within the first 100 days, 
adjusted for the duration of follow-up will be compared between groups using the 
Kruskal-Wallis test for all randomized patients. 
8. Functional status and symptoms at 6 months: The analytic design will be similar to the 
100 day approach. 
 
5.5.3. Analysis of Additional Clinical Factors 
1. Intervention Credibility: Intervention credibility scores will be compared between 
intervention conditions using the Kruskal-Wallis test.  
2. Exercise Activity:  LSI scores (at 30 days, 60 days, 100 days, 3 months and 6 months) 
will be compared between groups using the Kruskal-Wallis test, adjusting for baseline 
scores. 
3. Stress Reduction Activity: SRC scores (at 30 days, 60 days, 100 days, 3 months and 6 
months) will be compared between groups using the Kruskal-Wallis test, adjusting for 
baseline scores. 
 
5.6. 
Safety Analysis 
 
The reporting of serious adverse events will be consistent with standard BMT CTN procedures.  
The type and severity of adverse events will be described and compared between the four arms. 
 
 

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APPENDIX A 
 
HUMAN SUBJECTS 
 
 
Subject consent: Candidates for the study will be identified as described in Chapter 4 of the 
protocol.  The Principal Investigator or his/her designee at each transplant center will contact the 
candidates and enroll them onto the study.  The study coordinator at each center will provide the 
patient with information about the purpose of the study and obtain consent.  The Network will 
provide a template of the consent form to each center.  Each center will customize the template 
according to their local requirements and submit it for review by the local Internal Review Board 
(IRB).  The DCC will verify the adequacy of the consent forms.  Each center must provide 
evidence of IRB approval.  
 
 
Confidentiality: Confidentiality will be maintained by individual names being masked and 
assigned a patient identifier code.  The code relaying the patient’s identity with the ID code will 
be kept separately at the center.  The ID code will be transmitted to the network.   
 
 
Participation of women, children, minorities and other populations: Women and ethnic 
minorities will be included in this study.  Children will not be included. 
 
Accrual will be monitored within each center with the expectation that the enrolled patient 
population is representative of the transplanted patient population at each center.  Representation 
will be examined by comparing gender, race, ethnicity and age distributions.  Accrual of 
minority patients will be expected to be in proportion to the number of minority patients 
transplanted at each center.  The DCC and NHLBI will discuss enrollment anomalies with the 
centers. 
 
 
 
 

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APPENDIX B 
 
INFORMED CONSENTS 
AND 
EDUCATIONAL MATERIAL 
 
 
 
INFORMED CONSENT TO PARTICIPATE IN RESEARCH 
 

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Informed Consent to Participate in Research 
 
 
 
 
 
 
 
 
 
 
Your Name:  
 
 
 
 
 
 
 
 
 
 
 
Study Title: 
A Phase III Randomized, Multi-center Trial Testing Whether Exercise or 
Stress Management Improves Functional Status and Symptoms of Autologous 
and Allogeneic Recipients. 
Protocol: 
0902 
Co-Investigator: Stephanie J. Lee, M.D., M.P.H 
Fred Hutchinson Cancer Research Center  
1100 Fairview Avenue North 
Mailstop D5-290 
Seattle, WA 98109-1024 
Phone: 206-288- 7222 
 
Co-Investigator: Paul B. Jacobsen, Ph.D. 
H. Lee Moffitt Cancer Center & Research Institute 
12902 Magnolia Drive  
Tampa, FL 33612 
Phone: 813-745-3862 
Transplant Center 
Investigator:  
 
 
 
 
 
 
 
 
 
 
 
Sponsor: 
The National Institutes of Health (NIH), the National Heart, Lung, and Blood 
Institute, and the National Cancer Institute gave financial support for this 
research study through the Blood and Marrow Transplant Clinical Trials 
Network (BMT CTN).  
 

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Introduction 
You are invited to join a research study.  The main goal of this study is to learn whether patients 
who participate in an exercise program, a stress management program, or both programs will feel 
better after transplant compared to patients who do not participate in either program.  We also 
want to know what areas of your physical and emotional health might improve after transplant 
and how long any improvement may last.  
Your participation in the study will last 6 months.  Seven hundred people will participate.  You 
will have an equal chance of being placed in one 1 of 4 different groups.  Each group will receive 
a different program.  We will explain the 4 groups in this Consent Form.  All of the clinics in this 
study will report their results, so we can compare all of the groups at the end of the study. 
 
Group 1 
Group 2 
Group 3 
Group 4 
General Information 
Exercise 
Stress Management 
Exercise and 
Stress Management 
 
This Consent Form will tell you about the purpose of the research, its possible risks and benefits, 
other options available to you, and your rights as a participant in the study.  Please take your time 
to read and understand the information in this form before you make your decision.  
Everyone who takes part in research at [insert facility name] should know that: 
 Being in any research study is voluntary. 
 You may or may not benefit from being in the study.  Knowledge we gain from this study 
may benefit others. 
 If you join the study, you can leave the study at any time.   
 If you decide to leave the study, it will not affect your care at [insert name of facility or 
institution]. 
 Please ask the study staff questions about anything that you do not understand or if you 
would like to have more information. 
 You can ask questions now or any time during the study. 
 Please take the time you need to talk about the study with your doctor, study staff, and 
your family and friends.  It is your decision to be in the study.  If you decide to join, 
please sign and date the end of the Consent Form. 
You may wish to discuss other alternatives with your doctor.   
 

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1. Background 
This research study is sponsored by The National Institutes of Health (NIH), the National Heart, 
Lung, and Blood Institute (NHLBI), and the National Cancer Institute (NCI) through the Blood 
and Marrow Transplant Clinical Trials Network (BMT CTN).  
Previous studies suggest that patients who exercise or use stress management methods after 
transplant may experience better physical and emotional health than patients who do not 
exercise or use stress management techniques after transplant.  Although previous studies 
suggest benefits, we don't know if you will get any benefits by taking part in this study.  That is 
why we are doing this research study.  What we learn may help to improve the quality of life of 
other patients after transplant. 
 
2. Purpose 
The main goal of this study is to learn whether patients who participate in an exercise program, 
stress management program, or a combination of an exercise and stress management program 
will feel better after transplant compared to patients who do not participate in either program.  
We also want to know what parts of your physical and emotional health improve after transplant 
and how long any improvement lasts.  
 
3. The Right to Ask Questions and/or Leave the Study 
You have the right to ask questions about the study at any time.  If you have questions about 
your rights as a participant or you want to leave the study, please contact:  
[Insert contact info] 
 
 
 
Being in this study is voluntary.  You can choose not to be in this study, or leave this study at 
any time.   
If you choose to not join or you decide to leave this study, your regular medical care will not be 
affected in any way.  If you decide to not join this study, you will still receive the usual physical 
and emotional care given to transplant patients.  
Even if you leave the study, the information collected from your participation will be included in the 
study evaluation, unless you specifically ask that it not be included. 
Your study doctor and study staff will be available to answer any questions that you may have about 
joining or leaving this study. 
 

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4. Procedures 
If you decide to join this study, you will need to sign this Consent Form. We will give you a 
copy of the signed form to keep.   
You will continue to have regular physical exams, laboratory tests, and other evaluations that are 
standard care by your doctor and transplant center. 
Once you agree to join, we will randomly assign you to 1 of 4 groups before you have your 
transplant. 
Group 1 will get general information about transplantation and how to take care of 
themselves after their transplant.  
Group 2 will get information about exercise and be asked to exercise regularly after their 
transplant.  
Group 3 will get information about stress management and be asked to use stress 
management methods after their transplant. 
Group 4 will get information about exercise and stress management and be asked to exercise 
regularly and use stress management methods after their transplant. 
A member of the research team will meet with you to explain details about your group and the 
materials you will use for the study.  You will need to review some of the materials at home.  We 
think it will take you about one hour to go through the packet of materials.  If you do not have a 
DVD or CD player, equipment will be available in the clinic or hospital that you can use to 
review the materials. 
 
Details About the Study Groups 
 Group 1 - General Information  
If you are assigned to this group, you will get a DVD about transplantation and how you 
can take care of yourself after transplant.  The DVD is about 45 minutes in length and 
covers topics such as preparing for transplant, engraftment, early recovery and long-term 
recovery. 
 Group 2 - Exercise  
If you are assigned to this group, in addition to the general information DVD you will get 
a packet of materials along with a short (10 minute) introduction to exercising at home.  
Your packet of materials will include a DVD, a booklet that shows you how to exercise 
after your transplant and a log to help you keep track of your activity.  We will also give 
you an electronic step counter to help you track how much you walk for exercise. 
As part of the study, we may ask you to walk for exercise at a time and location of your 
choice as often as 3 to 5 times a week for up to 20-30 minutes each time. 
 Group 3 - Stress Management  
If you are assigned to the stress management group, in addition to the general information 
DVD you will get a packet of materials along with a short (10 minute) introduction to 
stress management.  Your packet will include a DVD, compact disc (CD), a booklet 

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which shows you different ways to better manage stress after your transplant, and a log to 
help you track the methods you use. 
As part of the study, we may ask you to use stress management techniques such as paced 
abdominal breathing, progressive muscle relaxation with guided imagery, and use of 
coping self-statements to decrease stress.  
 Group 4 - Exercise and Stress Management  
If you are assigned to the group that combines exercise and stress management, in 
addition to the general information DVD you will get a packet of materials along with a 
short (15 minute) introduction to exercise and stress management.  Your packet will 
include a DVD, and compact disc (CD), a booklet about exercise and stress management, 
a log to help you track your exercise and stress management activities, and an electronic 
step counter. 
As part of the study, we may ask you to walk for exercise at a time and location of your 
choice as often as 3 to 5 times a week for up to 20-30 minutes each time.  
We may also ask you to use stress management techniques such as paced abdominal 
breathing, progressive muscle relaxation with guided imagery, and use of coping self-
statements to decrease stress. 
 
Scheduled Study Visits or Phone Contacts 
A study visit or telephone contact is a meeting that you have with the person in charge of the 
study or another member of the research team.  You will need to have five (5) study visits or 
contacts over six months.  Your enrollment visit will be done in person.  The remaining follow-
up visits for this study may be done in person or by phone.   
Study Visits or Contacts 
1. Enrollment, any time between 6 weeks and one day before transplant – up to 40 minutes 
(if you enrolled more than two weeks before your transplant, you will also get an extra 
reminder call before your transplant).  At the enrollment visit you will complete baseline 
questionnaires (approximately 20 minutes), receive your materials, and may receive 
training based on your group assignment (approximately 10-20 minutes) 
2. One (1) month after transplant - 10 minutes.  You will talk with a member of the study 
team and complete questionnaires (5 minutes). 
3. Two (2) months - 10 minutes.  You will talk with a member of the study team and 
complete questionnaires (5 minutes). 
4. Three (3) months (100 days) - 15 minutes.  You will complete questionnaires (15 
minutes). 
5. Six (6) months - 15 minutes.  You will complete questionnaires (15 minutes). 
Your total length of study participation will last 6 months. 
 

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Study Evaluations 
Your study enrollment session and every follow-up visit will include several surveys for you to 
complete that may be on paper or asked by the study staff.  The surveys will help us evaluate the 
different activities of each group at the end of the study.  All of the in-person visits will happen 
during your regularly scheduled appointments. 
The surveys for this study will ask questions about:  
 Your physical and emotional health 
 How often and how long you have exercised between visits and contacts 
 The number of times you may have used certain methods to manage stress between visits 
and contacts 
 
Additional Evaluations and Procedures 
During the study, some of the research staff’s contacts with participants will be recorded on 
audio tape.  The purpose of this recording is to make sure that the research team members 
continue to carry out the research procedures correctly. You will be asked for permission before 
any audio recording of your contact with research staff. 
 
5. Alternative Treatments 
If you choose to not join or you decide to leave this study, your regular medical care will not be 
affected in any way.  Whether or not you join this study, you will receive the usual physical and 
emotional care given to transplant patients at your transplant center.  
Physical and emotional care choices may include:  
 Meeting with a nurse or social worker.  
 Attending patient support groups to help you with the stress and side effects of your 
treatment.  
Please talk with your doctor about other options.  Every treatment option has benefits and risks. 
Your study doctor will discuss these options with you.  If you decide not to participate in this 
research study, your medical care will not be affected in any way. 
 
6. Risks and Discomforts 
Small but possible risks for this current study are primarily related to exercise.  The chances that 
these things might happen to you are considered to be small because you will be screened for any 
existing health conditions (for example, heart or lung disease) as part of your evaluation prior to 
transplantation that would make it unsafe for you to exercise.  

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Possible risks from exercise include:  
 Shortness of breath (dyspnea) 
 Muscle or joint sprains (musculoskeletal injury) 
 Foot pain or blisters 
 Heat-related injury (dehydration) that might result from exercise training  
Muscle tensing as part of active relaxation and deep breathing for stress management may feel 
uncomfortable to some people.  You should not practice any stress management methods that 
feel painful or uncomfortable.   
If you do decide to participate, we will take extra measures to limit the chances of you getting 
hurt.  These measures include exercise plans that are a good fit for your physical condition and 
suggesting ways to prevent possible muscle strain and soreness as well as dehydration.  
If you have any of the problems due to exercising or using the stress management methods that 
we have described, tell the person in charge of this study or study staff at your next visit.  If these 
problems bother or worry you or if you have other problems, call the person in charge of this 
study at [telephone number] 
New risks might appear at any time during the study that are different from the risks listed in this 
Consent Form.  We will promptly tell you of any new information that might affect your 
decision to participate. 
 
7. Possible Benefits 
Taking part in this study may or may not make your health better.   
Earlier studies suggest that patients who exercise or use stress management methods after 
transplant may experience better physical and mental well-being than patients who do not 
exercise or use stress management methods after transplant.  Although earlier studies suggest 
benefits, we don't know if you will get any benefits by taking part in this study.  That is why we 
are doing this research study.  What we learn may help to improve the quality of life of other 
patients after transplant. 
 
8. New Information Available During the Study 
During this research study, new information about exercise or stress management methods or the 
risks and benefits of the study may become known to the study doctors.  If this happens, they will 
tell you about the new information.  The new information may mean that you can no longer 
participate in the study, or that you may not want to continue in the study.   
If this happens, the study doctor will stop your participation in the study and you will be offered all 
available care to suit your needs and medical condition. 
 

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9. Privacy, Confidentiality and Use of Information 
Your confidentiality is one of our main concerns.  We will do our best to make sure that the 
personal information in your medical record will be kept private.  However, we cannot guarantee 
total privacy.   
Your personal information may be given out if required by law.  If information from this study is 
published or presented at scientific meetings, your name and other personal information will not be 
used.  Your study number is not related to your name, social security number or medical record 
number at [insert facility name]. 
Information about your transplant from your original medical records may be seen or sent to 
national and international transplant registries, including:  
 The Center for International Blood and Marrow Transplant Research (CIBMTR) 
 The National Marrow Donor Program (NMDP) 
 The Food and Drug Administration (FDA) 
 The National Institutes of Health (NIH), which include the National Heart, Lung, and Blood 
Institute (NHLBI) and the National Cancer Institute (NCI) 
 Data Coordinating Center of the Blood and Marrow Transplant Clinical Trials Network 
(BMT CTN)  
 Other authorized study organizations   
 We will not identify you by name in any publications or reports that come from these 
organizations or groups. 
 
10.  Ending Your Participation 
The study doctor or the study sponsor may stop the study at any time.  We may ask you to leave 
the study if you do not follow directions or if you suffer from side effects of the treatment.  If 
you are asked to leave the study, the reasons will be discussed with you. 
Possible reasons to end your participation in this study include: 
 You do not meet the study requirements.   
 The study doctor decides that it would be harmful to you to stay in the study. 
 You are having serious side effects. 
 You cannot keep appointments. 
 The study is stopped for any reason. 
 

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11.  Physical Injury as a Result of Participation 
It is important that you tell the doctor responsible for this study if you feel that you have been 
injured because of taking part in this study.  You can tell the doctor in person or call him/her at 
__________________ [telephone number]. 
 
You will get medical treatment if you are injured as a result of taking part in this study.  You 
and/or your health plan will be charged for this treatment. The study will not pay for medical 
treatment.  
In case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form. 
 
12.  Compensation or Payment 
You will not be paid for your participation in the research study.  You will not get compensation or 
reimbursement for any extra expenses (travel, meals, etc.) you may have through your participation 
on this trial. 
 
13.  Costs & Reimbursements 
You and/or your health plan/insurance company will need to pay for all of the costs of treating 
your cancer.  Taking part in this study may or may not cost your insurance company more than 
the cost of getting regular cancer treatment.  However, participation in this study does not require 
any additional medical tests, evaluations or procedures so we do not anticipate that participation 
in this study will cost more than routine care. 
All costs of your care will need to be paid by you and/or your health plan/insurance company.   
The companies that make the materials used in this study did not plan or design this clinical trial.  
They will also not have a part in analyzing the results of this study. 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage.  You 
can print a copy of the “Clinical Trials and Insurance Coverage” information from this Web site. 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask for 
your free copy. 
 
14.  Ethical Review 
The ethical aspects of this research study have been reviewed and approved by [name of IRB]. 
 

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15.  Further Information 
If you need any information about this study, or if you have any problems while you are 
participating in this study you can contact the study doctor or his/her staff.  They may be contacted 
at the telephone numbers listed here. 
[Insert name and contact details] 
 
16.  Independent Contact 
If you wish to speak to someone not directly involved in the study, or if you have any complaints 
about any aspect of the project, the way it is being conducted or any questions about your rights as a 
research participant, then you may contact:  
[Insert appropriate contact details] 
 
 
 

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Health Insurance Portability and Accountability Act 1 (HIPAA1) Authorization to use and 
disclose individual health information for research purposes  
 
A. Purpose   
As a research participant, I authorize the Principal Investigators and the researcher’s staff to 
use and disclose my individual health information for the purpose of conducting the research 
study:  
A Phase III Randomized, Multi-center Trial Testing Whether Exercise or Stress Management 
Improves Functional Status and Symptoms of Autologous and Allogeneic Recipients. 
B. Individual Health Information to be Used or Disclosed  
My individual health information that may be used or disclosed to do this research includes:  
 Demographic information (for example: date of birth, sex, weight).  
 Medical history (for example: diagnosis, complications with prior treatment). 
 Findings from physical exams. 
 Laboratory test results obtained at the time of work up and after treatment (for example: 
blood tests, biopsy results).  
C. Parties Who May Disclose My Individual Health Information  
The researcher and the researcher’s staff may collect my individual health information from: 
(List hospitals, clinics or providers from which health care information can be requested). 
 
D. Parties Who May Receive or Use My Individual Health Information  
The individual health information disclosed by parties listed in item c and information 
disclosed by me during the course of the research may be received and used by the following 
parties: 
 Principal Investigators  
 
- Stephanie J. Lee, M.D., M.P.H, Co-Investigator  
- Paul B. Jacobsen, Ph.D., Co-Investigator  
 Members of the BMT CTN Data and Coordinating Center and 0902 Protocol Team 
 The Center for International Blood and Marrow Transplant Research (CIBMTR) and the 
National Marrow Donor Program (NMDP) 
 National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute 
(NCI), both of the National Institutes of Health (NIH), study sponsors  
 U.S. government agencies that are responsible for overseeing research such as the Food 
and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) 
 U.S. government agencies that are responsible for overseeing public health concerns such 
as the Centers for Disease Control (CDC) and federal, state and local health departments 
 
1 HIPAA is the Health Insurance Portability and Accountability Act of 1996, a federal law related to privacy of health 
information 

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 Other:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
E. Right to Refuse to Sign this Authorization  
I do not have to sign this Authorization.  If I decide not to sign the Authorization, I will not 
be allowed to participate in this study or receive any treatment related to research that is 
provided through the study. My decision not to sign this authorization will not affect any 
other treatment, payment, or enrollment in health plans or eligibility for benefits.   
F. Right to Revoke   
I can change my mind and withdraw this authorization at any time by sending a written 
notice to the Principal Investigator to inform the researcher of my decision. If I withdraw this 
authorization, the researcher may only use and disclose the protected health information 
already collected for this research study.  No further health information about me will be 
collected by or disclosed to the researcher for this study. 
G. Potential for Re-disclosure  
My individual health information disclosed under this authorization may be subject to re-
disclosure outside the research study and no longer protected. Examples include potential 
disclosures for law enforcement purposes, mandated reporting or abuse or neglect, judicial 
proceedings, health oversight activities and public health measures. 
H. This authorization does not have an expiration date. 
 

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TITLE: 
A Phase III Randomized, Multi-center Trial Testing Whether Exercise or Stress Management 
Improves Functional Status and Symptoms of Autologous and Allogeneic Recipients. 
PROTOCOL NUMBER: 
0902  
 
INVESTIGATORS: 
Stephanie J. Lee, M.D., M.P.H, Co-Investigator  
Paul B. Jacobsen, Ph.D., Co-Investigator  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant Name 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
I certify that I have provided a verbal explanation of the details of the research study, including 
the procedures and risks.  I believe the participant has understood the information provided. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Signature of Counseling Physician 
 
 
 
 
 
 
Date 
 
 

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APPENDIX C 
 
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