Conditions: Multiple Myeloma
Keywords: Multiple Myeloma Lenalidomide Maintenance Therapy Progression Long-term Anti-Myeloma Agents Hematologic Disorders
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 273
Healthy volunteers: no

Brief summary:
This study is designed to compare long-term outcomes among patients randomized on the BMT CTN 0702 protocol (NCT01109004), "A Trial of Single Autologous Transplant with or without Consolidation Therapy versus Tandem Autologous Transplant with Lenalidomide Maintenance for Patients with Multiple Myeloma". It is hypothesized that use of novel anti-myeloma agents will improve long-term progression-free survival (PFS) after high-dose melphalan followed by autologous hematopoietic cell transplantation (HCT) as compared to a second autologous transplantation.

Detailed description:
This study is designed to compare long-term outcomes among patients randomized on the BMT CTN 0702 protocol (NCT01109004). All patients who consent will be followed for death, progression, Second Primary Malignancies (SPMs), and Quality of Life (QOL). Patients who do not consent to the long-term follow-up mechanism or who have experienced progression on the BMT CTN 0702 study will be followed through the standard Center for International Blood and Marrow Transplant Research (CIBMTR) long-term follow-up mechanism. Additionally, patients who are eligible and are willing to continue with lenalidomide as maintenance therapy will be provided lenalidomide free of charge. These patients will continue to receive lenalidomide as maintenance therapy until disease progression or discontinuation due to toxicity, death, or withdrawal from the study. The endpoints assessed will include progression-free survival (PFS), overall survival (OS), event-free survival (EFS), incidence of second primary malignancies (SPM) and health quality of life (QOL).

Arms:
arm 1: Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance arm 2: Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance arm 3: Initial autologous transplant followed by lenalidomide maintenance

Interventions: intervention 1: Lenalidomide
Intervention descriptions: intervention 1: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.

Protocol document:
Prot_000.pdf: 
 
 
Continued, Long-Term Follow-Up and Lenalidomide Maintenance 
Therapy for Patients Who Have Enrolled on BMT CTN 0702  
 
(ClinicalTrials.gov Number: NCT02322320) 
 
BMT CTN PROTOCOL 0702 – Long-Term Follow-Up 
Version 2.0 
 
Study Chairpersons 
Amrita Krishnan, MD1*, George Somlo, MD1, Edward Stadtmauer, MD2 
 
Protocol Team 
 
Brianne Allison5 
Pam Budnick3 
Angela Dispenzieri, MD4  
Nancy Geller, PhD6 
Sergio Giralt, MD7 
John Koreth, MBBS, DPhil10 
Adam Mendizabal, PhD5 
Phil McCarthy, MD9 
Courtney Nelson5 
Hari Parameswaran, MD, MS11 
Marcelo C. Pasquini, MD, MS11 
Muzaffar Qazilbash, MD8 
David Vesole, MD12 
 
Sponsored by the National Institutes of Health 
National Heart, Lung, and Blood Institute 
National Cancer Institute 
 
 
 
1 City of Hope National Medical Center 
2 University of Pennsylvania Cancer Center 
3 National Marrow Donor Program 
4 Mayo Clinic Rochester 
5 The EMMES Corporation 
6 National Heart, Lung, and Blood Institute 
7 Memorial Sloan-Kettering Cancer Center 
8University of Texas, MD Anderson Cancer 
Center 
9 Roswell Park Cancer Institute 
10 Dana Farber Cancer Institute  
11 Center for International Blood and Marrow 
Transplant Research, Medical College of 
Wisconsin 
12 Hackensack University Medical Center 
*Corresponding Chairperson 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
i 
Core Study Participants: 
 
Affiliate and Cooperative Group Study 
Participants: 
BMT Program at Northside Hospital 
Case Western Reserve University Consortium  
    Oregon Health & Sciences University 
    University Hospitals of Cleveland  
City of Hope National Medical Center, Duarte, CA 
Dana Farber/Partners Cancer Center 
    Brigham & Women’s Hospital 
Duke University Medical Center 
Fred Hutchinson Cancer Research Center 
Memorial Sloan-Kettering Cancer Center 
Ohio State Consortium 
Ohio State 
Roswell Park Cancer Institute 
University of North Carolina Hospital at Chapel Hill 
Stanford Hospital and Clinics 
University of Florida College of Medicine 
University of Michigan Consortium 
University of Michigan 
Vanderbilt University 
University of Minnesota 
University of Nebraska Consortium 
     University of Kansas 
     University of Nebraska Medical Center  
University of Pennsylvania Cancer Center 
University of Texas, MD Anderson Cancer Center 
Washington University, Barnes Jewish Hospital 
 
 
Arizona Cancer Center 
Colorado Blood Cancer Institute 
H. Lee Moffitt Cancer Center  
Hackensack University Medical Center 
Jewish Hospital BMT Program 
Karmanos Cancer Institute/BMT 
Louisiana State University Health Sciences Center 
Medical College of Wisconsin 
Mount Sinai Medical Center 
North Shore University Hospital 
Penn State College of Medicine 
Rush University 
Sarah Cannon BMT Program 
Texas Transplant Institute 
UCSD/SCRIPPS School of Medicine  
University of Illinois 
University of Kentucky 
University of Miami 
University of Oklahoma 
University of Texas Southwestern Medical Center 
University of Wisconsin Hospital 
Wake Forest University Health Sciences 
West Virginia University Hospital 
 
 
 
 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
ii 
PROTOCOL SYNOPSIS – BMT CTN 0702 LONG-TERM FOLLOW-UP 
PROTOCOL  
 
Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients 
Who Have Enrolled on BMT CTN 0702  
 
Co-Principal Investigators: 
Amrita Krishnan, MD, George Somlo, MD, and  
Edward Stadtmauer, MD 
 
Study Design: 
The study is designed to provide continued, long-term follow-up 
on patients enrolled on BMT CTN 0702 who have not 
experienced progression, as well as to offer optional long-term 
lenalidomide maintenance therapy to those BMT CTN 0702 
patients who have completed 3 years of protocol-defined 
maintenance therapy without evidence of disease progression.  
 
Primary Objective: 
The primary objective is to compare progression-free survival 
(PFS) as a time to event analysis between the three randomized 
treatment arms from the BMT CTN 0702 protocol as a pairwise 
comparison. The analysis will be conducted once all surviving 
patients have been followed for at least 5-years post 
randomization on the BMT CTN 0702 protocol.   
 
Secondary Objectives: 
Secondary objectives include the cumulative incidence of 
second primary malignancies (SPM), probability of overall 
survival (OS), probability of event-free survival (EFS) and 
Health Quality of Life (QOL) on all patients, including those 
not receiving long-term lenalidomide maintenance therapy. 
 
Eligibility Criteria: 
Patients eligible for long-term follow-up are those who were 
enrolled and randomized on the BMT CTN 0702 protocol and 
who are alive at the end of the BMT CTN 0702 protocol-
defined follow-up period without progression.  Patients eligible 
for long-term lenalidomide maintenance therapy include 
patients who have completed 3 years of BMT CTN 0702 
protocol-defined lenalidomide maintenance therapy with no 
evidence of disease progression.  
 
Treatment/Follow-Up: 
All patients who consent to the long-term follow-up protocol 
will undergo study assessments every 6-months.  Patients 
eligible to continue with lenalidomide maintenance therapy will 
continue with the last tolerated dose of lenalidomide that was 
documented upon completion of BMT CTN 0702 maintenance 
therapy.  
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
iii 
Accrual Objective: 
It is anticipated that approximately 450 patients will be enrolled 
on this protocol based on assumed estimates of PFS from the 
BMT CTN 0702 study.  The total sample size may be as low as 
417 if the observed 3-year PFS on the BMT CTN 0702 is 55% 
but may be as high as 569 if the 3-year PFS is 75%.   
 
Study Duration: 
Patients will be followed until death, progression, withdrawal 
from the study, or through the end of 2018.  
 
Interim Analysis: 
No formal interim analyses are planned.    
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
iv 
Figure 1: Study Schema 
 
 
 
Outline of Study Schema for Long- 
Term Follow-Up and Lenalidomide 
Maintenance 
 
Follow patient for all 
long-term follow-up 
endpoints 
Follow patient for all 
long-term follow-up 
endpoints 
Patient meets eligibility criteria to 
receive long-term lenalidomide 
maintenance therapy 
Patient not eligible OR 
Patient declines long-term 
lenalidomide maintenance therapy 
Lenalidomide maintenance    
Continue with last tolerated dose 
taken upon completion of BMT 
CTN 0702 maintenance therapy 
 
Enrolled in BMT CTN 0702 and completed study 
specified follow-up without progression 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
v 
TABLE OF CONTENTS 
 
 
1. 
BACKGROUND AND RATIONALE ............................................................................ 1-1 
1.1. 
Background ...................................................................................................................... 1-1 
1.2. 
Lenalidomide Maintenance in Multiple Myeloma ........................................................ 1-1 
1.3. 
Second Primary Malignancies ........................................................................................ 1-3 
1.4. 
Rationale for Study ......................................................................................................... 1-4 
2. 
STUDY DESIGN ................................................................................................................ 2-1 
2.1. 
Study Overview ............................................................................................................... 2-1 
2.2. 
Hypothesis and Specific Objectives ............................................................................... 2-1 
2.2.1. 
Hypothesis ....................................................................................................................... 2-1 
2.2.2. 
Study Objectives ............................................................................................................. 2-1 
2.2.3. 
Secondary objectives include: ........................................................................................ 2-1 
2.3. 
Patient Eligibility............................................................................................................. 2-2 
2.3.1. 
Initial Patient Eligibility Criteria for Long-Term Follow-Up Only ............................. 2-2 
2.3.2. 
Patient Eligibility Criteria for Optional Long-term Lenalidomide Maintenance 
Therapy ............................................................................................................................ 2-2 
2.3.3. 
Patient Exclusion Criteria for Long-term Lenalidomide Maintenance Therapy......... 2-2 
2.4. 
Study Treatments............................................................................................................. 2-3 
2.4.1. 
Lenalidomide ................................................................................................................... 2-3 
2.4.2. 
Suggested Treatment Modification Guidelines for Maintenance Therapy.................. 2-3 
2.4.3. 
Lenalidomide Maintenance Dose Re-escalation: .......................................................... 2-5 
2.5. 
Supportive Care ............................................................................................................... 2-6 
2.5.1. 
Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) Prophylaxis ............. 2-6 
2.6. 
Participant Risks .............................................................................................................. 2-6 
2.6.1. 
Lenalidomide ................................................................................................................... 2-6 
2.7. 
Study Drug Supply .......................................................................................................... 2-7 
2.7.1. 
Lenalidomide (NSC 703813) ......................................................................................... 2-7 
3. 
STUDY ENDPOINTS AND DEFINITIONS ................................................................. 3-1 
3.1. 
Definition of Disease Progression .................................................................................. 3-1 
3.2. 
Primary Endpoint ............................................................................................................ 3-2 
3.2.1. 
Progression-Free Survival .............................................................................................. 3-2 
3.3. 
Secondary Endpoints....................................................................................................... 3-2 
3.3.1. 
Overall Survival .............................................................................................................. 3-2 
3.3.2. 
Event-free Survival ......................................................................................................... 3-2 
3.3.3. 
Incidence of Second Primary Malignancies .................................................................. 3-2 
3.3.4. 
Unexpected Grades 3-5 Adverse Events ....................................................................... 3-2 
3.3.5. 
Health Quality of Life ..................................................................................................... 3-3 
4. 
PATIENT ENROLLMENT AND EVALUATION ...................................................... 4-1 
4.1. 
Enrollment Procedures .................................................................................................... 4-1 
4.1.1. 
Eligibility and Enrollment .............................................................................................. 4-1 
4.1.2. 
Revlimid REMS® Lenalidomide Counseling ............................................................... 4-1 
4.2. 
Study Monitoring ............................................................................................................ 4-1 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
vi 
4.2.1. 
Follow-up Schedule ........................................................................................................ 4-1 
4.2.2. 
Data Reporting ................................................................................................................ 4-1 
4.3. 
Adverse Event Reporting ................................................................................................ 4-2 
4.3.1. 
Unexpected, Grades 3-5 Adverse Events ...................................................................... 4-2 
4.3.2. 
Reporting Second Primary Malignancies ...................................................................... 4-2 
4.3.3. 
Reporting Patient Deaths ................................................................................................ 4-3 
4.3.4. 
Pregnancy Reporting ....................................................................................................... 4-3 
4.4. 
Patient Assesssments....................................................................................................... 4-4 
4.4.1. 
Long-Term Follow-Up Only- Assessment Schedule .................................................... 4-4 
4.4.2. 
Long-Term Follow-Up and Long-Term Lenalidomide Maintenance Assessment 
Schedule ........................................................................................................................... 4-5 
4.4.3. 
Long-Term Follow-Up Assessment Schedule (Post-Progression) .............................. 4-6 
5. 
STATISTICAL CONSIDERATIONS ............................................................................ 5-1 
5.1. 
Study Design and Objectives.......................................................................................... 5-1 
5.2. 
Accrual, Registration and Follow-up ............................................................................. 5-1 
5.3. 
Analysis of the Primary Endpoint .................................................................................. 5-1 
5.4. 
Analysis of the Secondary Endpoints ............................................................................ 5-2 
5.5. 
Safety Oversight .............................................................................................................. 5-3 
 
 
LIST OF APPENDICES 
 
APPENDIX A  
PATIENT INFORMED CONSENT FORM 
APPENDIX B  
LENALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY 
TESTING GUIDELINES AND ACCEPTABLE BIRTH CONTROL 
METHODS 
APPENDIX C  
Revlimid REMS® PROGRAM 
APPENDIX D  
LENALIDOMIDE INFORMATION SHEET 
APPENDIX E  
RESEARCH SAMPLES 
APPENDIX F  
ADVERSE EVENTS 
APPENDIX G 
REFERENCES 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
1-1 
CHAPTER 1 
 
 
1. 
BACKGROUND AND RATIONALE 
 
1.1. Background 
 
Therapeutic advances in multiple myeloma (MM) have resulted in substantially improved 
survival.  Similarly, in a large population-based study of 45,595 MM patients, myeloma-specific 
5-year median overall survival (OS) improved from 36% to 68% under age 50, and from 34% to 
58% among patients of ages 51-65 years between 1973 and 2009.  
 
Post-transplant consolidation and maintenance strategies have also yielded improved 
progression-free survival (PFS) and OS.  The BMT CTN 0702 study randomized patients to 
receive two autologous hematopoietic cell transplants (HCT), or one autologous HCT and post 
transplant consolidation, or one autologous HCT with maintenance.  Of note, all patients receive 
a total of 3 years of maintenance therapy using lenalidomide.  Since the implementation of BMT 
CTN 0702, the experience with maintenance has broadened, and at least two large phase III 
clinical trials that continued lenalidomide maintenance for longer periods were associated with 
longer survival, compared to placebo.  This long-term follow-up protocol focuses on extending 
the follow-up period for all patients on BMT CTN 0702 to assess long-term outcomes such as 
PFS and incidence of SPMs.  A secondary objective is to provide patients with lenalidomide 
maintenance therapy free of charge until there is evidence of disease progression.   
 
1.2. Lenalidomide Maintenance in Multiple Myeloma 
 
There are three phase III studies that examined lenalidomide maintenance therapy versus placebo 
following autologous hematopoietic stem cell transplant (AHSCT)1,2,3 (Table 1.2).  The 
CALGB/ECOG 100104 (BMT CTN 0704) study randomized MM patients after induction 
therapy and single AHSCT to lenalidomide versus placebo until progression.  The induction 
regimens varied, with 74% of patients receiving a thalidomide- or lenalidomide-based induction 
regimen.  The median time to progression (TTP) was 46 months for the lenalidomide group and 
27 months for the placebo group (P<0.001).  The 3-year PFS was 66% for the lenalidomide 
group and 39% for the placebo group (P<0.001).  At a median follow-up of 34 months, the 3 
year OS rates were 88% for the lenalidomide group and 80% for the placebo group (P=0.028).  
The study was updated in 2013 and with a median follow-up of 48 months, the OS was 80% for 
the lenalidomide group and 70% for the placebo group (P=0.008)4.  The study was un-blinded at 
a median follow-up of 26 months because the primary endpoint (TTP) had been met and 67% of 
eligible placebo patients crossed over to receive lenalidomide.  A TTP and OS benefit for the 
lenalidomide arm remains despite the cross-over.   
 
The IFM 05-02 study treated MM patients after induction with a single (79%) or tandem AHSCT 
(21%) followed by a 2 cycle consolidation with lenalidomide before randomization to 
lenalidomide maintenance, originally until progression5.  The induction regimens were 
vincristine, doxorubicin and dexamethasone (VAD) or bortezomib and dexamethasone (VD).  
Approximately 25% of patients received consolidation with dexamethasone, cyclophosphamide, 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
1-2 
etoposide and cisplatin before AHSCT.  The median PFS was 41 months for the lenalidomide 
group and 23 months for the placebo group respectively (P<0.001).  The 4 year PFS was 43% for 
the lenalidomide group and 22% for the placebo group (P<0.001).  At 45 months of median 
follow-up, the OS was 74% for the lenalidomide group and 76% for the placebo group.  The 4 
year OS rate was 73% for the lenalidomide group and 75% for the placebo group respectively 
(P=0.7).  The study was un-blinded at median follow-up of approximately 30 months and all 
maintenance was stopped at a median time of 32 months for the lenalidomide arm due to concern 
regarding second primary malignancy (SPM) development (Section 1.3).  At a median follow-up 
of 60 months from randomization, lenalidomide maintenance improved PFS (42%) when 
compared to placebo (18%) (P<0.0001).  The 5 year OS is 68% in the lenalidomide group and 
67% in the placebo group (HR=1) and the median survival after first progression is 29 months 
for the lenalidomide group and 48 months in the placebo group (P<0.0001).   
 
Table 1.2: Lenalidomide Maintenance after Autologous Hematopoietic Cell 
 Transplantation for Multiple Myeloma 
Study 
Number of 
Patients 
Initial 
Dose (mg)  
Maintenance versus no Maintenance 
 
EFS or PFS 
OS 
McCarthy et al 
NEJM 2012 
460 
10 
TTP 
46 vs 27months (P<0.001) 
Median followup 34 m 
85 vs 77% (P=0.028) 
 
3-year PFS rate 
66% (95% CI, 59 to 73) 
vs 
39% (95% CI, 33 to 48) 
3 year OS rate 
88 % (95% CI, 84 to 93) 
vs 
80 % (95% CI, 74 to 86) 
EFS 
43 vs 27 months (P<0.001) 
 
McCarthy et al Clin  
Lym Myelom Leuk 2013 (Update) 
 
Median followup 48 m 
80 vs 70% (P=0.008) 
Attal et al 
NEJM 2012 
614 
10 
PFS 
41 vs 23 months (P<0.001) 
Median followup 45 m 
74 vs 76% (P=0.7) 
 
4 year PFS 
43 vs 22% (P<0.001) 
4 year OS 
73 vs75% (NS) 
EFS 
40 vs 23 months (P<0.001) 
 
Attal et al 
ASH 2013 abst 206 
5 year PFS 
42% vs 18% (P<0.001) 
Median followup 70 m 
5 year OS 
68 vs 67% (NS) 
Boccadoro et al 
JCO 2013 
202 (NIT) 
200 (IT) 
10 (3 of 4 
weeks 
monthly) 
Median PFS (combining NIT 
and IT groups) 
37 vs 26 months(P <0.001) 
5 year OS (combining NIT 
and IT groups) 
75 versus 58% (P=0.02) 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
1-3 
Study 
Number of 
Patients 
Initial 
Dose (mg)  
Maintenance versus no Maintenance 
 
EFS or PFS 
OS 
Palumbo et al 
ASH 2013 abst 
763 
194 (NIT) 
195 (IT) 
10: days 1 
to 21 of 28 
days +/-  
P 50: every 
other day 
3 year PFS (combining NIT and 
IT groups) 
RP: 60% vs 38% for R alone 
(P=0.003) 
31 month median followup 
(combining NIT and IT 
groups) 
3 year OS (NIT and IT) 
ND 
EFS: Event-free survival includes deaths, progressions and second cancers; IT: Intensive Therapy: NIT: Non-
intensive therapy; ND: No difference, NS: Not significant; OS: Overall Survival; P: Prednisone, PFS: Progression-
Free Survival, R: Lenalidomide.  Adapted with permission from McCarthy PL.  Part I: the role of maintenance 
therapy in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation.  J Natl 
Compr Canc Netw. 2013 Jan 1;11(1):35-42. 
 
Another lenalidomide maintenance study following chemotherapy versus tandem autologous 
HCT has been reported; RV-MM-PI-2093.  At a median follow-up of 49 months from 
chemotherapy versus tandem autologous HCT and a median follow-up of 35 months from 
randomization to lenalidomide maintenance versus no maintenance, the median PFS for 
lenalidomide maintenance was 37 months (including autologous HCT and non-HCT patients 
received maintenance) versus 26 months for patients not receiving maintenance (P<0.0001).  The 
5 year OS estimates were 75% and 58% for the lenalidomide maintenance and no maintenance 
groups respectively (P=0.02).  A meta-analysis of IFM 05 02, CALGB 100104, RV-MM-PI-209 
(MPR vs Mel200) and MM 015 (a non-transplant trial) found that lenalidomide maintenance 
when compared to placebo improves PFS and OS5.   
 
In another study by the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) Multiple 
Myeloma Working Group, newly diagnosed patients received lenalidomide and dexamethasone 
(RD) induction followed by randomization to cyclophosphamide/ lenalidomide/dexamethasone 
(CRD) or tandem autologous HCT with melphalan, and a second randomization occurred to 
lenalidomide/prednisone versus lenalidomide maintenance until progression6.  There was as 
superior PFS for the lenalidomide/prednisone maintenance arm when compared to lenalidomide 
alone: 62% versus 38%, (p=0.003).   
 
1.3. Second Primary Malignancies 
 
The lenalidomide group in CALGB/ECOG 100104 (BMT CTN 0704) had an increased 
incidence of hematologic toxicities (primarily neutropenia) and an increase in second primary 
malignancies (SPM).  There were 8/231(3.5%) hematologic malignancies, primarily Acute 
Myeloid Leukemia/Myelodysplastic Syndrome (AML/MDS) in lenalidomide group patients 
versus 1/229 (0.4%) in placebo group patients.  There were 10/231 (4.3%) versus 5 (2.1%) solid 
tumors in lenalidomide group and placebo group patients respectively, and 4/231 (1.7%) versus 
3/229 (1.3%) non-melanoma skin cancers.  In the 2013 update, one AML was reported in the 
lenalidomide arm (total 9/231 hematologic malignancies) and one case of ALL and MDS in two 
placebo arm patients who crossed over to lenalidomide6.  One solid tumor (renal cell carcinoma) 
was reported in another cross over patient and 4 non-melanoma skin cancers were reported; 3 in 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
1-4 
the lenalidomide arm and one in a cross over placebo patient.  The cumulative incidence risk 
(CIR) for the development of SPM was greater for the lenalidomide group when compared to the 
placebo group (p<0.008).  The CIR of progressive disease (p<0.001) or death (p<0.002) were 
greater for the placebo group when compared to the lenalidomide group.  When including deaths, 
progressions and SPMs as events, the median EFS was 43 months for the lenalidomide group 
and 27 months for the placebo group (P<0.001).   
 
The placebo group patients in the IFM 05-02 study did not cross over to receive lenalidomide at 
un-blinding.  The lenalidomide group had an increased incidence of hematologic toxicities 
(primarily neutropenia) and an increase in SPMs.  There were 13/306 (4.2%) hematologic 
malignancies, (primarily Acute Lymphoblastic Leukemia (ALL) and Hodgkin Lymphoma and 
AML/MDS) in lenalidomide group patients versus 5/302 (primarily AML/MDS only) in placebo 
group patients.  There were 10/306 (3.3%) versus 4/302 (1.3%) solid tumors in the lenalidomide 
group and placebo group patients respectively and 5/306 (1.6%) versus 3/302 (1.0%) non-
melanoma skin cancers.  When including deaths, progressions and SPMs as events, the median 
EFS was 40 months for the lenalidomide group and 23 months for the placebo group (P<0.001).  
An updated analysis was recently presented7. 
 
The SPM rate was approximately 4.5% in both maintenance arms (AHSCT and non-AHSCT). 
The risk factors for SPM development are not fully defined.  A meta-analysis was undertaken of 
6383 NDMM patients treated on Phase III transplant and non-transplant clinical trials, 3218 
receiving lenalidomide maintenance and 3165 receiving no maintenance8.  The CI of 
hematologic SPMs was higher for patients receiving lenalidomide maintenance when compared 
to placebo arm patients (HR: 3.8; 95% CI 2.11-6.86; p<0.001).  The CI of death was death at 60 
months was 26.2 (95% CI 22.4 -28.8) for the lenalidomide arm and 36.3 (95% CI 25.9-46.6) for 
the no maintenance arm.  There was a higher incidence of hematologic SPMs with oral 
melphalan when compared to IV melphalan (HR 3.3; 95% CI 1.46-7.46 p=0.004).  Previous 
work has demonstrated that monoclonal gammopathy of unknown significance (MGUS) and 
MM have both been associated with the development of AML/MDS9.  It is uncertain as to what 
the bone marrow defect is in MGUS and MM patients (not having received anti-MM therapy) 
that predisposes them to AML/MDS development.   
 
1.4. Rationale for Study 
 
This current protocol has the objective to compare long-term outcomes based on the randomized 
treatment groups from the BMT CTN 0702 protocol.  All consenting patients will continue to be 
monitored for the development of long-term complications with emphasis on second primary 
malignancies.  Patients who do not consent to the long-term follow-up mechanism or who have 
experienced progression on the BMT CTN 0702 study will be followed through the standard 
CIBMTR long-term follow-up mechanism.  Additionally, the protocol will extend the duration of 
lenalidomide maintenance for all patients enrolled in the BMT CTN 0702 study who have 
completed 3 years of maintenance and have not experienced disease progression.  
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-1 
CHAPTER 2 
 
 
2. 
STUDY DESIGN 
 
2.1. Study Overview 
 
This study is designed to compare long-term outcomes among patients randomized on the BMT 
CTN 0702 protocol.  All patients who consent will be followed for death, progression, SPMs and 
QOL.  Patients who do not consent to the long-term follow-up mechanism or who have 
experienced progression on the BMT CTN 0702 study will be followed through the standard 
CIBMTR long-term follow-up mechanism.  Additionally, patients who are eligible and are 
willing to continue with lenalidomide as maintenance therapy will be provided lenalidomide free 
of charge.  These patients will continue to receive lenalidomide as maintenance therapy until 
disease progression or discontinuation due to toxicity, death, or withdrawal from the study.  The 
endpoints assessed will include progression-free survival (PFS), overall survival (OS), event-free 
survival (EFS), incidence of second primary malignancies (SPM) and health quality of life 
(QOL). 
 
2.2. Hypothesis and Specific Objectives 
 
2.2.1. Hypothesis 
 
Use of novel anti-myeloma agents will improve long-term PFS after high-dose melphalan 
followed by autologous hematopoietic cell transplantation (HCT) as compared to a second 
autologous transplantation.  
 
2.2.2. Study Objectives 
 
The primary objective of this long-term follow-up protocol is to compare the PFS as a time to 
event analysis from randomization on the BMT CTN 0702 protocol between the three 
randomized treatment arms as a pairwise comparison.    The analysis will be conducted once all 
alive patients have been followed for 5-years post randomization on the BMT CTN 0702 
protocol.   
 
2.2.3. Secondary objectives include: 
 Overall survival from randomization on the BMT CTN 0702 protocol; 
 Event-free survival from randomization on the BMT CTN 0702 protocol; 
 Incidence from randomization on the BMT CTN 0702 protocol of second primary 
malignancies in long-term use of lenalidomide as maintenance therapy. 
 Health Quality of Life 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-2 
2.3. Patient Eligibility 
 
Patients must meet specified eligibility criteria to be enrolled on the study.  All questions 
regarding eligibility criteria should be directed to the BMT CTN 0702 Long-Term Follow-Up 
Protocol Coordinator at 301-251-1161. 
 
2.3.1. Initial Patient Eligibility Criteria for Long-Term Follow-Up Only 
 
Patients fulfilling the following criteria will be eligible to provide continued long-term follow-up 
data as part of this study:  
1. Enrolled and randomized on the BMT CTN 0702 protocol 
2. Alive at the completion of BMT CTN 0702 protocol specified follow-up defined as 4 
years post-randomization  
3.  Patients without evidence of disease progression at the completion of BMT CTN 0702 
protocol specified follow up. (see Section 3.1 for disease progression definition) 
4. Signed Informed Consent Form 
5. Patients with the ability to speak English or Spanish are eligible to participate in the HQL 
component of this trial.  
 
2.3.2. Patient Eligibility Criteria for Optional Long-term Lenalidomide Maintenance Therapy 
 
Patients fulfilling the following criteria will be eligible to provide continued long-term follow-up 
data AND receive long-term lenalidomide maintenance therapy as part of this study:  
1. Enrolled and randomized to BMT CTN 0702 
2. Completion of 3 years of maintenance therapy on BMT CTN 0702 
3. Registered in the mandatory Revlimid REMS® program (formerly the RevAssist® for 
Study Participants (RASP) program), and be willing and able to comply with the 
requirements of the Revlimid REMS® program, including counseling, pregnancy testing, 
and phone surveys. 
4. Signed informed consent form. 
5. Patients with the ability to speak English or Spanish are eligible to participate in the HQL 
component of this trial.  
 
2.3.3. Patient Exclusion Criteria for Long-term Lenalidomide Maintenance Therapy  
 
Patients who meet any of the following criteria will be ineligible to receive long-term 
lenalidomide maintenance therapy as part of this study*: 
1. Patients who have evidence of disease progression prior to enrollment (see Section 3.1 
for disease progression definition). 
                                         
* All patients will be followed for long-term outcomes.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-3 
2. Patients who were discontinued from BMT CTN 0702 lenalidomide maintenance 
therapy, for any reason, prior to the completion of the 3 years of 0702 maintenance. 
3. Female patients who are pregnant (positive -BetaHCG) or breastfeeding.  
4. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP 
unwilling to use contraceptive techniques (Appendix B) during the length of 
lenalidomide maintenance therapy. 
5. Patients who experienced thromboembolic events while on full anticoagulation during 
prior therapy with lenalidomide. 
6. Patients unwilling to take DVT prophylaxis. 
7. Patients who developed a second primary malignancy, excluding non-melanoma skin 
cancers after initiation of lenalidomide maintenance therapy on BMT CTN 0702.  
 
2.4. Study Treatments 
 
2.4.1. Lenalidomide 
 
Lenalidomide will be administered initially at the patient’s last documented dose prior to 
discontinuation of BMT CTN 0702 lenalidomide maintenance therapy.  Cycle duration is 28 
days.  Patients will continue lenalidomide until disease progression, or discontinuation due to 
toxicity, death, or withdrawal from the study.  Patients who discontinue lenalidomide due to any 
reason other than death, or withdrawal of consent will continue to be followed per Section 4.4.1 
 
2.4.2. Suggested Treatment Modification Guidelines for Maintenance Therapy   
 
In the presence of lenalidomide-related non-hematologic toxicities (Table 2.4.2a), the study drug 
will be held until the toxicity resolves, then restarted at a reduced dose as described in Table 
2.4.2b.  Dose modifications for hematologic toxicities are described in Table 2.4.2c.  If the 
patient is on DVT/PE prophylaxis or treatment, discontinuation or modifications of 
anticoagulation should be considered by the treating physician. 
 
Table 2.4.2a – Suggested Treatment Modification Guidelines for Long-Term Lenalidomide 
Grade by  NCI CTCAE# 1 
Action 
Non-blistering rash 
Grade 2- 3 
(Generalized rash ≥  25% BSA) 
Hold lenalidomide:  Follow weekly. 
If the toxicity resolves to ≤ grade 1 restart lenalidomide at next lower dose level.   
Non-blistering rash 
Grade 4 
Discontinue lenalidomide.  
Desquamating (blistering) rash 
any Grade 
Discontinue lenalidomide. 
Erythema multiforme 
≥  Grade 3 
(Severe (e.g., generalized rash or 
painful stomatitis); IV fluids, tube 
feedings, or TPN indicated) 
Discontinue lenalidomide.   If toxicity resolves to < grade 1 restart at next lower dose level. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-4 
Grade by  NCI CTCAE# 1 
Action 
Sinus bradycardia/ other 
cardiac arrhythmia 
Grade 2 
(Non urgent, medical intervention 
indicated 
OR Moderate) 
Hold lenalidomide.  
If the toxicity resolves to ≤ grade 1 restart lenalidomide at next lower dose level . 
≥  Grade 3 
(Incompletely controlled or 
controlled with device- e.g. 
pacemaker or Severe) 
Discontinue lenalidomide.   If toxicity resolves to < grade 1 restart at next lower dose level. 
Allergic reaction or 
hypersensitivity 
Grade 2-3 
(flushing; urticaria; dyspnea; drug 
fever≥ 38ºC – symptomatic 
bronchospasm;  parenteral  meds 
indicated) 
Hold lenalidomide  
If the toxicity resolves to ≤ grade 1 restart lenalidomide at next lower dose level.   
Grade 4 
(anaphylaxis) 
Discontinue lenalidomide 
Venous thrombosis/embolism 
≥  Grade 3 
(DVT or cardiac thrombosis; 
intervention indicated) 
Hold (interrupt) lenalidomide and start anticoagulation. Restart therapy per institutional guidelines. 
Glomerular filtration rate 
(Creatinine  Clearance) 
≥  Grade 3 
(≤   25%LLN, chronic dialysis not 
indicated) 
Hold (interrupt) lenalidomide.  
If creatinine clearance has improved to ≤ grade 2 restart at next lower dose level. 
Other non-hematologic toxicity 
assessed as Lenalidomide-
related 
≥  Grade 3 
Hold (interrupt) lenalidomide.   
If the toxicity resolves to ≤ grade 2 restart lenalidomide at next lower dose level.  
Hyperthyroidism or 
Hypothyroidism 
Hold lenalidomide. 
Evaluate etiology, and initiate appropriate therapy.  
Restart lenalidomide at next lower dose level. 
 
Peripheral Neuropathy 
Grade 2 with pain or Grade 3 
 
 
 
Hold lenalidomide. 
If the toxicity resolves to <Grade 1 restart therapy at next lower dose level.  
Peripheral Neuropathy 
Grade 4 
Discontinue lenalidomide. 
Constipation 
Grade 1-2 
Initiate bowel regimen and maintain dose level. 
Constipation 
> Grade 3 
Hold lenalidomide. 
If the toxicity resolves to <Grade 1 restart therapy at next lower dose level.   
Pregnancy3 
Discontinue lenalidomide study drug.  
1Please consult NCI CTCAE version 3.0  http://ctep.cancer.gov/reporting/ for complete Grade descriptions.  The “≥  Grade 3”  descriptions 
listed above are minimums 
3If a subject, or the partner of a male study subject, misses her period or if her pregnancy test or her menstrual bleeding is abnormal, pregnancy 
testing and counseling must be performed (Section 4.4.5).  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-5 
Table 2.4.2b – Lenalidomide Dose Reduction Steps During  
Long-Term Maintenance Therapy 
Lenalidomide Dose Reduction Steps for Non-Hematologic Toxicity 
Dose at Time of Toxicity 
Dose reduction 
15 mg daily 
10 mg daily  
10 mg daily  
5 mg daily  
5 mg daily  
5 mg daily for 21 days every 28 days 
5 mg daily for 21 days every 28 days 
Discontinue lenalidomide 
 
Table 2.4.2c – Lenalidomide Dose Modifications for Hematologic Toxicities 
Lenalidomide Dose Modifications for Hematologic Toxicities 
Dose at Time of Toxicity 
Action 
15 mg per day 
If ANC is < 1000/µL or the platelet count is < 50,000/µL, then 
lenalidomide will be held for up to 8 weeks.  Lenalidomide drug 
may be re-instituted at 10 mg per day once the ANC is ≥ 1000/µL 
and the platelet count is ≥ 50,000/µL.  If, however, after an 8 week 
treatment delay, the ANC remains < 1000/µL or the platelet count 
< 50,000/µL, maintenance therapy will be discontinued. 
10 mg per day 
If ANC is < 1000/µL or the platelet count is < 50,000/µL, then 
lenalidomide will be held for up to 8 weeks.  Lenalidomide may be 
re-instituted at 5 mg per day once the ANC is ≥ 1000/µL and the 
platelet count is ≥ 50,000/µL.  If however, after an 8 week 
treatment delay, the ANC remains < 1000/µL or the platelet count 
< 50,000/µL, maintenance therapy will be discontinued. 
5 mg per day 
If ANC is < 1000/µL or the platelet count is < 50,000/µL, then 
lenalidomide will be held for up to 8 weeks.  Once the ANC is ≥ 
1000/µL and the platelet count is ≥ 50,000/µL, then lenalidomide 
may be re-instituted at 5 mg per day for 21 days of a 28-day cycle.  
If, however, after an 8 week treatment delay, the ANC remains < 
1000/µL or the platelet count < 50,000/µL, maintenance therapy 
will be discontinued. 
5 mg per day for 21 of 28 days 
If ANC is < 1000/µL or the platelet count is < 50,000/µL, then 
maintenance therapy will be discontinued. 
 
2.4.3. Lenalidomide Maintenance Dose Re-escalation: 
 
If a dose reduction has occurred and ANC ≥ 1000/µL and platelet count is ≥ 75,000/µL, the 
study drug dose may be re-escalated as shown in Table 2.4.2b, one step per cycle to a maximum 
of 15 mg daily.  
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-6 
2.5. Supportive Care 
  
2.5.1. Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) Prophylaxis 
 
Patients receiving dexamethasone and thalidomide as remission induction therapy for MM have 
an increased risk of developing DVT/PE.  This risk may be as high as 10%.  It is unclear whether 
the risk is the same in patients receiving lenalidomide as a single agent and as maintenance 
therapy after autologous transplantation.  Treating physicians should be aware of this risk and 
have heightened vigilance regarding this possible toxicity.  Aspirin should be administered per 
institutional guidelines during lenalidomide maintenance therapy unless the patient is treated 
with alternate prophylaxis of either low molecular weight heparin or coumadin.   
 
2.6. Participant Risks 
 
2.6.1. Lenalidomide 
 
Common toxicities described for lenalidomide include: 
 
 Neurologic: Somnolence, dizziness, headache, confusion, tremor, loss of co-ordination, 
asthenia, paresthesia, numbness, and leukoencephalopathy (radiographic findings). 
 Hematologic: anemia, neutropenia, leucopenia, lymphopenia and thrombocytopenia; 
thromboembolic events (deep vein thrombosis and pulmonary embolism).   
 Gastrointestinal: Constipation, dehydration, dry mouth, diarrhea, dyspepsia, nausea, 
vomiting and stomatitis. 
 Constitutional: Weakness, insomnia, rigors, chills, sweating, weight loss and fever. 
 Reproductive: teratogenicity and miscarriage. 
 Musculoskeletal: arthralgia, back/neck pain, joint pain, muscle cramp and weakness. 
 Cardiac: hypotension. 
 Dermatologic: rash, dry skin, itching. 
 Endocrine: hypothyroidism. 
 Infection. 
 Pulmonary: cough, dyspnea. 
 Metabolic: hypokalemia, liver damage. 
 Renal: increased creatinine, renal failure. 
 
Pregnancy reporting: 
See Section 4.2.3, Adverse Event Reporting. 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-7 
Other instructions related to lenalidomide: 
Only one cycle of therapy may be dispensed to the patient each month.  During long-term 
lenalidomide maintenance, a maximum 28-day supply may be dispensed.  Lenalidomide 
capsules should be swallowed whole, and should not be broken, chewed or opened.  If a dose of 
lenalidomide is missed, it should be taken as soon as possible on the same day.  If it is missed for 
the entire day, it should not be made up.  Patients taking more than the prescribed dose of 
lenalidomide should be instructed to seek emergency medical care if needed and contact study 
staff immediately.   
 
2.7. Study Drug Supply 
 
2.7.1. Lenalidomide (NSC 703813) 
 
Lenalidomide will be provided by Celgene and distributed by Biologics, Incorporated.  
Patients must be registered in the Revlimid REMS® program (formerly RevAssist® for 
Study Participants (RASP) program) in order to receive lenalidomide through the program 
(please see Appendix C). 
 
NOTE: 
Before lenalidomide is dispensed, patients must 1) have a negative pregnancy 
test (if applicable) and 2) be counseled by a trained counselor. BMT CTN 0702 
Long-Term Follow-Up Study patients must be counseled through the Revlimid 
REMS® program. A maximum 28-day supply may be dispensed to a patient at 
one time.  
 
Chemical Name:  3-(4’-amino-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-2,6-piperidinedione 
 
Other Names:       CC-5013, Revlimid®, CDC-501 
 
Classification:      Immunomodulatory Agent  
 
CAS Registry Number:       191732-72-6 
 
Molecular Formula:   C13H13N303 
 
 
M.W.:   259.25 
 
Mechanism of Action: 
Lenalidomide, a thalidomide analog, is an immunomodulatory agent with a spectrum of activity 
that is still under investigation.  Some of its effects include inhibition of inflammation, inhibition 
of angiogenesis, inhibition of hematopoietic tumor cell proliferation, modulation of stem cell 
differentiation and up regulating responses of T cells and NK cells.  
 
Drug Supply and Storage: 
Celgene supplies and Biologics, Inc. distributes lenalidomide 5 mg (size 2) hard gelatin capsules in 
tamper-evident, child-resistant, opaque, high density polyethylene (HDPE) bottles with HDPE caps.  
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-8 
The capsules also contain anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, and 
magnesium stearate.  
 
Lenalidomide (Revlimid®) will be provided to research subjects for the duration of their 
participation in this trial at no charge to them or their insurance providers.  Lenalidomide will be 
provided in accordance with the Revlimid REMS® program of Celgene Corporation.  Per 
standard Revlimid REMS® requirements all physicians who prescribe lenalidomide for research 
subjects enrolled into this trial, and all research subjects enrolled into this trial, must be 
registered in and must comply with all requirements of the Revlimid REMS® program.  
Prescriptions must be filled within 7 days.  
 
All study participants must be registered into the mandatory Revlimid REMS® program, and be 
willing and able to comply with the requirements of the Revlimid REMS® program including 
counseling and phone surveys. 
 
Any unused lenalidomide supplies distributed through the Revlimid REMS® program must be 
returned as instructed through the Revlimid REMS® program. 
 
Administration: 
Take lenalidomide by mouth with or without food.  Do not crush, chew or open capsules. 
 
Dispensing:  
Only enough lenalidomide for one cycle may be dispensed at one time.  The drug will be mailed 
directly to the patient through the Revlimid REMS® program.  
 
Patient Care Implications and Counseling: 
Risks Associated with Pregnancy 
Lenalidomide is structurally related to thalidomide.  Thalidomide is a known human teratogenic 
active substance that causes severe life-threatening birth defects.  An embryofetal development 
study in animals indicates that lenalidomide produced malformations in the offspring of female 
monkeys who received the drug during pregnancy.  The teratogenic effect of lenalidomide in 
humans cannot be ruled out.  Therefore, a risk minimization plan to prevent pregnancy must be 
observed. 
 
Definition of female of childbearing potential (FCBP) 
This protocol defines a female of childbearing potential as a sexually mature female who: 1) has 
not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 
for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 
consecutive months). 
 
Before starting study drug:   
 
Female Subjects:   
 FCBP must have two negative pregnancy tests (minimum sensitivity of 50 mIU/mL) 
prior to starting study drug.  The first pregnancy test must be performed within 10-14 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-9 
days prior to the start of study drug and the second pregnancy test must be performed 
within 24 hours prior to the start of study drug (prescriptions must be filled within 7 days 
as required by Revlimid REMS®).  The subject may not receive study drug until the 
Investigator has verified that the results of these pregnancy tests are negative. 
 
 FCBP must either commit to continued abstinence from heterosexual intercourse or begin 
TWO acceptable methods of birth control, one highly effective method and one 
additional effective method AT THE SAME TIME, at least 4 weeks before starting 
lenalidomide.  FCBP must also agree to ongoing pregnancy testing.  
 
Male Subjects:   
 Must agree to use a latex condom during sexual contact with females of childbearing 
potential while participating in the study and for at least 28 days following 
discontinuation from the study even if he has undergone a successful vasectomy.  
 
All Subjects: 
 Only enough lenalidomide for one cycle of therapy may be dispensed with each cycle of 
therapy.  
 If pregnancy or a positive pregnancy test does occur in a study subject or the partner of a 
male study subject during study participation, lenalidomide must be immediately 
discontinued. 
 
Counseling Requirements for the Revlimid REMS® program: 
 This program provides education and counseling on the risks of fetal exposure, blood 
clots and reduced blood counts.  Counseling will be provided by Biologics, Inc. prior to 
drug distribution please refer to Appendix C (Revlimid REMS® Program).  Patients will 
be required to receive counseling every 28 days during treatment with lenalidomide, 
follow the pregnancy testing and birth control requirements of the program that are 
appropriate and take telephone surveys regarding compliance with the program.  
 
Potential Drug Interactions: 
Periodic monitoring of digoxin levels is recommended during co-administration with lenalidomide.   
 
Monitor patients receiving concomitant warfarin per standard practice guidelines. 
 
Lenalidomide is not a substrate of human CYP enzymes, nor is it an inhibitor or inducer. 
 
Drug Ordering and Accountability: 
The Revlimid REMS® program provides education and counseling on the risks of fetal 
exposure, blood clots and reduced blood counts.  Counseling will be provided by Biologics, Inc. 
prior to drug distribution.  Please refer to Appendix C (Revlimid REMS® Program).  The patient 
will be required to receive counseling every 28 days during treatment with lenalidomide, follow 
the pregnancy testing and birth control requirements of the program that are appropriate in order 
to take the telephone surveys regarding compliance with the program.  All physicians must be 
registered prescribers of Revlimid® in the Revlimid REMS® program.  Physician registration 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
2-10 
allows access to the Revlimid REMS® software to enroll patients in the Revlimid REMS® 
program.  Please reference Appendix E (Revlimid REMS® Program) and follow the directions 
for submitting the registration.  Biologics, the distributor of the lenalidomide, will not dispense 
or ship Revlimid® prior to Celgene’s receipt of registration.  Prescription information MUST BE 
entered using the Revlimid REMS® study specific electronic prescription form found in 
Appendix C (Revlimid REMS® Program).  An authorization number must be on the 
prescription form at the time of faxing.  A maximum of a 28-day supply of Revlimid® may be 
dispensed per cycle sent to the actual address noted on the Revlimid REMS® electronic 
prescription form.  Biologics will verify the authorization number and complete the patient 
counseling.  Patients will be provided with instructions from Biologics with each new dispense 
on the procedures for return of any un-used Revlimid® capsules.   
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
3-1 
CHAPTER 3 
 
 
3. 
STUDY ENDPOINTS AND DEFINITIONS 
 
3.1. Definition of Disease Progression 
 
Disease progression will be evaluated as defined below and will be evaluated relative to the 
patient’s best response on BMT CTN 0702  
 
Disease Progression (PD) from CR or sCR requires one or more of the following: 
 A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL. 
 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours. 
 Abnormal FLC levels of >10 mg/dl, only in patients without measurable paraprotein in 
the serum and urine.  
 At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy. 
 Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. 
 Development of new bone lesions or soft tissue plasmacytomas.  
 Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not 
attributable to any other cause. 
 
Progressive Disease (PD) for patients not in CR or sCR, progressive disease requires one or 
more of the following: 
 >25% increase in the level of the serum monoclonal paraprotein, which must also be an 
absolute increase of at least 0.5 g/dL. 
 >25% increase in 24-hour urine protein electrophoresis, which must also be an absolute 
increase of at least 200 mg/24 hours. 
 Absolute increase in the difference between involved and uninvolved FLC levels 
(absolute increase must be >10 mg/dl), only in patients without measurable paraprotein in 
the serum and urine.  
 >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which 
must also be an absolute increase of at least 10%. 
 Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. 
 Development of new bone lesions or soft tissue plasmacytomas.  
 Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not 
attributable to any other cause. 
 NOTE: Development of a compression fracture does not exclude continued response and 
may not indicate progression. 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
3-2 
3.2. Primary Endpoint 
 
3.2.1. Progression-Free Survival  
 
The primary objective is to compare progression-free survival (PFS) as a time to event analysis 
between the three randomized treatment arms from the BMT CTN 0702 protocol as a pairwise 
comparison.  The analysis will be conducted once all alive patients have been followed for 5-
years post randomization on the BMT CTN 0702 protocol.  Patients are considered a failure of 
the primary endpoint if they die or suffer from disease progression.  The time to this event is the 
time from randomization on the BMT CTN 0702 protocol until progression, death, or initiation 
of non-protocol anti-myeloma therapy.  Patients will be censored at loss to follow-up or end of 
2018, whichever comes first.   
 
3.3. Secondary Endpoints  
 
3.3.1.  Overall Survival 
 
The event is death from any cause.  Overall survival time will be calculated as the time from 
randomization on the BMT CTN 0702 protocol until death, loss to follow-up or the end of the 
study, whichever comes first.  Patients alive at the time of last observation or lost to follow-up 
will be censored at the date of last contact.  Overall survival will be compared between treatment 
arms once all alive patients have been followed for 5-years post randomization on the BMT CTN 
0702 protocol.   
 
3.3.2. Event-free Survival  
 
Event-free survival (EFS) time will be calculated as the time from randomization on the BMT 
CTN 0702 protocol until death from any cause, disease progression, or second primary 
malignancy, whichever comes first.  Patients alive at the time of last observation or lost to 
follow-up will be censored at the date of last contact.  Event-free survival will be compared 
between treatment arms once all alive patients have been followed for 5-years post 
randomization on the BMT CTN 0702 protocol.   
 
3.3.3. Incidence of Second Primary Malignancies 
 
The event is development of a second malignancy, excluding non-melanoma skin cancers, after 
randomization on the BMT CTN 0702 protocol.  The cumulative incidence of SPMs will be 
described for all patients enrolled in this long-term follow-up study treating death as a competing 
risk and censoring patients alive at the time of last observation or lost to follow-up.  Incidence of 
second primary malignancies will be compared between treatment arms once all alive patients 
have been followed for 5-years post randomization on the BMT CTN 0702 protocol. SPMs will 
also be described by histologic type.  
 
3.3.4. Unexpected Grades 3-5 Adverse Events 
 
Unexpected grades 3-5 adverse events will be tabulated and compared by treatment arm.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
3-3 
 
3.3.5. Health Quality of Life 
 
The FACT-BMT version 4.0 instrument is comprised of a general core questionnaire, the FACT-
G, which evaluates the health-related quality of life (HQL) of patients receiving treatment for 
cancer, and a specific module, BMT Concerns, which addresses disease and treatment-related 
questions specific to bone marrow transplant.  The FACT-G consists of four subscales developed 
and normed in cancer patients:  Physical Well-being, Social/Family Well-being, Emotional Well-
being, and Functional Well-being.  Each subscale is positively scored, with higher scores 
indicating better functioning.  The FACT-BMT Total, which is the grand total of all items in the 
FACT-G and BMT modules, will be used as the outcome measure in summarizing the FACT-
BMT data. 
 
The MOS SF-36 instrument is a general assessment of health quality of life with eight 
components: Physical Functioning, Role Physical, Pain Index, General Health Perceptions, 
Vitality, Social Functioning, Role Emotional, and Mental Health Index.  Each domain is 
positively scored, indicating that higher scores are associated with positive outcome.  This scale 
has been widely applied in a variety of outcome studies and is being used in this protocol as a 
generic measure of quality of life.  To facilitate comparison of the results with published norms, 
the Physical Component Summary (PCS) and Mental Component Summary (MCS) will be used 
as the outcome measures in summarizing the SF-36 data. 
 
HQL will be described and compared between all treatment arms utilizing the FACT-BMT self 
report, transplant specific questionnaire and the generic quality of life tool (SF-36).  The 
questionnaires will be scored according to standard procedures.  The self report questionnaires 
will be completed yearly until disease progression. Only English and Spanish speaking patients 
are eligible to participate in the HQL component of this study. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
4-1 
CHAPTER 4  
 
 
4. 
PATIENT ENROLLMENT AND EVALUATION 
 
4.1. Enrollment Procedures 
 
4.1.1. Eligibility and Enrollment  
 
All BMT CTN 0702 patients who are alive and progression-free at the completion of the BMT 
CTN 0702 protocol specified follow-up period are eligible to be followed for long-term 
outcomes in this protocol.  Patients who do not consent to the long-term follow-up mechanism or 
who have experienced progression on the BMT CTN 0702 study will be followed through the 
standard CIBMTR long-term follow-up mechanism.  Patients who have completed 3 years of 
0702 lenalidomide maintenance without evidence of disease progression are also eligible to 
receive continued, long-term lenalidomide maintenance therapy.  Once the study has been 
described to the patient and informed consent has been obtained, an authorized user at the 
clinical center completes the 0702 Long Term Follow Up protocol Enrollment form in the 
Advantage Electronic Data Capture (AdvantageEDCSM) system.  
 
4.1.2. Revlimid REMS® Lenalidomide Counseling 
 
Lenalidomide counseling will be provided through the Revlimid REMS® program for patients 
who will receive long-term lenalidomide as part of this study.  Biologics Inc. will supply all 
counseling prior to drug distribution.  Requirements are outlined in the Study Drug Supply 
Section 2.7.  
 
4.2. Study Monitoring  
 
4.2.1. Follow-up Schedule 
 
Follow-up visits will occur every 6 months for all patients, beginning from the date of study 
entry on the long-term follow-up protocol, until death, progression, withdrawal of consent, or the 
end of the study.   
 
4.2.2. Data Reporting 
 
Criteria for Forms Submission 
Criteria for timeliness of submission for all study forms are detailed in the Data Management 
Handbook.  Forms that are not entered into the web-based data entry system within the specified 
time will be considered delinquent.  A missing form will continue to be required either until the 
form is entered into the web based data entry system and integrated into the Data and 
Coordinating Center’s (DCC's) master database, or until an exception is granted and entered into 
the Missing Form Exception File, as detailed in the Data Management Handbook. 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
4-2 
4.3. Adverse Event Reporting 
 
4.3.1. Unexpected, Grades 3-5 Adverse Events 
 
Reporting of Adverse Events (AE) in the long-term follow-up protocol will follow the same 
mechanism as the BMT CTN 0702 parent clinical trial for patients receiving long-term 
lenalidomide maintenance therapy.  AEs will be reported according to the BMT CTN Manual of 
Procedures.   The BMT CTN Data and Safety Monitoring Board (DSMB) will be responsible for 
the safety and oversight of this long-term follow-up protocol.    Unexpected, grades 3-5 adverse 
events will be reported through the expedited AE reporting system in AdvantageEDC using 
NCI’s Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.  Unexpected, 
grade 4-5 AEs must be reported within 24 hours of knowledge of the event.  Unexpected, grade 3 
AEs must be reported within three business days of knowledge of the event.   
The descriptions and grading scales found in the NCI Common Terminology Criteria for 
Adverse Events (CTCAE) Version 4.0 will be utilized for AE reporting and can be found at 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.  
 
Selected expected serious AEs (Appendix F - Table F-1) require expedited reporting with an 
Individual Case Safety Report (ICSR).  Additionally, selected AEs of interest (Appendix F - 
Table F-2) will require expedited reporting through an ICSR, if they fulfill serious criteria 
according to the Code of Federal Regulations Title 21 (21 CFR 312.32) and occur after the 
administration of lenalidomide and up to 30 days after the permanent discontinuation of 
lenalidomide.  See Appendix F for additional details on expedited reporting. 
 
The aforementioned adverse event reporting criteria are for patients who receive long-term 
lenalidomide maintenance therapy.  Patients not eligible for receiving long-term lenalidomide 
maintenance therapy or patients who have permanently discontinued lenalidomide maintenance 
will not require reporting of unexpected grades 3-5 adverse events or ICSRs with the exception 
of second primary malignancies as noted in 4.3.2.  All patients will be required to report deaths 
as noted in section 4.3.3.   
 
4.3.1.1. 
Adverse Event Reporting Following Progression  
- 
If a patient meets the protocol defined definition of progression (Chapter 3),  
Unexpected Grade 3-5 Adverse Events and events listed in Appendix K are no longer 
required to be reported on the Adverse Event Form once the patient is more than 28 
days from their last dose of lenalidomide. However, SPMs should continue to be 
reported within three business days of the knowledge of the event through the end of 
the study follow up period.  
 
4.3.2. Reporting Second Primary Malignancies 
 
All second primary malignancies (SPM), excluding non-melanoma skin cancers, experienced by 
patients enrolled on the long-term follow-up study will be reported using the Adverse Event 
forms (AE1-AE6) in AdvantageEDC and must be reported within three business days of 
knowledge of the event.  The Event Description of the Adverse Event forms should include 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
4-3 
histologic type. Patients who do not consent or who have progressed on the BMT CTN 0702 
protocol will have SPMs reported through the standard CIBMTR reporting mechanism.   
 
4.3.2.1. 
Adverse Event Reporting Following an SPM  
Adverse Event reporting following an SPM is dependent on the treatment received for the 
reported SPM.  
- 
If a patient experiences an SPM resulting in permanent discontinuation of 
lenalidomide and initiation of non-protocol systemic therapy, Unexpected Grade 3-5 
Adverse Events and events listed in Appendix K will are no longer required to be 
reported on the Adverse Event Form once the patient is more than 28 days from their 
last dose of lenalidomide.  
- 
If a patient experiences an SPM that does not result in permanent discontinuation of 
lenalidomide, Adverse Events will continue to be reported as per section 4.2.3 and 
appendix K of the protocol.  
- 
Requests to discontinue Adverse Event Reporting for events that do not meet the 
criteria above will be considered on a case by case basis.  
 
4.3.3. Reporting Patient Deaths 
 
Recipient Death Information must be entered into AdvantageEDC within 24 hours of knowledge 
of the patient’s death for patients who are enrolled in the long-term follow-up protocol.  If the 
cause of death is unknown at that time, it need not be recorded at that time.  However, once the 
cause of death is determined, the form must be updated in the web-based data entry system.  
Patients who do not consent or who have progressed on the BMT CTN 0702 protocol will have 
deaths reported through the standard CIBMTR reporting mechanism.   
 
4.3.4. Pregnancy Reporting 
 
Pregnancies occurring while the subject is on lenalidomide or within four weeks after the 
subject’s last dose of lenalidomide are considered expedited reportable events.  If the subject is 
on lenalidomide, it is to be discontinued immediately and the subject is to be instructed to return 
any unused portion of lenalidomide to the Investigator.  The pregnancy, suspected pregnancy, or 
positive pregnancy test must be reported within 24 hours of the Investigator’s knowledge of the 
pregnancy using the Adverse Event Forms in AdvantageEDC.  
 
The Investigator will follow the subject until completion of the pregnancy, and must report the 
outcome of the pregnancy and neonatal status as specified below.  The Investigator will provide 
this information as a follow-up to the initial report. 
 
If the outcome of the pregnancy meets the criteria for immediate classification as a SAE (i.e., 
spontaneous or therapeutic abortion [any congenital anomaly detected in an aborted fetus is to be 
documented], stillbirth, neonatal death, or congenital anomaly), the Investigator should follow 
the procedures to report the event within 24 hours of the Investigator’s knowledge of the event). 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
4-4 
Any suspected fetal exposure to lenalidomide must be reported within 24 hours of being made 
aware of the event.  The patient should be referred to an obstetrician/gynecologist experienced in 
reproductive toxicity for further evaluation and counseling. 
 
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs.  In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to lenalidomide should also be reported. 
 
In the case of a live “normal” birth, the outcome should be reported as soon as the information is 
available.   
 
Male Subjects 
If a female partner of a male subject taking investigational product becomes pregnant, the male 
subject taking lenalidomide should notify the Investigator, and the pregnant female partner 
should be advised to call her healthcare provider immediately. 
 
4.4. Patient Assesssments  
 
Data collection is designed around the following three scenarios: 
 Patients who enroll on the long-term follow-up protocol but who do not receive long-
term lenalidomide for maintenance (see section 4.4.1) 
 Patients who enroll on the long-term follow-up protocol and who receive long-term 
lenalidomid for maintenance (see section 4.4.2) 
 Patients who progress prior to or during the long-term follow-up protocol (see section 
4.4.3) 
 
4.4.1. Long-Term Follow-Up Only- Assessment Schedule  
 
Table 4.4.1 summarizes patient clinical assessments over the course of the study for patients who 
have not progressed prior to enrollment on this study and who are not receiving long-term 
lenalidomide.  
 
The following evaluations will be performed at initiation of long-term follow-up, and then every 
6 months (+/-30 days, unless otherwise noted) until progression, death, or withdrawal from the 
study, unless otherwise noted below: 
1. History and physical exam, including height and weight 
2. Evaluation for the occurrence of progression every 6 months  
3. Evaluation for the occurrence of second primary malignancies  
4. Health Quality of Life (HQL) instruments will be completed yearly after 
randomization on BMT CTN 0702 until disease progression or the end of 2018. 
5. Optional blood samples for future research will be collected prior to the initiation of 
long-term follow-up, and at disease progression. 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
4-5 
Table 4.4.1 – Evaluations During Long-Term Follow-Up 
Study Assessments 
Long-term follow-up  Assessment Timepoints 
0 
6 
12 
18 
24 
30 
36 
42 
R5Y 
R6Y 
R7Y 
History and Physical Examination 
X  X  
X  
X  
X  
X  
X  
X  
 
 
 
HQL Instruments1 
 
 
 
 
 
 
 
 
X  
X  
X  
Optional Blood Samples for Research2 
X 
Event-driven – at disease progression 
 
 
 
1HQL assessments at R5Y, R6Y, and R7Y are a continuation of HQL on BMTCTN 0702. These instruments should be 
completed yearly from randomization on BMT CTN 0702. There is a +/- 6 month window on HQL assessments to allow for 
capture at the scheduled 6 month patient visits.  
2 Optional blood samples will be collected from patients who provided consent prior to the initiation of long-term follow-up and 
again at disease progression (where applicable). 
 
4.4.2. Long-Term Follow-Up and Long-Term Lenalidomide Maintenance Assessment Schedule 
 
Table 4.4.2 summarizes patient clinical assessments over the course of the study for patients who 
elect to receive long-term lenalidomide maintenance therapy as part of this study.   
 
The following evaluations will be performed at initiation of long-term lenalidomide maintenance 
therapy, and then every 6 months (+/-30 days, unless otherwise noted) until progression, death, 
or withdrawal from the study unless otherwise noted below: 
1. History and physical exam; 
2. Required evaluation for Lenalidomide: Pregnancy test, serum HCG (sensitivity of at 
least 50 mIU/mL) for female of childbearing potential (FCBP): 
a. FCBP with regular or no menstruation must have a pregnancy test weekly for 
the first 28 days and then every 28 days while on lenalidomide maintenance 
therapy (including breaks in therapy); at discontinuation of lenalidomide and at 
Day 28 post the last dose of lenalidomide.  Females with irregular menstruation 
must have a pregnancy test weekly for the first 28 days and then every 14 days 
while on therapy (including breaks in therapy), at discontinuation of 
lenalidomide and at Day 14 and Day 28 post the last dose of lenalidomide. 
b. The subject must follow the requirements of the Revlimid REMS® program of 
the Celgene Corporation.  This program provides education and counseling on 
the risks of fetal exposure, blood clots and reduced blood counts.  The patient 
will be required to receive counseling every 28 days during treatment with 
lenalidomide, follow the pregnancy testing and birth control requirements of the 
program that are appropriate in order to take the  telephone surveys regarding 
compliance with the program.   
c. Patients will require CBC with differential prior to the monthly supply of 
lenalidomide. These laboratory tests may be done remotely and sent to the 
transplant center. 
3. Evaluation for the occurrence of progression every 6 months  
4. Evaluation for the occurrence of second primary malignancies  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
4-6 
5. Health Quality of Life (HQL) instruments will be completed yearly after 
randomization on BMT CTN 0702 until disease progression or the end of 2018. 
6. Optional blood samples for future research will be collected prior to the initiation of 
maintenance therapy and at disease progression. 
 
Table 4.4.2 – Evaluations During Long-Term Maintenance Therapy 
Study Assessments 
Long-term  Maintenance Assessment Timepoints 
0 
6 
12 
18 
24 30 
36 
42 
R5Y 
R6Y 
R7Y 
History and Physical Examination 
X  X  X  
X  
X  
X  
X  
X  
 
 
 
HQL Instruments1 
 
 
 
 
 
 
 
 
X  
X  
X  
Optional Blood Samples for Research2 
X 
Event-driven – at disease progression 
1 HQL assessments at R5Y, R6Y, and R7Y are a continuation of HQL on BMTCTN 0702. These instruments should be 
completed yearly from randomization on BMT CTN 0702. There is a +/- 6 month window on HQL assessments to allow for 
capture at the scheduled 6 month patient visits.   
2 Optional blood samples will be collected from patients who provided consent prior to the initiation of long-term follow-up 
and again at disease progression (where applicable). 
 
4.4.3. Long-Term Follow-Up Assessment Schedule (Post-Progression) 
 
Patients who progress prior to enrollment on this study or patients who progress while on the 
long-term follow-up protocol will have outcomes collected through the standard CIBMTR long-
term follow-up mechanism.   


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
5-1 
CHAPTER 5 
 
 
5. 
STATISTICAL CONSIDERATIONS 
 
5.1. Study Design and Objectives 
 
The primary motivation of this long-term follow-up protocol is to provide a mechanism to follow 
patients randomized on BMT CTN 0702 who have not experienced progression prior to 
enrollment on the long-term follow-up protocol for long-term outcomes including PFS, OS, EFS, 
incidence of SPMs and QOL.  Patients who do not consent to the long-term follow-up 
mechanism or who have experienced progression on the BMT CTN 0702 study will be followed 
through the standard CIBMTR long-term follow-up mechanism.  The primary objective is to 
compare PFS as a time to event analysis across the 3 different randomized treatment arms from 
the BMT CTN 0702 protocol.  The analysis will be conducted once all living patients have been 
followed for 5-years post randomization on the BMT CTN 0702 protocol.  The secondary 
objective is to provide lenalidomide as maintenance therapy to eligible patients until progression.   
 
5.2. Accrual, Registration and Follow-up 
 
It is anticipated that approximately 450 patients will be enrolled on this protocol based on 
assumed estimates of PFS estimates from the BMT CTN 0702 study.  The total sample size may 
as low as 417 if the observed 3-year PFS on the BMT CTN 0702 is 55% but may be as high as 
569 if the 3-year PFS is 75%.  Follow-up on this protocol will continue through December 31, 
2018.   
 
5.3. Analysis of the Primary Endpoint 
 
The primary analysis will include all randomized subjects from the BMT CTN 0702 protocol, 
classified according to their randomized treatment allocation, irrespective of treatment actually 
received [intent-to-treat].  The time to this event is the time from randomization on the BMT 
CTN 0702 protocol to progression, initiation of non-protocol anti-myeloma therapy, or death 
from any cause.  Patients will be censored at loss to follow-up or end of 2018, whichever comes 
first.  Deaths without progression are treated as failures no matter when they occur.  The analysis 
will be conducted once all living patients have been followed for 5-years post randomization on 
the BMT CTN 0702 protocol. 
 
Data for patients not enrolled on the long-term follow-up protocol will be included from the 
BMT CTN 0702 protocol.  Additionally, patients who do not consent to the long-term follow-up 
or who have progressed on the BMT CTN 0702 protocol will be followed according to the 
standard CIBMTR long-term follow-up mechanism.  The treatment arms will be compared with 
a two-sided log-rank test stratified on risk status.  Tests will be performed pair-wise at the .01667 
level in order to maintain study-wide type I error at 0.05.  PFS will be compared between 
treatment arms as a time to event analysis.  A secondary analysis of PFS will be conducted using 
Cox regression, adjusting for demographic and baseline characteristics which are statistically 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
5-2 
different between treatment arms (p<0.1).  Additionally, discontinuation of lenalidomide 
maintenance will be considered as a time-varying covariate in the Cox regression model.      
 
5.4. Analysis of the Secondary Endpoints 
 
Overall Survival 
The event is death from any cause.  Overall survival (OS) time will be calculated as the time 
from randomization on the BMT CTN 0702 protocol to death, loss to follow-up or the end of the 
study, whichever comes first.  Patients alive at the time of last observation or lost to follow-up 
will be censored at the date of last contact.  The Kaplan-Meier estimate of survival will be 
estimated at 5 years post randomization on the BMT CTN 0702 protocol along with 
corresponding 95% confidence intervals.  Overall survival will be compared between treatment 
arms using a two-sided log-rank test once all alive patients have been followed for 5-years post 
randomization on the BMT CTN 0702 protocol.   
 
Event-Free Survival 
Event-free survival (EFS) time will be calculated as the time from randomization on the BMT 
CTN 0702 protocol to death, progression, second primary malignancy, loss to follow-up or the 
end of the study, whichever comes first.  Patients alive at the time of last observation or lost to 
follow-up will be censored at the date of last contact.  The Kaplan-Meier estimate of EFS will be 
estimated at 5 years post randomization on the BMT CTN 0702 protocol along with 
corresponding 95% confidence intervals.  Overall survival will be compared between treatment 
arms using a two-sided log-rank test once all alive patients have been followed for 5-years post 
randomization on the BMT CTN 0702 protocol.   
 
Second Primary Malignancies 
The event is the development of any SPMs, excluding non-melanoma skin cancers, as described 
in Chapter 3.  Death without SPMs will be considered a competing risk for this event.  
Cumulative incidence function will be used to calculate this endpoint and time of randomization 
on the BMT CTN 0702 protocol will be the starting point for the analysis.  Estimates at 5 years 
will be described along with 95% confidence intervals.  The cumulative incidence of SPMs will 
be compared between treatment arms using a two-sided Gray’s test once all alive patients have 
been followed for 5-years post randomization on the BMT CTN 0702 protocol. SPMs will also 
be described by histologic type.    
 
Unexpected Grades 3-5 Adverse Events 
Unexpected grades 3-5 adverse events will be tabulated and compared across treatment arms.  
AEs will be described using the Medical Dictionary for Regulatory Activities (MedDRA) and 
classified according to the system organ class and preferred term.  Summaries by type and 
severity by treatment arm will be provided.   
 
Health Quality of Life 
Health quality of life (HQL) will be compared between all treatment groups utilizing the FACT-
BMT self report, transplant specific questionnaire and the generic quality of life tool, the SF-36.  
Only English and Spanish speaking patients are eligible to participate in the HQL component of 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
5-3 
this trial.  Outcomes of the HQL assessments will be described once all alive patients have been 
followed for five years post randomization on the BMT CTN 0702 protocol.   
5.5. Safety Oversight 
 
The BMT CTN DSMB will monitor the accruing safety and efficacy data on an approximate 6-
month basis as per the DSMB charter.  The DSMB will make recommendations to the NHLBI 
regarding release of data to investigators and the general public.   
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-1 
APPENDIX A 
 
PATIENT INFORMED CONSENT 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-2 
Informed Consent to Participate in Research 
 
 
 
 
 
 
 
 
 
 
 
 
Your Name:  
__________________________________ 
 
Study Title:  
Continued, Long-Term Follow-Up and Lenalidomide Maintenance 
Therapy for Patients Who Have Enrolled on BMT CTN 0702 
Protocol: 
BMT CTN 0702 Long-Term Follow-Up 
Principal 
Investigator:  
Insert local PI information 
Sponsor: 
The National Institutes of Health (NIH) is sponsoring this study by 
providing financial support for the coordination of this study through the 
Blood and Marrow Transplant Clinical Trials Network (BMT CTN).  
Celgene is supplying the study drug lenalidomide. 
 
 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-3 
1. Introduction  
We invite you to join this clinical trial, also known as a research study. You are being asked to 
join because: 
1. You took part in the study, A Trial of Single Autologous Transplant with or without 
Consolidation Therapy versus Tandem Autologous Transplant with Lenalidomide 
Maintenance for Patients with Multiple Myeloma, also called BMT CTN 0702 
2. After your autologous transplant, you finished 3 years of maintenance treatment for the BMT 
CTN 0702 study 
3. Your disease did not return or worsen (this is also called disease progression) during the 
BMT CTN 0702 study. 
Because there’s no cure for Multiple Myeloma (MM), maintenance treatment (chemotherapy) 
is given to slow the return of your disease after an autologous transplant. We are doing this 
study to learn how well maintenance treatment works to control your disease long-term (more 
than 3 years after transplant).  
For this study, the type of maintenance treatment you will get is lenalidomide. Lenalidomide is 
the same medication you have received for the first 3 years as maintenance following your 
autologous transplant. Lenalidomide is a chemotherapy drug used to slow down relapse.   
This study will include 450 participants. You participation on this study is expected to last until 
your disease returns or progresses.  
This Consent Form will tell you about the purpose of the study, the possible risks and benefits, 
other options available to you, and your rights as a participant in the study.  
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 quit the study at any time.  
 If you decide to quit the study, it will not affect your care at [insert name of facility or 
institution]. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-4 
 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 and your doctor will discuss other follow-up treatment choices if you do not want to 
participate in this study.    
 
2. Study Background 
The National Institutes of Health (NIH), through the Blood and Marrow Transplant Clinical 
Trials Network (BMT CTN), are providing staff support and money for this research study. The 
BMT CTN and the NIH will make decisions about how to manage the study.  
Celgene will supply the drug, lenalidomide, for this study.  
 
For this study, we will give you maintenance treatment (lenalidomide) to slow down the relapse 
of your disease.  We will watch your health closely (this is also called follow-up) after your 
autologous transplant.  
There’s no cure for multiple myeloma (MM). After transplant, the disease will almost always 
return, or relapse. Even with maintenance treatment, MM will relapse. Your doctor doesn’t know 
how long it will take for the disease to return.   
3. Study Purpose 
We are inviting you to take part in this study because you finished the BMT CTN 0702 study and 
your disease did not return or worsen. We are doing this study to learn more about ways to 
prevent or delay relapse of multiple myeloma (MM). We also want to know how well you do 
long-term (more than 3 years) after transplant.   
You will get maintenance treatment and have a physical evaluation (test) every 6 months to see if 
you still have MM in your body. This study will help doctors make the best choice about long-
term treatment after autologous transplant for patients with MM. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-5 
4. Rights to Ask Questions and/or Withdraw  
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 not to take part or leave this study, it will not affect your regular medical care 
in any way.  
Your study doctor and study staff will be available to answer any questions that you may have 
about taking part in or leaving this study.  
5. Study Tests 
We will check (test) your health every 6 months until the end of the study. This is called long-term 
follow-up maintenance treatment, after transplant. We will stop the study tests if your disease 
returns or relapses.   
Before You Start Maintenance Treatment 
You will need to have several check-ups and tests before you begin maintenance therapy. These 
tests include:  
 Physical exam, including height and weight 
 A pregnancy test using a blood sample (if you are a woman able to have children). This test 
will be done about 2 weeks before you start maintenance treatment. If you are pregnant or 
breastfeeding, you can’t take part in this study. 
 Tests to check for cancer as decided by your doctors. These tests would normally be done 
even if you were not on a research study and may include:  
o Bone marrow aspiration and biopsy (see Section 6: Risks and Discomforts) 
o Blood tests (up to 4 – 5 tablespoons) 
o Urine tests 
 Optional blood samples for future research (see Section 17: Blood Samples for Future 
Research).  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-6 
We will also ask you to take a quality of life survey. The survey will ask about: 
 Any side effects of your treatment 
 Any health problems 
 How well you can do things that are important to you 
 How you relate to other people  
 Your feelings.  
An interviewer will contact you to take the survey. These interviews will take about 30 minutes 
and will be done at a time that works for you. You may skip any questions you wish.  
During Your Maintenance Treatment 
You will keep taking lenalidomide during long-term maintenance treatment. If you stopped 
taking lenalidomide for the BMT CTN 0702 study, you will start taking it again. You will stay 
on maintenance treatment until your cancer returns, or relapses. If your cancer does not relapse 
during the study, you will keep taking lenalidomide until the study ends.  
We will give you the same dose of lenalidomide that you were taking when you finished the 
BMT CTN 0702 study. We will give you lenalidomide as a pill to take once a day.  
 Swallow the lenalidomide pills whole, with water, at the same time each day.  Don’t break, 
chew or open the pills. If you take more lenalidomide than you were prescribed, you should 
seek emergency medical care and contact the study staff immediately. 
 If you miss a dose of lenalidomide, take it as soon as you remember on the same day.  If you 
miss taking your dose for the entire day, take your regular dose the next scheduled day. Don’t 
take 2 doses to make up for the missed dose.   
We will watch your health closely during maintenance treatment, including how well your 
organs work (function). We will lower your dose or stop the treatment if your organs don’t 
handle the treatment well. We will raise your dose or re-start the treatment when your organs 
start to work well again.  
We will modify the dose and/or may stop the maintenance treatment if you:  
 Have a serious side effect, like severe diarrhea or skin rash  
 Have low blood cell counts  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-7 
We will stop the maintenance treatment if you:  
 Are a woman and become pregnant, or there is a chance that you are pregnant 
 Don’t follow the study directions, or 
 Choose to leave the study. 
You’ll get lenalidomide for this study through the RevAssist for Study Participants (REVLIMID 
REMS™ Program. You will only get a 28-day supply of lenalidomide at a time. Because you 
took part in the BMT CTN 0702 study, you are already registered for the program.  
Return all leftover lenalidomide pills through the REVLIMID REMS™ Program. Your doctor 
will tell you how to return the pills.  
Females that are pregnant or can become pregnant shouldn’t touch the lenalidomide pills or pill 
bottles, unless they wear gloves. 
Health Evaluations (tests) 
You will visit the clinic every 6 months. At each clinic visit you will have: 
 Physical exam, including height and weight 
 A pregnancy test using a blood sample (if you are a woman able to have children). If you are 
pregnant or breastfeeding, you must leave the study. We will give you a pregnancy test: 
o 24 or less hours before your first dose of lenalidomide 
o Next, once a week for 4 weeks 
o Then, once every 4 weeks until the study ends. If you have irregular periods (the number 
of days in your menstrual cycle is different each month), you will take a pregnancy test 
once every 2 weeks until the study ends.  
o Last, 4 weeks after you stop taking lenalidomide. 
 Counseling once every 4 weeks on the risks of lenalidomide including: 
o Reasons not to share lenalidomide or donate blood 
o Risks to the unborn 
o Risk of changes in numbers of blood cells and blood clots 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-8 
o Reminder not to break, chew or open the lenalidomide pills. 
This counseling is part of the Revlimid REMSTM education program for the study drug. You 
get the Lenalidomide Information Sheet for Patients Enrolled in Clinical Research Studies 
with each new supply of lenalidomide. 
 Tests to check for cancer as decided by your doctors. These tests would normally be done 
even if you were not on a research study and may include: 
o Bone marrow aspiration and biopsy (see Section 6: Risks and Discomforts) 
o Blood tests (up to 4 – 5 tablespoons) 
o Urine tests 
 Optional blood samples for future research (see Section 17: Blood Samples for Future 
Research).    
You can do these tests at a clinic near your home. Your clinic will send your test results to the 
study doctor.   
We will also ask you to take a quality of life survey once per year (see Before You Start 
Maintenance Treatment).  
6. Risks and Discomforts  
You will have side effects while on the study. Side effects can range from mild to serious. The 
risks and discomforts of long-term maintenance treatment after transplant are the same if you 
join this study, or if you don’t join this study. 
Your healthcare team may give you medicines to help with side effects like nausea (feeling sick 
to your stomach). In some cases, side effects can last a long time or may never go away.  
Risks of Medications  
The risks of the chemotherapy drugs you get as part of the treatment are listed below. How often 
patients get each of the side effects are shown in Table 1. Risks and Side Effects. 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-9 
Table 1. Risks and Side Effects 
Likely 
What it means: This type of side effect is expected in more than 20% 
of patients. This means that 21 or more patients out of 100 might get 
this side effect. 
Less Likely 
What it means: This type of side effect is expected in 20% of patients 
or fewer. This means that 20 patients or fewer out of 100 might get 
this side effect. 
Rare, but Serious 
What it means: This type of side effect is expected in fewer than 3% 
of patients. This means that 3 patients (or fewer) out of 100 might get 
this side effect. It doesn’t happen very often, but is serious when it 
does. 
 
 
 
 
 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-10 
Lenalidomide (Revlimid®) 
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in 20% of patients 
or less) 
Rare, but Serious  
(May happen in less than 3% 
of patients) 
 Low number of white 
blood cells 
(neutrophil/granulocyte) 
 Low number of platelets 
in the blood with 
increased risk of 
bleeding  
 Feeling tired 
 Itchy skin 
 Skin rash with flaky, 
bumpy skin 
 Constipation 
 Diarrhea 
 Nausea (feeling sick to 
your stomach)  
 
 Anemia (low number of red 
blood cells) 
 Low number of white blood 
cells (leukocytes) 
 Cough 
 Fever, with chills 
 Trouble sleeping  
 Excessive sweating 
 Weight loss because not 
feeling hungry  
 Belly pain 
 Vomiting (throwing up) 
 Low amount of thyroid 
hormone in the blood 
 Swelling and redness of the 
skin with sores  
 Sores in the mouth, 
intestines, and anus 
 Infection 
 Feeling dizzy 
 Headache 
 Swelling, pain and ache in 
 Allergic reactions (swelling 
of the skin, face or throat) 
that can cause you to pass 
out (faint) or lead to death   
 Rash with skin peeling and 
mouth sores that can lead 
to death  
 Outer layer of skin 
(epidermis) comes apart 
from the middle layer 
(dermis), which can lead to 
death 
 Pancreatitis (swelling of 
the intestines, stomach, or 
pancreas) 
 High number of enzymes in 
the blood 
 Fast death of cancer cells 
that can hurt organs like the 
kidneys 
 Temporary growth in 
tumor or worsening of 
tumor-related problems 
 Reversible damage to brain 
tissue that can lead to coma 
 Kidney damage that could 
require dialysis  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-11 
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in 20% of patients 
or less) 
Rare, but Serious  
(May happen in less than 3% 
of patients) 
joints and muscles of back, 
arms and legs 
 Trouble breathing 
 Blood clots (clumps of solid 
blood in your vein) that can 
lead to death 
 Second cancers 
 
 
We don’t know if second cancers are caused by lenalidomide or other drugs. Other research 
looked at the number of patients who got second cancers after taking lenalidomide for: 
 Diseases other than multiple myeloma, AND 
 Relapsed multiple myeloma. 
In these studies, no difference was shown in the number of patients who got second cancers. 
Researchers for other studies of lenalidomide are still watching patients to see if they get second 
cancers. We will give you any new information that we learn about second cancers.  
Risk to the Unborn 
The treatments in this study haven’t been proven to be safe at any stage of pregnancy or nursing 
(breast feeding). If you are pregnant or nursing, you can’t join this study. If lenalidomide is taken 
during pregnancy, it may cause birth defects or death to an unborn baby.    
Women and men must refrain from all acts of vaginal sex (abstinence) or use 2 types of effective 
birth control while receiving maintenance treatment. You must use effective birth control during the 
entire study and for 28 days after stopping maintenance treatment. Effective birth control is defined 
as the following: 
1. Refraining from all acts of vaginal sex (abstinence)  
2. Consistent use of birth control pills 
3. Injectable birth control methods (Depo-Provera, Norplant) 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-12 
4. Tubal sterilization or male partner who has undergone a vasectomy 
5. Placement of an IUD (intrauterine device) 
6. Use of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam every 
time you have sex. 
Females taking lenalidomide have blood clots more often. Because of this, you should talk to 
your doctor about birth control pills and hormone replacement therapy, and the risks and 
benefits. 
You do not need to use effective birth control only if you are a woman and cannot have children 
because you: 
 Had a hysterectomy (your ovaries and uterus were removed), OR 
 Had a bilateral oophorectomy (your ovaries were removed), OR 
 Went through menopause (post-menopausal). 
Reproductive Risks  
The drugs used in this research study may damage your reproductive organs, affect your ability to 
have children, or cause birth defects if you take them while you are pregnant or nursing.  
Both women who can become pregnant and their male partners should use birth control while on 
this study and for 28 days after maintenance treatment is stopped. If you or your partner 
becomes pregnant during this study, you must tell the study doctor immediately.  
Your doctor will discuss the risks to your unborn child and options with you.  
It is important that females who aren’t pregnant or nursing don’t become pregnant while part of 
the study. If you are a woman and become pregnant while on this study, we will stop the 
maintenance treatment drug right away.  
Your study doctor will watch your health closely while you are pregnant and for 30 days after 
the pregnancy ends. 
 
Females who join the study 
If you are female and can become pregnant, you will need to take a pregnancy test before you 
start the study. You should discuss ways to prevent pregnancy while you’re in the study. Women 
who have gone through puberty might experience irregular menstrual cycles or their cycle might 
stop forever. This doesn’t mean that you can’t become pregnant. You must still use 2 effective 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-13 
forms of birth control during the study and continue with it for 28 days after you finish 
maintenance treatment.  
Be sure to talk with your doctor about options for fertility planning, like storing your eggs, 
before starting chemotherapy treatment. 
 
Males who join the study 
If you are male, your body may not be able to produce sperm (become sterile). Be sure to talk 
with your doctor about options for fertility planning, like banking your sperm, before starting 
chemotherapy treatment. 
Damage to the vital organs in your body 
Your vital organs include your heart, lungs, liver, intestines, kidneys, bladder and brain. The 
chemotherapy and GVHD drugs may hurt these organs. You may develop lung problems from 
chemotherapy or an infection.  
Some patients can have veno-occlusive disease (VOD) of the liver. Patients with VOD become 
jaundiced (yellow skin), have problems with their liver, retain too much water (feel swollen and 
uncomfortable), and have stomach swelling and pain.  
If there is serious damage to your vital organs, you may have to stay in the hospital longer or 
return to the hospital after your transplant. Many patients get better, but these complications can 
cause permanent damage to your organs or death. 
Serious infections 
It may take many months for your immune system to recover from the chemotherapy, GVHD 
and maintenance therapy drugs. There is an increased risk of infection during this time when 
your body is healing. We will give you drugs to reduce the chance of infection, but they may not 
work. If you have an infection, you may have to stay in the hospital longer or return to the 
hospital after transplant. Many patients get better, but some infections can cause death. 
Relapse (return) of disease or a new blood cancer 
Your disease may come back even if the transplant was successful at first. In rare cases, a new 
blood cancer may develop from your cells. If cancer develops in your blood cells, you may need 
more chemotherapy or another transplant. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-14 
Other Treatments or Medicines 
Some medicines react with each other, and it is important that you tell the study doctor or staff 
about any other drugs, treatments, or medicines you are taking. This includes non-prescription or 
over-the-counter medicines, vitamins, and herbal treatments.  
It is also important that you tell the study staff about any changes to your medicines while you’re 
in the study. 
Risks of Blood Draws 
The risks and side effects of having blood taken from your arm with a needle include: 
 Pain, like a pinch 
 Swollen, red and sore skin where the needle went 
 Bruising 
 Feeling faint or dizzy 
Risks of Bone Marrow Aspiration and Biopsy 
The risks and side effects of anesthesia drug injection include: 
 Pain, like a pinch 
 Burning feeling in your skin and hip bone 
The risks and side effects of a bone marrow aspiration and biopsy include: 
 Pressure and pain in hip 
 Bleeding 
 Bruising 
 Ache in hip bone and muscles 
 Infection (this is rare) 
Unforeseen Risks  
New risks might appear at any time during the study. These risks might be different from what is 
listed in this Consent Form. We will promptly tell you about new information that may affect 
your decision to take part in the study.  
For more information about risks and side effects, ask your study doctor. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-15 
Statement that You Understand the Study Drug Risks and Side Effects  
Females Who Can Become Pregnant 
Please read each statement carefully. Next to each statement that you agree with, write your 
initials in the space provided. 
_____  My doctor discussed the risks and side effects of lenalidomide with me. I understand that 
if I am pregnant or become pregnant while taking lenalidomide, my unborn baby may 
have birth defects or could die. 
_____  I understand that effective birth control includes: 
 Refraining from all acts of vaginal sex (abstinence)  
 Consistent use of birth control pills 
 Injectable birth control methods (Depo-Provera, Norplant) 
 Tubal sterilization or male partner who has undergone a vasectomy 
 Placement of an IUD (intrauterine device) 
 Use of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam 
every time you have sex. 
_____  I must not take lenalidomide if I am pregnant or can become pregnant and am not using 2 
types of effective birth control. Also, I must not take lenalidomide if I am nursing.  
_____  I understand that I can become pregnant if: 
 I have vaginal sex,  
 My uterus and/or ovaries haven’t been removed (no hysterectomy), 
 I’ve had one or more menstrual periods in the last 2 years, and 
 I haven’t gone through menopause. 
_____  I must refrain from all acts of vaginal sex (abstinence) or use 2 types of effective birth 
control:  
 For 28 or more days before starting lenalidomide 
 While taking part in the study, even if you stop taking lenalidomide 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-16 
 For 28 or more days after you stop taking lenalidomide. 
_____  I understand that I must have pregnancy tests done at my clinic at: 
 About 2 weeks before starting lenalidomide 
 24 or less hours before my first dose of lenalidomide 
 Once a week for 4 weeks 
 Once every 4 weeks until the study ends. If I have irregular periods, I will take a 
pregnancy test once every 2 weeks until the study ends.  
 When I have been taken off lenalidomide 
 4 weeks after I stop taking lenalidomide. 
_____  I will immediately stop taking lenalidomide and tell my doctor if I become pregnant or 
think I might be pregnant during the study. I must talk to my doctor if I stop using 2 types 
of effective birth control or before changing types of birth control. 
_____  I am not pregnant now, and I will not try to become pregnant for 28 days or longer after I 
finish the study. 
_____  I understand that lenalidomide will be prescribed only for me. I will not share it with 
anyone, not even someone that has symptoms like mine. I will keep it out of reach of 
children. I will never give it to females who are pregnant or able to have children. 
_____  I will return all leftover study drugs through the Revlimid REMS™  Program.  
_____  I understand that I can’t donate blood while taking lenalidomide. Also, I can’t donate 
blood for 28 days after I stop taking lenalidomide. 
Females Who Can’t Become Pregnant 
Please read each statement carefully. Next to each statement that you agree with, write your 
initials in the space provided. 
_____  My doctor discussed the risks and side effects of lenalidomide with me. I understand that 
if a female is pregnant or becomes pregnant while taking lenalidomide, her unborn baby 
may have birth defects or could die. 
_____  I am not pregnant now and I’m not able have children because:  
 I went through menopause 2 years ago or longer (no periods or spotting) 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-17 
 I had my uterus removed (hysterectomy) and/or both ovaries removed (bilateral 
oophorectomy). 
_____  I understand that lenalidomide will be prescribed only for me. I will not share it with 
anyone, not even someone that has symptoms like mine. I will keep it out of reach of 
children. I will never give it to females who are pregnant or able to have children. 
_____  I will return all leftover study drugs through the Revlimid REMS™  Program.  
_____  I understand that I can’t donate blood while taking lenalidomide. Also, I can’t donate 
blood for 28 days after I stop taking lenalidomide. 
Males 
Please read each statement carefully. Next to each statement that you agree with, write your 
initials in the space provided. 
_____  My doctor discussed the risks and side effects of lenalidomide with me. I understand that 
if a female is pregnant or becomes pregnant while taking lenalidomide, her unborn baby 
may have birth defects or could die. 
_____  I understand that effective birth control includes: 
 Refraining from all acts of vaginal sex (abstinence)  
 Consistent use of birth control pills 
 Injectable birth control methods (Depo-Provera, Norplant) 
 Tubal sterilization or male partner who has undergone a vasectomy 
 Placement of an IUD (intrauterine device) 
 Use of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam 
every time you have sex. 
_____  I understand that I must never have vaginal sex without 2 types of effective birth control, 
even if I had a vasectomy. I must use 2 types of effective birth control while I take 
lenalidomide and for 28 days after I stop taking lenalidomide. 
_____  I will tell my doctor if I have vaginal sex with a female and don’t use 2 types of effective 
birth control. I will tell my doctor if I think that my sexual partner might be pregnant. I 
will tell my sexual partner to tell her doctor immediately if she becomes pregnant or 
thinks she might be pregnant.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-18 
_____  I understand that lenalidomide will be prescribed only for me. I will not share it with 
anyone, not even someone that has symptoms like mine. I will keep it out of reach of 
children. I will never give it to females who are pregnant or able to have children. 
_____  I will return all leftover study drugs through the Revlimid REMS™  Program.  
_____  I understand that I can’t donate blood while taking lenalidomide. Also, I can’t donate 
blood for 28 days after I stop taking lenalidomide. 
7. Alternative Treatments 
Participation in this study is optional. If you choose not to take part, you may still receive long-
term follow-up after your transplant. The evaluations you would have could be very similar to 
what would have if you join this study.  
Your study doctor will talk with you about your options. If you decide not to participate in this 
study, your medical care will not be affected in any way. 
8. Possible Benefits 
Taking part in this study will not make your health better. The information from this study will 
help doctors learn more about ways to treat multiple myeloma.  
This information could help people with multiple myeloma who may need a transplant in the 
future. 
9. New Information Available During the Study 
During this research study, the study doctors may learn about new information about the risks and 
benefits of the study. 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 will offer you all 
available care to suit your needs and medical conditions. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-19 
10. 
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 is kept private. However, we cannot guarantee total 
privacy.  
All your medical and demographic information (such as race and ethnicity, gender and 
household income) will be kept private and confidential. (Name of Transplant Center) and the 
organizations listed below will not disclose your participation by any means of communication 
to any person or organization, except by your written request, or permission, or unless required 
by federal, state or local laws, or regulatory agencies.  
Individuals authorized by the organizations below will have access to your research and medical 
information. They may use this information for inspections or audits to study the outcomes of 
your treatment. In agreeing to participate, you consent to such inspections and to the copying of 
parts of your records, if required by these organizations. 
We may give out your personal information 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.  
Information about your transplant from your original medical records may be seen or sent to 
national and international transplant registries, including:  
 /Institution/ 
 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 and Coordinating Center of the Blood and Marrow Transplant Clinical Trials Network 
(BMT CTN)  
 Data and Safety Monitoring Board (DSMB), not part of /Institution/ 
 Study investigators.   


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-20 
We will not identify you by name in any publications or reports that come from these organizations 
or groups. 
Information that does not include personally identifiable information about this study has been or 
will be submitted, at the appropriate and required time, to the government-operated clinical trial 
registry data bank, which contains registration, results, and other information about registered 
studies.   
This data bank can be accessed by you and the general public at www.ClinicalTrials.gov. Federal 
law requires clinical trial information for certain studies to be submitted to the data bank. 
For questions about access to your medical records, please contact /name/ at /number. 
11. 
Ending Your Participation 
The study doctor or the study sponsor may stop the study at any time, and we may ask you to 
leave the study. We may ask you to leave the study if you do not follow directions or if you 
suffer from side effects of the tests. If we ask you to leave the study, the reasons will be 
discussed with you. Possible reasons to end your participation in this study include: 
 Your disease returns or worsens during the study.  
 You need a medical treatment not allowed in this study. 
 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 as directed. 
 The study is stopped for any reason. 
We ask that you talk with the research doctor and your regular doctor before you leave the study. 
Your doctors will tell you how to stop safely and talk with you about other treatment choices.  
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. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
A-21 
12. 
Physical Injury as a Result of Participation  
It is important that you tell your doctor, __________________ [investigator's name(s)] or study 
staff 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 all available medical treatment if you are injured from 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 you are injured in this study, you do not lose any of your legal rights to ask for or receive 
payment by signing this form. 
13. 
Compensation or Payment 
You will not be paid for taking part in this study. You will not be paid or reimbursed for any extra 
costs (for example, travel and meals) from taking part in this study.  
You will have no rights to any patents or findings from this study. You will not be compensated 
for any patents or findings from this study.
14. 
Costs and Reimbursements 
Most of the visits for this research study are standard medical care  after your autologous transplant 
and will be billed to your insurance company. You and/or your health plan/insurance company will 
need to pay for some or all of the costs of standard treatment in this study.   
You will get the study drug, lenalidomide, for free from Celgene. You and your health insurance 
plan will not be charged for the drug. 
You or your insurance will not be charged for optional blood samples for research on this study. 
You will not pay for any extra tests that are being done for the study. 
Some health plans will not pay these costs for people taking part in studies. Check with your 
health plan or insurance company to find out if they will pay. 
For questions about your costs, financial responsibilities, and/or medical insurance coverage for 
your transplant and this study, please contact /Center/ Financial Counselor at /Number/. 
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. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-22 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy.
15. 
For More Information 
If you need more information about this study, or if you have problems while taking part in this 
study, you can contact the study doctor or his/her staff.  
They can be reached at the telephone numbers listed here: 
[Insert name and contact details] 
16. 
 Contact Someone about Your Rights 
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] 
The ethical aspects of this study have been reviewed and approved by [name of IRB]. 
17. 
Blood Samples for Future Research (Optional)  
This section of the informed consent form is about future research studies that will use blood 
samples from people who are taking part in the main study. You may choose to give samples for 
these future research studies if you want to. You can still be a part of the main study even if you 
say 'no' to give samples for future research studies. 
Researchers are trying to learn more about how the human body processes the drugs used for 
transplant and how the body recovers after transplant. This research is meant to gain knowledge 
that may help people in the future and make transplants even more successful.  
If you agree to provide blood samples, here is what will happen: 
 We will collect two extra blood samples at the same time you have routine blood tests done. 
The amount of blood collected from you is about 6 teaspoons (31 ml) each time.  
We will collect blood samples at two times during the study: 
o First clinic visit after you join the study 
o Last clinic visit at the end of the study  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-23 
 The blood samples will be sent to the BMT CTN Repository for processing and storage. A 
repository is a place that protects, stores and sends out samples for approved research studies. 
All research samples will be given a bar code that cannot be linked to you by future 
researchers testing your samples. 
 Materials stored in the Repository will be used mainly by clinicians and researchers in the 
BMT CTN network. In the future, the unused research samples and clinical data will be made 
available outside of this network.  
 Researchers can apply to study the materials stored in the Repository. The BMT CTN 
Steering Committee and/or the BMT CTN Executive Committee must approve each request 
before they will share samples or information with researchers. This is to make sure that the 
investigators requesting the samples are qualified, and that the research is of high quality. 
 DNA from your stored blood samples might be used in genome-wide association (GWA) 
studies for a future project either done or supported by the National Institutes of Health 
(NIH). Genome-wide association studies are a way for scientists to find genes that have a 
role in human disease or treatment. Each study can look at hundreds of thousands of genetic 
changes at the same time. 
If your coded samples are used in such a study, the researcher is required to add your test 
results and sample information into a shared, public research database. This public 
database is called the NIH Genotype and Phenotype Database and it is managed by the 
National Center for Biotechnology Information (NCBI). The NCBI will never have any 
information that would identify you, or link you to your information or research samples.  
Some general things you should know about letting us store your blood samples for research are: 
 We will only store samples from people who give us permission. 
 Research is meant to gain knowledge that my help people in the future. You will not get any 
direct benefit from taking part. Additionally, you or your doctor will not be given results and 
they will not be added to your medical record. 
 A possible risk is the loss of confidentiality about your medical information. We will use 
safety measures with both your samples and clinical information to make sure that your 
personal information will be kept private. The chance that this information will be given to 
someone else is extremely small.  
 Your blood will be used only for research and will not be sold. The research done with your 
blood may help to develop new products in the future. You will not get paid for any samples 
or for any products that may be developed from current or future research. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-24 
You can change your mind at any time about allowing us to use your samples and health 
information for research.  
We ask that you contact [Principal Investigator] in writing and let him/her know you do not want 
us to use your research samples or health information for research. His/her mailing address is on 
the first page of this form. However, samples and information that have already been shared with 
other researchers cannot be taken back or destroyed.  
Making Your Choice  
Please read each sentence below and think about your choice. After reading each sentence, 
please indicate your choice below. If you have any questions, please talk to your doctor or nurse, 
or call our research review board at ___________________.  
No matter what you decide to do, it will not affect your care. 
Statement of Consent for Research Samples 
The purpose of storing blood samples, the procedures involved, and the risks and benefits have 
been explained to me. I have asked all the questions I have at this time and I have been told 
whom to contact if I have more questions. I have been told that I will be given a signed copy of 
this consent form to keep. 
I understand that I do not have to allow the use of my blood for research. If I decide to not let 
you store research samples now or in the future, it will not affect my medical care in any way. 
I voluntarily agree that my blood and information can be stored indefinitely by the BMT CTN 
and/or NHLBI Repositories for research to learn about, prevent, or treat health problems. I also 
understand that my DNA and health information may or may not be used in genome-wide 
association studies. 
Blood 
 I agree to allow my blood samples to be stored for research. 
 I do not agree to allow my blood samples to be stored for research. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-25 
Health Insurance Portability and Accountability Act 1 (HIPAA2) Authorization to use and 
disclose individual health information for research purpose 
 
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:  
Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients Who 
Have Enrolled on BMT CTN 0702  
 
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 transplant (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: 
 Dr. Amrita Krishnan, Study Chairperson and staff/laboratories at City of Hope National 
Medical Center 
­ Dr. George Somlo, Study Chairperson and staff/laboratories at City of Hope National 
Medical Center 
                                         
2 HIPAA is the Health Insurance Portability and Accountability Act of 1996, a federal law related to privacy of health 
information 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-26 
­ Dr. Edward Stadtmauer, Study Chairperson and staff/laboratories at University of 
Pennsylvania Cancer Center. 
Study Sponsors  
 National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI), 
both of the National Institutes of Health (NIH),  
1. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Data and Coordinating 
CenterU.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) 
2. 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 
3. Celgene (the manufacturer of lenalidomide) 
4. Biologics, Inc (the distributor of lenalidomide). 
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, t he 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 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-27 
disclosures for law enforcement purposes, mandated reporting or abuse or neglect, judicial 
proceedings, health oversight activities and public health measures. 
H. Genetic Information Nondiscrimination Act (GINA)  
A new federal law (2009), called the Genetic Information Nondiscrimination Act (GINA) 
generally makes it illegal for health insurance companies, group health plans, and employers of 
15 or more persons to discriminate against you based on your genetic information.  
Health insurance companies and group health plans may not request your genetic information 
that we get from this research. This means that they must not use your genetic information when 
making decisions regarding insurability. Be aware that this new federal law will not protect you 
against genetic discrimination by companies that sell life insurance, disability insurance, or long-
term care insurance. 
I. This authorization does not have an expiration date. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-28 
TITLE: Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients 
Who Have Enrolled on BMT CTN 0702  
PROTOCOL NUMBER: BMT CTN #0702 Long-term Follow-Up Study 
PRINCIPAL INVESTIGATOR:  
Name: 
Address: 
Email:  
Phone:  
 
 
 
 
 
 
 
 
 
 
 
Fax:  
I have read and understood this Consent Form. The nature and purpose of the research study has 
been explained to me. 
 I have had the chance to ask questions, and understand the answers I have been given. I 
understand that I may ask questions at any time during the study. 
 I freely agree to be a participant in the study. 
 I understand that I may not directly benefit from taking part in the study. 
 I understand that, while information gained during the study may be published, I will not be 
identified and my personal results will stay confidential. 
 I have had the chance to discuss my participation in this research study with a family member 
or friend. 
 I understand that I can leave this study at any time, and doing so will not affect my current care 
or prevent me from receiving future treatment. 
 I understand that I will be given a copy of this signed consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Counseling Physician 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Counseling Physician 
 
    
 
 
 
Date 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-29 
 
 
 
 
PATIENT INFORMED CONSENT FORM 
 
 
 
 
Informed Consent to Participate in Long-Term Follow-Up Research 
 
 
 
 
 
 
 
 
 
 
 
 
Your Name:  
__________________________________ 
 
Study Title:  
Continued, Long-Term Follow-Up and Lenalidomide Maintenance 
Therapy for Patients Who Have Enrolled on BMT CTN 0702 
Protocol: 
BMT CTN 0702 Long-Term Follow-Up 
Principal 
Investigator:  
Insert local PI information 
Sponsor: 
The National Institutes of Health (NIH) is sponsoring this study by 
providing financial support for the coordination of this study through the 
Blood and Marrow Transplant Clinical Trials Network (BMT CTN).  
Celgene is supplying the study drug lenalidomide. 
 
 
 
 
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-30 
1. Introduction  
We invite you to join this clinical trial, also known as a research study. You are being asked to 
join because: 
 You took part in the study, A Trial of Single Autologous Transplant with or without 
Consolidation Therapy versus Tandem Autologous Transplant with Lenalidomide 
Maintenance for Patients with Multiple Myeloma, also called BMT CTN 0702 
 Your disease did not return or worsen (this is also called disease progression) during the 
BMT CTN 0702 study. 
Because there’s no cure for Multiple Myeloma (MM), the disease almost always returns or 
worsens. We are doing this study to learn how well patients do more than 3 years after 
autologous transplant.  
This study will include 450 participants. Your participation on this study is expected to last until 
your disease returns or progresses.  
This Consent Form will tell you about the purpose of the study, the possible risks and benefits, 
other options available to you, and your rights as a participant in the study.  
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 quit the study at any time.  
 If you decide to quit 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.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-31 
You and your doctor will discuss other follow-up treatment choices if you do not want to 
participate in this study.    
This consent form tells you about the study.  The Principal Investigator (the person in charge of 
this research) or a co-worker of the Principal Investigator will also describe this study to you and 
answer all of your questions.  Furthermore, throughout your follow up questions will be 
answered as needed.  Before you decide whether or not to take part, read the information below 
and ask questions about anything you do not understand.  Taking part in this follow-up study is 
entirely your choice. 
2. Study Background 
The National Institutes of Health (NIH), through the Blood and Marrow Transplant Clinical 
Trials Network (BMT CTN), are providing staff support and money for this research study. The 
BMT CTN and the NIH will make decisions about how to manage the study.  
For this study, we will watch your health closely (this is also called follow-up) after your 
autologous transplant.  
There’s no cure for MM. After transplant, the disease will almost always return, or relapse. Some 
patients may keep getting treatment after transplant called maintenance treatment. Maintenance 
treatment is given to slow down relapse. Even with maintenance treatment, MM will relapse. 
Your doctor doesn’t know how long it will take for the disease to return.   
3. Study Purpose 
We are inviting you to take part in this study because you completed the BMT CTN 0702 study 
and your disease did not return or worsen.  We are doing this study to learn more about ways to 
prevent or delay relapse of multiple myeloma (MM). We also want to know how well you do 
long-term (more than 3 years) after transplant.   
You will have a physical evaluation (test) every 6 months to see if you still have Multiple 
Myeloma (MM) in your body. This study will help doctors make the best choice about long-term 
treatment after autologous transplant for patients with MM. 
4. Rights to Ask Questions and/or Withdraw 
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] 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-32 
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 not to take part or leave this study, it will not affect your regular medical care 
in any way.  
Your study doctor and study staff will be available to answer any questions that you may have 
about taking part in or leaving this study.  
5. Study Tests 
We will check (test) your health before you enter the study and every 6 months after that. This is 
called long-term follow-up after transplant. We will stop the study tests if your disease returns or 
relapses. 
You will need to have several check-ups and tests for this study. You will visit the clinic every 6 
months. At each clinic visit you will have: 
 Physical exam, including height and weight 
 Tests to check for cancer as decided by your doctors. These tests would normally be done 
even if you were not on a research study. These tests may include: 
o Bone marrow aspiration and biopsy (see Section 6: Risks and Discomforts) 
o Blood tests (up to 4 – 5 tablespoons) 
o Urine tests 
 Optional blood samples for future research (see Section 17: Blood Samples for Future 
Research).    
You can do these tests at a clinic near your home. Your clinic will send your test results to the 
study doctor.   
We will also ask you to take a quality of life survey each year. The survey will ask about: 
 Any side effects of your treatment 
 Any health problems 
 How well you can do things that are important to you 
 How you relate to other people  
 Your feelings.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-33 
An interviewer will contact you before you start long-term follow-up. These interviews will take 
about 30 minutes and will be done at a time that works for you. You may skip any questions you 
wish.  
6. Risks and Discomforts  
You will have side effects while on the study. Side effects can range from mild to serious. The 
risks and discomforts of long-term follow-up after transplant are the same if you join this study, 
or if you don’t join this study. 
Risks of Blood Draws 
The risks and side effects of having blood taken from your arm with a needle include: 
 Pain, like a pinch 
 Swollen, red and sore skin where the needle went 
 Bruising 
 Feeling faint or dizzy 
Risks of Bone Marrow Aspiration and Biopsy 
The risks and side effects of anesthesia drug injection include: 
 Pain, like a pinch 
 Burning feeling in your skin and hip bone 
The risks and side effects of a bone marrow aspiration and biopsy include: 
 Pressure and pain in hip 
 Bleeding 
 Bruising 
 Ache in hip bone and muscles 
 Infection (this is rare) 
Unforeseen Risks  
New risks might appear at any time during the study. These risks might be different from what is 
listed in this Consent Form. We will promptly tell you about new information that may affect 
your decision to take part in the study.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-34 
For more information about risks and side effects, ask your study doctor. 
7. Alternative Treatments 
Participation in this study is optional. If you choose not to take part, you may still receive long-
term follow-up after your transplant. The evaluations you would have could be very similar to 
whatyou  would have if you join this study.  
Your study doctor will talk with you about your options. If you decide not to participate in this 
study, your medical care will not be affected in any way. 
8. Possible Benefits 
Taking part in this study will not make your health better. The information from this study will 
help doctors learn more about ways to treat multiple myeloma.  
This information could help people with multiple myeloma who may need a transplant in the 
future. 
9. New Information Available During the Study 
During this research study, the study doctors may learn about new information about the risks and 
benefits of the study. 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 will offer you all 
available care to suit your needs and medical conditions. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-35 
10. 
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 is kept private. However, we cannot guarantee total 
privacy.  
All your medical and demographic information (such as race and ethnicity, gender and 
household income) will be kept private and confidential. (Name of Transplant Center) and the 
organizations listed below will not disclose your participation by any means of communication 
to any person or organization, except by your written request, or permission, or unless required 
by federal, state or local laws, or regulatory agencies.  
Individuals authorized by the organizations below will have access to your research and medical 
information. They may use this information for inspections or audits to study the outcomes of 
your treatment. In agreeing to participate, you consent to such inspections and to the copying of 
parts of your records, if required by these organizations. 
We may give out your personal information 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.  
Information about your transplant from your original medical records may be seen or sent to 
national and international transplant registries, including:  
 /Institution/ 
 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 and Coordinating Center of the Blood and Marrow Transplant Clinical Trials Network 
(BMT CTN)  
 Data and Safety Monitoring Board (DSMB), not part of /Institution/ 
 Study investigators.   


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-36 
We will not identify you by name in any publications or reports that come from these organizations 
or groups. 
Information that does not include personally identifiable information about this study has been or 
will be submitted, at the appropriate and required time, to the government-operated clinical trial 
registry data bank, which contains registration, results, and other information about registered 
studies.   
This data bank can be accessed by you and the general public at www.ClinicalTrials.gov. Federal 
law requires clinical trial information for certain studies to be submitted to the data bank. 
For questions about access to your medical records, please contact /name/ at /number. 
11. 
Ending Your Participation 
The study doctor or the study sponsor may stop the study at any time, and we may ask you to 
leave the study. We may ask you to leave the study if you do not follow directions or if you 
suffer from side effects of the tests. If we ask you to leave the study, the reasons will be 
discussed with you. Possible reasons to end your participation in this study include: 
 Your disease returns or worsens during the study.  
 You need a medical treatment not allowed in this study. 
 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 as directed. 
 The study is stopped for any reason. 
We ask that you talk with the research doctor and your regular doctor before you leave the study. 
Your doctors will tell you how to stop safely and talk with you about other treatment choices.  
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. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-37 
12. 
Physical Injury as a Result of Participation  
It is important that you tell your doctor, __________________ [investigator's name(s)] or study 
staff 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 all available medical treatment if you are injured from 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 you are injured in this study, you do not lose any of your legal rights to ask for or receive 
payment by signing this form. 
13. 
Compensation or Payment 
You will not be paid for taking part in this study. You will not be paid or reimbursed for any extra 
costs (for example, travel and meals) from taking part in this study.  
You will have no rights to any patents or findings from this study. You will not be compensated 
for any patents or findings from this study.
14. 
Costs and Reimbursements 
Most of the visits for this research study are standard medical care after your autologous transplant 
and will be billed to your insurance company. You and/or your health plan/insurance company will 
need to pay for some or all of the costs of standard treatment in this study.   
You or your insurance will not be charged for optional blood samples for research on this study. 
You will not pay for any extra tests that are being done for the study. 
Some health plans will not pay these costs for people taking part in studies. Check with your 
health plan or insurance company to find out if they will pay. 
For questions about your costs, financial responsibilities, and/or medical insurance coverage for 
your transplant and this study, please contact /Center/ Financial Counselor at /Number/. 
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 them 
to send you a free copy.


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-38 
15. 
For More Information 
If you need more information about this study, or if you have problems while taking part in this 
study, you can contact the study doctor or his/her staff.  
They can be reached at the telephone numbers listed here: 
[Insert name and contact details] 
16. 
 Contact Someone about Your Rights 
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] 
The ethical aspects of this study have been reviewed and approved by [name of IRB]. 
17. 
Blood Samples for Future Research (Optional)  
This section of the informed consent form is about future research studies that will use blood 
samples from people who are taking part in the main study. You may choose to give samples for 
these future research studies if you want to. You can still be a part of the main study even if you 
say 'no' to give samples for future research studies. 
Researchers are trying to learn more about how the human body processes the drugs used for 
transplant and how the body recovers after transplant. This research is meant to gain knowledge 
that may help people in the future and make transplants even more successful.  
If you agree to provide blood samples, here is what will happen: 
 We will collect two extra blood samples at the same time you have routine blood tests done. 
The amount of blood collected from you is about 6 teaspoons (31 ml) each time.  
We will collect blood samples at two times during the study: 
o First clinic visit after you join the study 
o Last clinic visit at the end of the study  
 The blood samples will be sent to the BMT CTN Repository for processing and storage. A 
repository is a place that protects, stores and sends out samples for approved research studies. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-39 
All research samples will be given a bar code that cannot be linked to you by future 
researchers testing your samples. 
 Materials stored in the Repository will be used mainly by clinicians and researchers in the 
BMT CTN network. In the future, the unused research samples and clinical data will be made 
available outside of this network.  
 Researchers can apply to study the materials stored in the Repository. The BMT CTN 
Steering Committee and/or the BMT CTN Executive Committee must approve each request 
before they will share samples or information with researchers. This is to make sure that the 
investigators requesting the samples are qualified, and that the research is of high quality. 
 DNA from your stored blood samples might be used in genome-wide association (GWA) 
studies for a future project either done or supported by the National Institutes of Health 
(NIH). Genome-wide association studies are a way for scientists to find genes that have a 
role in human disease or treatment. Each study can look at hundreds of thousands of genetic 
changes at the same time. 
If your coded samples are used in such a study, the researcher is required to add your test 
results and sample information into a shared, public research database. This public 
database is called the NIH Genotype and Phenotype Database and it is managed by the 
National Center for Biotechnology Information (NCBI). The NCBI will never have any 
information that would identify you, or link you to your information or research samples.  
Some general things you should know about letting us store your blood samples for research are: 
 We will only store samples from people who give us permission. 
 Research is meant to gain knowledge that my help people in the future. You will not get any 
direct benefit from taking part. Additionally, you or your doctor will not be given results and 
they will not be added to your medical record. 
 A possible risk is the loss of confidentiality about your medical information. We will use 
safety measures with both your samples and clinical information to make sure that your 
personal information will be kept private. The chance that this information will be given to 
someone else is extremely small.  
 Your blood will be used only for research and will not be sold. The research done with your 
blood may help to develop new products in the future. You will not get paid for any samples 
or for any products that may be developed from current or future research. 
You can change your mind at any time about allowing us to use your samples and health 
information for research.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-40 
We ask that you contact [Principal Investigator] in writing and let him/her know you do not want 
us to use your research samples or health information for research. His/her mailing address is on 
the first page of this form. However, samples and information that have already been shared with 
other researchers cannot be taken back or destroyed.  
Making Your Choice  
Please read each sentence below and think about your choice. After reading each sentence, 
please indicate your choice below. If you have any questions, please talk to your doctor or nurse, 
or call our research review board at ___________________.  
No matter what you decide to do, it will not affect your care. 
Statement of Consent for Research Samples 
The purpose of storing blood samples, the procedures involved, and the risks and benefits have 
been explained to me. I have asked all the questions I have at this time and I have been told 
whom to contact if I have more questions. I have been told that I will be given a signed copy of 
this consent form to keep. 
I understand that I do not have to allow the use of my blood for research. If I decide to not let 
you store research samples now or in the future, it will not affect my medical care in any way. 
I voluntarily agree that my blood and information can be stored indefinitely by the BMT CTN 
and/or NHLBI Repositories for research to learn about, prevent, or treat health problems. I also 
understand that my DNA and health information may or may not be used in genome-wide 
association studies. 
Blood 
 I agree to allow my blood samples to be stored for research. 
 I do not agree to allow my blood samples to be stored for research. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-41 
Health Insurance Portability and Accountability Act 1 (HIPAA3) Authorization to use and 
disclose individual health information for research purpose 
 
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:  
Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients Who 
Have Enrolled on BMT CTN 0702  
 
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 transplant (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: 
 Dr. Amrita Krishnan, Study Chairperson and staff/laboratories at City of Hope National 
Medical Center 
­ Dr. George Somlo, Study Chairperson and staff/laboratories at City of Hope National 
Medical Center 
                                         
3 HIPAA is the Health Insurance Portability and Accountability Act of 1996, a federal law related to privacy of health 
information 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-42 
­ Dr. Edward Stadtmauer, Study Chairperson and staff/laboratories at University of 
Pennsylvania Cancer Center. 
Study Sponsors  
 National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI), 
both of the National Institutes of Health (NIH),  
 Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Data and Coordinating 
Center 
 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 
 Celgene (the manufacturer of lenalidomide) 
 Biologics, Inc (the distributor of lenalidomide). 
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, t he 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 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-43 
disclosures for law enforcement purposes, mandated reporting or abuse or neglect, judicial 
proceedings, health oversight activities and public health measures. 
H. Genetic Information Nondiscrimination Act (GINA)  
A new federal law (2009), called the Genetic Information Nondiscrimination Act (GINA) 
generally makes it illegal for health insurance companies, group health plans, and employers of 
15 or more persons to discriminate against you based on your genetic information.  
Health insurance companies and group health plans may not request your genetic information 
that we get from this research. This means that they must not use your genetic information when 
making decisions regarding insurability. Be aware that this new federal law will not protect you 
against genetic discrimination by companies that sell life insurance, disability insurance, or long-
term care insurance. 
I. This authorization does not have an expiration date. 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
CONFIDENTIAL 
A-44 
TITLE: Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients 
Who Have Enrolled on BMT CTN 0702  
PROTOCOL NUMBER: BMT CTN #0702 Long-term Follow-Up Study 
PRINCIPAL INVESTIGATOR:  
Name: 
Address: 
Email:  
Phone:  
 
 
 
 
 
 
 
 
 
 
 
Fax:  
I have read and understood this Consent Form. The nature and purpose of the research study has 
been explained to me. 
 I have had the chance to ask questions, and understand the answers I have been given. I 
understand that I may ask questions at any time during the study. 
 I freely agree to be a participant in the study. 
 I understand that I may not directly benefit from taking part in the study. 
 I understand that, while information gained during the study may be published, I will not be 
identified and my personal results will stay confidential. 
 I have had the chance to discuss my participation in this research study with a family member 
or friend. 
 I understand that I can leave this study at any time, and doing so will not affect my current care 
or prevent me from receiving future treatment. 
 I understand that I will be given a copy of this signed consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Counseling Physician 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Counseling Physician 
 
    
 
 
 
Date


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
B-1 
 
APPENDIX B 
 
LENALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY 
TESTING GUIDELINES AND ACCEPTABLE  
BIRTH CONTROL METHODS 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
B-2 
APPENDIX B 
 
LENALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY TESTING 
GUIDELINES AND ACCEPTABLE BIRTH CONTROL METHODS 
 
 
Risks Associated with Pregnancy 
Lenalidomide is structurally related to thalidomide.  Thalidomide is a known human teratogenic 
active substance that causes severe life-threatening birth defects.  An embryofetal development 
study in animals indicates that lenalidomide produced malformations in the offspring of female 
monkeys who received the drug during pregnancy.  The teratogenic effect of lenalidomide in 
humans cannot be ruled out.  Therefore, a risk minimization plan to prevent pregnancy must be 
observed. 
 
The use of lenalidomide in pregnant females and nursing mothers has not been studied nor has 
the effect of the lenalidomide on human eggs and sperm.  The risks to a fetus are not known.  
However, because lenalidomide is related to thalidomide, and thalidomide is known to cause 
severe birth defects, the following requirements must be observed. 
 
Females of childbearing potential (FCBP)† must agree to use two reliable forms of contraception 
simultaneously or to practice complete abstinence from heterosexual intercourse during the 
following time periods related to this study: 1) for at least 28 days before starting study drug; 2) 
while participating in the study; and, 3) for at least 28 days after discontinuation from the study.  
The two methods of reliable contraception must include one highly effective method (i.e. 
intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, 
partner’s vasectomy) and one additional effective (barrier) method (i.e. latex condom, 
diaphragm, cervical cap).  FCBP must be referred to a qualified provider of contraceptive 
methods if needed.   
 
Criteria for females of childbearing potential (FCBP) 
This protocol defines a female of childbearing potential as a sexually mature female who: 1) has 
not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 
for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 
consecutive months). 
 
Counseling 
All counseling will be conducted through the Revlimid REMS® program. 
 
For a female of childbearing potential, lenalidomide is contraindicated unless all of the following 
are met (i.e., all females of childbearing potential must be counseled concerning the following 
risks and requirements prior to the start of lenalidomide):  
                                         
† A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or 
bilateral oophorectomy; or, 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has 
had menses at any time in the preceding 24 consecutive months). 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
B-3 
 She understands the potential teratogenic risk to the unborn child 
 She understands the need for effective contraception, without interruption, 28 days before 
starting study treatment, throughout the entire duration of study treatment, dose 
interruption and 28 days after the end of study treatment 
 She should be capable of complying with effective contraceptive measures 
 She is informed and understands the potential consequences of pregnancy and the need to 
notify her study doctor immediately if there is a risk of pregnancy 
 She understands the need to commence the study treatment as soon as study drug is 
dispensed following a negative pregnancy test 
 She understands the need and accepts to undergo pregnancy testing based on the 
frequency outlined in this protocol 
 She acknowledges that she understands the hazards and necessary precautions associated 
with the use of lenalidomide 
The investigator must ensure that for females of childbearing potential: 
 Complies with the conditions for pregnancy risk minimization, including confirmation 
that she has an adequate level of understanding 
 Acknowledge the aforementioned requirements 
For a female NOT of childbearing potential, lenalidomide is contraindicated unless all of the 
following are met (i.e., all females NOT of childbearing potential must be counseled concerning 
the following risks and requirements prior to the start of lenalidomide):  
 She acknowledges that she understands the hazards and necessary precautions associated 
with the use of lenalidomide 
Traces of lenalidomide have been found in semen.  Male patients taking lenalidomide must meet 
the following conditions (i.e., all males must be counseled concerning the following risks and 
requirements prior to the start of lenalidomide): 
 Understand the potential teratogenic risk if engaged in sexual activity with a pregnant 
female or a female of childbearing potential 
 Understand the need for the use of a condom even if he has had a vasectomy, if engaged 
in sexual activity with a pregnant female or a female of childbearing potential.   
 
Contraception 
Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable 
forms of contraception simultaneously or to practice complete abstinence from heterosexual 
contact during the following time periods related to this study: 1) for at least 28 days before 
starting study drug; 2) while participating in the study; 3) during dose interruptions; and, 4) for at 
least 28 days after study treatment discontinuation.  
The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method.  FCBP must be referred to a qualified provider of 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
B-4 
contraceptive methods if needed.  T he following are examples of highly effective and additional 
effective methods of contraception:   
Highly effective methods: 
 Intrauterine device (IUD) 
 Hormonal (birth control pills, injections, implants) 
 Tubal ligation 
 Partner’s vasectomy 
Additional effective methods: 
 Male condom 
 Diaphragm 
 Cervical Cap 
 
Because of the increased risk of venous thromboembolism in patients with multiple myeloma 
taking lenalidomide and dexamethasone, combined oral contraceptive pills are not 
recommended.  If a patient is currently using combined oral contraception the patient should 
switch to one of the effective method listed above.  The risk of venous thromboembolism 
continues for 4 to 6 weeks after discontinuing combined oral contraception.  The efficacy of 
contraceptive steroids may be reduced during co-treatment with dexamethasone. 
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk 
of infection at the time of insertion and irregular vaginal bleeding.  Prophylactic antibiotics 
should be considered particularly in patients with neutropenia.  
 
Pregnancy testing 
Medically supervised pregnancy tests with a minimum sensitivity of 50 mIU/mL must be 
performed for females of childbearing potential, including females of childbearing potential who 
commit to complete abstinence, as outlined below. 
 
Before starting study drug 
Female Patients:  
FCBP must have two negative pregnancy tests (minimum sensitivity of 50mIU/mL) prior to 
starting study drug.  The first pregnancy test must be performed within 10 to 14 days prior to the 
start of study drug and the second pregnancy test must be performed within 24 hours prior to the 
start of study drug (prescriptions must be filled within 7 days as required by the Revlimid 
REMS®  program).  The patient may not receive study drug until the study doctor has verified 
that the results of these pregnancy tests are negative. 
Male Patients: 
Must practice complete abstinence or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, during 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
B-5 
dose interruptions and for at least 28 days following study drug discontinuation, even if he has 
undergone a successful vasectomy.   
 
During study participation and for 28 days following study drug discontinuation  
Female Patients: 
 FCBP with regular or no menstrual cycles must agree to have pregnancy tests weekly for 
the first 28 days of study participation and then every 28 days while on study, at study 
discontinuation, and at day 28 following study drug discontinuation.  If menstrual cycles 
are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 
14 days while on study, at study discontinuation, and at days 14 and 28 following study 
drug discontinuation.   
 At each visit, the Investigator must confirm with the FCBP that she is continuing to use 
two reliable methods of birth control.   
 Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted at a minimum of every 28 days.  
 If pregnancy or a positive pregnancy test does occur in a study patient, study drug must 
be immediately discontinued. 
 Pregnancy testing and counseling must be performed if a patient misses her period or if 
her pregnancy test or her menstrual bleeding is abnormal.  Study treatment must be 
discontinued during this evaluation. 
 Females must agree to abstain from breastfeeding during study participation and for at 
least 28 days after study drug discontinuation. 
Male Patients: 
 Counseling about the requirement for complete abstinence or condom use during sexual 
contact with a pregnant female or a female of childbearing potential and the potential 
risks of fetal exposure to lenalidomide must be conducted at a minimum of every 28 
days.   
 If pregnancy or a positive pregnancy test does occur in the partner of a male study patient 
during study participation, the investigator must be notified immediately. 
Additional precautions 
 Patients should be instructed never to give this medicinal product to another person and 
to return any unused capsules to the study doctor at the end of treatment. 
 Female patients should not donate blood during treatment and for at least 28 days 
following discontinuation of lenalidomide. 
 Male patients should not donate blood, semen or sperm during treatment or for at least 28 
days following discontinuation of lenalidomide. 
 Only enough study drug for 28 days or one cycle of therapy (whichever is shorter) may 
be dispensed with each cycle of therapy.  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
C-1 
APPENDIX C 
 
REVLIMID REMS® PROGRAM 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
C-2 
APPENDIX C 
 
 
 
Revlimid Overview 
Revlimid REMS® for Study Participants 
 
Revlimid REMS® description:  
A program that allows patients enrolled in authorized clinical trials access to free Revlimid® through 
the Revlimid REMS® program.  
Access to the Revlimid REMS® Program:  
1. All physicians must be registered prescribers of Revlimid® in the Revlimid REMS® 
Program All clinical sites must have access to the Revlimid REMS® software to enroll 
patients in the Revlimid REMS® program  
1) Prescriber submits Registration Form via fax or RevAssist® Online (RAO for Revlimid) to 
Celgene Customer Care.  
2) Prescriber is registered within 15 minutes.  
3) Registration confirmation fax is sent to prescriber’s office via fax.  (For RAO, the 
confirmation notification is displayed on the screen immediately)  
4) Starter Kit is sent to prescriber’s office (overnight).  The starter kit will contain the following:  
 
Instructions For Prescribers  
 
Patient Resource Packs  
 
Guide to English and Non-English Materials  
 
Computer software used to generate Patient-Physician Agreement Forms (PPAF)  
 
2. All studies must have an FDA letter of IND exemption or an active IND, active IRB  
approval and Celgene required regulatory documents.  
3. Patients must sign the research specific IRB-approved informed consent and be enrolled in 
a Celgene-approved Medical Affairs clinical trial using Revlimid®  
4. Celgene Customer Care Center must be contacted to confirm if a patient needs to be 
registered by calling 1-888-423-5436. 
5. Patients must also sign the appropriate PPAF form and follow all the procedures of the 
Revlimid REMS® Program   
1) Patient and Prescriber complete the PPAF together. 
2) The form is faxed to Celgene Customer Care or submitted electronically through RAO. 
3) Patient is registered within 15 minutes.  
4) Confirmation fax is sent to prescribing office notifying them that the patient is now 
registered.  For RAO, the confirmation notification is displayed on the screen 
immediately.  
6. Patients and prescribers must take the phone surveys as required by the Revlimid 
REMS® Program (The PPAF generated for the patient determines which phone survey 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
C-3 
questions will be asked.)  An authorization number is provided at the completion of the 
phone survey, the authorization number should be noted on the prescription form.  
Patient Survey requirements: 
 
For men: Do not need to call Celgene the first month but must call monthly starting the 
second month. 
 
For females of non - child bearing potential: Must call for the first month and then call 
every 6 months after. 
 
For females of child bearing potential: Must call for the first month and then every month 
after. 
 
Prescribing Revlimid® in the Revlimid REMS® program  
 
Celgene Medical Affairs Operations will activate the study with Biologics upon receipt of all 
required regulatory documents.   
 
Biologics will not dispense or ship Revlimid® prior to Celgene’s notification of activation.  
 
Prescription information MUST BE entered using the BMT CTN 0702 Revlimid REMS® 
study specific electronic prescription form.  This form can be found on the BMT CTN 
SharePoint website (https://bmtctnsp.net) 
 
An authorization number must be on the prescription form at the time of faxing.  
 
Prescriptions for Revlimid® must be sent to Biologics Clinical Trial Division at the 
following FAX number: 919-256-0794  
 
Only a 28-day supply of Revlimid® may be provided per cycle sent to the actual address 
noted on the Revlimid REMS® electronic prescription form.  
 
Biologics will verify the authorization number and complete the patient counseling.  
 
Protocol compliance and drug return  
 
Patients will be provided with instructions from Biologics with each new dispense on the 
procedures for return of any un-used Revlimid® capsules.  (Patients will be instructed to call 
the 1-800 number to request a prepaid return envelope as per the commercial drug return 
procedures)  
 
Sites may request that patients maintain a diary and/or to bring their bottles in for a pill count 
at each visit in order to review “patient compliance.” However, they are not responsible for 
“drug accountability.”  
 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
C-4 
IMPORTANT INFORMATION ABOUT RevAssist® 
 
 
 
 
 
 
 
How to Fill a REVLIMID® (lenalidomide) Prescription  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
To avoid fetal exposure REVLIMID®(lenalidomide) is only available under a special restricted distribution program 
called Revlimid REMS® 
 
Only prescribers registered with Revlimid REMS® can prescribe REVLIMID®(lenalidomide) 
 
Only Revlimid REMS®contract pharmacies can dispense REVLIMID®(lenalidomide) 
 
In order to receive REVLIMID® (lenalidomide), patients must enroll in Revlimid REMS®and agree to comply with the 
requirements of the Revlimid REMS® program 
 
Information about REVLIM®(lenalidomide) and the Revlimid REMS® program can be obtained by calling the Celgene 
Customer Care Center toll-free at 1-888-423-5436, or at www. REVLIMID.com 
 
1. 
Healthcare provider (HCP) instructs patient to complete patient survey  
2. 
HCP completes survey  
3. 
HCP completes patient prescription form  
4. 
HCP obtains Revlimid REMS®authorization number  
5. 
HCP provides authorization number on patient prescription form  
6. 
HCP faxes form, including prescription  
7. 
HCP advises patient that a representative from a Revlimid REMS® contract pharmacy will contact them  
8. 
Revlimid REMS® contract pharmacy conducts patient education  
9. 
Revlimid REMS® contract pharmacy calls for confirmation number  
10. 
 Revlimid REMS® contract pharmacy ships REVLIMID® to patient with the FDA-approved MEDICATION GUIDE  
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
D-1 
APPENDIX D 
 
LENALIDOMIDE INFORMATION SHEET 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
D-2 
APPENDIX D 
 
LENALIDOMIDE INFORMATION SHEET 
 
This information sheet is current as of June 24, 2009.  A current information sheet will be 
given with your supply of lenalidomide.  FOR PATIENTS ENROLLED IN CLINICAL 
RESEARCH STUDIES 
Please read this Lenalidomide Information Sheet before you start taking lenalidomide and each 
time you get a new supply, since there may be new information.  This Lenalidomide Information 
Sheet does not take the place of an informed consent to participate in clinical research or talking 
to your study doctor or healthcare provider about your medical condition or your treatment.   
What is the most important information I should know about lenalidomide? 
1. Lenalidomide may cause birth defects (deformed babies) or death of an unborn baby.  
Lenalidomide is similar to the medicine thalidomide.  It is known thalidomide causes life-
threatening birth defects.  Lenalidomide has not been tested in pregnant women but may also 
cause birth defects. 
 
If you are a female who is able to become pregnant: 
 Do not take lenalidomide if you are pregnant or plan to become pregnant 
- 
for 28 days before starting lenalidomide 
- 
while taking lenalidomide  
- 
during dose interruptions of lenalidomide  
- 
for 28 days after stopping lenalidomide  
 Stop taking lenalidomide if you become pregnant during lenalidomide treatment 
 Do not breastfeed while taking lenalidomide 
 You must have pregnancy testing done at the following times 
- 
within 10 – 14 days and again 24 hours prior to the first dose of lenalidomide  
- 
weekly for the first 28 days 
- 
every 28 days after the first month or every 14 days if you have irregular 
menstrual periods 
o if you miss your period or have unusual menstrual bleeding 
o 28 days after the last dose of lenalidomide (14 and 28 days after the last dose 
if menstrual periods are irregular) 
 You must practice complete abstinence or use two reliable, separate forms of 
effective birth control at the same time:  
- 
for 28 days before starting lenalidomide 
- 
while taking lenalidomide 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
D-3 
- 
during dose interruptions of lenalidomide  
- 
and for 28 days after stopping lenalidomide 
 Female partners of males taking lenalidomide should be advised to call their own 
physician right away if they get pregnant.  
 Study doctors, healthcare providers and patients should report all cases of pregnancy 
to the National Cancer Institute and the pharmaceutical collaborator, Celgene 
Corporation at 1-888-423-5436. 
 
If you are a male: 
It is not known if lenalidomide passes into semen.  
 Male patients, including those who have had a vasectomy, must use a latex condom 
during sexual intercourse with a pregnant female or a female that can become 
pregnant: 
- 
While you are taking lenalidomide   
- 
for 28 days after you stop taking lenalidomide   
 Male patients should not donate sperm or semen while taking lenalidomide and for 
28 days after stopping lenalidomide.  
 
2. Lenalidomide may cause a reduction in the number of white blood cells and platelets.  
This can lead to increased risk of infection and bleeding.  You may need a blood transfusion 
or certain medicines if your blood counts drop too low.  You will have blood tests done as 
part of the clinical research trial in which you are participating.  This is discussed in the 
informed consent document. 
 
3. Lenalidomide may cause an increased chance for blood clots in the veins and in the 
lungs.  Call your study doctor or get emergency medical care right away if you get the 
following signs or symptoms: 
 shortness of breath 
 chest pain 
 arm or leg swelling 
 
4. Lenalidomide restrictions in sharing lenalidomide and donating blood: 
 
 Do not share lenalidomide with other people 
 Do not give blood while you take lenalidomide and for 28 days after stopping 
lenalidomide  
 You will get no more than a 28-day supply of lenalidomide at one time 
Additional information is provided in the informed consent form and you can ask your study 
doctor for more information. 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
E-1 
APPENDIX E 
 
RESEARCH SAMPLES 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
E-2 
OPTIONAL RESEARCH SPECIMENS 
 
Patients consenting to the optional future research will have blood samples collected for future 
research supporting this protocol.  All research sample aliquots will be given unique bar code 
designations that cannot be linked back to the participant’s name or other identifying 
information.  Laboratory test results, clinical information, etc., associated with the coded samples 
are provided to the Investigator only after completion of the protocol.  Samples sent to 
researchers cannot be linked with any remaining samples at the repository. 
 
Patient samples will be collected both prior to the initiation of long-term follow-up and at disease 
progression.  All research samples will be collected and shipped same-day to the BMT CTN 
Repository for processing and sample aliquot storage. Sample collection and shipping procedures 
are detailed in the BMT CTN 0702 Long-Term Follow-Up Laboratory Sample Guide. 
 
Under current guidelines of the BMT CTN, any request to utilize samples from the biorepository 
is first reviewed by the protocol team.  Upon approval, the request is then reviewed by the BMT 
CTN Biomarkers Committee, which advises the Executive or Steering Committee.  Following 
approval by these boards, samples are then released from the BMT CTN biorepository. 
 
 
 
 
 


BMT CLINICAL TRIALS NETWORK  
 
                                                                 Multiple Myeloma Long-Term Follow-Up Protocol – 0702
 
Version 2.0 dated April 28, 2016 
 
E-3 
 
Type of Sample 
Type of Processing 
Dates Samples Obtained 
Shipping Specifications 
Storage 
Location 
Patient 
Research 
Peripheral 
Blood 
Specimen 
(Serum)  
6 mL peripheral 
blood 
Collect blood sample in 
a Red/Gray Top BD 
SST™ Tube with Silica 
Clot Activator & 
Polymer Gel.  Let 
sample sit upright in 
rack for 30 minutes.  
Centrifuge for 10 
minutes.  Gel barrier 
will form separating the 
serum specimen from 
clot.  Prepare tube for 
transport along with 
other research samples. 
Prior to initiation of long-term follow-
up and at disease progression. 
Serum blood tube will be 
shipped at ambient 
temperature on the day of 
collection, to the BMT 
CTN Research Repository 
by priority overnight FED 
EX delivery for processing 
and final frozen storage of 
serum aliquots.  Guidelines 
for specimen handling and 
shipment to the BMT CTN 
Central Processing 
Laboratory/BMT CTN 
Research Repository are 
detailed in the 0702 Long-
Term Follow-Up 
Laboratory Sample Guide 
BMT CTN 
Research 
Repository 
Patient 
Research 
Peripheral 
Blood 
Specimen 
(Plasma) 
5 mL peripheral 
blood 
Collect blood sample in 
a 5 mL fill, white top 
plastic Greiner 
Vacuette ® PST tube.  
Gently mix sample 
with EDTA by 
inverting the tube 8-
10 times.  Centrifuge 
for 10 minutes.   Gel 
barrier will form 
separating the plasma 
specimen from cells.  
Prepare tube for 
transport along with 
other research samples. 
Prior to initiation of long-term follow-
up and at disease progression.. 
Plasma blood tube will be 
shipped at ambient 
temperature on the day of 
collection, to the BMT 
CTN Research Repository 
by priority overnight FED 
EX delivery for processing 
and final frozen storage of 
serum aliquots.  Guidelines 
for specimen handling and 
shipment to the BMT CTN 
Central Processing 
Laboratory/ Research 
Repository is detailed in the 
0702 Long-TermFollow-Up 
Laboratory Sample Guide 
BMT CTN 
Research 
Repository 


BMT CLINICAL TRIALS NETWORK  
 
                                                                 Multiple Myeloma Long-Term Follow-Up Protocol – 0702
 
Version 2.0 dated April 28, 2016 
 
E-4 
 
Type of Sample 
Type of Processing 
Dates Samples Obtained 
Shipping Specifications 
Storage 
Location 
Patient 
Research 
Peripheral 
Blood 
Specimen 
(PBMC) 
20 mL 
peripheral blood 
Collect peripheral 
blood sample in two 10 
mL fill, green top 
plastic BD Vacutainer® 
tube, containing 
Sodium-Heparin 
anticoagulant.  Gently 
mix sample by 
inversion 8-10 times to 
mix sample well with 
heparin anticoagulant. 
 
No additional sample 
processing is required. 
Prior to initiation of long-term follow-
up therapy and at disease progression. 
Peripheral blood tubes will 
be shipped at ambient 
temperature on the day of 
collection, to the BMT 
CTN Research Repository 
by priority overnight FED 
EX delivery for processing 
and final frozen storage of 
isolated viable PBMC 
aliquots.  Guidelines for 
specimen handling and 
shipment to the BMT CTN 
Central Processing 
Laboratory/BMT CTN 
Research Repository is 
detailed in the 0702 Long-
Term Follow-Up 
Laboratory Sample Guide 
BMT CTN 
Research 
Repository 
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
 
 
F-1 
APPENDIX F 
 
ADVERSE EVENTS 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
 
 
F-2 
APPENDIX F 
 
ADVERSE EVENTS 
 
 
Selected expected serious AEs (Table F-1) and grade 3-5 unexpected AEs according to the 
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 
4.0 require expedited reporting with an Individual Case Safety Report (ICSR) through 
completion of the Adverse Event Forms.  Additionally, selected AEs of interest (Table F-2) will 
require expedited reporting through an ICSR, if they fulfill serious criteria and occur after the 
administration of lenalidomide. Refer to Chapter 4 regarding reporting of SPMs and other 
reporting requirements.  
 
 
 
TABLE F-1: SERIOUS ADVERSE EVENTS THAT REQUIRE EXPEDITED 
REPORTING BY INDIVIDUAL CASE SAFETY REPORTS (ICSR)1  
 
Adverse Event 
Seriousness or 
Capture 
Method¹ 
Collection Form 
ALLERGY/IMMUNOLOGY  
 
 
Anaphylactic reaction  
SAE 
ICSR  
CARDIAC 
  
  
Asystole 
SAE 
ICSR 
Atrial Ventricular Block 
SAE 
ICSR 
Congestive Heart Failure 
SAE 
ICSR 
Myocardial Infarction 
SAE 
ICSR 
Pericarditis 
SAE 
ICSR 
Pericardial disease 
SAE 
ICSR 
Pericardial 
effusion 
(including 
tamponade) 
SAE 
ICSR 
Prolongation of QTc interval 
SAE 
ICSR 
Sinus Bradycardia  
SAE 
ICSR 
Supraventricular Tachycardia 
SAE 
ICSR 
Ventricular Tachycardia 
SAE 
ICSR 
Pulmonary hypertension 
SAE 
ICSR 
COAGULATION 
 
 
Disseminate intravascular coagulation 
(DIC) 
SAE 
ICSR 
DERMATOLOGY 
 
 
Erythema 
multiforme 
(toxic 
epidermal necrolysis) 
SAE 
ICSR 
Sweet's Syndrome (acute neutrophilic 
dermatosis) 
SAE 
ICSR 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
 
 
F-3 
Adverse Event 
Seriousness or 
Capture 
Method¹ 
Collection Form 
Pyoderma gandrenosum 
SAE 
ICSR 
Vasculitis 
SAE 
ICSR 
ENDOCRINE 
 
 
Hyperthyroidism 
SAE 
ICSR 
GASTROINTESTINAL 
 
 
Ileus 
(functional 
obstruction 
of 
bowel, i.e., neuroconstipation) 
SAE 
ICSR 
GI Perforation 
SAE 
ICSR 
Diverticulitis  
SAE  
ICSR  
Ischemic bowel  
SAE  
ICSR  
HEMORRHAGE  
 
 
Central Nervous system 
SAE 
ICSR 
HEPATOBILIARY/PANCREAS 
 
 
Liver dysfunction/failure (Clinical - 
CTCAE) 
SAE 
ICSR 
Pancreatitis 
SAE 
ICSR 
NEUROLOGY 
 
 
Neurology – Peripheral neuropathy  
SAE 
ICSR  
Neuropathy: Motor  
SAE 
ICSR  
Neuropathy: Sensory  
SAE 
ICSR  
Syncope (fainting)2 
SAE 
ICSR  
CNS ischemia 
SAE 
ICSR  
Coma 
SAE 
ICSR  
Cranial palsy  
SAE 
ICSR  
Seizure  
SAE 
ICSR  
Spinal cord compression  
SAE 
ICSR  
Brain Edema 
SAE 
ICSR 
Encephalopathy  
SAE 
ICSR 
Leukoencephalopathy syndrome 
including reversible posterior 
leukoencephalopathy syndrome 
[RPLS]) or (Leukoencephalopathy  
radiographic findings) 
SAE 
ICSR 
PULMONARY/UPPER 
RESPIRATORY 
 
 
Acute Respiratory Distress Syndrome 
SAE 
ICSR 
Alveolar Hemorrhage 
SAE 
ICSR 
Pleural effusion (non-malignant) 
SAE 
ICSR 
Pneumonitis/Pulmonary 
Infiltrates 
(absence of infection) 
SAE 
ICSR 
Pulmonary Hypertension 
SAE 
ICSR 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
 
 
F-4 
Adverse Event 
Seriousness or 
Capture 
Method¹ 
Collection Form 
RENAL/GENITOURINARY 
 
 
Renal failure 
SAE 
ICSR 
SYNDROMES 
 
 
Tumor flare 
SAE 
ICSR 
Tumor lysis syndrome 
SAE 
ICSR 
VASCULAR 
 
 
Acute vascular leak syndrome  
SAE  
ICSR  
DEATH  
 
 
Sudden death 
SAE  
ICSR  
OTHER 
 
 
Second malignancies 
SAE 
ICSR 
1 Serious Adverse events are defined by the 21 CFR (312.32a): AE that results in death, requires hospitalization, 
persistent or significant disability or incapacity, congenital anomaly, that is life threatening or considered as 
medically important.  
 
 
TABLE F-2: EXPECTED ADVERSE EVENTS OF INTEREST THAT WILL REQUIRE 
EXPEDITED REPORTING IF THEY MEET SERIOUS ADVERSE EVENT CRITERIA 
AND OCCUR AFTER THE INITIATION OF LENALIDOMIDE AND THROUGH 28 
DAYS AFTER THE DISCONTINUATION OF LENALIDOMIDE 
 
Adverse Event 
Seriousness or 
Capture Method¹ 
Collection 
Form 
AUDITORY/EAR 
 
 
Hearing loss 
SAE 
ICSR 
CARDIAC 
  
  
Atrial fibrillation  
SAE 
ICSR 
Atrial flutter 
SAE 
ICSR 
COAGULATION 
 
 
Deep vein thrombosis 
SAE 
ICSR 
Pulmonary emboli3 
SAE 
ICSR 
HEMORRHAGE  
 
 
Hemorrhage, Gastrointestinal 
SAE 
ICSR 
Hemorrhage, Pulmonary  
SAE  
ICSR  
METABOLIC/LABORATORY 
 
 
Elevation of ALT ≥ 2.5x ULN 
SAE 
ICSR 
Elevation of AST ≥2.5x ULN 
SAE 
ICSR 
Elevation of Bilirubin ≥ 3x ULN 
SAE 
ICSR 
MUSCULOSCELETAL/SOFT TISSUE  
 
 
Muscular weakness  
SAE  
ICSR  
NEUROLOGY 
 
 
Neurology – Peripheral neuropathy  
SAE 
ICSR  


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
 
 
F-5 
Adverse Event 
Seriousness or 
Capture Method¹ 
Collection 
Form 
Neuropathy: Motor  
SAE 
ICSR  
Neuropathy: Sensory  
SAE 
ICSR  
Syncope (fainting) 
SAE 
ICSR  
OCULAR/VISUAL  
 
 
Vision – Blurred vision  
SAE 
ICSR 
PAIN  
 
 
Pain – Neuralgia  
SAE  
ICSR  
INFECTION 
 
 
Febrile neutropenia 
SAE  
ICSR  
DEATH  
 
 
Sudden death 
SAE  
ICSR  
OTHER 
 
 
Second malignancies 
SAE 
ICSR 
1 Serious Adverse events as defined by the 21 CFR (312.32a): AE that results in death, requires 
hospitalization, persistent or significant disability or incapacity, congenital anomaly, that is life 
threatening or considered as medically important.  
 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
 
 
G-1 
 
APPENDIX G 
 
REFERENCES 
 


BMT CLINICAL TRIALS NETWORK 
Multiple Myeloma Long-Term Follow-Up Protocol – 0702 
Version 2.0 dated April 28, 2016 
 
 
G-2 
APPENDIX G 
 
REFERENCES 
 
                                                                                                                                   
1 Boccadoro M, Cavallo F, Gay FM, Raimondo FD, Nagler A, Montefusco V et al. 
Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous 
transplantation (MEL200) plus lenalidomide maintenance or no maintenance in newly diagnosed 
multiple myeloma (MM) patients. Journal of Clinical Oncology 2013; 31(suppl:8509a). 
2 McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG et al. 
Lenalidomide after stem-cell transplantation for multiple myeloma. The New England journal of 
medicine 2012; 366(19): 1770-81. 
3 Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T et al. Lenalidomide 
maintenance after stem-cell transplantation for multiple myeloma. The New England journal of 
medicine 2012; 366(19): 1782-91. 
4 McCarthy P, Owzar K, Hofmeister CC, Richardson PG, Hassoun H, Stadtmauer EA et al. 
Analysis of Overall Survival (OS) in the Context of Cross-Over from Placebo to Lenalidomide 
and the Incidence of Second Primary Malignancies (SPM) in the Phase III Study of 
Lenalidomide Versus Placebo Maintenance Therapy Following Autologous Stem Cell 
Transplant (ASCT) for Multiple Myeloma (MM) CALGB (Alliance) ECOG BMTCTN. Clinical 
Lymphoma Myeloma and Leukemia 2013; 13(Supplement 1): S28,S15-5. 
5 Singh PP, Kumar S, LaPlant BR, Gertz MA, Dispenzieri A, Leif Bergsagel P et al. 
Lenalidomide Maintenance Therapy In Multiple Myeloma: A Meta-Analysis Of Randomized 
Trials. Blood 2013; 407a. 
6 Palumbo A, Gay F, Spencer A, Raimondo FD, Zdenek A, Larocca A et al. A phase III study of 
ASCT 
vs 
cyclophosphamide-lenalidomide-dexamethasone 
and 
lenalidomide-prednisone 
maintenance vs lenalidomide alone in newly diagnosed myeloma patients. Blood 2013; 763a. 
7 Attal M, Lauwers-Cances V, Marit G, Caillot D, Facon T, Hulin C et al. Lenalidomide 
Maintenance After Stem-Cell Transplantation For Multiple Myeloma: Follow-Up Analysis Of 
The IFM 2005-02 Trial. Blood 2013; 406a. 
8 Palumbo A, Bringhen S, Rajkumar SV, Lupparelli G, Usmani S, Waage A et al. Second 
primary malignancies (SPM) in newly diagnosed myeloma (MM) patients treated with 
lenalidomide (Len): Meta-analysis of 6,383 individual patient data (IPD). Journal of clinical 
oncology : official journal of the American Society of Clinical Oncology 2013; 31(suppl; abstr 
8517). 
9 Mailankody S, Pfeiffer RM, Kristinsson SY, Korde N, Bjorkholm M, Goldin LR et al. Risk of 
acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its 
precursor disease (MGUS). Blood 2011; 118(15): 4086-92. 

SAP_001.pdf: 
Version 1.0 
1 
May 15, 2019 
Client Confidential 
 
 
 
 
 
 
 
BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
 
 
BMT CTN 07LT:  Continued, Long-Term Follow-Up and Lenalidomide Maintenance 
Therapy for Patients Who Have Enrolled on BMT CTN 0702 
 
 
 
 
 
 
Version 1.0   Date: May 15, 2019       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prepared by: ____________________________________________  Date: _________________ 
                                                                         Protocol Statistician 
 
 
(DDMMMYYYY) 
 
 
 
 
 
Reviewed by: ____________________________________________ Date: _________________ 
                                                                         DCC Statistician Leadership 
 
(DDMMMYYYY) 
 
 
 
 
 
Approved by: ____________________________________________ Date: _________________ 
                                                                        Protocol Chair/Protocol Officer 
 
(DDMMMYYYY) 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
2 
May 15, 2019 
Client Confidential 
Table of Contents 
1. 
General Review of Study Design and Process ................................................................................ 4 
1.1 
Study Objectives ........................................................................................................................................ 4 
1.1.1 
Primary Objective .................................................................................................................................. 4 
1.1.2 
Secondary Objectives........................................................................................................................... 4 
1.2 
Study Design and Procedures ................................................................................................................. 4 
1.2.1 
Primary Hypothesis and Primary Endpoint ....................................................................................... 4 
1.2.2 
Accrual Plan and Randomization ........................................................................................................ 5 
1.2.3 
Duration of Follow-up ........................................................................................................................... 5 
1.3 
Inclusion and Exclusion Criteria .............................................................................................................. 6 
1.4 
Treatment Description .............................................................................................................................. 6 
1.5 
Response Variables and Data Collection Time Points ........................................................................ 6 
2. 
General Statistical Considerations ................................................................................................... 7 
2.1 
Sample Size and Power Calculations .................................................................................................... 7 
2.2 
Handling Missing Data .............................................................................................................................. 7 
2.3 
Multiple Comparisons ............................................................................................................................... 8 
2.4 
Interim Analyses and Stopping Guidelines ............................................................................................ 8 
2.5 
Timing of Analysis ..................................................................................................................................... 8 
2.6 
Software ...................................................................................................................................................... 8 
2.7 
Analysis Populations ................................................................................................................................. 8 
2.7.1 
Primary Analysis Population ................................................................................................................ 9 
2.7.2 
Safety Analysis and Analysis Population ........................................................................................... 9 
2.8 
General Analysis Guidelines .................................................................................................................. 10 
2.8.1 
Changes to the planned analyses .................................................................................................... 10 
3. 
Participant Characteristics and Compliance .................................................................................. 11 
3.1 
Demographics and Baseline Characteristics ...................................................................................... 11 
3.2 
Participant Compliance ........................................................................................................................... 12 
4. 
Analysis Plan ..................................................................................................................................... 12 
4.1 
Analysis of the Primary Endpoint .......................................................................................................... 12 
4.2 
Analysis of the Secondary Endpoints ................................................................................................... 13 
4.3 
Supplemental Analyses .......................................................................................................................... 14 
5. 
Template of Proposed Table/Figure/Listing (TFL) Shells ............................................................. 15 
6. 
References ......................................................................................................................................... 15 
Appendix .................................................................................................................................................... 16 
Exhibit 07LT-1:  Participant Disposition and Follow-Up ............................................................................. 16 
Exhibit 07LT-2A:  Participant Demographics and Baseline Characteristics ............................................ 16 
Exhibit 07LT-2B:  Participant Demographics and Baseline Characteristics (07LT-enrolled 
participants) ....................................................................................................................................................... 19 
Exhibit 07LT-3: Progression-free Survival (Primary Analysis of PFS) ..................................................... 21 
Exhibit 07LT-4A: Multivariate Cox Regression Analysis of Progression-free Survival (Secondary 
Analysis of PFS) – 0702 baseline factors ..................................................................................................... 23 
Exhibit 07LT-4B: Multivariate Cox Regression Analysis of Progression-free Survival from Initiation of 
Lenalidomide (Secondary Analysis of PFS) ................................................................................................. 24 
Exhibit 07LT-5:  Overall Survival .................................................................................................................... 25 
Exhibit 07LT-6:  Event-Free Survival ............................................................................................................ 26 
Exhibit 07LT-7:  Cumulative Incidence of First SPM .................................................................................. 27 
Exhibit 07LT-8:  SPM Histologic Type........................................................................................................... 28 
Exhibit 07LT-9A:  Unexpected Grades 3-5 Adverse Events in Participants Initiating Lenalidomide on 
BMT CTN 07LT1 ............................................................................................................................................... 29 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
3 
May 15, 2019 
Client Confidential 
Exhibit 07LT-9B:  Unexpected Grades 3-5 Adverse Events in Participants Enrolled on BMT CTN 
07LT Who Did Not Initiate Lenalidomide ...................................................................................................... 29 
Exhibit 07LT-10:  Health Quality of Life:  FACT-BMT for BMT CTN 07LT English/Spanish-Speaking 
Participants........................................................................................................................................................ 30 
Exhibit 07LT-11:  Health Quality of Life:  SF-36 for BMT CTN 07LT English/Spanish-Speaking 
Participants........................................................................................................................................................ 31 
Supplemental Exhibit 07LT-1:  Enrollment ................................................................................................... 32 
Supplemental Exhibit 07LT-2:  Significant Protocol Deviations ................................................................ 32 
Supplemental Exhibit 07LT-3:  Permanent Discontinuation of Lenalidomide ......................................... 32 
Supplemental Exhibit 07LT-4:  Primary Cause of Death ............................................................................ 32 
Supplemental Exhibit 07LT-5A: Multivariate Cox Regression Analysis of Overall Survival  – 0702 
baseline factors ................................................................................................................................................ 34 
Supplemental Exhibit 07LT-5B: Multivariate Cox Regression Analysis of Overall Survival from 
Initiation of Lenalidomide ................................................................................................................................ 35 
Supplemental Exhibit 07LT-6A: Multivariate Cox Regression Analysis of Event-free Survival  – 0702 
baseline factors ................................................................................................................................................ 36 
Supplemental Exhibit 07LT-6B: Cause-specific Multivariate Cox Regression Analysis of the 
Components of Event-free Survival ............................................................................................................... 37 
Supplemental Exhibit 07LT-6C: Multivariate Cox Regression Analysis of Event-free Survival from 
Initiation of Lenalidomide ................................................................................................................................ 39 
Supplemental Exhibit 07LT-6:  Landmark Analysis of PFS ....................................................................... 40 
Supplemental Exhibit 07LT-7:  Landmark Analysis of OS ......................................................................... 41 
Supplemental Exhibit 07LT-8:  Landmark Analysis of EFS ....................................................................... 42 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
4 
May 15, 2019 
Client Confidential 
Protocol  
BMT CTN #07LT is titled “Continued, Long-Term Follow-Up and Lenalidomide Maintenance 
Therapy for Patients Who Have Enrolled on BMT CTN 0702.” 
1. General Review of Study Design and Process 
1.1 Study Objectives  
BMT CTN protocol 07LT is a follow-up study to BMT CTN 0702, which was a Phase 3, multi-
center trial designed to compare progression-free survival and additional outcomes between 
patients randomized to one of three treatment arms: 
• 
Autologous transplant followed by a second autologous transplant then maintenance therapy 
(Auto/Auto) 
• 
Autologous transplant followed by consolidation therapy with lenalidomide (Revlimid), 
bortezomib (Velcade) and dexamethasone (RVD) then followed by maintenance therapy 
(Auto/RVD) 
• 
A single autologous transplant followed by maintenance therapy (Auto/Maint)  
1.1.1 
Primary Objective 
The primary objective of the study is to compare progression-free survival (PFS) as a time to 
event analysis between the three randomized treatment arms from the BMT CTN 0702 protocol 
as a pairwise comparison.  The analysis will be conducted once all alive patients have been 
enrolled for 5 years post randomization on the BMT CNT 0702 protocol. 
1.1.2 
Secondary Objectives 
The secondary objectives of the study are:   
• 
Cumulative incidence of second primary malignancies (SPM) 
• 
Probability of overall survival (OS) 
• 
Probability of event-free survival (EFS)  
• 
Health Quality of Life (QOL) 
1.2 Study Design and Procedures  
1.2.1 
Primary Hypothesis and Primary Endpoint 
The primary hypothesis of this study and the original BMT CTN 0702 study is that the use of 
novel anti-myeloma agents will improve long-term PFS after high-dose melphalan followed by 
autologous hematopoietic cell transplantation (HCT) as compared to a second autologous 
transplantation.  
To correspond with the primary objective to compare progression-free survival (PFS) as a time 
to event analysis between the three randomized treatment arms from the BMT CTN 0702 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
5 
May 15, 2019 
Client Confidential 
protocol as a pairwise comparison, the main null and alternative hypotheses of the study are 
that the different treatment arms will have different rates of long-term PFS: 
H01:  PFSAuto/Auto = PFSAuto/RVD  
HA1:  PFSAuto/Auto ≠ PFSAuto/RVD  
 
H01:  PFSAuto/Auto = PFSAuto/Maint 
HA1:  PFSAuto/Auto ≠ PFSAuto/Maint 
 
H01:  PFSAuto/RVD = PFSAuto/ Maint 
HA1:  PFSAuto/RVD ≠ PFSAuto/ Maint 
 
These three hypotheses will each be tested with a two-sided stratified log rank test at the 
α=0.05 / 3 level using a Bonferroni correction to control the overall type I error rate.  
The primary endpoint is PFS.  Patients are considered a failure of the primary endpoint if they 
die or suffer from disease progression.  The time to this event is the time from randomization on 
the BMT CTN 0702 protocol until progression, death, or initiation of non-protocol anti-myeloma 
therapy, or until last myeloma follow-up through December 2018 if there is no event.   
1.2.2 
Accrual Plan and Randomization  
Participants were eligible to accrue on to BMT CTN 07LT as soon as they finished the earlier of 
3 years of maintenance therapy on BMT CTN 0702 or four years of follow up on BMT CTN 
0702.  The protocol was approved after some participants had already finished 3 years of 
maintenance on BMT CTN 0702 so they were eligible to enroll when the protocol was activated, 
and there may have been a period when the participant was on commercially-available 
lenalidomide or other treatment.  The protocol was activated in March 2015, and accrual was 
targeted through the beginning of 2018 to allow a window of time after the last person enrolled 
on BMT CTN 0702 would be eligible for BMT CTN 07LT. 
Randomization occurred on the parent BMT CTN 0702 trial, which had a 1:1:1 randomization 
ratio with permuted blocks.  Randomization on the parent trial was also stratified by patient risk 
and center.  There was no additional randomization on BMT CTN 07LT.     
1.2.3 
Duration of Follow-up 
Participants will be followed for until death, progression, withdrawal from study, or the end of 
2018.  The randomization date on the BMT CTN 0702 trial will be the start time for most of the 
analyses, except for the secondary analysis of PFS which starts at initiation of maintenance 
therapy and includes discontinuation of lenalidomide as a time-varying covariate.   


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
6 
May 15, 2019 
Client Confidential 
1.3 Inclusion and Exclusion Criteria 
As a follow-on study, the 07LT protocol is open for enrollment of participants randomized on 
0702 who have completed 3 years of maintenance therapy on 0702 or 4 years of follow-up on 
0702, have not died or had clinical progression, and have signed the 07LT informed consent 
form.   
Participants who have completed 3 years of maintenance therapy on BMT CTN 0702 are 
eligible for continued maintenance therapy on 07LT if they are willing and able to comply with 
the requirements of the Revlimid REMS® program, and have signed an informed consent.  
Participants who are pregnant, breastfeeding, unwilling to take DVT prophylaxis, had 
thromboembolic events while on full anticoagulation during lenalidomide use, or had secondary 
primary malignancies after initiation of lenalidomide on BMT CTN 0702 are ineligible for 
initiating BMT CTN 07LT maintenance therapy. 
1.4 Treatment Description 
Lenalidomide will be administered initially at the patient’s last documented dose prior to 
discontinuation of BMT CTN 0702 lenalidomide maintenance therapy.  Cycle duration is 28 
days.  Patients will continue lenalidomide until disease progression, or discontinuation due to 
toxicity, death, or withdrawal from the study.  Patients who discontinue lenalidomide due to any 
reason other than death or withdrawal of consent will continue to be followed. 
In the presence of lenalidomide-related non-hematologic toxicities, the study drug will be 
withheld until the toxicity resolves, then restarted at a reduced dose as described in the 
protocol.  Dose modifications for hematologic toxicities are described in the protocol.  If the 
patient is on DVT/PE prophylaxis or treatment, discontinuation or modifications of 
anticoagulation should be considered by the treating physician. 
If a dose reduction has occurred and ANC ≥ 1000/µL and platelet count is ≥ 75,000/µL, the 
study drug dose may be re-escalated as shown in the protocol, one step per cycle to a 
maximum of 15 mg daily. 
1.5 Response Variables and Data Collection Time Points 
Participants are evaluated for the primary endpoint of progression-free survival (death, disease 
progression, initiation of non-protocol myeloma therapy) and for the following secondary 
endpoints: 
• 
Overall survival 
• 
Event-free survival (no progression, death, or SPM) 
• 
Incidence of SPM 
• 
Unexpected grades 3-5 adverse events 
• 
Health quality of life 
 
Patients have visits every six months until death, progression, withdrawal of consent, or the end 
of the study. 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
7 
May 15, 2019 
Client Confidential 
Participants who receive long-term lenalidomide maintenance therapy are required to report 
unexpected grades 3-5 adverse events until the patient progresses or until 28 days from their 
last dose of lenalidomide.  These require expedited reporting within 24 hours – 3 business days 
of the site’s knowledge of the event, depending on the type of event.  The protocol specifies 
additional rules for reporting requirements of AEs after an SPM depending on the treatment 
received for the SPM, and for reporting serious expected adverse events and selected AEs of 
interest.   
Participants who do not receive lenalidomide maintenance or have permanently discontinued 
lenalidomide maintenance not required to report adverse events except for SPMs.   
For all participants on 07LT, SPMs must be reported within three business days of knowledge of 
the event and deaths must be reported within 24 hours of knowledge of the participant’s death.  
Non-melanoma skin cancers are not required to be reported. 
Health quality of life surveys are completed at visits corresponding to 5, 6, and 7 years from 
original randomization on 0702. 
2. General Statistical Considerations 
Unless stated otherwise: 
• 
For continuous outcomes, descriptive statistics will include the number of subjects (n), 
mean, standard deviation, median, minimum and maximum.  
• 
For categorical outcomes, frequencies and percentages will be displayed for categorical 
data.  
• 
All statistical comparisons made using 2-sided pairwise tests will be compared to an 
α=0.05/3 significance level. 
2.1 Sample Size and Power Calculations 
The projected sample size for this study was determined from the available sample size of the 
parent study, BMT CTN 0702, and the rate of progression-free survival on 0702.  Seven 
hundred and fifty-eight participants enrolled on 0702, and it was anticipated that the sample size 
on 07LT could range from 417 to 569 for 3-year PFS ranging from 55% to 75%. 
2.2 Handling Missing Data 
All participants who were randomized on the parent protocol BMT CTN 0702 will be included in 
the analysis for BMT CTN 07LT.  Data for patients not enrolled on the long-term follow-up 
protocol will be included with two parts combined: 1) 0702 data until their end of participation on 
the BMT CTN 0702 protocol; 2) follow up data provided through the Center for International 
Blood and Marrow Transplant Research (CIBMTR).   
For time-to-event variables, participants who have not had an event or competing risk event will 
be censored at the time data for the endpoint is no longer available.  For Quality of Life 
analyses, participants will be excluded at a particular time point if they do not complete the 
surveys within a +/- 90-day window for the particular time point in the analysis. 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
8 
May 15, 2019 
Client Confidential 
The time of progression that was adjudicated on BMT CTN 0702 by the 0702 Endpoint Review 
Committee (ERC) will be used for participants who progressed on BMT CTN 0702.  There is no 
adjudication of progression on BMT CTN 07LT, so progression will be determined by site-
reported responses. 
For the primary endpoint of PFS and the secondary endpoints of EFS, overall survival and 
cumulative incidence of SPM, and for tabulation of cause of death, data from the BMT CTN 
0702, BMT CTN 07LT, and from the CIBMTR will be used.     
2.3 Multiple Comparisons 
All tests for treatment group differences that compare 2 groups at a time will be compared at the 
0.05/3 significance level to adjust for the pairwise testing.  Kaplan Meier estimates, cumulative 
incidence estimates, and hazard ratios for treatment groups will be presented with 98.3% 
confidence limits. 
2.4 Interim Analyses and Stopping Guidelines 
There will be no interim analyses on BMT CTN 07LT and no adjustments for prior testing of the 
endpoints on the 0702 study. 
There are no official stopping guidelines for BMT CTN 07LT.  The BMT CTN DSMB monitors 
the safety and efficacy data on an approximate 6-month basis, and makes recommendations to 
the NHLBI regarding release of data to investigators and the general public. 
2.5 Timing of Analysis 
Follow-up for the BMT CNT 07LT protocol continues until the end of 2018; this is approximately 
when all living patients have been enrolled for 5-years post randomization on the BMT CTN 
0702 protocol.  The BMT CTN 07LT analysis will begin upon the completion of all data entry and 
cleaning including retrieval of CIBMTR data after the follow-up is finished. 
2.6 Software 
All analyses will be conducted using SAS version 9.4 or higher, or R version 3.3.2 or higher.  
2.7 Analysis Populations  
The following analysis populations will be used: 
0702-enrolled 
Will include all patients randomized on protocol BMT CTN 0702.  Data from the BMT CTN 
0702 protocol, BMT CTN 07LT protocol, and CIBMTR will be used 
07LT-enrolled 
Will include patients enrolled on protocol BMT CTN 07LT only.  Data will be limited to data 
provided during 07LT follow-up.  This population will be used for tabulation of unexpected 
grades 3-5 events, analysis of health quality of life, and study protocol deviations. 
 
Some of the analyses will use a subset of these populations.  These are described in the 
section for each endpoint. 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
9 
May 15, 2019 
Client Confidential 
2.7.1 
Primary Analysis Population 
0702-enrolled population 
The primary analysis population, 0702-enrolled population, will include all participants 
randomized on the parent trial, BMT CTN 0702, in the arm to which they were assigned (intent-
to-treat), regardless of treatment received.  This population will be used for the analysis of the 
primary endpoint, PFS, as well as for the secondary endpoints of overall survival, EFS, and 
SPM.  This population will be used to tabulate reasons for permanent withdrawal from 
lenlidomide maintenance therapy. 
07LT-enrolled population 
The 07LT-enrolled population will include all participants enrolled on BMT CTN 07LT.  This 
population will be used for the analysis of adverse events and of health quality of life, and for 
descriptions of study accrual, and study protocol deviations. 
No adjustments for post-randomization review of eligibility. 
For analyses with the 0702-enrolled population, all participants for the BMT CTN 0702 trial will 
be included in the BMT CTN 07LT analysis, even those adjudicated to be ineligible by the BMT 
CTN 0702 Endpoint Review Committee or determined to be ineligible after data review post 
enrollment.  Similarly, analyses limited to the 07LT population will include all participants 
enrolled on BMT CTN 07LT, including any participants determined post enrollment to be 
ineligible for BMT CTN 07LT. 
2.7.2 
Safety Analysis and Analysis Population 
The 07LT-enrolled population is comprised of two groups of participants – those who are taking 
long-term lenalidomide maintenance therapy, and those who have never started maintenance 
therapy.  Safety data is collected differently for participants taking lenalidomide and or patients 
who never stated lenalidomide on 07LT or discontinued it. 
For participants enrolled on BMT CTN 07LT who are taking long-term lenalidomide 
maintenance therapy, unexpected, grades 3-5 adverse events will be reported through the 
expedited AE reporting system in AdvantageEDC using NCI’s Common Terminology Criteria for 
Adverse Events (CTCAE) Version 4.0.  Unexpected, grade 4-5 AEs must be reported within 24 
hours of knowledge of the event.  Unexpected, grade 3 AEs must be reported within three 
business days of knowledge of the event.  Selected expected serious AEs (protocol Appendix F 
- Table F-1) require expedited reporting.  Additionally, selected AEs of interest (protocol 
Appendix F - Table F-2) will require expedited reporting, if they fulfill serious criteria according to 
the Code of Federal Regulations Title 21 (21 CFR 312.32) and occur after the administration of 
lenalidomide and up to 30 days after the permanent discontinuation of lenalidomide.  See 
protocol Appendix F for additional details on expedited reporting. 
For participants enrolled on BMT CTN 07LT follow-up only, or for BMT CTN 07LT participants 
who have permanently discontinued lenalidomide maintenance for more than 28-30 days, or for 
participants who have met the protocol defined definition of progression, reporting of 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
10 
May 15, 2019 
Client Confidential 
unexpected grades 3-5 adverse events, selected serious AEs, or selected AEs of interest will 
not require reporting with the exception of second primary malignancies. 
Deaths are required to be reported for all patients enrolled on 07LT within 24 hours of the site’s 
knowledge of the patient’s death.   
Unexpected grades 3-5 adverse events will be tabulated and compared across treatment arms 
for the BMT CTN 07LT population. Summaries by type and severity of adverse events will be 
provided. Safety data will be summarized using Medical Dictionary for Regulatory Activities 
(MedDRA) Coding Version 20.0 or above. 
Secondary primary malignancies (SPMs) in the BMT CTN 0702 population will be analyzed as a 
secondary outcome using cumulative incidence curves and Gray’s test for treatment group 
comparisons.  SPMs will also be described by treatment group and histologic type. 
Primary causes of deaths will be tabulated, and survival will be analyzed as a secondary 
outcome using Kaplan Meier curves and stratified log rank tests. 
2.8 General Analysis Guidelines 
There are no planned sub-group analyses or sensitivity analyses. 
Any changes to the planned analyses or any ad hoc analyses will be documented and clarified 
in each analysis report (through the time of the report) and may be documented in updated 
versions of the SAP.  Ad hoc analyses will be included as supplemental exhibits and noted to be 
analyses that are not part of the pre-planned analyses. 
There are no pre-defined ancillary studies for the BMT CTN 07LT protocol.  Optional research 
samples for future analysis are being collected for those enrolled in 07LT.  Any analyses with 
these samples will be described separately and will be conducted at time points not affecting the 
analyses described in this SAP. 
2.8.1 
Changes to the planned analyses 
Clarifications from the BMT CTN 07LT protocol 
The protocol specified that for the primary endpoint of PFS, deaths will be counted as failures 
no matter when they occur.  This is clarified to note that deaths that occur prior to the end of 
2018 will be counted as failures and deaths that occur after progression will use time to 
progression rather than time to death for the primary analysis.  Deaths through the end of 
follow-up in December 2018 will be counted, but deaths that occur between the end of BMT 
CTN 07LT in December 2018 and the database closure for the analysis will not be counted. 
The protocol specified that for some of the secondary outcomes, the analysis would be 
completed once all alive patients have been followed for 5-years post randomization on the 
BMT CTN 0702 protocol.  This is clarified to note that the secondary outcomes will be analyzed 
at the same time as the primary analysis -- once all alive patients have been followed for 5-
years post randomization on the BMT CTN 0702 protocol or the end of 2018. 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
11 
May 15, 2019 
Client Confidential 
The protocol specified that a Cox model would be used to analyze PFS data, but did not require 
that treatment group and risk strata be included in the model.  These factors will be included in 
the models. 
Supplemental analyses of EFS and OS have been added to incorporate a Cox model analysis 
adjusting for baseline risk factors for the 0702-enrolled population and to incorporate a Cox 
model investigating EFS, baseline risk factors, and discontinuation of lenalidomide among the 
population that initiated maintenance therapy.  Additional cause-specific analyses will show the 
Cox model results for each component of EFS, with censoring at the time of the other 
components. 
Additional supplemental landmark analyses of PFS, OS, and EFS have been added to explore 
these outcomes between those on long term lenalidomide and those not on long term 
lenalidomide. 
3. Participant Characteristics and Compliance  
3.1 Demographics and Baseline Characteristics  
Descriptive statistics for demographics and baseline characteristics will be presented by 
randomized treatment group for participants enrolled on BMT CTN 0702 and separately for 
participants enrolled on BMT CTN 07LT.   
Testing of treatment group differences among all participants enrolled on BMT CTN 0702 will be 
conducted to determine which characteristics to include the in the Cox regression model for 
PFS.  Factors with a significance level <0.1 based on a chi-square test of differences using all 
three treatment arms (not pairwise tested) will be included in the Cox regression model.  Factors 
to be summarized include, but are not limited to, those listed below.  Factors to be considered 
for inclusion in the Cox regression model and tested for treatment group differences are limited 
to those marked in the second column below. 
For the factor of ERC-adjudicated disease response at study entry, 2 categorizations will be 
considered:  CR or greater vs less than CR, and VGPR or greater vs less than VGPR. 
 
Factors for descriptive summary statistics 
 
Factors to consider for inclusion in 
Cox model 
Baseline data from 0702 randomization 
 
Baseline disease risk strata (as randomized) 
Will be included even if no difference 
among treatment groups 
Baseline disease risk strata (updated post randomization) 
Will not be included 
Gender 
Will be considered for inclusion 
Ethnicity 
 Will be considered for inclusion 
Race 
 Will be considered for inclusion 
Karnofsky performance score 
 Will be considered for inclusion 
ERC-adjudicated disease response at BMT CTN 0702 study 
entry 
 Will be considered for inclusion 
Age at 0702 enrollment 
 Will be considered for inclusion 
Pre-0702 initial therapy for myeloma (doublets/triplets/other) 
Will be considered for inclusion 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
12 
May 15, 2019 
Client Confidential 
Factors for descriptive summary statistics 
 
Factors to consider for inclusion in 
Cox model 
Baseline data for those enrolled on 07LT 
 
Baseline disease risk strata (as randomized) 
Will not be included 
Gender 
Will not be included 
Ethnicity 
Will not be included 
Race 
Will not be included 
Karnofsky performance score 
Will not be included 
ERC-adjudicated disease response at BMT CTN 0702 study 
entry 
Will not be included 
Age at 07LT enrollment 
Will not be included 
  
3.2 Participant Compliance 
A table listing significant protocol deviations/violations will be provided separately for those who 
continued lenalidomide maintenance therapy and those who did not, by treatment group for 
participants enrolled on 07LT.  Reasons for permanent withdrawal of lenalidomide maintenance 
therapy will be tabulated. 
A consort diagram will be provided to illustrate BMT CTN 07LT accrual, disposition, and follow 
up.   
4. Analysis Plan  
4.1 Analysis of the Primary Endpoint 
The primary analysis of PFS will include all randomized subjects from the BMT CTN 0702 
protocol, classified according to their randomized treatment allocation, irrespective of treatment 
received [intent-to-treat].  The time to this event is the time from randomization on the BMT CTN 
0702 protocol to progression, initiation of non-protocol anti-myeloma therapy (this includes 
lenalidomide if the dose is above 15mg), or death from any cause reported on BMT CTN 0702, 
BMT CTN 07LT, or to the CIBMTR.  Patients will be censored at loss to follow-up or end of 
2018, whichever comes first.  For those lost to follow-up, if loss occurred during 0702, censoring 
will occur at last myeloma evaluation before loss to follow-up.  For those lost to follow-up on 
BMT CTN 07LT, censoring will occur at the last contact date reported on the study status follow-
up form.  For those who completed BMT CTN 0702 but did not enroll on 07LT, censoring will 
occur at the last evaluation of progression provided by the CIBMTR. 
The treatment arms will be compared with a two-sided log-rank test stratified on risk status.  
Tests will be performed pair-wise at the 0.05/3 level to maintain type I error at 0.05 for this 
endpoint in this analysis. A Kaplan-Meier plot of PFS and 5-year estimates of PFS will be 
provided by treatment group. 
A secondary analysis of PFS will be conducted using Cox regression, with treatment arm and 
risk strata as covariates, and adjusting for demographic and baseline characteristics which are 
statistically different between treatment arms (p<0.1) for covariates specified in section 3.1.  
Start time will be randomization on BMT CTN 0702.   


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
13 
May 15, 2019 
Client Confidential 
In another secondary analysis of PFS, discontinuation of lenalidomide maintenance will be 
considered as a time-varying covariate in a separate Cox regression model for those who 
initiated lenalidomide; in this model, the outcome will be the time to progression or death from 
initiation of lenalidomide.  Initiation of maintenance lenalidomide on BMT CTN 0702 will be the 
start time for this analysis.  CIBMTR data will be used to determine whether participants who 
discontinued study lenalidomide also discontinued commercial lenalidomide.  The limited 
interpretation will be noted for this analysis, since it will include non-randomized comparisons 
and there may be bias in who enrolled in BMT CTN 07LT.    
4.2 Analysis of the Secondary Endpoints 
Overall Survival 
The event is death from any cause.  Overall survival (OS) time will be calculated as the time 
from randomization on the BMT CTN 0702 protocol to death, loss to follow-up or the end of the 
study, whichever comes first.  CIBMTR data will be used to supplement BMT CTN 0702/07LT 
data.  Patients alive at the time of last observation or lost to follow-up will be censored at the 
date of last contact either for CIBMTR-reported data or 0702/07LT-reported data.  The Kaplan-
Meier estimate of survival will be estimated at 5 years post randomization on the BMT CTN 
0702 protocol along with corresponding 98.3% confidence intervals.  Overall survival will be 
compared between treatment arms using a stratified two-sided log-rank test in pairwise 
comparisons of treatment groups.  The analysis population will be the 0702-enrolled population, 
with data from CIBMTR included. 
Event-Free Survival 
Event-free survival (EFS) time will be calculated as the time from randomization on the BMT 
CTN 0702 protocol to death, progression, second primary malignancy, loss to follow-up or the 
end of the study, whichever comes first.  Patients alive at the time of last observation or lost to 
follow-up will be censored at the date of last contact.  The analysis population will be the 0702-
enrolled population with follow up data from the CIBMTR included as needed.  The Kaplan-
Meier estimate of EFS will be estimated at 5 years post randomization on the BMT CTN 0702 
protocol along with corresponding 98.3% confidence intervals.  Event-free survival will be 
compared between treatment arms using a stratified, two-sided log-rank test in pairwise 
comparisons of treatment groups. 
Second Primary Malignancies 
The event is the development of the first SPM post randomization on BMT CTN 0702, excluding 
non-melanoma skin cancers.  Death without SPMs will be considered a competing risk for this 
event.  The analysis population is the 0702-enrolled population, and CIBMTR data will be used 
to supplement BMT CTN 0702/07LT data.  Start time is randomization on BMT CTN 0702.  
Cumulative incidence function will be used to calculate this endpoint and time of randomization 
on the BMT CTN 0702 protocol will be the starting point for the analysis.  Estimates at 5 years 
will be described along with 98.3% confidence intervals.  The cumulative incidence of SPMs will 
be compared between treatment arms using stratified two-sided Gray’s test in pairwise 
comparisons of treatment groups. SPMs will also be described by histologic type.     It will be 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
14 
May 15, 2019 
Client Confidential 
noted that reporting of SPM is not required after progression, and the CIBMTR data will be used 
to supplement 07LT data. 
Unexpected Grades 3-5 Adverse Events 
Unexpected grades 3-5 adverse events occurring post enrollment on BMT CTN 07LT will be 
tabulated and compared across treatment arms and lenalidomide status for participants enrolled 
in BMT CTN 07LT.  CIMBTR data will not be used. AEs will be described using the Medical 
Dictionary for Regulatory Activities (MedDRA) and classified according to the system organ 
class and preferred term.  Summaries by type and severity by treatment arm will be provided, 
and tabulations will be separated into tables for those who initiated maintenance on BMT CTN 
07LT and those who did not.   
Health Quality of Life 
Health quality of life (HQL) will be compared between all treatment groups utilizing the FACT-
BMT self-report, transplant-specific questionnaire and the generic quality of life tool, the SF-36.  
Only English and Spanish speaking patients are eligible to participate in the HQL component of 
this trial.  Participants were not required to complete the HQL questionnaires after progression; 
therefore, only HQL completed prior to progression will be summarized.  The limitations in 
interpretation of this analysis will be noted with the presentation of the results.  HQL at each 
time point from BMT 0702 baseline through 5 years post randomization on BMT CTN 0702 will 
be summarized using simple descriptive statistics (median, mean, SD or SE).  No formal 
statistical analyses will be conducted.  As 5 year data is only available for those participants on 
07LT, this analysis will focus solely on 07LT participants. 
4.3 Supplemental Analyses 
A supplemental analysis of OS will be included in which OS is analyzed using Cox regression, 
with treatment arm and risk strata as covariates, and will include demographic and baseline 
characteristics which are statistically different between treatment arms (p<0.1) for covariates 
specified in section 3.1.  Start time will be randomization on BMT CTN 0702 and all participants 
randomized on 0702 will be included.   
 
Supplemental analysis of EFS will be included.   
• 
The first will analyze EFS using Cox regression, with treatment arm and risk strata as 
covariates, and will include demographic and baseline characteristics which are 
statistically different between treatment arms (p<0.1) for covariates specified in section 
3.1.  Start time will be randomization on BMT CTN 0702 and all participants randomized 
on 0702 will be included.   
• 
The second will explore cause-specific hazards for each component of EFS.  Cox models 
with treatment arm, risk strata, and demographic/baseline covariates as specified above 
will be used.  Start time will be randomization on BMT CTN 0702 and all participants 
randomized on 0702 will be included.  For each component, the other components of EFS 
will be considered censoring events.   
• 
The third will analyze EFS using Cox regression in the subset of 0702 participants who 
initiated lenalidomide maintenance therapy. In this model, the outcome will be the time to 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
15 
May 15, 2019 
Client Confidential 
progression or death and the start time will be initiation of maintenance lenalidomide.  
Discontinuation of lenalidomide maintenance will be considered as a time-varying 
covariate.  Treatment group, strata, and baseline covariates used in the first EFS 
regression analysis will also be included.  The limited interpretation will be noted for this 
analysis, since it will include non-randomized comparisons and there may be bias in who 
enrolled in BMT CTN 07LT and continued on lenalidomide maintenance.  
 
Supplemental landmark analyses will be included.  The endpoints of PFS, OS, and EFS will be 
explored in the 0702-enrolled population who is alive four years post randomization (OS) or who 
is alive and progression- or event-free (for PFS and EFS respectively).  A log rank test will 
compare each outcome for the groups determined by those who were taking lenalidomide at 
four years post randomization compared to those who were not.  Kaplan meier estimates of 
each outcome at 5 years post randomization will be provided for each lenalidomide status 
group.   
5. Template of Proposed Table/Figure/Listing (TFL) Shells  
The templates for the Tables, Figures, and Listings are provided in the Appendix of this SAP.  
These templates are for illustration purposes only, and may not be the final layout or wording 
chosen for publications or presentations.  Actual format of the tables and figures may differ and 
will be subject to change in the final analysis report and/or publication.  Editorial changes in 
presentation or content will not necessarily be described in the changes to planned analyses 
section of the report or SAP updates.   
6. References  
Cox D. Regression models and lifetables (with discussion). Journal of the Royal Statistical 
Society 1972;Series B:187-220. 
Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the 
presence of competing risks: new representations of old estimators. Stat Med 1999;18:695-706. 
Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. 
Annals of Statistics 1988, 16: 1141-1154. 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
16 
May 15, 2019 
Client Confidential 
Appendix 
 
Exhibit 07LT-1:  Participant Disposition and Follow-Up 
The consort diagram will start with the 0702-enrolled population and at a minimum will provide 
information about the number enrolled, transplanted with initial autologous transplant, and 
started lenalidomide maintenance therapy in each arm.   Adiagram will be provided showing the 
number of participants enrolled on BMT CTN 0702/07LT, treatment assignment, and initiation of 
long-term lenalidomide maintenance therapy on BMT CTN 0702/07LT.  A table will be provided 
with descriptive statistics on length of follow-up by assigned treatment arm. 
Reasons for not enrolling on BMT CTN 07LT will be tabulated for participants on BMT CTN 
0702. 
Exhibit 07LT-2A:  Participant Demographics and Baseline Characteristics 
Baseline characteristics and demographics will be described for 0702-enrolled participants by 
frequencies and percentages for categorical covariates, and minimum, maximum, median, 
mean, and standard error for continuous covariates.  The following covariates from 0702 study 
entry may be included:  
• 
Treatment group assignment 
• 
Baseline risk status (at time of randomization and updated to include any changes 
entered for baseline risk status) 
• 
Gender 
• 
Ethnicity 
• 
Race  
• 
Patient age at time of 0702 enrollment 
• 
Endpoint Review Committee-adjudicated disease status at BMT CTN 0702 study entry 
• 
Karnofsky performance score at time of 0702 enrollment 
 
Other baseline covariates will be summarized at the request of the investigators.  P-values for 
treatment group comparisons will not be provided. 
 
 
Treatment Arm 
 
 
Auto/Auto 
(N=247) 
N (%) 
Auto/RVD 
(N=254) 
N (%) 
Auto/Maintenance 
(N=257) 
N (%) 
Total 
(N=758) 
N (%) 
Gender 
 
 
 
 
  Female 
 
 
 
 
  Male 
 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
17 
May 15, 2019 
Client Confidential 
 
Treatment Arm 
 
 
Auto/Auto 
(N=247) 
N (%) 
Auto/RVD 
(N=254) 
N (%) 
Auto/Maintenance 
(N=257) 
N (%) 
Total 
(N=758) 
N (%) 
Ethnicity 
 
 
 
 
  Hispanic or Latino 
 
 
 
 
  Not Hispanic or Latino 
 
 
 
 
  Unknown 
 
 
 
 
  Not Answered 
 
 
 
 
Race 
 
 
 
 
  American Indian/Alaska Native 
 
 
 
 
  Asian 
 
 
 
 
  Hawaiian/Pacific Islander 
 
 
 
 
  Black or African American 
 
 
 
 
  White 
 
 
 
 
  More than One Race 
 
 
 
 
  Other, Specify 
 
 
 
 
  Unknown 
 
 
 
 
  Not Answered 
 
 
 
 
Karnofsky Performance Score 
 
 
 
 
 90 - 100 
 
 
 
 
 70 - 80 
 
 
 
 
 Less than 70 
 
 
 
 
Baseline disease risk strata (at 
randomization) 
 
 
 
 
  High 
 
 
 
 
  Standard 
 
 
 
 
Baseline disease risk strata  (data 
entry updated post randomization) 
 
 
 
 
  High 
 
 
 
 
  Standard 
 
 
 
 
 
 
 
 
 
Age group at 0702 enrollment, years  
 
 
 
  20-29 
 
 
 
 
  30-39 
 
 
 
 
  40-49 
 
 
 
 
  50-59 
 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
18 
May 15, 2019 
Client Confidential 
 
Treatment Arm 
 
 
Auto/Auto 
(N=247) 
N (%) 
Auto/RVD 
(N=254) 
N (%) 
Auto/Maintenance 
(N=257) 
N (%) 
Total 
(N=758) 
N (%) 
  60-70 
 
 
 
 
ERC-adjudicated 0702 baseline 
disease response 
 
 
 
 
  Stringent complete response 
 
 
 
 
  Complete response 
 
 
 
 
  Near complete response 
 
 
 
 
  Very good partial response 
 
 
 
 
  Partial response 
 
 
 
 
  Stable disease 
 
 
 
 
  Progression 
 
 
 
 
  Not evaluable 
 
 
 
 
Baseline response (grouped) 
 
 
 
 
  CR or Stringent CR 
 
 
 
 
Baseline response (grouped) 
 
 
 
 
  VGPR, near CR, CR, or stringent CR  
 
 
 
CIBMTR-collected pre-0702 initial 
myeloma therapy 
 
 
 
 
  Doublets 
 
 
 
 
  Triplets 
 
 
 
 
  Other 
 
 
 
 
  
Age at 0702 enrollment, years 
 
 
 
 
  Min 
 
 
 
 
  Max 
 
 
 
 
  Median 
 
 
 
 
  Mean 
 
 
 
 
  StdDev 
 
 
 
 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
19 
May 15, 2019 
Client Confidential 
Exhibit 07LT-2B:  Participant Demographics and Baseline Characteristics (07LT-enrolled 
participants) 
 
 
Treatment Arm 
 
 
Auto/Auto 
(N=) 
N (%) 
Auto/RVD 
(N=) 
N (%) 
Auto/Maintenance 
(N=) 
N (%) 
Total 
(N=) 
N (%) 
Gender 
 
 
 
 
  Female 
 
 
 
 
  Male 
 
 
 
 
Ethnicity 
 
 
 
 
  Hispanic or Latino 
 
 
 
 
  Not Hispanic or Latino 
 
 
 
 
  Unknown 
 
 
 
 
  Not Answered 
 
 
 
 
Race 
 
 
 
 
  American Indian/Alaska Native 
 
 
 
 
  Asian 
 
 
 
 
  Hawaiian/Pacific Islander 
 
 
 
 
  Black or African American 
 
 
 
 
  White 
 
 
 
 
  More than One Race 
 
 
 
 
  Other, Specify 
 
 
 
 
  Unknown 
 
 
 
 
  Not Answered 
 
 
 
 
Karnofsky Performance Score at 
0702 enrollment 
 
 
 
 
 90 - 100 
 
 
 
 
 70 - 80 
 
 
 
 
 Less than 70 
 
 
 
 
Baseline disease risk strata at 
randomization 
 
 
 
 
  High 
 
 
 
 
  Standard 
 
 
 
 
Baseline disease risk strata (data 
entry updated post randomization) 
 
 
 
 
  High 
 
 
 
 
  Standard 
 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
20 
May 15, 2019 
Client Confidential 
 
Treatment Arm 
 
 
Auto/Auto 
(N=) 
N (%) 
Auto/RVD 
(N=) 
N (%) 
Auto/Maintenance 
(N=) 
N (%) 
Total 
(N=) 
N (%) 
Age group at 07LT enrollment, years  
 
 
 
  20-29 
 
 
 
 
  30-39 
 
 
 
 
  40-49 
 
 
 
 
  50-59 
 
 
 
 
  60-70 
 
 
 
 
ERC-adjudicated 0702 baseline 
disease response 
 
 
 
 
  Stringent complete response 
 
 
 
 
  Complete response 
 
 
 
 
  Near complete response 
 
 
 
 
  Very good partial response 
 
 
 
 
  Partial response 
 
 
 
 
  Stable disease 
 
 
 
 
  Progression 
 
 
 
 
  Not evaluable 
 
 
 
 
Baseline response (grouped) 
 
 
 
 
  CR or Stringent CR 
 
 
 
 
Baseline response (grouped) 
 
 
 
 
  VGPR, near CR, CR, or stringent CR  
 
 
 
CIBMTR-collected pre-0702 initial 
myeloma therapy 
 
 
 
 
  Doublets 
 
 
 
 
  Triplets 
 
 
 
 
  Other 
 
 
 
 
 
Age at 07LT enrollment, years 
 
 
 
 
  Min 
 
 
 
 
  Max 
 
 
 
 
  Median 
 
 
 
 
  Mean 
 
 
 
 
  StdDev 
 
 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
21 
May 15, 2019 
Client Confidential 
Exhibit 07LT-3: Progression-free Survival (Primary Analysis of PFS) 
Figure template for illustration only
Kaplan Meier Estimates and 98.3% Confidence Intervals 
 
Auto/Auto 
Auto/RVD 
Auto/Maint 
5-year Estimates: 
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
 
Pairwise Tests of Treatment Group Differences 
 
 
First Event3 
 
 
Comparison 
N 
Total 
Events 
PRG or 
NPT 
DTH 
Stratified 
Log-rank 
(Abs(Z))1 
p-
value2 
Auto/Auto to 
Auto/RVD 
247 
254 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
X.X 
0.XX 
Auto/Auto to 
Auto/Maintenance 
247 
257 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
X.X 
0.XX 
Auto/RVD to 
Auto/Maintenance 
254 
257 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
X.X 
0.XX 
1Absolute value of the Z statistic is reported; does not indicate direction. 
2P-values are compared to the α=0.05/3 level for statistical significance. 
3Only the first event (clinical progression (PRG), non-protocol anti-myeloma therapy initiation (NPT), death) 
is counted. 
0
6
12
18
24
30
36
42
48
54
60
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Progression-Free Survival Probability
Auto/Maint
Auto/RVD
Auto/Auto
247
240
230
220
200
190
180
170
160
150
140
254
240
230
220
200
190
180
170
160
150
140
257
240
230
220
200
190
180
170
160
150
140
Auto/Auto
Auto/Maint
Auto/RVD
N at Risk


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
22 
May 15, 2019 
Client Confidential 
Notes for primary analysis: 
 
Analysis population:  0702-enrolled 
 
Events:   
• 
Clinical progression  
• 
initiation of non-protocol antimyeloma therapy  
• 
death  
BMT CTN 0702 Endpoint Review Committee data will be used for events when available (in 
general, during the first 38 months of follow-up on 0702).  CIBMTR data will be used. 
 
Censoring: 
• 
the date of last myeloma data collected through 0702 or 07LT  or from the CIBMTR 
 
Testing: 
• 
two-sided log-rank test stratified on risk status at randomization.  Significance level for 
each pairwise test is 0.05/3.    
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
23 
May 15, 2019 
Client Confidential 
Exhibit 07LT-4A: Multivariate Cox Regression Analysis of Progression-free Survival 
(Secondary Analysis of PFS) – 0702 baseline factors 
 
Maximum Likelihood Estimates and Hazard Ratios 
 
 
Hazard Ratio 
 
Covariate 
 
 
Point 
Estimate 
Lower 
Confidence 
Limit  
Upper  
Confidence 
Limit 
Model 
Parameter 
Estimate  
p-value 
Auto/Auto treatment arm 
vs Auto/Maintenance 
arm1 
 
 
 
 
 
 
Auto/Auto treatment arm 
vs Auto/RVD arm1 
 
 
 
 
 
 
Auto/RVD treatment arm 
vs Auto/Maintenance 
arm1 
 
 
 
 
 
 
Risk strata—High risk vs 
Risk strata—Standard 
risk 
 
 
 
 
 
 
 
 
 
 
 
 
 
(other adjustment factor 
as needed) 
 
 
 
 
 
 
(other adjustment factor 
as needed) 
 
 
 
 
 
 
(other adjustment factor 
as needed) 
 
 
 
 
 
 
1P-values are compared to the 0.05/3 significance level. 
Figure: A forest plot for the hazard ratios and confidence intervals may also be provided. 
 
Notes for this secondary analysis: 
Model covariates: 
• 
Treatment group 
• 
Randomized risk strata 
• 
Any of the factors in column 2 of the table in Section 3.1 that have a test for treatment 
group differences that is significant at the 0.1 level 
• 
No interactions will be included. 
 
Model building and testing: 
• 
Analysis population is 0702 participants  
• 
Time to PFS is calculated from randomization 
• 
proc phreg in SAS, no model selection procedures  


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
24 
May 15, 2019 
Client Confidential 
Exhibit 07LT-4B: Multivariate Cox Regression Analysis of Progression-free Survival from 
Initiation of Lenalidomide (Secondary Analysis of PFS)  
 
 
Maximum Likelihood Estimates and Hazard Ratios 
 
 
Hazard Ratio 
 
Covariate 
 
 
Point 
Estimate 
Lower 
Confidence 
Limit  
Upper 
Confidence 
Limit 
Model 
Parameter 
Estimate  
p-value 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
 
Auto/Auto treatment arm vs 
Auto/RVD arm1 
 
 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
 
Risk strata—High risk vs  
Risk strata—Standard risk 
 
 
 
 
 
 
Permanent discontinuation of 
lenalidomide (time-
dependent) 
 
 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
 
 
1 P-values are compared to the 0.05/3 significance level. 
Figure: A forest plot for the hazard ratios and confidence intervals may also be provided. 
 
Notes for this secondary analysis: 
Model covariates: 
• 
Treatment group 
• 
Randomized risk strata 
• 
Any of the factors in column 2 of the table in Section 3.1 that have a test for treatment 
group differences that is significant at the 0.1 level.  ERC-adjudicated baseline disease 
response will be tested using 2 categorizations (CR or better, VGPR or better).  If both are 
significant at the 0.1 level, the one that is more significant will be used in the model. 
• 
No interactions 
• 
Permanent discontinuation of lenalidomide as a time varying covariate.  
 
Model building and testing: 
• 
Analysis population is 0702 participants who initiated lenalidomide 
• 
Time to PFS is calculated from start time of lenalidomide 
• 
Proc phreg in SAS, no model selection procedure  
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
25 
May 15, 2019 
Client Confidential 
Exhibit 07LT-5:  Overall Survival 
Figure template for illustration only 
Overall Survival by Treatment Arm  
 
Kaplan Meier Estimates and 98.3% Confidence Intervals 
 
Auto/Auto 
Auto/RVD 
Auto/Maint 
5-year Estimates: 
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
 
 
Stratified Log-Rank Test for Treatment Group Differences 
Treatment Group Comparison 
p-value1 
Auto/Auto vs Auto/RVD 
0.XX 
Auto/Auto vs Auto/Maint 
0.XX 
Auto/RVD vs Auto/Maint 
0.XX 
1Significance level is 0.05/3 for each pairwise comparison. 
 
 
 
 
0
6
12
18
24
30
36
42
48
54
60
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Survival Probability
Auto/Maint
Auto/RVD
Auto/Auto
247
240
230
220
200
190
180
170
160
150
140
254
240
230
220
200
190
180
170
160
150
140
257
240
230
220
200
190
180
170
160
150
140
Auto/Auto
Auto/Maint
Auto/RVD
N at Risk


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
26 
May 15, 2019 
Client Confidential 
Exhibit 07LT-6:  Event-Free Survival 
Figure template for illustration only 
Event-Free Survival by Treatment Arm  
 
 
Kaplan Meier Estimates and 98.3% Confidence Intervals 
 
Auto/Auto 
Auto/RVD 
Auto/Maint 
5-year Estimates:   
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
 
Stratified Log-Rank Test for Treatment Group Differences 
 
 
 
First Event3 
 
Comparison 
N 
Total 
Number 
with an 
Event 
PRG or 
NPT 
SPM 
DTH 
p-value1 
Auto/Auto to 
Auto/RVD 
247 
254 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
0.XX 
Auto/Auto to 
Auto/Maintenance 
247 
257 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
0.XX 
Auto/RVD to 
Auto/Maintenance 
254 
257 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
0.XX 
1Significance level is 0.05/3 for each pairwise comparison. 
 
0
6
12
18
24
30
36
42
48
54
60
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Survival Probability
Auto/Maint
Auto/RVD
Auto/Auto
247
240
230
220
200
190
180
170
160
150
140
254
240
230
220
200
190
180
170
160
150
140
257
240
230
220
200
190
180
170
160
150
140
Auto/Auto
Auto/Maint
Auto/RVD
N at Risk


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
27 
May 15, 2019 
Client Confidential 
 
Exhibit 07LT-7:  Cumulative Incidence of First SPM 
Figure template for illustration only 
Cumulative Incidence of First SPM by Treatment Arm  
 
Cumulative Incidence Estimates and 98.3% Confidence Intervals 
 
Auto/Auto 
Auto/RVD 
Auto/Maint 
5-year Estimates: 
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
 
Stratified Gray’s Test for Treatment Group Differences 
Treatment Group Comparison 
p-value1 
Auto/Auto vs Auto/RVD 
0.XX 
Auto/Auto vs Auto/Maint 
0.XX 
Auto/RVD vs Auto/Maint 
0.XX 
1Significance level is 0.05/3 for each pairwise comparison. 
 
 
 
0
6
12
18
24
30
36
42
48
54
60
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Incidence
Auto/Maint
Auto/RVD
Auto/Auto
247
240
230
220
200
190
180
170
160
150
140
254
240
230
220
200
190
180
170
160
150
140
257
240
230
220
200
190
180
170
160
150
140
Auto/Auto
Auto/Maint
Auto/RVD
N at Risk


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
28 
May 15, 2019 
Client Confidential 
 
Exhibit 07LT-8:  SPM Histologic Type 
 
Auto/Auto 
Auto/RVD 
Auto/Maint 
Total 
 
N 
% 
N 
% 
N 
% 
N 
% 
All1 
XXX 
100.0 
XXX 
100.0 
XXX 
100.0 
XXX 
100.0 
Hematologic SPM 
XXX 
XX.X 
XXX 
XX.X 
XXX 
XX.X 
XXX 
XX.X 
  High-Level Group Term 1 
XXX 
 
XXX 
 
XXX 
 
XXX 
 
  High-Level Group Term 2 
XXX 
 
XXX 
 
XXX 
 
XXX 
 
  (etc.) 
XXX 
 
XXX 
 
XXX 
 
XXX 
 
Solid Tumor SPM 
XXX 
XX.X 
XXX 
XX.X 
XXX 
XX.X 
XXX 
XX.X 
  High-Level Group Term 1 
XXX 
 
XXX 
 
XXX 
 
XXX 
 
  High-Level Group Term 2 
XXX 
 
XXX 
 
XXX 
 
XXX 
 
  (etc.) 
XXX 
 
XXX 
 
XXX 
 
XXX 
 
1More than one SPM may be reported per participant.  SPM reporting on BMT CTN 0702 and 07LT is not 
required after progression.  Supplemental data is provided by the CIBMTR. 
 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
29 
May 15, 2019 
Client Confidential 
Exhibit 07LT-9A:  Unexpected Grades 3-5 Adverse Events in Participants Initiating 
Lenalidomide on BMT CTN 07LT1 
 
 
Auto/Auto 
N       % 
Auto/RVD  
N       % 
Auto/Maint  
N       % 
Total 
All Unexpected Grades 
3-5 Adverse Events 
 
XX    100.0 
XX    100.0 
XX    100.0 
XX    100.0 
System Organ Class 
(SOC) 
Preferred 
Term 
 
 
 
 
SOC1 
ALL 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
 
PT1 
(just N) 
(just N) 
(just N) 
(just N) 
 
PT2 
(just N) 
(just N) 
(just N) 
(just N) 
SOC2 
ALL 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
 
PT1 
(just N) 
(just N) 
(just N) 
(just N) 
 
PT2 
(just N) 
(just N) 
(just N) 
(just N) 
(etc.) 
(etc.) 
 
 
 
 
Severity 
 
 
 
 
 
Grade 3 
 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
Grade 4 
 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
Grade 5 
 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
1 The reporting requirements differ for participants taking lenalidomide. 
Exhibit 07LT-9B:  Unexpected Grades 3-5 Adverse Events in Participants Enrolled on 
BMT CTN 07LT Who Did Not Initiate Lenalidomide 
 
 
Auto/Auto 
N       % 
Auto/RVD  
N       % 
Auto/Maint  
N       % 
Total 
All Unexpected Grades 
3-5 Adverse Events 
 
XX    100.0 
XX    100.0 
XX    100.0 
XX    100.0 
System Organ Class 
(SOC) 
Preferred 
Term 
 
 
 
 
SOC1 
ALL 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
 
PT1 
(just N) 
(just N) 
(just N) 
(just N) 
 
PT2 
(just N) 
(just N) 
(just N) 
(just N) 
SOC2 
ALL 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
 
PT1 
(just N) 
(just N) 
(just N) 
(just N) 
 
PT2 
(just N) 
(just N) 
(just N) 
(just N) 
(etc.) 
(etc.) 
 
 
 
 
Severity 
 
 
 
 
 
Grade 3 
 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
Grade 4 
 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
Grade 5 
 
XX    XX.X 
XX    XX.X 
XX    XX.X 
XX    XX.X 
 
 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
30 
May 15, 2019 
Client Confidential 
Exhibit 07LT-10:  Health Quality of Life:  FACT-BMT for BMT CTN 07LT English/Spanish-
Speaking Participants 
Note:  The analysis is limited to questionnaires for BMT 07LT-enrolled participants who have not 
died or progressed.  The interpretation of results is limited.  Questionnaires not completed within 
the analysis target window are excluded. 
 
Treatment Arm 
Auto/Auto (N=XXX) 
Auto/RVD (N=XXX) 
Auto/Maint (N=XXX) 
N 
Median Mean StdErr 
N 
Median Mean StdErr 
N 
Median Mean StdErr 
FACT BMT 
Concerns 
(10 Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
FACT-G 
Total (27 
Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
FACT-BMT 
Total (37 
Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
FACT-BMT 
Trial 
Outcome 
Index (24 
Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
Figures may also be provided. 
 


BMT CTN Protocol 07LT Statistical Analysis Plan (SAP) 
v1.0 
Version 1.0 
31 
May 15, 2019 
Client Confidential 
Exhibit 07LT-11:  Health Quality of Life:  SF-36 for BMT CTN 07LT English/Spanish-
Speaking Participants 
Note:  The analysis is limited to questionnaires for BMT CTN 07LT-enrolled participants who 
have not died or progressed.  The interpretation of results is limited.  Questionnaires not 
completed within the analysis target window are excluded. 
 
Treatment Arm 
Auto/Auto (N=XXX) 
Auto/RVD (N=XXX) 
Auto/Maint (N=XXX) 
N 
Median Mean StdErr 
N 
Median Mean StdErr 
N 
Median Mean StdErr 
Physical 
Well-Being  
(7 Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
Social / 
Family 
Well-Being  
(7 Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
Emotional 
Well-Being  
(6 Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
Functional 
Well-Being 
(7 Items) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
R1Y 
 
 
 
 
 
 
 
 
 
 
 
 
R2Y 
 
 
 
 
 
 
 
 
 
 
 
 
R3Y 
 
 
 
 
 
 
 
 
 
 
 
 
R4Y 
 
 
 
 
 
 
 
 
 
 
 
 
R5Y 
 
 
 
 
 
 
 
 
 
 
 
 
Figures may also be provided. 


 
Version 1.0 
32 
May 15, 2019 
Client Confidential 
Supplemental Exhibit 07LT-1:  Enrollment  
A table will be provided showing actual yearly accrual for each 07LT participating center from 
07LT study initiation to accrual closure.  
A table will be provided showing time to last contact summarized separately for participants 
enrolled on BMT CTN 07LT, and for participants not enrolled on BMT CTN 07LT.  
Supplemental Exhibit 07LT-2:  Significant Protocol Deviations 
A table listing significant protocol deviations/violations will be provided separately for those who 
continued lenalidomide maintenance therapy on 07LT and those who did not, by treatment 
group for participants enrolled on 07LT.   
Supplemental Exhibit 07LT-3:  Permanent Discontinuation of Lenalidomide 
A table will be provided to describe the reasons for permanent discontinuation of lenalidomide 
maintenance therapy for BMT CTN 0702-enrolled participants who initiated therapy on BMT 
CTN 07LT.   For particpants who have confirmed they continued on commercial lenalidomide, 
discontinuation data will be based on discontinuation of commercial lenalidomide.   
Supplemental Exhibit 07LT-4:  Primary Cause of Death 
A table summarizing the primary cause of death by treatment group will be provided; the table 
will be separated into adjudicated deaths and unadjudicated deaths.  Primary cause of death is 
adjudicated by the BMT CTN 0702 Endpoint Review Committee (ERC) for most participants 
who died within 38 months of enrollment on 0702. For deaths where cause is not adjudicated by 
the ERC, if the participant progressed prior to death without a secondary malignancy, cause of 
death will be reported as progression; if the person progressed prior to death and also reported 
an SPM, cause of death will be reported as progression/SPM; if the person did not progress 
prior to death but reported an SPM, cause of death will be reported as SPM; if the person did 
not progress prior to death and did not report an SPM, site-reported cause of death will be 
reported.  
 
Treatment Arm 
Total 
Auto/Auto 
Auto/RVD 
Auto/Maint  
N 
% 
N 
% 
N 
% 
N 
% 
Enrolled 
247 
100.0 
254 100.0 257 
100.0 758 
100.0 
Total deaths  
 
 
 
 
 
 
 
 
  Deaths adjudicated by BMT CTN 0702 ERC  
 
 
 
 
 
 
 
 
  Deaths not adjudicated by BMT CTN 0702 ERC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ERC-Adjudicated Deaths 
 
 
 
 
 
 
 
 


 
Version 1.0 
33 
May 15, 2019 
Client Confidential 
 
Treatment Arm 
Total 
Auto/Auto 
Auto/RVD 
Auto/Maint  
N 
% 
N 
% 
N 
% 
N 
% 
Primary Cause of Death 
 
 
 
 
 
 
 
 
Disease Recurrence or Persistence 
Secondary Malignancy 
 
 
 
 
 
 
 
 
[Reason 3] 
 
 
 
 
 
 
 
 
[Reason 4] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Deaths with Cause Not Adjudicated  
 
 
 
 
 
 
 
 
Primary Cause of Death 
 
 
 
 
 
 
 
 
Disease Recurrence or Persistence 
Secondary Malignancy 
 
 
 
 
 
 
 
 
Disease recurrence or persistence/secondary 
malignancy 
 
 
 
 
 
 
 
 
[Reason 4] 
 
 
 
 
 
 
 
 
[Reason 5] 
 
 
 
 
 
 
 
 
 
 
 


 
Version 1.0 
34 
May 15, 2019 
Client Confidential 
Supplemental Exhibit 07LT-5A: Multivariate Cox Regression Analysis of Overall Survival  
– 0702 baseline factors 
 
Maximum Likelihood Estimates and Hazard Ratios 
 
Hazard Ratio 
 
Covariate 
Point 
Estimate 
Confidence 
limit  
Confidence 
limit 
Model 
Parameter 
Estimate  
p-value 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
Auto/Auto treatment arm vs 
Auto/RVD arm1 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
Risk strata—High risk vs 
Risk strata—Standard risk 
 
 
 
 
 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
1P-values are compared to the 0.05/3 significance level. 
Figure: A forest plot for the hazard ratios and confidence intervals may also be provided. 
 
Notes for this secondary analysis: 
Model covariates: 
• 
Treatment group 
• 
Randomized risk strata 
• 
Any of the factors in column 2 of the table in Section 3.1 that have a test for treatment 
group differences that is significant at the 0.1 level.  ERC-adjudicated baseline disease 
response will be tested using 2 categorizations (CR or better, VGPR or better).  If both are 
significant at the 0.1 level, the one that is more significant will be used in the model. 
• 
No interactions will be included. 
 
Model building and testing: 
• 
Analysis population is 0702 participants  
• 
Time to OS is calculated from randomization 
• 
proc phreg in SAS, no model selection procedures  
 
 


 
Version 1.0 
35 
May 15, 2019 
Client Confidential 
Supplemental Exhibit 07LT-5B: Multivariate Cox Regression Analysis of Overall Survival 
from Initiation of Lenalidomide 
 
 
Maximum Likelihood Estimates and Hazard Ratios 
 
Hazard Ratio 
 
Covariate 
Point 
Estimate 
Lower 
Confidence 
Limit  
Upper 
Confidence 
Limit 
Model 
Parameter 
Estimate  
p-value 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
Auto/Auto treatment arm vs 
Auto/RVD arm1 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
Risk strata—High risk vs  
Risk strata—Standard risk 
 
 
 
 
Permanent discontinuation of 
lenalidomide (time-
dependent) 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
(other adjustment factor as 
needed) 
 
 
 
 
1 P-values are compared to the 0.05/3 significance level. 
Figure: A forest plot for the hazard ratios and confidence intervals may also be provided. 
 
Notes for this secondary analysis: 
Model covariates: 
• 
Treatment group 
• 
Randomized risk strata 
• 
Any of the factors in column 2 of the table in Section 3.1 that have a test for treatment 
group differences that is significant at the 0.1 level.  ERC-adjudicated baseline disease 
response will be tested using 2 categorizations (CR or better, VGPR or better).  If both are 
significant at the 0.1 level, the one that is more significant will be used in the model. 
• 
No interactions 
• 
Permanent discontinuation of lenalidomide as a time varying covariate.  
 
Model building and testing: 
• 
Analysis population is 0702 participants who initiated lenalidomide 
• 
Time to PFS is calculated from start time of lenalidomide 
• 
Proc phreg in SAS, no model selection procedure 


 
Version 1.0 
36 
May 15, 2019 
Client Confidential 
Supplemental Exhibit 07LT-6A: Multivariate Cox Regression Analysis of Event-free 
Survival  – 0702 baseline factors 
 
Maximum Likelihood Estimates and Hazard Ratios 
 
Cox model Parameter 
Hazard Ratio 
Covariate 
Estimate 
p-value  
Point 
Estimate 
Confidence 
limit  
Confidence 
limit 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Auto/Auto treatment arm vs Auto/RVD 
arm1 
 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Risk strata—High risk vs 
Risk strata—Standard risk 
 
 
 
 
 
 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
1P-values are compared to the 0.05/3 significance level. 
Figure: A forest plot for the hazard ratios and confidence intervals may also be provided. 
 
Notes for this secondary analysis: 
Model covariates: 
• 
Treatment group 
• 
Randomized risk strata 
• 
Any of the factors in column 2 of the table in Section 3.1 that have a test for treatment 
group differences that is significant at the 0.1 level.  ERC-adjudicated baseline disease 
response will be tested using 2 categorizations (CR or better, VGPR or better).  If both are 
significant at the 0.1 level, the one that is more significant will be used in the model. 
• 
No interactions will be included. 
 
Model building and testing: 
• 
Analysis population is 0702 participants  
• 
Time to EFS is calculated from randomization 
• 
proc phreg in SAS, no model selection procedures  


 
Version 1.0 
37 
May 15, 2019 
Client Confidential 
Supplemental Exhibit 07LT-6B: Cause-specific Multivariate Cox Regression Analysis of 
the Components of Event-free Survival  
 
 
Maximum Likelihood Estimates and Hazard Ratios:  Event=Progression, Censoring 
Events=SPM, Death 
 
Cox model Parameter 
Hazard Ratio 
Covariate 
Estimate 
p-value  
Point 
Estimate 
 
Confidence 
limit  
 
Confidence 
limit 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Auto/Auto treatment arm vs Auto/RVD 
arm1 
 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Risk strata—High risk vs  
Risk strata—Standard risk 
 
 
 
 
 
Permanent discontinuation of 
lenalidomide 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
1 P-values are compared to the 0.05/3 significance level. 
 
 
Maximum Likelihood Estimates and Hazard Ratios:  Event=SPM, Censoring 
Events=Progression, Death 
 
Cox model Parameter 
Hazard Ratio 
Covariate 
Estimate 
p-value  
Point 
Estimate 
 
Confidence 
limit  
 
Confidence 
limit 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Auto/Auto treatment arm vs Auto/RVD 
arm1 
 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Risk strata—High risk vs  
Risk strata—Standard risk 
 
 
 
 
 
Permanent discontinuation of 
lenalidomide 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
1 P-values are compared to the 0.05/3 significance level. 


 
Version 1.0 
38 
May 15, 2019 
Client Confidential 
 
 
Maximum Likelihood Estimates and Hazard Ratios:  Event=Death, Censoring 
Events=Progression, SPM 
 
Cox model Parameter 
Hazard Ratio 
Covariate 
Estimate 
p-value  
Point 
Estimate 
 
Confidence 
limit  
 
Confidence 
limit 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Auto/Auto treatment arm vs Auto/RVD 
arm1 
 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Risk strata—High risk vs  
Risk strata—Standard risk 
 
 
 
 
 
Permanent discontinuation of 
lenalidomide 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
1 P-values are compared to the 0.05/3 significance level. 
 
 
Figure: A forest plot for the hazard ratios and confidence intervals may also be provided. 
 
 
 


 
Version 1.0 
39 
May 15, 2019 
Client Confidential 
Supplemental Exhibit 07LT-6C: Multivariate Cox Regression Analysis of Event-free 
Survival from Initiation of Lenalidomide  
 
 
Maximum Likelihood Estimates and Hazard Ratios 
 
Cox model Parameter 
Hazard Ratio 
Covariate 
Estimate 
p-value  
Point 
Estimate 
 
Confidence 
limit  
 
Confidence 
limit 
Auto/Auto treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Auto/Auto treatment arm vs Auto/RVD 
arm1 
 
 
 
 
 
Auto/RVD treatment arm vs 
Auto/Maintenance arm1 
 
 
 
 
 
Risk strata—High risk vs  
Risk strata—Standard risk 
 
 
 
 
 
Permanent discontinuation of 
lenalidomide 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
(other adjustment factor as needed) 
 
 
 
 
 
1 P-values are compared to the 0.05/3 significance level. 
Figure: A forest plot for the hazard ratios and confidence intervals may also be provided. 
 
 


 
Version 1.0 
40 
May 15, 2019 
Client Confidential 
Supplemental Exhibit 07LT-6:  Landmark Analysis of PFS 
Figure template for illustration only 
Progression-Free Survival by 4-Year Lenalidomide Status  
 
 
 
Kaplan Meier Estimates and 95% Confidence Intervals 
 
Lenalidomide taken at 
4 years post 
randomization 
Lenalidomide not 
taken at 4 years post 
randomization 
5-year Estimates:   
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
 
Log-Rank Test for Group Differences 
 
 
 
 
Comparison 
N 
Total 
Number 
with an 
Event 
p-value1 
Lenalidomide use at 4 years 
Yes 
No 
 
xxx 
xxx 
 
XXX 
XXX 
 
 
0.XX 
1Significance level is 0.05. 
48
54
60
66
72
78
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Survival Probability
Lenalidomide Not Taken at 4 Yrs
Lenalidomide Taken at 4 Yrs
100
85
70
55
40
25
100
80
65
50
35
20
No
Yes
N at Risk
Use at 4 Yrs


 
Version 1.0 
41 
May 15, 2019 
Client Confidential 
 
Supplemental Exhibit 07LT-7:  Landmark Analysis of OS 
Figure template for illustration only 
Overall Survival by 4-Year Lenalidomide Status  
 
 
 
Kaplan Meier Estimates and 95% Confidence Intervals 
 
Lenalidomide taken at 
4 years post 
randomization 
Lenalidomide not 
taken at 4 years post 
randomization 
5-year Estimates:   
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
 
48
54
60
66
72
78
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Survival Probability
Lenalidomide Not Taken at 4 Yrs
Lenalidomide Taken at 4 Yrs
100
85
70
55
40
25
100
80
65
50
35
20
No
Yes
N at Risk
Use at 4 Yrs


 
Version 1.0 
42 
May 15, 2019 
Client Confidential 
Log-Rank Test for Group Differences 
 
 
 
 
Comparison 
N 
Total 
Number 
with an 
Event 
p-value1 
Lenalidomide use at 4 years 
Yes 
No 
 
xxx 
xxx 
 
XXX 
XXX 
 
 
0.XX 
1Significance level is 0.05. 
 
Supplemental Exhibit 07LT-8:  Landmark Analysis of EFS 
Figure template for illustration only 
Event-Free Survival by 4-Year Lenalidomide Status  
 
 
 
 
48
54
60
66
72
78
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Survival Probability
Lenalidomide Not Taken at 4 Yrs
Lenalidomide Taken at 4 Yrs
100
85
70
55
40
25
100
80
65
50
35
20
No
Yes
N at Risk
Use at 4 Yrs


 
Version 1.0 
43 
May 15, 2019 
Client Confidential 
Kaplan Meier Estimates and 95% Confidence Intervals 
 
Lenalidomide taken at 
4 years post 
randomization 
Lenalidomide not 
taken at 4 years post 
randomization 
5-year Estimates:   
XX.X (XX.X, XX.X) 
XX.X (XX.X, XX.X) 
 
Log-Rank Test for Group Differences 
 
 
 
First Event 
 
Comparison 
N 
Total 
Number 
with an 
Event 
PRG or 
NPT 
SPM 
DTH 
p-value1 
Lenalidomide use at 4 years 
Yes 
No 
 
xxx 
xxx 
 
XXX 
XXX 
 
XXX 
XXX 
 
XXX 
XXX 
 
XXX 
XXX 
 
 
0.XX 
1Significance level is 0.05.