Clinical trial NCT01463670
Conditions: Multiple Myeloma
Keywords: LENALIDOMIDE (CC-5013) BONE MARROW 11-107
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2011-10-28; Completion date: 2021-03-19
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine whether this disease will get better if treated with higher doses of Lenalidomide even if the disease returns while taking low doses of Lenalidomide. In patients with multiple myeloma treated with Lenalidomide maintenance, the disease will return. However, the physician currently does not know if the disease would respond to treatment with higher doses of Lenalidomide. This is very important for patients with multiple myeloma because the number of drugs available to treat the disease are limited. It is important to know if Lenalidomide remains still effective and if it can still be used in this situation. This study will try to find out what effects, good and/or bad higher doses of Lenalidomide has on the patient and the disease after it has returned.

Detailed description:

Arms: arm 1: The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT or on continuous/maintenance therapy after initial treatment.
Interventions: intervention 1: lenalidomide
Intervention descriptions: intervention 1: patients will begin therapy with lenalidomide 25 mg daily, 21 days out of a 28 day schedule. All patients will be evaluated monthly after every cycle. The dose will be adjusted downward in response to side effects and according to specific guidelines. Symptomatic POD occurring at any time during the study will result in removal of the patient from the study. After 2 cycles of lenalidomide, patients with at least stable disease (SD) will continue lenalidomide indefinitely until asymptomatic POD, at which time dexamethasone will be added at a dose of 40mg weekly. On the other hand, patient with asymptomatic POD after 2 cycles of lenalidomide will have dexamethasone added at a dose of 40 mg weekly. Patients with any type of POD after any cycle that includes dexamethasone will be taken off study. Patients can remain on study on lenalidomide or lenalidomide/dexamethasone indefinitely as long as they do not have POD as stated above and they tolerate the treatment.

Protocol documents:
Prot_SAP_000.pdf: 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
A Phase II Clinical Trial of Lenalidomide Intensification in Patients with 
Serologic/ As ymptomatic Progression of Multiple Myeloma While on 
Lenalidomide Maintenance 
 
PROTOCOL FACE PAGE FOR 
MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL 
 
Principal 
Hani Hassoun, MD 
Medicine: Lymphoma/Myeloma 
Co-Principal 
Investigator(s)/Department: 
Sergio Giralt, MD 
Medicine: BMT 
Investigator(s)/Department: 
David Chung, MD 
Heather Landau, MD 
Nikoletta Lendvai, MD, PhD 
Alex Lesokhin, MD 
Elyn Riedel, MA 
Ephraim Casper, MD 
Audrey Hamilton, MD 
Mila Gorsky, MD 
Han Xiao, MD 
John Fiore, MD 
Stuart Lichtman, MD 
Steven Sugarman, MD 
Arlyn Apollo, MD 
Pamela Drullinsky,  MD 
Zoe Goldberg, MD 
Kenneth Ng, MD 
Tiffany Troso-Sandoval, MD 
Michelle Boyar, MD 
Philip Caron, MD, PhD 
Nancy Mills, MD 
Stephanie Smith-Marrone, MD 
Carolyn Wasserheit-Lieblich, MD 
Anna Dee, MS, NP-C 
Ewa Chauvin, MSN, ANP-C 
Medicine: BMT 
Medicine: BMT 
Medicine: Lymphoma/Myeloma 
Medicine: Lymphoma/Myeloma 
Epidemiology and Biostatistics 
Medicine: All Network Sites 
Medicine: Basking Ridge 
Medicine: Basking Ridge 
Medicine: Basking Ridge 
Medicine: Commack 
Medicine: Commack 
Medicine: Commack 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
Medicine: BMT 
Medicine: Myeloma 


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Consenting 
Professional(s)/Department: 
David Chung, MD 
Sergio Giralt, MD 
Heather Landau, MD 
Hani Hassoun, MD 
Nikoletta Lendvai, MD 
Alex Lesokhin, MD 
Ephraim Casper, MD 
Audrey Hamilton, MD 
Mila Gorsky, MD 
Han Xiao, MD 
John Fiore, MD 
Stuart Lichtman, MD 
Steven Sugarman, MD 
Arlyn Apollo, MD 
Pamela Drullinsky,  MD 
Zoe Goldberg, MD 
Kenneth Ng, MD 
Tiffany Troso-Sandoval, MD 
Michelle Boyar, MD 
Philip Caron, MD, PhD 
Nancy Mills, MD 
Stephanie Smith-Marrone, MD 
Carolyn Wasserheit-Lieblich, 
MD 
Medicine: BMT 
Medicine: BMT 
Medicine: BMT 
Medicine: Lymphoma/Myeloma 
Medicine: Lymphoma/Myeloma 
Medicine: Lymphoma/Myeloma 
Medicine: All Network Sites 
Medicine: Basking Ridge 
Medicine: Basking Ridge 
Medicine: Basking Ridge 
Medicine: Commack 
Medicine: Commack 
Medicine: Commack 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Rockville Centre 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
Medicine: Sleepy Hollow 
 
Please Note: A Consenting Professional must have completed the mandatory Human Subjects 
Education and Certification Program. 


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Participating  Institutions 
PI's Name 
Site's Role 
Montefiore Medical Center 
Ira Braunschweig, MD 
Data Collection 
Weill Cornell Medical College 
Tomer Mark, MD 
Data Collection 
North Shore LIJ 
Ruthee-Lu Bayer, MD 
Data Collection 
University of Rochester Medical Center 
Michael W, Becker , MD 
Data Collection 
SUNY Downstate 
Gurinder Sidhu, MD 
Data Collection 
Stamford Hospital 
Michael Bar, MD 
Data Collection 
Columbia University Medical Center 
Markus Mapara, MD 
Data Collection 
SUNY Upstate 
Teresa Gentile, MD 
Data Collection 
 
 
Memorial Sloan-Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 


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IRB#: 11-107A(12) 
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Table of Contents 
1.1 
PROTOCOL SUMMARY AND/OR SCHEMA .................................................................................... 6 
1.2 Background and Rational ............................................................................................................... 6 
1.3 Study Design and Objectives .......................................................................................................... 7 
1.4 Patients Eligibility ............................................................................................................................ 7 
1.5 Treatment Intervention ......................................................................................................................... 7 
1.6 Outcome Measurements ..................................................................................................................... 7 
1.7 Statistical Considerations ............................................................................................................... 7 
1.8 Study Schema ............................................................................................................................................ 8 
2.0 
OBJECTIVES AND SCIENTIF IC AIMS ................................................................................................. 9 
3.1 
BACKGROUND AND RATIONALE ............................................................................................... 9 
3.2 
Overview on Upfront Treatment of Multiple Myeloma ................................................................... 9 
3.2.1 
Initial therapy ............................................................................................................... 10 
3.2.2 
Autologous Stem Cell Transplantation ................................................................................. 10 
3.2.3 
Post Transplant Maintenance Therapy ............................................................................ 10 
3.3 
Rationale for the study ............................................................................................................. 12 
3.3.1 
Rationale for Lenalidomide Intensification Dose ................................................................. 12 
3.3.2 
Rationale for patient population under study ....................................................................... 13 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION ................................................................... 15 
4.2 
Design ................................................................................................................................ 15 
4.3 
Intervention ......................................................................................................................... 15 
5.1 
THERAPEUTIC/DIAGNOSTIC AGENTS ................................................................................. 16 
5.2 
Lenalidomide ...................................................................................................................... 16 
5.2.1 Clinical Pharmacology ........................................................................................................... 17 
5.2.2 
Supplier(s) .............................................................................................................................. 18 
5.2.3 
Dosage form .................................................................................................................... 18 
5.2.4 
Packaging ................................................................................................................ 18 
5.2.5 
Storage ........................................................................................................................ 18 
5.2.6 
Prescribing Information .................................................................................................... 18 
5.2.7 
Pregnancy Testing ....................................................................................................... 18 
5.3 
Dexamethasone ...................................................................................................................... 19 


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5.3.1 Description ..................................................................................................................... 19 
5.3.2 
Form ....................................................................................................................... 19 
5.3.3 
Storage and Stability ................................................................................................... 19 
5.3.4 
Handling ........................................................................................................................... 20 
5.3.5 
Availability and ordering .............................................................................................. 20 
5.3.6 
Preparation ................................................................................................................. 20 
6.1 
CRITERIA FOR SUBJECT ELIGIBIL ITY ..................................................................................... 20 
6.2 
Subject Inclusion Criteria ......................................................................................................... 20 
6.3 
Subject Exclusion Criteria ........................................................................................................ 21 
7.0 
RECRUITMENT PLAN ................................................................................................................ 21 
8.0 
PRETREATMENT EVALUATION................................................................................................ 23 
9.1 
TREATMENT/INTERVENTION PLAN ................................................................................................. 24 
9.2 
Treatment Plan ................................................................................................................... 24 
9.3 
Cycle Delay and Dose Modification Guidelines ....................................................................... 25 
9.3.1. Instruction for Initiation of a New Cycle ............................................................................... 25 
9.3.2. Lenalidomide Dose Reduction Guidelines .......................................................................... 26 
9.3.3. Lenalidomide Dose Reduction Levels ................................................................................... 28 
9.2.4 Dexamethasone Dose Reduction Guidelines ........................................................................ 28 
9.2.5 Dexamethasone dose reduction levels .............................................................................. 29 
9.3 
Supportive Care ....................................................................................................................... 30 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION ............................................................ 30 
Correlative Studies ......................................................................................................................... 31 
Schedule of Study Assessments .................................................................................................... 32 
11.1 TOXICITIES/SIDE EFFECTS .................................................................................................. 33 
11.2 Expected Side Effects of Lenalidomide ...................................................................................... 34 
11.3 Expected Side Effects of Dexamethasone ............................................................................... 36 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ............................................ 37 
13.0 CRITERIA FOR REMOVAL FROM STUDY .................................................................................... 39 
14.0 BIOSTATISTICS ............................................................................................................................... 40 
15.1 RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES .......... 41 
15.2 Research Participant Registration ................................................................................................ 41 
15.1.1 Research Participant Registration for Collaborating Sites ................................................. 41 
15.3 Randomization ......................................................................................................................... 42 


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16.1 DATA MANAGEMENT ISSUES ....................................................................................................... 42 
16.1.1 Data and Source Documentation for Collaborating Sites ...................................................... 42 
16.1.2 Data and Source Documentation Submission for Participating Sites .................................... 43 
16.1.3 Data and Source Documentation Submission Timelines for Participating Sites .................... 43 
16.1.4 Data Review and Queries for Participating Site Data .................................................................... 43 
16.2 Quality Assurance .................................................................................................................... 44 
16.2.1 Investigator responsibilities .................................................................................................. 44 
16.2.2 Retention of Records ........................................................................................................... 44 
16.2.3 Quality Assurance for Participating Sites ................................................................................ 45 
16.2.4 Response Review ............................................................................................................... 45 
16.3 Data and Safety Monitoring .......................................................................................................... 46 
16.4 Regulatory Documentation ......................................................................................................... 46 
16.4.1 Amendments ....................................................................................................................... 47 
16.4.2 Additional IRB Correspondence .......................................................................................... 47 
16.4.3 Document maintenance ....................................................................................................... 48 
16.5 Noncompliance .......................................................................................................................... 48 
17.1 PROTECTION OF HUMAN SUBJECTS ..................................................................................... 48 
17.2 Privacy ............................................................................................................................... 49 
17.3 Serious Adverse Event (SAE) Reporting ................................................................................. 49 
17.2.1 Reporting SAE to Study Supporter (Celgene Corporation) ................................................. 51 
17.4 Serious Adverse Event (SAE) Reporting for Participating Sites ............................................... 52 
17.5 Safety Reports ............................................................................................................................ 53 
18.1 INFORMED CONSENT PROCEDURES ......................................................................................... 55 
18.2 FOR PARTICIPATING SITES ................................................................................................ 55 
19.0 REFERENCES .................................................................................................................................. 56 


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1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
1.1 Background and Rational 
 
The standard first line therapy for patients with multiple myeloma includes 2 phases: An initial 
treatment, which usually consists of a combination of several drugs given for 3 to 6 cycles, followed 
by consolidation with autologous stem cell transplantation using high dose melphalan (HDM/ASCT). 
In recent years, the HDM/ASCT consolidation phase has often been replaced by a continuous 
phase, in which some or all the drugs used as initial treatment are continued beyond the initial 3-6 
cycles. Lenalidomide is often chosen for this continuous phase, due to its convenient oral 
administration, becoming a continuous/maintenance treatment. In additions, two major large studies 
recently presented at the ASCO and ASH meetings in 2010, have emphasized the role of 
maintenance therapy with low dose lenalidomide after HDM/ASCT. Both studies have shown a 
statistically significant improvement in the progression free survival for patients receiving 
maintenance therapy with low dose lenalidomide after HDM/ASCT. Although the improvement in 
overall survival is currently not fully established (there is a trend toward increased OS), it is clear at 
this time that maintenance therapy post HDM/ASCT has been widely adopted by myeloma experts. 
Therefore, most patients who initiate therapy for multiple myeloma will remain on maintenance 
therapy with low dose lenalidomide as part of their initial treatment. 
 
However, most of these patients will eventually progress while on lenalidomide therapy. Patients 
with “symptomatic progression of disease (POD)” defined by new symptomatic bone lesions, 
progressive anemia, hypercalcemia, or progressive renal failure attributable to the multiple 
myeloma, usually in association with a rise in the serum or urine paraprotein, will require re- 
induction therapy with combination chemotherapy to prevent further organ deterioration. 
However, the subset of patients with “serologic or asymptomatic POD”, i.e. whose only evidence 
of disease progression is an increase in the paraprotein level by > 25% above plateau baseline, 
have a variable natural history with many patients not showing symptomatic progression for 
months. Based on the results of the initial phase I trial of lenalidomide in which higher responses 
were seen with higher doses of lenalidomide, we hypothesize that in patients relapsing on 
lenalidomide maintenance doses of 5-15 mg orally daily, the disease could be brought under 
control by increasing the dose of lenalidomide (intensification) to 25 mg. However, the response 
rates and tolerance of lenalidomide dose intensification in the setting of lenalidomide 
maintenance is unknown, which is the basis for the proposed clinical trial. 
 
For the purpose of clarity, the term asymptomatic POD will be used henceforward to designate 
serologic only POD, while symptomatic POD will be used to designate POD associated with 
progression of organ damage. 


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1.2 Study Design and Objectives 
 
The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in 
patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT 
or as continuous/maintenance therapy after initial treatment. The primary objective of this trial is 
to determine the overall response rate (ORR) at 6 months and the toxicity of lenalidomide 
administered at a dose of 25 mg orally, days 1 to 21 of a 28 day-cycle, without or with 
dexamethasone added after 2 cycles, in patients with multiple myeloma found to have 
asymptomatic POD while on a maintenance lenalidomide dose of 15 mg daily or less. 
 
 
1.3 Patients Eligibility 
 
Patients with multiple myeloma with evidence of asymptomatic POD while on lenalidomide 
maintenance post HDT/ASCT or on continuous/maintenance therapy as part of first line therapy 
will be eligible to participate in this trial. Patients will need to have progression of disease 
documented as defined by modified IMWG criteria and will have no evidence of progression of 
organ damage (progression of severe anemia, renal failure, hypercalcemia, bone disease). 
 
1.4 Treatment  Intervention 
 
After registration patients will begin therapy with lenalidomide 25 mg daily, 21 days out of a 28 
day schedule. All patients will be evaluated monthly after every cycle. The dose will be adjusted 
downward in response to side effects and according to specific guidelines. Symptomatic POD 
occurring at any time during the study will result in removal of the patient from the study. After 2 
cycles of lenalidomide, patients with at least stable disease (SD) will continue lenalidomide 
indefinitely until asymptomatic POD, at which time dexamethasone will be added at a dose of 
40mg weekly. On the other hand, patient with asymptomatic POD after 2 cycles of lenalidomide 
will have dexamethasone added at a dose of 40 mg weekly. Patients with any type of POD after 
any cycle that includes dexamethasone will be taken off study. Patients can remain on study on 
lenalidomide or lenalidomide/dexamethasone indefinitely as long as they do not have POD as 
stated above and they tolerate the treatment. 
 
1.5 Outcome Measurements 
 
The response to treatment intervention will be measured using a modified version of the widely 
accepted Uniform International Response Criteria in multiple myeloma. To determine  
response, patients’ disease will be assessed at the beginning of every cycle and compared to 
the new baseline established within two weeks prior to initiation of lenalidomide intensification. 
 
1.6 Statistical  Considerations 
 
The focus of this study is to estimate the overall response rate (>PR) to lenalidomide 


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intensification with or without dexamethasone at 6 months. A single stage design that 
differentiates between response rates of 15% and 30% will be used to assess efficacy of 
lenalidomide intensification with or without dexamethasone.  The probabilities of a type I error 
(falsely accepting a non-promising therapy) and type II error (falsely rejecting a promising 
therapy) are set to 0.10 and 0.10, respectively.  The null hypothesis response rate is based on 
the response rate to the standard of care therapy in patients previously exposed to  
thalidomide who have relapsed or refractory disease. A total of 53 patients will be accrued.  At 
the conclusion of the study, if a least 12 of the 53 patients respond by 6 months the treatment 
will be declared a success. 
 
 
1.7 Study Schema 
 
 
 
 
*Note that patients with symp tomatic 
POD after any cycle will be taken off 
study 
 
 
Off Trial 
Start Lenalidomide 25 mg Orally 21/28days 
Asymptomatic POD 
after 2 cycles 
> SD after 2 cycles 
Continue Lenalidomide 
orally, daily, 21/28 days 
until asymptomatic POD 
Asymptomatic POD 
Patients with MM meeting the following eligibility criteria: 
1. 
On maintenance lenalidomide as part of initial  line of 
therapy 
2. 
With asymptomatic POD and no active organ damage 
Add dexamethasone 40mg 
weekly until asymptomatic POD 
Asymptomatic POD 
after any cycle 


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2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
 
Primary objective: 
 
 To determine the overall response rate (CR, VGPR, PR, and MR) after 6 months of 
lenalidomide intensification administered initially at a dose of 25 mg orally days 1 to 21 of a 
28 day-cycle, with or without the addition of dexamethasone, in patients with multiple 
myeloma found to have asymptomatic progression of their disease while on maintenance 
lenalidomide dose of 15mg mg daily or less. 
 
Secondary objectives: 
 
  To determine rates of > Grade 2 toxicity according to the Common Terminology Criteria for 
Adverse Events (CTCAE) Version 4.0 
  To determine the overall response rate (CR, VGPR, and PR) at 6 months from initiation of 
lenalidomide intensification therapy of lenalidomide given as a single agent. 
  To determine progression free survival: The PFS is defined as the time from registration to 
relapse/progression, death, initiation of non-protocol anti myeloma therapy, loss to follow up 
or end of study whichever comes first. 
  To determine OS:  The OS is defined as the time from registration to death, loss to follow-up 
or the end of the study, whichever comes first.  Patients alive at the time of last observation 
are considered censored. 
 
 
3.0 
BACKGROUND AND RATIONALE 
3.1 
Overview on Upfront Treatment of Multiple Myeloma 
 
Multiple myeloma (MM) is a disease characterized by a malignant plasma cell proliferation, bone 
destruction and immunodeficiency. Median age at diagnosis is approximately 70 years.  It is 
responsible for about 1 percent of all cancer-related deaths in Western Countries.1-3 The disease 
accounts for an estimated 15,000 new cancer cases per year in the United States, as well as 
approximately 11,000 deaths2.  Based on the United Kingdom (UK) Myeloma Forum and the 
Nordic Myeloma Study Group recommendations1 and National Comprehensive Cancer Network 
(NCCN) Practice Guidelines4, chemotherapy is indicated for the management of myeloma 
presenting with myeloma-related organ damage (referred to as symptomatic myeloma as   
opposed to asymptomatic myeloma). Standard first line treatment for patients with symptomatic 
multiple myeloma deemed eligible for transplantation, consists of 2 phases of treatment: The first  
is referred to as the initial therapy and consists of various combinations of therapeutic agents. The 
second consists of high dose melphalan followed by autologous stem cell transplant 
(HDM/ASCT)5,6. Attempts to cure myeloma through high-dose therapy followed by autografting or 
even allografting have largely failed due to both relapsed disease and treatment-related mortality 
(TRM).Although high-dose therapy with autologous transplantation is safe and has low TRM (< 
5%), it is associated with a continuing and nearly universal risk of disease relapse and 
progression.  Therefore, despite the potential benefits of newer treatments, multiple myeloma 


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remains an incurable disease and relapse occurs in almost all patients, with a median survival 
period of 5 to 7 years5,6. 
3.1.1 Initial therapy 
 
The regimens currently recommended in the NCCN guidelines for initial therapy of MM in patients 
who are candidates for HDM/ASCT include dexamethasone, thalidomide and dexamethasone, 
Lenalidomide and dexamethasone, liposomal doxorubicin. Vincristine and dexamethasone (DVD), 
as well as several bortezomib based regimens4. In previously untreated patients, bortezomib has 
shown activity as a single agent7-9 and also in combination with dexamethasone7,10, 
thalidomide/dexamethasone11,12, melphalan/prednisone (MP)13,14, dexamethasone and 
adriamycin15,16 as well as Lenalidomide and dexamethasone.  It is widely accepted that in patients 
who will undergo HDM/ASCT, melphalan-containing regimens should be avoided since stem cell 
collection may be subsequently hampered. 
 
 
3.1.2 Autologous Stem Cell Transplantation 
 
There have been two large prospective trials in France (IFM 90) and in UK (MRC 9), and one 
large retrospective study of myeloma patients in Nordic countries, showing a survival benefit for 
HDM/ASCT compared to conventional chemotherapy17-19. In the larger study, IFM 90, newly 
diagnosed untreated patients less than 65 years of age with DS stage II or III MM were 
randomized to either SCT after up to 6 cycles of VMCP alternating with BCNU, vincristine, 
doxorubicin and prednisone (BVAP) or conventional chemotherapy with 18 cycles of VMCP 
alternating with BVAP. The SCT regimen was MEL 140 mg/m2 and TBI, and recombinant 
interferon alpha (IFNα) was administered to patients in both groups until relapse. By intent-to- 
treat, SCT patients had a significantly higher response rate (CR+VGPR 38% versus 14%) than 
those receiving conventional chemotherapy. At a median follow-up of 37 months in the 
chemotherapy group and 41 months in the SCT group, the latter had significantly longer PFS and 
OS.  The other two studies have confirmed these results although the dose of melphalan given 
was 200 mg/m2 and radiation therapy was not used. Based on these trials, autologous stem cell 
transplantation using melphalan 200 mg/m2 has become part of the standard treatment of 
symptomatic multiple myeloma. Smaller studies have reached similar conclusions6,20. 
Although HDM/ASCT has improved response rate6,17,18,20 and overall survival17,18,20,21 rate in 
patients with MM, all patients eventually relapse. Clinical trials have investigated the use of 
consolidation22 and maintenance23-26 therapy post-transplant to extend the duration of response. 
 
3.1.3 Post Transplant Maintenance Therapy 
 
One approach to improving disease control after HDM/ASCT is the use of post-transplant 
interventions, such as interferon and, more recently, anti-angiogenic agents such as thalidomide 
and lenalidomide. The use of thalidomide as post-transplant maintenance has been studied in 
several randomized trials24,25,27.  The IFM 99-02 trial randomized patients after tandem 
autologous transplantation (using melphalan 140mg/m2 for the first and melphalan 200mg/m2 for 


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the second transplant) to either no maintenance, maintenance with pamidronate or maintenance 
with thalidomide and pamidronate.  Patients received thalidomide for a median of 15 months. 
The major treatment-related side effect was neuropathy (68% of patients).  Patients who received 
thalidomide had improved EFS and OS.  Of note, patients who achieved a VGPR after 
transplantation did not benefit from thalidomide maintenance27.  This suggests that the benefit of 
post-transplant thalidomide might result from upgrading responses. 
New immunomodulatory drugs (IMiDs®) such as lenalidomide are now commonly used in clinical 
practice.  The side effect profile of lenalidomide is superior to that of thalidomide.  In normal 
volunteers the most common adverse events with lenalidomide are rash and pruritus.  Phase II 
trials of lenalidomide plus dexamethasone for upfront therapy of myeloma demonstrate high 
response rates11. Lenalidomide, a member of the new immunomodulatory class of drugs has 
recently demonstrated high-response rates and favorable side effect profile in upfront and salvage 
trials28,29.  A Phase II trial at the Mayo Clinic used lenalidomide and dexamethasone as induction 
therapy.  The overall response rate was 91%. The Phase III MM009 trial of lenalidomide and 
dexamethasone versus dexamethasone alone for relapsed/refractory MM reported response   
rates of 61% with combination therapy compared to 22% with dexamethasone alone.29 Hence, 
based on both a more favorable side effect profile and higher CR rates, lenalidomide appears to 
be a superior drug for maintenance therapy. 
 
In 2010 two large randomized trials were presented both in the meeting of the American Society of 
Clinical Oncology in Chicago and the meeting of the American Society of Hematology in Orlando 
exploring the use of single agent lenalidomide as post transplant maintenance therapies. 
McCarthy et al. presented the results of CALGB 100104 whose primary endpoint was to 
investigate the role of maintenance lenalidomide in prolonging time to progression (TTP) following 
single autologous SCT.30 Patients with chemosensitive disease after an initial autologous SCT 
were randomized at day 100-110 post-ASCT to lenalidomide 10 mg/day or placebo until disease 
progression. A total of 554 patients were registered during the third interim analysis, and 33% of 
the required number of events (progression or death before progression) had been observed. The 
median follow-up is 17.5 months. The number of events among 231 pts randomized to 
lenalidomide was 37 compared to 84 among 229 pts randomized to placebo. The one-sided 
unadjusted P-value was < 0.0001. The estimated hazard ratio was 0.35 (95% CI=0.24, 0.53) 
corresponding to a 65% reduction in event risk (progression or death) in the lenalidomide arm. 
The estimated median TTP was 22.5 months for the placebo arm. The preliminary estimated 
median TTP was 45.5 months for the study arm. Benefits were seen regardless of whether patients 
received lenalidomide or thalidomide as induction therapy. Comparing lenalidomide versus  
placebo, post-randomization, pooled Gr 3-5 AEs, there were significantly more episodes of 
thrombocytopenia (11% versus 3%, p=0.01), neutropenia (44% vs 8%, p<0.0001) and anemia 
(5% vs 1%, p=0 .0082) with lenalidomide. No significant differences in incidence of febrile 
neutropenia, infection, fatigue, neuropathy, rash, thromboembolic events were seen. 
Lenalidomide patients discontinued therapy due to AEs more frequently than placebo (13% vs 
2%). Attal et al. presented the results of a similar trial performed by the Intergroup Francophone 
du Myelome that enrolled 614 patients who had undergone autologous stem cell transplantation 
for non-progressive myeloma within the previous six months31. Patients were randomly assigned 
to placebo (307 patients) or 10 mg to 15 mg of lenalidomide daily (307 patients) until relapse. 


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After a median follow-up of 24 months, only 25% of the lenalidomide group experienced 
progression or death compared with 47% of the placebo group. Maintenance with lenalidomide 
improved three- year PFS from randomization by 34% in the placebo group compared with 68% in 
lenalidomide group (HR=0.46). Benefits were seen regardless of response to induction therapy10. 
These 2 studies have consolidated the role of maintenance therapy, in particular lenalidomide, 
after autologous stem cell transplantation.  It is unknown whether use of post-transplant 
maintenance lenalidomide until disease progression will provide similar EFS and OS to either 
tandem transplantation or a single transplant followed by consolidation and maintenance. This is 
currently being actively investigated. However, maintenance therapy with low dose lenalidomide 
has been widely embraced and most patients will be receiving this treatment following 
HDM/ASCT. 
 
3.2 
Rationale for the study 
 
As mentioned above, all patients with multiple myeloma treated with the currently available 
treatment modalities and strategies will eventually relapse. Patients on maintenance lenalidomide 
are no exception to this rule. However, it is currently unknown whether these patients whose 
disease progress, while on low dose lenalidomide as maintenance therapy, will respond to 
treatment with higher doses (considered standard doses, but for the purpose of this trial referred to 
as intensification) of lenalidomide. Currently it is widely perceived among physicians that these 
patients have a disease that is lenalidomide resistant and there is an actual risk of these patients 
being denied access to a potentially very effective agent, if given at higher (standard) dose. 
 
3.2.1 Rationale for Lenalidomide Intensification Dose 
 
The maximum tolerated dose (MTD) of lenalidomide as a daily dose is 25 mg with dose-limiting 
toxicity (DLT) being grade 3/4 myelosuppression. The Phase I trial of single agent lenalidomide 
demonstrated higher response rates with increasing dosage with 20%, 66%, and 69% of patients 
having at least a minimal response when receiving 10 mg, 25 mg, and 50 mg respectively32. Based 
on the pharmacokinetic data of the phase I trial, and the favorable toxicity profile observed, a 
randomized Phase II study has been reported that examined a higher dose with an interrupted 
schedule: 15 mg twice daily versus 30 mg daily on a 3 weeks on / 1 week off schedule 33. This 
study examined 70 patients randomized to the two schedules.  Fifty-seven patients were analyzed 
for toxicity and 46 for response.  In this heavily pre-treated group of patients, 24% had a CR or 
PR or minimal response and only 16% had progressive disease.  One patient developed grade 3 
neuropathy.  The most common grade 1 and 2 toxicities were fatigue, self-limited rash, muscle 
cramps and diarrhea.  Grade 3 or 4 myelosuppression was seen in 26% (n=15) of patients. Eleven 
of these 15 patients had undergone a prior autologous transplant; most (n=11) were on the 15 mg 
twice a day dose.  The daily dosing schedule was felt to be more favorable based on its toxicity 
profile and simplicity of administration with best opportunity for compliance.  There was no 
evidence that an interrupted schedule enhanced long-term tolerability or response. Thus, there is 
data supporting the dose related response to lenalidomide and its optimal efficacy/tolerability ratio 
with 25 mg given daily for 21 days every 28 days. 


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3.2.2 Rationale for patient population under study 
 
 
3.2.2.1 
Relapse Patterns Post-Autologous Stem Cell Transplantation 
 
The two largest reports of the natural history of relapse post autograft in myeloma were both 
reported prior to the advent of lenalidomide and bortezomib. Alegre et al. reported on the 
outcomes of 280 patients who had relapsed after transplantation and had data available in the 
Spanish registry34. The clinical patterns of relapse fell into one of four categories: 
a) Insidious relapse characterized by asymptomatic elevations of the blood or urine protein 
occurred in 18% of patients. 
b) Classic relapse characterized by an increase in monoclonal component along with clinical 
symptoms occurred in 66% of patients 
c) Plasmacytomas occurred in 14% of patients and was characterized by presentation with 
multiple extramedullary plasmacytomas. 
d) Plasmacytic leukemia  as the  initial clinical manifestation of relapse occurred  in 2% of 
patients. 
 
Median overall survival after relapse was 14 months for the whole group with a significant 
difference in the OS of patients with the insidious form of relapse when compared to those with 
symptomatic or plasma cell leukemia patterns of relapse (18 months vs 12 months v/s 5 months 
respectively; p < 0.001). 
 
Lenhoff et al. reviewed the outcomes of 397 patients who had relapsed after autologous 
transplantation between 1994 and 199735.  The patterns of relapse after transplantation were 
classified based on a modification of a model presented by Alegre et al. The insidious pattern 
accounted for 31% , the classical pattern for 51%, and the plasmacytoma pattern for 14% of all 
relapses and characterized by bone marrow or extramedullary plasmacytoma with minor or no 
other signs of relapse and finally transformed disease which accounts for 4% of relapses and 
presents as plasma cell leukemia or immunoblastic lymphoma. No association was found 
between the pattern of relapse and any of the clinical features at diagnosis. The insidious form of 
relapse was significantly less common in patients who had attained complete response after 
transplantation than in patients who had not (17% versus 40% of the relapses, respectively). 
Patients who relapsed with transformed disease had a significantly shorter duration of first 
response after transplantation (median 3 months) compared to patients relapsing with an 
insidious (median 20 months), classical (median 20 months) or plasmacytoma (median 24 
months) pattern. Survival was related to the type of relapse and longest in patients with the 
insidious pattern (median 39 months) and shortest in patients with transformed disease (median 
2 months). Patients with the classical pattern of relapse were subdivided into two groups; those 
with skeletal clinical symptoms only at relapse (n=46) and those with additional symptoms such 
as cytopenias, hypercalcemia, renal insufficiency, etc. (n=37). Patients with only skeletal 
symptoms had a median survival after relapse of 30 months, while those with additional 
symptoms had a significantly shorter median survival of 18 months. 


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Patients relapsing with an insidious or classical form of disease with skeletal events only, or after 
a long lasting first response were likely to respond well to conventional salvage therapy. In 
contrast, relapse with multiple symptoms, transformed disease or a short duration of first 
response implied bad prognosis. Of the 162 patients who relapsed 49% received a melphalan 
based salvage regimen with 59% having at least a 25% reduction in tumor burden, 34% received 
a VAD like re-induction with a 46% response rate, 8% received thalidomide with a 67% response 
rate and 8% received a second autograft as salvage therapy  with an 83% response rate. 
Response to relapse therapy was important for survival after relapse. Patients with a partial 
response or better to relapse therapy had a median survival of 36 months vs 37 months for minor 
responders and 8 months for nonresponders. The median survival after start of relapse therapy 
was 33 months for complete and partial responders and 26 months for minor responders and 7 
months for non responding patients. Sixty-one patients have been treated for subsequent. 
More recently Kumar et al reported on the outcomes of patients relapsing after autologous 
transplant in the era of lenalidomide and bortezomib therapy36. Among 494 patients, undergoing 
auto-SCT within 12 months of diagnosis they identified 124 patients who had relapsed within 12 
months of high dose therapy, this group had a significantly shorter median overall survival (OS) 
from diagnosis (26.6 vs 90.7 months) and from SCT than those relapsing later in the course of 
their disease. Median survival from relapse was only 10.8 months in the early relapse group 
compared to 41.8 months for the rest. Among the 97 patients who relapsed early after transplant, 
patients who received thalidomide, bortezomib and/or lenalidomide) had a better survival than 
those that did not receive those drugs 15.9 months vs 4.5 months. Benefits of exposure to 
lenalidomide, bortezomib or thalidomide were confirmed in a larger series of 387 patients reported 
by the same authors. Those relapsing after the year 2000 had a median overall survival of 23.9 
versus 11.8 months (P < .001) for those who relapsed prior to this date. Patients treated with 
thalidomide, lenalidomide, or bortezomib had longer survival from relapse (30.9 vs 14.8 months; P 
< .001)37. 
 
With the results of CALGB100104 and IFM05 it is likely that many patients will now be relapsing 
on lenalidomide maintenance which consists of lower doses of lenalidomide without 
dexamethasone.  Based on the results of the phase I study of lenalidomide we hypothesize that 
intensifying the dose of lenalidomide could potentially re-establish control of the disease in up to 
30% of myeloma patients with asymptomatic relapses, therefore saving the use of other agents 
for future use. 
 
3.2.2.2 
M SKCC Experience with Relapse after HDM/ASCT 
 
We have recently reviewed the pattern of relapse in 40 patients who have participated in CALGB 
100104 clinical trial and enrolled at MSKCC between 2005 and 2009. Among these 40 patients, 
relapse from CR or progression has occurred in 16 patients. The first evidence for 
relapse/progression was detected by Immunofixation in four patients who were in CR; SPEP with 
increase in M spike in five patients (3 who were in PR and 2 in VGPR); and free light chain assay 
in five patients (four who were in CR and one in PR). Only two among the 16 patients were found 
to have relapse/progression of disease after development of symptoms due to organ damage, 
triggering an evaluation by MRI that lead to the diagnosis of relapse/progression. This data would 


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indicate, contrary to the previous two reports detailed above by Lenhoff et al. and Alegre et al., that 
asymptomatic relapse (referred to as insidious relapse by these authors) is currently the most 
common pattern of relapse nowadays. This is most likely related to the availability of the free light 
chain assay which allows earlier detection of disease relapse and progression. In addition, the 
prospective aspect of the CALGB 100104 clinical trial that called for a rigorous monitoring of the 
patients every three months, certainly contributed to the earlier detection of relapse and 
progression prior to the development of organ damage. Despite the small sample of this 
observation, we are confident that the most common form of relapse and/or progression in patients 
receiving maintenance therapy after HDM/ASCT is asymptomatic. Hence, we anticipate that  
patient recruitment within this population will be facilitated. 
 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.1 
Design 
 
In this multi-center Phase II single arm trial, 53 patients fulfilling the eligibility criteria, will be  
treated with lenalidomide 25 mg PO daily for 21 out of 28 day cycles. The patients’ responses to 
the treatment will be assessed after every cycle. Patients who have asymptomatic POD after 2 
cycles will have dexamethasone added at a dose of 40 mg PO weekly. Patients who have at least 
SD after 2 cycles will continue lenalidomide single agent until asymptomatic POD, at which time 
they will have dexamethasone added at a dose of 40 mg PO weekly.  Patients will be taken off 
study if they have symptomatic POD after any cycle, if they have any type of POD after 
dexamethasone is added, or if they do not tolerate the treatment. The patients taken off study due 
to any type of POD, will be considered failures for the primary response endpoint if progression 
occurred within 6 months.  Patients who are removed from study prior to completing 2 cycles of 
therapy for reasons other than POD will be considered inevaluable for response and will be 
replaced. Accrual will continue until 53 evaluable patients have been accrued.  Patients who have 
received any study drug will be evaluated for safety. 
 
4.2 
Intervention 
 
Patients with asymptomatic POD while on maintenance lenalidomide after HDM/ASCT or on 
continuous/maintenance therapy after initial treatment will be enrolled on this clinical trial and will 
undergo the following interventions: 
 
  Patients will have their disease fully reassessed in order to establish a new pre- 
therapy baseline within 2 weeks of initiation of treatment. 
  Patients will receive lenalidomide at a dose of 25 mg PO daily for 21 days out of 
28-days-cycles. 
  Patient will be evaluated for response and toxicity after every cycle. 
  Patients with at least SD after 2 cycles of lenalidomide will continue on 
lenalidomide until asymptomatic POD, at which time dexamethasone 
will be added at a dose of 40 mg PO weekly at the next cycle. 


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 
  Patients with asymptomatic POD after 2 or more cycles of lenalidomide will have 
dexamethasone added to lenalidomide at a dose of 40 mg PO weekly at the next 
cycle. 
  Patients with further asymptomatic POD after at any cycle of lenalidomide and 
dexamethasone will be taken off study and treated at the discretion of the 
treating physician. Note that further POD after the addition of dexamethasone 
will be determined compared to the new M spike baseline just prior to the 
addition of dexamethasone. 
  Note that patients with symptomatic POD at any point in time during treatment will 
be taken off study. 
 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
5.1 
Lenalidomide 
 
Lenalidomide, a thalidomide analogue, is an immunomodulatory agent with anti-angiogenic 
properties.  The chemical name is 3-(4-amino-1-oxo 1,3-dihydro -2H-isoindol-2-yl) piperidine-2,6- 
dione and it has the following chemical structure: 
 
Chemical Structure of Lenalidomide 
 
 
O 
O 
H 
N 
N 
O 
 
NH2 
 
3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl) piperidine-2,6-dione 
 
The empirical formula for lenalidomide is C13H13N3O3, and the gram molecular weight is 259.3. 
 
Lenalidomide is off-white to pale-yellow solid powder. It is soluble in organic solvent/water 
mixtures, and buffered aqueous solvents. Lenalidomide is more soluble in organic solvents and 
low pH solutions. Solubility was significantly lower in less acidic buffers, ranging from about 0.4 to 
0.5 mg/ml. Lenalidomide has an asymmetric carbon atom and can exist as the optically active 
forms S(-) and R(+), and is produced as a racemic mixture with a net optical rotation of zero. 


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5.1.1 Clinical Pharmacology 
 
Mechanism of Action: 
The mechanism of action of lenalidomide remains to be fully characterized. Lenalidomide 
possesses immunomodulatory and antiangiogenic properties.  Lenalidomide inhibited the 
secretion of pro-inflammatory cytokines and increased the secretion of anti-inflammatory 
cytokines from peripheral blood mononuclear cells.  Lenalidomide inhibited cell proliferation with 
varying effectiveness (IC50s) in some but not all cell lines.  Of cell lines tested, lenalidomide was 
effective in inhibiting growth of Namalwa cells (a human B cell lymphoma cell line with a deletion 
of one chromosome 5) but was much less effective in inhibiting growth of KG-1 cells (human 
myeloblastic cell line, also with a deletion of one chromosome 5) and other cell lines without 
chromosome 5 deletions.  Lenalidomide inhibited the expression of cyclooxygenase-2 (COX-2) 
but not COX-1 in vitro. 
 
Pharmacokinetics and Drug Metabolism: 
 
Absorption: 
 
Lenalidomide, in healthy volunteers, is rapidly absorbed following oral administration with 
maximum plasma concentrations occurring between 0.625 and 1.5 hours post-dose. 
Co-administration with food does not alter the extent of absorption (AUC) but does reduce the 
maximal plasma concentration (Cmax) by 36%. The pharmacokinetic disposition of lenalidomide 
is linear. Cmax and AUC increase proportionately with increases in dose. Multiple dosing at the 
recommended dose-regimen does not result in drug accumulation. 
 
Pharmacokinetic analyses were performed on 15 multiple myeloma patients treated in the phase I 
studies.  Absorption was found to be rapid on both Day 1 and Day 28 with time to maximum blood 
levels ranging from 0.7 to 2.0 hours at all dose levels (5mg, 10mg, 25mg, and 50mg).  No plasma 
accumulation was observed with multiple daily dosing.  Plasma lenalidomide declined in a 
monophasic manner with elimination half-life ranging from 2.8 to 6.1 hours on both Day 1 and 28  
at all 4 doses.  Peak and overall plasma concentrations were dose proportional over the dosing 
range of 5mg to 50mg.  Exposure (AUC) in multiple myeloma patients is 57% higher than in 
healthy male volunteers. 
 
Pharmacokinetic Parameters: 
 
Distribution: 
 
In vitro (14C)-lenalidomide binding to plasma proteins is approximately 30%. 
 
Metabolism and Excretion: 
 
The metabolic profile of lenalidomide in humans has not been studied. In healthy volunteers, 
approximately two-thirds of lenalidomide is eliminated unchanged through urinary excretion. The 
process exceeds the glomerular filtration rate and therefore is partially or entirely active.  Half-life 
of elimination is approximately 3 hours. 


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5.1.2 Supplier(s) 
 
Celgene Corporation will supply Revlimid® (lenalidomide) to study participants at no 
charge through Celgene’s Revlimid Risk Evaluation and Mitigation Strategy™ (REMS) 
(formerly known as RevAssist® Program). 
5.1.3 Dosage form 
 
Lenalidomide will be supplied as capsules for oral administration. 
 
5.1.4 Packaging 
 
Lenalidomide will be shipped directly to patients. Bottles will contain a sufficient number of 
capsules for one cycle of dosing. 
 
5.1.5 Storage 
 
Lenalidomide should be stored at room temperature away from direct sunlight and protected from 
excessive heat and cold. 
 
5.1.6 Pre scribing Information 
 
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 Celgene Corporation’s Revlimid REMS® program.  Per standard Revlimid 
REMS® program 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. 
 
Only enough lenalidomide for one cycle of therapy will be supplied to the patient each cycle. 
 
 
5.1.7 Pregnancy Te sting 
Pregnancy tests for females of childbearing potential.  A female of childbearing potential (FCBP) 
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). 
 
Pregnancy tests must occur within 10 – 14 days and again within 24 hours prior to prescribing 
lenalidomide for Cycle 1 (prescriptions must be filled within 7 days).  FCBP with regular or no 
menstruation must have a pregnancy test weekly for the first 28 days and then every 28 days 
while on 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 


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lenalidomide (see Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and 
Acceptable Birth Control Methods). 
 
5.2 
Dexamethasone 
 
 
5.2.1 De scription 
 
Dexamethasone is a synthetic adrenocortical steroid. Corticosteroids are naturally-occurring 
chemicals produced by the adrenal glands located above the kidneys. Corticosteroids affect the 
function of many cells within the body and suppress the immune system. Corticosteroids also 
block inflammation and are used in a wide variety of inflammatory diseases affecting many 
organs. 
The molecular weight for dexamethasone is 392.47.  It is designated chemically as 9-fluoro- 
11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. The empirical formula is C22H29FO5 
and the structural formula is: 
 
 
 
 
 
Dexamethasone is stable in air and almost insoluble in water. 
 
 
5.2.2 Form 
 
Dexamethasone is a white to practically white, odorless, crystalline powder. It is available in 2 or 4 
mg tablets (commercially) for oral administration.  Each tablet contains dexamethasone as the 
active ingredient, and the following inactive ingredients: calcium phosphate, lactose, magnesium 
stearate, and starch. The tablet shell may contain the following: D&C Yellow 10, FD&C Yellow 6, 
and/or FD&C Blue 1. 
 
5.2.3 Storage and Stability 
 
All investigational study drugs will be stored in a locked, safe area to prevent unauthorized 
access.  Dexamethasone should be stored at controlled room temperature, 68-77◦F (20-25◦C) 
and not frozen, and according to label requirements. 


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5.2.4 Handling 
Dexamethasone should be handled by trained pharmacy staff.  The use of gloves and other 
appropriate protective clothing is recommended as necessary. 
 
 
5.2.5 Availability and ordering 
Dexamethasone supply will be obtained through commercial supply.  The investigator will order 
drug supply from commercial supply and will not be provided for the current trial. 
 
5.2.6 Preparation 
 
Dexamethasone is an oral drug, and does not require specific preparation details. 
 
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.1 
Subject Inclusion Criteria 
 
Patients fulfilling the following criteria will be eligible for entry into this study: 
 
  Patients must be 18 years of age or above at the time of enrollment. 
  Patients must show evidence of asymptomatic relapse and/or progression of disease 
(increasing M spike in serum or urine by consensus criteria) while on lenalidomide 
maintenance after HDM/ASCT as part of initial line of therapy. Patients who have not 
had an HDM/ASCT as part of initial line of therapy but who are on 
continuous/maintenance lenalidomide after initial therapy will be permitted on study. 
  Patient must have myeloma that is measurable by either serum or urine evaluation of the 
monoclonal component or by assay of serum free light chains.  Measurable disease is 
defined as one or more of the following: serum M-protein > 0.5 g/dl, urine M-protein > 
200 mg/24 h, and/or serum FLC assay: involved FLC level > 10 mg/dL with abnormal 
serum FLC ratio. 
  Patients must have adequate organ function including: Hepatic function with Bilirubin < 
2x the upper limit of normal and ALT and AST < 3 x the upper limit of normal; renal 
function with creatinine clearance > 60 ml/min using the Cockcroft-Gault formula; 
hematologic function as defined by an absolute neutrophil count > 1000 neutrophils per 
microliter, platelet > 50,000 platelets per microliter and hemoglobin of > 9 gm/dL without 
transfusion support. 
  All study participants must be registered into the mandatory Revlimid REMS® program, 
and be willing and able to comply with the requirements of the REMS® program. 
 Females of child bearing potential (FCBP)1 must adhere to the scheduled pregnancy 
testing as required in the Revlimid REMS® program. FCBP must have a negative serum 
 
 
1 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). 


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or urine pregnancy test with a sensitivity of at least  50 mIU/mL within 10 – 14 days and 
again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be 
filled within 7 days) andmust 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 28 days 
before she starts taking lenalidomide.  FCBP must also agree to ongoing pregnancy 
testing.  Men must agree to use a latex condom during sexual contact with a FCBP even 
if they have had a successful vasectomy.  See Appendix: Risks of Fetal Exposure, 
Pregnancy Testing Guidelines and Acceptable Birth Control Methods. 
 
6.2 
Subject Exclusion Criteria 
 
The following patients will be ineligible for registration onto this study: 
 
  Patients with symptomatic relapse and/or progression of multiple myeloma. (Appendix A). 
  Patients with plasma cell leukemia. 
  Karnofsky performance score less than 70% or ECOG performance status greater than 2. 
  Patients with uncontrolled bacterial, viral or fungal infections (currently taking 
medication and progression of clinical symptoms). 
  Patients with prior malignancies except resected basal cell carcinoma or treated cervical 
carcinoma in situ or other cancer treated with curative intent > 5 years previously. 
Cancer treated with curative intent < 5 years previously will not be allowed unless 
approved by the Protocol Chairs. 
  Female patients who are pregnant (positive -HCG) or breastfeeding. (Lactating 
females must agree not to breast feed while taking lenalidomide). 
  Patients seropositive for the human immunodeficiency virus (HIV). 
  Prior organ transplant requiring immunosuppressive therapy. 
  Patients who were previously exposed to higher doses of lenalidomide and who 
developed severe adverse events at higher doses that preclude incremental 
dosing. 
 
7.0 
RECRUITMENT PLAN 
 
This study will be conducted at MSKCC and other collaborating medical centers that are 
members of the newly established Tri-State Transplant Consortium. It is anticipated that 15 
patients will be enrolled from MSKCC and 38 patients will be enrolled from the collaborating 
centers. At MSKCC, patients will be recruited from the large population of patients who currently 
undergo (or have undergone) HDM/ASCT either on the currently accruing transplant clinical trial 
(IRB # 09-171), or past clinical trial (IRB # 05-080), which both include  maintenance therapy  
with lenalidomide after HDM/ASCT as part of management; patients will also be recruited   
among patients who have been transplanted off protocol and receive maintenance lenalidomide 
after transplantation, a practice that has been gaining momentum in the past year. Patients who 
have not had an ASCT as part of initial line of therapy but are on continuous/maintenance 
lenalidomide will also be permitted on study.This trial will also be open at collaborating centers 
which have agreed to participate and we anticipate that a substantial proportion of patients will 


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be accrued through this collaboration. All patients will be registered through MSKCC. All  
patients will be enrolled and followed by physicians at MSKCC and collaborating centers. All co- 
investigators agree to follow the treatment in the protocol and to conduct the proposed 
investigation according to recognized principles of good clinical practice. Participation is 
voluntary. Efforts will be made to ensure that women and minority groups are adequately 
represented in this trial. Each patient must be informed about the neoplastic nature of his/her 
disease and willingly consent to participating in this study. Every patient will be informed of the 
procedures to be followed, the potential benefits, side effects, risks, and discomforts of the trial 
and of potential therapeutic alternatives. All participants will be required to sign statements of 
informed consent and research authorization that conform to FDA, IRB and HIPAA guidelines. 
Informed consent will be documented by the use of a written consent form that has been 
approved by the MSKCC IRB. 
 
Potential research subjects will be identified by a member of the patient’s treatment team, the 
protocol investigator, or research team at Memorial Sloan-Kettering Cancer Center (MSKCC). If 
the investigator is a member of the treatment team, s/he will screen their patient’s medical 
records for suitable research study participants and discuss the study and their potential for 
enrolling in the research study. Potential subjects contacted by their treating physician will be 
referred to the investigator/research staff of the study. 
 
The principal investigator may also screen the medical records of patients with whom they do 
not have a treatment relationship for the limited purpose of identifying patients who would be 
eligible to enroll in the study and to record appropriate contact information in order to approach 
these patients regarding the possibility of enrolling in the study. This will allow the study team to 
keep track of all patients on lenalidomide maintenance therapy for multiple myeloma that may 
subsequently be eligible to enroll onto this study. The study staff and PI will review lists from 
Darwin queries. The patients on these queries will be tracked via a log. 
 
During the initial conversation between the investigator/research staff and the patient, the 
patient may be asked to provide certain health information that is necessary to the recruitment 
and enrollment process. The investigator/research staff may also review portions of their 
medical records at MSKCC in order to further access eligibility. They will use the information 
provided by the patient and/or medical record to confirm that the patient is eligibile and to 
contact the patient regarding study enrollment. If the patient turns out to ineligible for the 
research study, the research staff will destroy all information collected on the patient during the 
initial conversation and medical records review, except for any information that must be 
maintained for screening log purposes. 
 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment 
team. The recruitment process outlined presents no more than minimal risk to the privacy of the 
patients who are screened and minimal PHI will be maintained as part of a screening log. For 
these reasons, we seek a (partial) limited waiver of authorization for the purposes of (1) 
reviewing medical records to identify potential research subjects and obtain information relevant 
to the enrollment process; (2) conversing with patients regarding possible enrollment; (3) 


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handling of PHI contained within those records and provided by the potential subjects; and (4) 
maintaining information in a screening log of patients approached (if applicable). 
 
This limited waiver will apply only to MSKCC. Any participating sites that require a limited waiver 
must obtain it from their own local IRB/Privacy Board (PB) via a separate protocol addendum or 
request.  It is the responsibility of the MSKCC staff to confirm the participating data collection 
site(s) have a limited waiver approved by their local IRB(s)/PBs. 
 
 
8.0 
PRETREATMENT EVALUATION 
 
The following tests will be done within 7 da ys prior to enrollment: 
 
  Mandatory pregnancy test, serum or urine HCG (sensitivity of at least  50 mIU/mL) for 
FCBP. 
Women are required to have 2 pregnancy tests prior initiation of lenalidomide as follows 
(Appendix B): 
o The first is required within 10 to 14 days prior to prescribing lenalidomide 
o The second within 24 hours of prescribing lenalidomide and prescription must be 
filled within 7 days. 
 
The following tests will be done within 14 days prior to enrollment: 
 
  History and physical exam including vital signs, height, weight, performance status, and 
toxicity assessment using CTCAE 4.0. 
 
  Serum M-spike studies: Serum protein electrophoresis (SPEP), serum immunofixation (IF) 
and quantitative immunoglobulins, and serum free light chain assay 
 
  Urine M-spike studies: Twenty-four hour urine for total volume and total protein (TV, TP), 
immunofixation (IF), protein electrophoresis (UPEP), N-telopeptides and creatinine 
clearance using the Cockcroft-Gault formula 
 
 Comprehensive Metabolic Panel (includes Albumin, Alkaline Phosphatase, ALT, AST, 
BUN, Calcium, Carbon dioxide, Chloride, Creatinine, Glucose, Potassium, Sodium, Total 
Bilirubin, Total Protein), beta2-microglobulin, C-reactive protein, LDH 
 
  CBC with differential 
 
  INR/PTT, BNP, and troponin. 
 
  Electrocardiogram (EKG) 
 
  Mandatory pregnancy test, serum or urine HCG (sensitivity of at least  50 mIU/mL) for 
FCBP. 
Women are required to have 2 pregnancy tests prior initiation of lenalidomide as follows 


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(Appendix B): 
o The first is required within 10 to 14 days prior to prescribing lenalidomide 
o The second within 24 hours of prescribing lenalidomide and prescription must be 
filled within 7 days. 
 
The following tests will be performed within 56 days prior to patient enrollment: 
  Hepatitis A, B, C serologies and HIV l/2 test 
 
  A skeletal survey that should be reviewed at MSKCC or the participating site if not 
performed at MSKCC or the participating site. (Please note: the skeletal survey is not 
required if a PET scan has been completed) 
 
  PET scan or total body MRI if available (optional) 
 
  A routine bone marrow examination, including biopsy sample for H & E stain and 
immunohistochemical staining for CD 138, CD20, kappa and lambda light chains; bone 
marrow aspirate samples for Giemsa staining, flow-cytometry, cytogenetic analysis, and 
FISH analysis for chromosomes 1,  4, 11, 13, 14, 17 abnormalities 
 
 
9.0 
TREATMENT/INTERVENTION  PLAN 
9.1 
Treatment Plan 
 
Lenalidomide dose will begin at 25 mg PO daily for 21 days of a 28-day-cycle adjusted 
for toxicity, if necessary.  Once the dose of lenalidomide is reduced for toxicity, no dose- 
re- escalation is permitted. 
 
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. 
 
Only one cycle of therapy may be dispensed to the patient each month. 
Lenalidomide capsules should be swallowed whole, and should not be broken, 
chewed or opened. 
 
Special Handling Instructions:  Females of childbearing potential should not handle 
or administer lenalidomide unless they are wearing gloves. 
 
Record of administration:  Accurate records will be kept in the source documents of all 
drug administration (including prescribing and dosing). Patients will be instructed to bring 
their complete medication diary (refer to Appendix D) to each study visit for assessment of 
compliance. 


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 
Patient will be evaluated for response and toxicity after every cycle and the response 
to lenalidomide intensification will be assessed after every cycle of therapy. 
 
o Patients with at least SD after 2 cycles of lenalidomide will continue on 
lenalidomide until asymptomatic POD at which time dexamethasone will be 
added at a dose of 40 mg PO weekly for the next cycle. 
 
o Patients with asymptomatic POD after 2 cycles of lenalidomide will have 
dexamethasone added to lenalidomide at a dose of 40 mg PO weekly with the 
next cycle. 
 
o Patients with further asymptomatic POD after any cycle of lenalidomide and 
dexamethasone will be taken off study and treated at the discretion of the 
treating physician. Note that further POD after the addition of dexamethasone 
will be determined compared to the new M spike baseline just prior to the 
addition of dexamethasone. 
 
Once patients are started on dexamethasone, they will also receive prophylaxis 
medication including Bactrim DS, one tablet PO TIW, fluconazole, 100 mg PO Daily, ASA 
81 mg PO daily, and a PPI. 
 
Note that patients with symptomatic POD at any point in time during treatment will 
be taken off study. 
 
 
9.2 
Cycle Delay and Dose Modification Guidelines 
 
Within a week prior to the first day of each new treatment cycle, the patient will be evaluated for 
possible toxicities that may have occurred due to previous doses. Toxicities will be assessed 
according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI 
CTCAE), version 4.0. Cycle delays and dose modifications will be made based on the toxicity 
experienced during the previous cycle of therapy or the ones encountered on any of the treatment 
days. Doses of study drug that need to be held WITHIN a cycle are skipped and will not be made 
up later in the cycle. 
 
9.2.1. Instruction for Initiation of a New Cycle 
 
A new course of treatment may begin on the scheduled Day 1 of a new cycle if: 
 
The ANC is ≥ 1,000/μL 
The platelet count is ≥ 50,000/μL 
Hemoglobin is ≥ 8g/dL 
Any drug-related side effect rash, allergic reaction/hypersensitivity, sinus bradycardia/ 


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other cardiac arrhythmia adverse event, dyspepsia, gastritis, gastric or duodenal ulcer or 
confusion or mood alterations that may have occurred has resolved to ≤ grade 1 severity 
Any other drug-related adverse events that may have occurred have resolved to ≤ grade 2 
severity. 
 
If these conditions are not met on Day 1 of a new cycle, the subject will be evaluated weekly and a 
new cycle of lenalidomide will not be initiated until the toxicity has resolved as described above. If 
the toxicity does not resolve after four weeks of delay, the patient will be taken off study. 
 
If dosing of lenalidomide was halted during the previous cycle and was restarted with a one-level 
dose reduction without requiring an interruption for the remainder of the cycle, then that reduced 
dose level will be initiated on Day 1 of the new cycle. 
 
If dosing of lenalidomide was omitted for the remainder of the previous cycle or if the new cycle is 
delayed due to toxicity newly encountered on the scheduled Day 1, then the new cycle will be 
started with dose modifications as described in Section 9.2.3. 
 
9.2.2. Lenalidomide Dose Reduction Guidelines 
 
Table 3: Dose Modification for Lenalidomide 
NCI CTC v 3.0 Toxicity 
Grade 
Day 2 – 14 of Cycle 
≥ Day 15 of Cycle 
Grade 3 neutropenia 
associated with fever 
(temperature ≥ 38.5oC or 
Grade 4 neutropenia) 
   Hold (interrupt dose) 
   Follow CBC weekly 
   If neutropenia has resolved 
to ≤ grade 2 prior to Day 21, 
restart at next lower dose 
level and continue the cycle 
until Day 21. 
   Omit lenalidomide for 
remainder of the cycle 
   If neutropenia is the only 
toxicity for which a dose 
reduction is required, G-CSF 
may be used and the dose 
maintained for the next cycle 
at the treating physician’s 
discretion 
Thrombocytopenia ≥ 
Grade 3 (platelet count < 
50,000/mm3) 
   Hold (interrupt dose) 
   Follow CBC weekly 
   If thrombocytopenia 
resolves to ≤ grade 2 prior 
to Day 21, restart at next 
lower dose level and 
continue the cycle until Day 
21 
   Hold anticoagulation for 
platelet count < 50,000/mm3 
   Omit lenalidomide for 
remainder of cycle 
   Hold anticoagulation for 
platelet count < 50,000/mm3 


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Anemia ≥ Grade 3 (Hgb 
< 8g/dL 
   Hold (interrupt dose) 
   Follow CBC weekly 
   If anemia resolves to ≤ 
grade 2 prior to Day 21, 
restart at next lower dose 
level and continue the cycle 
until Day 21 
   Omit lenalidomide for 
remainder of cycle 
Non-blistering rash 
Grade 3 
   Hold (interrupt dose) 
   Follow weekly 
   Omit lenalidomide for 
remainder of cycle 
   If the toxicity resolves to ≤ 
grade 1 prior to Day 21, 
restart at next lower dose 
level and continue the cycle 
until Day 21 
Non-blistering rash 
Grade 4 
   Discontinue lenalidomide 
study drug 
   Discontinue lenalidomide 
study drug 
Desquamating 
(blistering) rash - any 
Grade 
   Discontinue lenalidomide 
study drug 
   Discontinue lenalidomide 
study drug 
Erythema multiforme ≥ 
Grade 3 
   Discontinue lenalidomide 
study drug 
   Discontinue lenalidomide 
study drug 
Sinus bradycardia/other 
cardiac arrhythmia Grade 
2 
   Hold (interrupt) dose 
 
Follow at least weekly 
   If toxicity resolves to ≤ 
grade 1 prior to Day 21, 
restart at next lower dose 
level and continue the cycle 
until Day 21 
   Omit lenalidomide for 
remainder of cycle 
Sinus bradycardia/other 
cardiac arrhythmia ≥ 
Grade 3 
   Discontinue lenalidomide 
study drug 
   Discontinue lenalidomide 
study drug 
Allergic reaction or 
hypersensitivity Grade 2- 
3 
   Hold (interrupt) dose 
   Follow at least weekly 
   If toxicity resolves to ≤ 
grade 1 prior to Day 21, 
restart at next lower dose 
level and continue the cycle 
until Day 21 
   Omit lenalidomide for 
remainder of cycle 
Allergic reaction or 
hypersensitivity Grade 4 
   Discontinue lenalidomide 
study drug 
   Discontinue lenalidomide 
study drug 


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Venous 
thrombosis/embolism ≥ 
Grade 3 
   Hold (interrupt dose) and 
start anticoagulation; restart 
at investigator’s discretion 
(maintain dose level) 
   Omit lenalidomide for 
remainder of cycle 
Other non-hematologic 
toxicity assessed as 
Lenalidomide-related ≥ 
Grade 3 
   Hold (interrupt dose) 
   Follow at least weekly 
   If toxicity resolves to ≤ 
grade 1 prior to Day 21, 
restart at next lower dose 
level and continue the cycle 
until Day 21 
   Omit lenalidomide for 
remainder of cycle 
Hyperthyroidism or 
hypothyroidism 
   Omit lenalidomide for 
remainder of cycle, evaluation 
etiology, and initiate 
appropriate therapy 
   See Instructions for  
Initiation of a New Cycle 
and reduce the dose of 
lenalidomide by 1 dose level 
   Omit lenalidomide for 
remainder of cycle, 
evaluation etiology, and 
initiate appropriate therapy 
   See Instructions for Initiation 
of a New Cycle and reduce 
the dose of lenalidomide by 
1 dose level 
 
 
9.2.3. Le nalidomide Dose Reduction Levels 
 
 
Lenalidomide Dose Reduction Steps 
Starting Dose 
25 mg daily for 21 days every 28 days 
Dose Level -1 
20 mg daily for 21 days every 28 days 
Dose Level -2 
15 mg daily for 21 days every 28 days 
Dose Level -3 
10 mg daily for 21 days every 28 days 
Dose level -4 
5 mg daily for 21 days every 28 days 
Dose level -5 
Discontinue lenalidomide 
 
 
9.2.4 Dexame thasone Dose Reduction Guidelines 
 
Table 4: Dose Modification for Dexamethasone 
Dyspepsia 
≥ Grade 3 
 
Hold (interrupt) 
dexamethasone until ≤ 
grade 1 
  Reduce dexamethasone by 1 
dose level and restart 


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Gastritis, 
gastric or duodenal ulcer 
≥ Grade 3 
 
Hold 
(interrupt) 
dexamethasone until ≤ 
grade 1 
  Reduce dexamethasone by 1 
dose level and restart 
Edema 
≥ Grade 3 
  Reduce dexamethasone by 1 dose 
level 
  Use diuretics, as needed 
Confusion or mood 
alternations 
≥ Grade 2 
 
Hold (interrupt) 
dexamethasone until ≤ 
grade 1 
  Reduce dexamethasone by 1 
Muscle weakness 
≥ Grade 3 
  Reduce dexamethasone by 1 dose 
  If symptoms persist, continue to 
reduce dexamethasone by 1 dose 
level, as needed 
Hyperglycemia 
≥ Grade 3 
  Reduce dexamethasone by 1 dose 
level 
  Treat with insulin or oral 
hypoglycemics, as needed 
Acute pancreatitis 
≥ Grade 3 
  Discontinue dexamethasone 
and take patient off study 
Other non-hematologic 
toxicity assessed as 
dexamethasone related 
≥ Grade 3 
  Hold dexamethasone for 
remainder of cycle 
 
Reduce dexamethasone by 1 
dose level 
 
9.2.5 Dexame thasone dose reduction levels 
 
Dexame thasone Dose Reduction Ste ps 
Starting Dose 
40mg weekly on days 1, 8, 15 and 22 of each 28-day 
cycle 
Dose Level -1 
20mg weekly on days 1, 8, 15 and 22 of each 28-day 
cycle 


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Dose Level –2 
12mg weekly on days 1, 8, 15 and 22 of each 28-day 
cycle 
Dose Level -3 
4mg weekly on days 1, 8, 15 and 22 of each 28-day 
cycle 
 
9.3 
Supportive Care 
 
• 
Monthly IV bisphosphonates (either Zometa or Pamidronate according to 
institutional preference) may be initiated or continued according to local institutional 
practice. 
• 
Patients can receive filgrastim or pegylated filgrastim for an ANC < 109/L. 
• 
Radiation therapy is not permitted concurrently in this trial. 
• 
Transfusion thresholds for blood product support should be per institutional 
guidelines.  All blood products will be irradiated. 
• 
Treating physicians should be aware of the increased risk of DVT and PE with 
lenalidomide when combined with dexamethasone and have heightened vigilance 
regarding this possible toxicity. There is no clear evidence that the risk of DVT is 
increased on lenalidomide alone. Aspirin 325 mg/day orally should be administered 
during lenalidomide therapy when associated with dexamethasone unless the 
patient is treated with alternate prophylaxis of either low molecular weight heparin 
or Coumadin. This will be left to the discretion of the treating physician. 
• 
Concurrent use of erythropoietin requires full anticoagulation of patients with 
therapeutic doses of LMWH or Coumadin. Anticoagulation should be held for 
platelet counts <50,000/mm3. 
• 
Prophylaxis therapy should be added when patient start dexamethasone including 
fluconazole 100mg PO daily, Bactrim DS, three days a week, and a PPI daily. 
 
 
10.1 EVALUATION DURING TREATMENT/INTERVENTION 
 
During the intervention period, the patients will be assessed in the clinic before initiation of 
every cycle and will have the following evaluation done before every cycle, within one 
week of day 1 of the cycle: 
 
• 
History and physical exam including vital signs, weight, and performance status. 
• 
Review medication diary. Patients will be given a medication diary at the beginning 
of each cycle to  document lenalidomide administration. 
• 
CBC with differential and platelet count 
• 
Comprehensive metabolic panel with LDH and phosphorus. The comprehensive 
metabolic panel includes albumin, alkaline phosphatase, ALT, AST, BUN, calcium, 
carbon dioxide, chloride, creatinine, glucose, potassium, sodium, total bilirubin, and 
total protein. 


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• 
Myeloma response assessment: Including serum studies (Protein electrophoresis, 
Quantitative Immunoglobulins, Immunofixation and free light chain assay) and 24h 
urine studies (protein electrophoresis, Total protein, Immunofixation, and creatinine 
clearance) 
• 
Toxicity assessment using CTCAE 4.0: maximum grade and status of ≥ grade 2 
adverse events. 
• 
Bone marrow aspiration and biopsy to be performed only when indicated to 
document CR or progression. 
• 
Radiological evaluation when needed to document response or progression. 
• 
Required evaluation for Lenalidomide: Pregnancy test, serum or urine HCG 
(sensitivity of at least 50 mIU/mL) for female of childbearing potential (FCBP): 
• 
FCBP with regular or no menstruation must have a pregnancy test weekly for the 
first 28 days and then every 28 days while on 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 (Appendix B). 
• 
All patients must be counseled about pregnancy precautions, risks of fetal exposure 
and other risks. The counseling must be done on Day 1 of each cycle (or at a 
minimum of every 28 days) and at drug discontinuation. See Appendix: Education 
and Counseling Guidance Document. A Lenalidomide Information Sheet (Appendix 
D) will be supplied with each medication dispense. 
 
The same evaluation will repeated at the end of study, within 4 weeks of the last dose. On 
day 15 of each cycle the patient will have a CBC. Pre-screening assessments may be used 
for Cycle 1/Day 1 if they were complete within 7 days of initiation of cycle 1. 
 
 
Correlative Studies 
Patients who give their consent to optional sample collection for research studies will have 
blood samples (6 CPT tubes and 1 SST tube) collected for research on immune function 
prior to lenalidomide dose escalation, Cycle 1, Day 15 (+/- 3 days)  following dose 
escalation, prior to addition of dexamethasone, and Day 15 (+/- 3 days)  following the 
addition of dexamethasone.  Research blood samples will be collected during the time of 
standard toxicity evaluation during lenalidomide therapy.  The standard treatment schedule 
includes a 7 day rest period prior to the administration of the next cycle. Thus, the day 15 
time point has been selected to allow for an analysis of immune endpoints during the period 
when study drug is being administered. 
In addition, 5-7 cc of bone marrow aspirate (in 
EDTA) will be collected at the time of registration.  Samples will be sent to MSKCC for 
central processing, cataloguing, and storage. 


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Time Point 
Window for 
Collection 
Tubes 
Baseline/pre- 
lenalidomide 
escalation 
Day -7(consent must 
be signed) through 
Cycle 1/Day 1 
5-7cc bone 
marrow aspirate 
(6) CPT tubes 
(1) SST tube 
Cycle 1/Day 15 
Cycle 1/ Day 15 (+/- 3 
days) 
(6) CPT tubes 
(1) SST tube 
Pre-dexamethasone 
addition 
Between 
asymptomatic 
progression and 
addition of 
dexamethasone 
(6) CPT tubes 
(1) SST tube 
Day 15 post- 
dexamethasone 
addition 
Day 15 (+/- 3 days) 
post-dexamethasone 
addition 
(6) CPT tubes 
(1) SST tube 
 
 
Schedule of Study Assessments 
Required Studies / Testing 
Pretreatment 
w ithin 8 weeks 
Pretreatme 
nt w ithin 28 
days 
Pretreatment 
w ithin 14 
days 
Before  Every 
Cycle (within 
1 week of 
day 1) 8 
On day 15 
of each 
cycle 
End o
Stud 
(Within 
weeks of 
dose) 
Infor med Consent 
X 
History and Physical Examination 
(Height 7  and Weight) 
X 
X 
X 
Vital Signs 
X 
X 
X 
Rev iew medication diary 
X 
X 
Toxicity assessment 
X 
X 
X 
Pr egnancy Test
2
 
X3 
X3 
X3 
Register patient into the Rev limid 
REMS™ program 
X 
Perf ormance Status (Karnofsky 
Performance Score or ECOG) 
X 
X 
X 
CBC w ith Differential and platelet 
count 
X 
X 
X 
X 
Comprehensive Metabolic Panel 6 
X 
X 
X 
LDH, Phosphorus 
X 
X 
X 
B2 Microglobulin, Albumin 
X 
X 
X 
INR/ PTT, BNP, troponin 
X 
Hepat itis A, B, and C and HIV 1/2 
test 
X 
Serum Multiple Myeloma Disease 
Assessment 
 Protein electrophoresis 
 Quantitative 
X 
X 
X 


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1 To be perf or med w ithin 8 w eeks of registration. 
2 Pregnancy tests for females of childbearing potential: A female of childbearing potent ial (FCBP) is a sexually 
mature female w ho: 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). 
3 Pregnancy tests must occur w ithin 10 – 14 days and again w ithin 24 hours prior to prescribing lenalidomide for 
Cycle 1 (pr escriptions must be f illed w ithin 7 days). FCBP w ith regular or no menstruat ion must have a pr egnancy 
test w eekly for the f irst 28 days and then every 28 days w hile on ther apy (including breaks in ther apy); at 
discontinuat ion of lenalidomide and at Day 28 post the last dose of lenalidomide. Females w ith irregular 
menstruat ion mus t have a pregnancy test w eekly for the f irst 28 days and then every 14 days w hile on therapy 
(including breaks in therapy), at discont inuation of lenalidomide and at Day 14 and Day 28 post the last dose of 
lenalidomide (see Appendix: Ris ks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control 
Methods) 
4 Unilateral bone marrow aspirate and biopsy w ill be done on ly to conf ir m complet e remission in patients w ith negative 
biochemical evidence of disease. 
5 If the baseline urine paraprotein level is less than 200mg/24hrs, the UPEP is not required. 
6 Albumin, Alkaline Phosphatase, ALT, AST, BUN, Calc ium, Carbon dioxide, Chloride, Creat inine, Glucose, Potassium, 
Sodium, Total Bilirubin, Total Prot ein 
7 Height only required during pretreat ment evaluation. 
8 Pre-screening assessments may be used f or Cycle 1/ Day 1 if they w ere complet e w ithin 7 days of initiation of cycle 1. 
9 Optional blood w ill be collected prior to dose escalat ion (baseline), 15 days (+/- 3 days) post dose escalation, prior to 
addit ion of dexamethasone, and 15 days (+/- 3 days)post addition of dexamethasone. 
10A skeletal survey is only required f or screening if PET scan w as not completed. 
 
11.0  TOXICITIES/SIDE EFFECTS 
 
The patients will be evaluated every 28 days before initiation of a new 
cycle of treatment. All toxicities with a maximum grade and status of ≥ 
grade 2 will be graded using the Common Terminology Criteria for 
Immunoglobulins 
 Immunof ixation 
 Serum Free Light Chain 
Assay 
24 hour Urine Multiple My eloma 
Disease  assessment 
 Protein electrophoresis 
 Immunof ixation 
 Total volume, total protein 
 Creatinine clear ance 
 
X 
X5 
X 
EKG 
X 
Skelet al Survey 
X1,10 
X 
PET scan or total body MRI if 
available (opt ional) 
X1 
Bone Marrow Aspirate and Biopsy for 
   Mor phology 
   Cytogenet ics and FISH 
analysis 
  Tissue Banking 
X1 
X4 
Opt ional Research Blood
9
 
X 
Opt ional Research Bone Marrow 
Aspirate 
X 


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Adverse Events (CTCAE) Version 4.0. 
 
11.1 Expected Side Effects of Lenalidomide 
 
Most frequently reported adverse events reported during clinical studies with lenalidomide 
in oncologic and non-oncologic indications, regardless of presumed relationship to study 
medication include the following: 
 
Likely: 
  Feeling tired (fatigue) 
  Loss of strength (asthenia) 
  Loose, frequent bowel movements (diarrhea) 
  Difficulty moving bowels (constipation) 
  Altered sense of taste  (dysgeusia) 
  Nose bleed (epistaxis) 
  Decrease in red blood cells that can cause tiredness (anemia) 
  Decrease in white blood cells that can make you more prone to infections (neutropenia) 
  Decrease in platelets which can cause you to bruise or bleed easily(thrombocytopenia) 
  Blurred vision 
  Abnormal sense of touch 
  Pain and decreased sensastion in nerves 
 
Le ss Like ly: 
  Fever 
  Problem with moving food through digestive system (gastrointestinal motility disorder) 
  Weight loss, loss of appetite 
  Dry mouth 
  Nausea 
  Vomiting 
  Chills 
  Indigestion (dyspepsia) 
  Muscular weakness 
  Stroke 
  Tingling sensation (paresthesia) 
  Swelling or edema (including peripheral) 
  Itching and dry skin (pruritis) 
  Rash 
  Sores on the skin (pyoderma gangrenosum) 
  Cough 
  Shortness of breath (dyspnea) 
  Fainting (syncope) 
  Dizziness 
  Drowsiness 
  Headache 
  Difficulty sleeping (insomnia) 
  Bleeding 
  Difficulty breathing (respiratory distress) 


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  Excessive sweating (hyperhidrosis) 
  Fever with a decrease in white blood cells that help fight infections (febrile neutropenia) 
  Shortage of all types of blood cells including red blood cells, white blood cells, and 
platelets (pancytopenia) 
  Infection, especially when white blood cell count is low 
  Blood clots (thromboembolic event) 
  Excessive loss of body water (dehydration) 
  High blood sugar (hyperglycemia) 
  Uncontrolled blood sugar (diabetes mellitus) 
  Higher than normal blood uric acid (hyperuricemia) 
  Higher than normal level of iron in body (iron overload) 
  Lower than normal level of thyroid hormone (hypothyroidism) 
  Lens of eye becomes cloudy (cataracts) 
  High blood pressure (hypertension) 
  Low blood pressure (hypotension) 
  Joint pain (arthralgia) 
  Back pain 
  Muscle pain (myalgia) 
  Muscle cramp / spasm 
  Altered mood 
  Depression 
  Irregular heartbeat (atrial fibrillation) 
  Failure of the heart (cardiac failure) 
  Heart attack (acute myocardial infarction) 
  Fast heartbeat (tachycardia) 
  Not enough blood flow to heart muscle (myocardial ischemia) 
  Kidney damage (renal failure) 
  Abnormal liver function tests 
 
Rare but Serious 
  Fever with a decrease in white blood cells that help fight infections (Febrile 
neutropenia) 
  Blood clot in or around the lungs (Pulmonary embolism) 
  Deep vein thrombosis or blood clots in larger blood vessels 
  Atrial fibrillation or irregular heartbeat 
  Pneumonia or an infection of the lungs 
  Sepsis or an infection of the blood 
  Inflammation of the pancreas, which causes increase in pancreatic enzymes (lipase), 
which could result in abdominal pain and discomfort 
  Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat (anaphylaxis) 
  Kidney failure or inability of the kidneys to remove waste from the body 
  Muscle breakdown (rhabdomyoiysis) 
  Swelling of the lungs 
  Severe skin rash with blisters that can involve the inside of the mouth and other parts of 
the body (erythema multiforme) 
  Serious allergic skin reactions that begin as a rash in one area and later cover more of 
the body, leading to separation of the top layer of skin (Stevens- Johnson syndrome / 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
toxic epidermal necrolysis) 
  Damage to organs in the body when donor cells attack host organs, which may cause 
yellowing of the eyes and skin, itchy dry skin, or muscle weakness (Graft versus host 
disease) 
  Complications caused by the break-down products of dying cancer cells, which can 
include high potassium, high phosphorous, high uric acid in the blood and urine, low 
calcium, and can result in kidney damage (Tumor lysis syndrome) 
  Cancer of bone marrow caused by chemotherapy 
  A new cancer resulting from treatment of earlier cancer 
  Low blood cell counts that may cause infection, anemia, spontaneous bleeding, or easy 
bruising (Myelodysplastic syndrome) 
  Increase in size of the cancerous lymph nodes, rash, and slight fever (Tumor flare 
reaction) 
  Brain damage which may cause headache, seizure, or blindness 
(leukoencephalopathy) 
11.2 Expected Side Effects of Dexamethasone 
 
Likely 
 
  Increased appetite 
  Weight gain 
  Sleep disturbance 
  Hypertension 
  Fluid retention, ankle swelling 
  Bruising 
  Susceptibility to Infection 
  Mood changes 
  Slow wound healing 
  Depression 
  Hyperglycemia, which may lead to fatigue, weight loss, excessive thirst and frequent 
urination. 
Le ss Likely 
 
  Loss of appetite 
  Muscle twitching 
  Increased thirst, frequent urination 
  Increased perspiration 
  Diarrhea 
  Nausea 
  Headache 
  Bone thinning 
  Spinal fracture or fracture of bones 
  Tachycardia 
  Fungal infections 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
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Amended:  04/14/15 
 
 
  Anxiety 
 
Unlikely 
  Blurred vision 
  Personality changes 
  Hypokalemia 
  Swelling and/or redness of skin 
  Allergic skin reactions 
  Itching 
  Hirsutism 
  Muscle weakness or loss of muscle mass 
  Rupture of tendons 
  Menstrual cycle disturbances 
  Facial puffiness, leading to the appearance of a “moon face” hormonal disturbances 
  Hiccups. 
  Development of diabetes 
 
Rare but serious 
 
  Stomach ulcers with bleeding that may cause hematemesis, blood in the stool and 
abdominal pain. 
  Bowel perforation, irritation and bleeding of the esophagus 
  Heart failure 
  Allergic reaction that may lead to shortness of breath, abdominal cramps and hypotension 
  Convulsions, brain swelling, 
  Cataracts 
  Glaucoma and increased blood pressure in the eye 
  Pancreatic inflammation, abdominal swelling 
  DVT or PE 
  Aseptic necrosis of the hip 
 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME 
ASSESSMENT 
Patients enrolled in this trial must have asymptomatic progression of disease only. The new 
baseline that will be used for comparison to assess the response to lenalidomide intensification 
with or without the addition of dexamethasone at 6 months will have to be established within 
two weeks prior to day 1 of cycle 1. Prior values will not be acceptable. 
Patients’ disease status at each data collection period will be evaluated based on the International 
Uniform Response Criteria.  All disease responses, including after addition of dexamethasone, 
will be relative to the established baseline disease status within 2 weeks prior to day1 of cycle 1, 
i.e. prior to lenalidomide intensification. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
International Uniform Response Criteria (modified) 
Stringent Complete Response (sCR): 
  sCR requires, in addition to CR (defined below), all of the following: 
  Normal free light chain ratio (FLC). 
  Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. 
 
 
Complete Response (CR) requires all of the following: 
 
 Absence of the original monoclonal paraprotein in serum and urine by routine 
electrophoresis and by immunofixation. 
 Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if 
biopsy is performed; 
 No increase in size or number of lytic bone lesions on radiological investigations 
(development of a compression fracture does not exclude CR)*; and, 
  Disappearance of soft tissue plasmacytomas. 
 
 
*If not clinically indicated, radiographs are not required to document CR. 
 
 
Very Good Partial Response (VGPR) requires, in addition to PR (defined below), all of the 
following: 
 
  Serum or urine paraprotein detectable by immunofixation but not on electrophoresis, 
OR 
 Greater than or equal to 90% reduction in serum paraprotein plus urine paraprotein <100 
mg/24hrs. 
 
Partial Response (PR) requires one of the following: 
 
 Greater than or equal to 50% reduction in the level of the serum monoclonal paraprotein 
and/or reduction in 24 hour urinary monoclonal paraprotein either by greater than or equal 
to 90% or to <200 mg/24 hours in light chain disease. 
 If the only measurable non-bone marrow parameter is FLC, greater than or equal to 50% 
reduction in the difference between involved and uninvolved FLC levels or a 50% 
decrease in level of involved FLC with 50% decrease in ratio, 
 If the bone marrow is the only measurable parameter, greater than or equal to 50% 
reduction in bone marrow plasma cells given that the baseline count was greater or equal 
to 30%, 
 Greater than or equal to 50% reduction in the size of soft tissue plasmacytomas (by 
radiography or clinical examination). 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
Minor Response (MR) 
 
 ≥ 25% to ≤ 49% reduction in the level of serum monoclonal protein (SPEP) 
  If present, a 50% to 89% reduction in 24-hour light chain excretion, which still exceeds 
200 mg/24 hr. 
  If the serum and urine M-protein are unmeasurable a ≥25% to ≤49% decrease in the 
difference between involved and uninvolved FLC levels is required in place  of the M- 
protein criteria. 
  25% to 49 % reduction in the size of soft tissue plasmacytomas (by clinical or radiographic 
examination) 
 
 
Stable Disease (SD) 
  Patients who do not meet criteria for  sCR, CR, VGPR, PR or progressive disease are 
considered to have stable disease (SD). 
 
 
Progressive Disease (POD) 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. 
 
  >25% increase in the difference between involved and uninvolved FLC levels   (absolute 
increase must be >10 mg/dl), 
  >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 that the development of a compression fracture does not exclude continued response 
and may not indicate progression. 
 
 
13.0  CRITERIA FOR REMOVAL FROM STUDY 
 
Treatment with study drugs is to be discontinued when any of the following occurs: 
 
  Symptomatic POD, i.e. with organ damage at any point in time during the treatment 
  Asymptomatic POD, i.e. without organ damage after at least one cycle of lenalidomide 
and dexamethasone 
  Adverse event(s) that, in the judgment of an Investigator, may cause severe or permanent 
harm or which rule out continuation of study drug 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
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IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
  Major violation of the study protocol 
  Withdrawal of consent 
  Patient is lost to follow-up 
  Suspected or confirmed pregnancy. If pregnancy or a positive pregnancy test does occur 
in a study subject or the partner of a male study subject during study participation, study 
drug must be immediately discontinued. 
 
Any possible premature discontinuation would be documented adequately with reasons being 
stated, and information would have to be issued according to local requirements (e.g., IRB, 
regulatory authorities, etc.). 
 
 
14.0 BIOSTATISTICS 
 
The primary objective of this study is to estimate overall response rate (> PR) to lenalidomide 
intensification with or without dexamethasone at 6 months.   A single stage design that 
differentiates between response rates of 15% and 30% will be used to assess efficacy of 
lenalidomide intensification with or without dexamethasone. 
The probabilities of a type I error (falsely accepting a non-promising therapy) and type II error 
(falsely rejecting a promising therapy) are set to 0.10 and 0.10, respectively.  The null 
hypothesis response rate is based on the response rates ranging from 12.5% to 16.4% to the 
standard of care therapy in patients previously exposed to thalidomide who have relapsed or 
refractory disease (reference Webber and Dimopoulos papers38,39). A total of 53 patients will be 
accrued. At the conclusion of the study, if a least 12 of the 53 patients respond by 6 months  
the treatment will be declared a success.  At the end of the study, the response rate will be 
estimated and a confidence interval will be constructed. 
We expect to accrue 53 patients in two years with approximately 10-15 patients accrued from 
MSKCC and the remaining patients accrued from the other centers. 
The incidence of toxicities of grade 2 or higher toxicities (CTCAE version 4.0), the incidence of 
probable viral fungal and bacterial infections, and the incidence of treatment-related mortality, i.e., 
from causes other than relapse or progression, will be recorded for each patient after each cycle 
and at the end of study visit. Safety data will be described in a variety of ways, both graphically 
and in tabular form. 
 
Progression free survival is defined as the time from treatment initiation to relapse/progression, 
death, initiation of non-protocol anti myeloma therapy, or last follow-up.  Overall survival is defined 
as time from treatment initiation until death or last follow-up.  Progression free and overall survival 
will be estimated using the Kaplan-Meier method. 
 
We will estimate the response rate (CR, VGPR, and PR) by 6 months from initiation of 
lenalidomide intensification of lenalidomide given as single agent. For this calculation, 
patients who have asymptomatic progression after 2 cycles of lenalidomide and receive 
dexamethasone will be considered failures. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
15.0 RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION 
PROCEDURES 
15.1 Research Participant Registration 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility. 
 
Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
 
During the registration process registering individuals will be required to complete a protocol 
specific Eligibility Checklist. 
 
All participants must be registered through the Protocol Participant Registration (PPR)  
Office at Memorial Sloan-Kettering Cancer Center. PPR is available Monday through Friday 
from 8:30am – 5:30pm at 646-735-8000. Registrations must be submitted via the PPR 
Electronic Registration System (http://ppr/). The completed signature page of the written 
consent/RA or verbal script/RA, a completed Eligibility Checklist and other relevant 
documents must be uploaded via the PPR Electronic Registration System. 
 
 
15.1.1 Research Participant Registration for Collaborating Sites 
 
Central registration for this study will take place at Memorial Sloan Kettering Cancer Center 
(MSKCC). 
To complete registration and enroll a participant from another institution, the study staff at that site 
must contact the designated research staff at MSKCC to notify him/her of the participant 
registration. The site staff then needs to fax registration/eligibility documents to Clinical Trials 
Office, MCT Core Research Staff at (646-227-2482). 
The following documents must be sent for each enrollment within 24 hours of the informed 
consent form being signed: 
  The completed or partially completed MSKCC eligibility checklist 
  The signed informed consent and signed HIPAA Authorization form (Research 
Authorization) 
  Supporting source documentation for eligibility questions (laboratory results, pathology 
report, radiology reports, MD notes, physical exam sheets, medical history, prior treatment 
records, and EKG report). 
 
Upon receipt, the research staff at Memorial Sloan-Kettering Cancer Center will conduct an 
interim review of all documents.   If the eligibility checklist is not complete, the patient will be 
registered PENDING and the site is responsible for sending a completed form within 30 days of 
the consent. 
If the eligibility checklist is complete, participant meets all criteria, all source documentation is 
received, the participating site IRB has granted approval for the protocol, and the site is in good 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
standing with MSKCC, the MSKCC research staff will send the completed registration documents 
to the MSKCC Protocol Participant Registration (PPR) Office to be enrolled as stated in section 
15.1.  The participant will be registered. 
 
Once eligibility has been established and the participant is registered, the participant will be 
assigned an MSKCC Clinical Research Database (CRDB) number (protocol participant number). 
This number is unique to the participant and must be written on all data and correspondence for 
the participant.  This protocol participant number will be relayed back to study staff at the 
registering site via e-mail and will serve as the enrollment confirmation. 
 
15.2 Randomization 
 
There is no randomization in this study 
 
 
16.1 DATA MANAGEMENT ISSUES 
 
All patients will be enrolled on protocol at MSKCC and other collaborating centers.  We expect to 
enroll the necessary 53 patients onto the study in 2 years. 
 
A Research Study Assistant (RSA) will be assigned to the study at MSKCC.  The responsibilities 
of the RSA include project compliance, data collection, abstraction and entry, data reporting, 
regulatory monitoring, problem resolution and prioritization, and coordination of the activities of 
the protocol study team. 
 
The data collected for this study will be entered into electronic Case Report Forms (eCRFs) by 
the assigned MSKCC RSA.  Source documentation will be available to support the computerized 
patient record. 
 
16.1.1 Data and Source Documentation for Collaborating Sites 
Data 
Electronic Case Report Forms (eCRFs), directions for use and sign off requirements have been 
generated for this study. The MSKCC Principal Investigator or designee will provide eCRFs to 
participating sites.  The participating Site PI is responsible for ensuring these forms are completed 
accurately and in a timely manner. 
 
Source Documentation 
 
Source documentation refers to original records of observations, clinical findings and evaluations 
that are subsequently recorded as data. Source documentation should be consistent with data 
entered into eCRFs. Relevant source documentation to be submitted throughout the study 
includes: 
  Baseline measures to assess pre–protocol disease status (ex. Skeletal 
survey, bone marrow) 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
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Amended:  04/14/15 
 
 
  Treatment records 
  Grade 2-5 toxicities/adverse events not previously submitted with SAE Reports 
  Response designation 
Source documentation should include a minimum of two identifiers to allow for data verification. 
MSK will maintain the confidentiality of any subject-identifable information it may encounter. 
 
16.1.2 Data and Source Docume ntation Submission for Participating Sites 
 
The site is responsible for data entry using the Electronic Data Capture (EDC) system. Instructions 
for EDC access and guidelines are provided in the study procedure manual. 
 
 
16.1.3 Data and Source Documentation Submission Time lines for Participating Sites 
 
Data and source documentation to support data should be transmitted via the EDC system to 
MSKCC according to the following chart: 
 
 
Baseline 
During Treatment 
Cycles 
SAE 
End of Therapy 
SUBMISSION SCHEDULE 
 
Source Documentation 
Within 24 
hours 
(see section 
15.1.1) 
Within 24 hours (see 
section 17.2.1 and 17.3); 
updates to be submitted 
as available 
CRFs 
Within 7 days 
of visit 
within 14 days of the 
end of cycle 
Within 14 days of 
visit 
REQUIRED FOLDERS/FORMS 
Screening Folder 
X 
Baseline Folder 
X 
Adverse Event Form 
X 
X 
X 
X 
Concomitant Medications 
Form 
X 
X 
X 
Correlative Form (if 
applicable) 
X 
X 
X 
Cycle (#) Folder 
X 
Off Study Folder 
X 
Serious Adverse Event Form 
X 
 
16.1.4 Data Review and Queries for Participating Site Data 
Research staff at MSKCC will review data and source documentation as it is submitted. Data will 
be monitored against source documentation and discrepancies will be sent as queries to the 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
participating sites, which the sites will resolve electronically in the EDC system. MSKCC will 
perform oversight of the data management of this trial. 
 
Participating sites should respond to data queries within 14 days of receipt. 
 
 
16.1 Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and completeness of 
registration data.  Routine data quality reports will be generated to assess missing data and 
inconsistencies.  Accrual rates and extent and accuracy of evaluations and follow-up will be 
monitored periodically throughout the study period and potential problems will be brought to the 
attention of the study team for discussion and action 
 
Random-sample data quality and protocol compliance audits will be conducted by the study team, 
at a minimum of two times per year, more frequently if indicated. 
 
16.1.1 Investigator responsibilities: 
 
Monthly telephone conference calls will be conducted among the collaborating center staff. 
Investigator responsibilities are set out in the ICH guideline for Good Clinical Practice (GCP) and 
in the US Code of Federal Regulations. 
 
Investigators must enter study data onto CRFs or other data collection system.  The 
Investigator will permit study-related audits by Celgene or its representatives, IRB/EC review, 
and regulatory inspection(s) (e.g., FDA, EMEA, TPP), providing direct access to the facilities 
where the study took place, to source documents, to CRFs, and to all other study documents. 
 
The Investigator, or a designated member of the Investigator’s staff, must be available at some 
time during audits to review data and resolve any queries and to allow direct access to the 
subject’s records (e.g., medical records, office charts, hospital charts, and study related charts) 
for source data verification.  The data collection must be completed prior to each visit and be 
made available to the Celgene representative so that the accuracy and completeness may be 
checked. 
16.1.2 Retention of Records: 
 
All documentation pertaining to the conduct of the study and the distribution of the study drug, that 
is copies of CRFs and source documents (original documents, data, and records [e.g., hospital 
records; clinical and office charts; laboratory notes; memoranda; subject’s diaries or evaluation 
checklists; SAE reports, pharmacy dispensing records; recorded data from automated  
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiches; photographic negatives, microfilm, or magnetic media; x-rays; subject files; and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved   
in the clinical study; documents regarding subject treatment and study drug accountability; original 
signed informed consents, etc.]), and all IRB correspondence will be retained for at least 3 years 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
after the investigation is completed. 
 
16.1.3 Quality Assurance for Participating Sites 
 
Each site participating in the accrual of patients to this protocol will be audited by the staff of the 
MSKCC study team for protocol and regulatory compliance, data verification and source 
documentation. Audits may be accomplished in one of two ways: (1) selected patients records can 
be audited on-site at participating sites or (2) source documents for selected patients will be sent  
to MSKCC for audit. Audits will usually be determined by patient accrual numbers and rate of 
accrual, but can also be prompted by reported SAEs or request of Lead PI. 
 
Audits will be conducted at least once shortly after initiation of patient recruitment at a site, and if 
possible, at the end or closeout of the trial at a site and during the trial if the trial lasts 3 or more 
years. At a minimum, audits will be conducted once a year but more frequently, if indicated. 
The audit will include a review of source documentation to evaluate compliance for: 
 
  Informed consent documents and procedures 
  Adherence to eligibility criteria 
  Protocol defined treatment 
  Required baseline, on study and follow-up protocol testing 
  IRB documents (submitted amendments, annual continuing review reports, SAEs) 
  Required specimen submission 
  Pharmacy review, if applicable 
  Case Report Form submissions to MSKCC: timing and accuracy 
 
A wrap-up session will be conducted at the outside site and preliminary findings will be discussed 
with the outside site PI and research team. The preliminary results will be sent to the MSKCC PI. 
Each audit will be summarized and a final report will be sent to the PI at the audited participating 
institution within 30 days of the audit. The report will include a summary of findings, patient by 
patient case review, specific recommendations on any performance and/or shortcomings and 
request for corrective action, when necessary. When corrective action is required, the 
participating institution must reply within 45 days of receipt of audit report with their corrective 
action plan. 
 
A copy of the audit report and corrective action plan (if applicable) submitted by the outside site 
must be sent to the MSKCC IRB, CRQA and maintained in the department’s protocol regulatory 
binder. 
 
16.1.4 Response Review 
Since therapeutic efficacy is a stated primary objective, patients’ responses at all sites are subject 
to review by MSKCC’s Therapeutic Response Review Committee (TRRC). Radiology, additional 
lab reports and possibly bone marrow biopsies and/or aspirates will need to be obtained from the 
outside sites for MSKCC TRRC review and confirmation of response assessment. These 
materials must be sent to MSKCC within sixty days of request to the site. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
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IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
 
16.2 Data and Safety Monitoring 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan-Kettering Cancer Center were 
approved by the National Cancer Institute in September 2001.  The plans address the new policies 
set forth by the NCI in the document entitled “Policy of the National Cancer Institute for Data and 
Safety Monitoring of Clinical Trials” which can be found 
at:  http://www.cancer.gov/clinicaltrials/conducting/dsm-guidelines/page1. The DSM Plans at 
MSKCC were established and are monitored by the Office of Clinical Research.  The MSKCC Data 
and Safety Monitoring Plans can be found on the MSKCC Intranet at: 
http://smsk psps9/dept/ocr/OCR%20Website%20Documents/Clinical%20Research%20Quality%20  
Assurance%20(CRQA)/MSKCC%20Data%20and%20Safety%20Monitoring%20Plan.pdf 
 
There are several different mechanisms at MSKCC by which clinical trials are monitored for 
data, safety and quality.  There are institutional processes in place for quality assurance (e.g., 
protocol monitoring, compliance and data verification audits, therapeutic response, and staff 
education on clinical research QA) and departmental procedures for quality control, plus there 
are two institutional committees that are responsible for monitoring the activities of our clinical 
trials programs. The committees: Data and Safety Monitoring Committee (DSMC) for Phase I 
and II clinical trials, and the Data and Safety Monitoring Board (DSMB) for Phase III clinical 
trials, report to the Center’s Research Council and Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assessed for its level 
of risk and degree of monitoring required. Every type of protocol (e.g., NIH sponsored, in-house 
sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed and the 
monitoring procedures will be established at the time of protocol activation. 
16.3 Regulatory  Documentation 
 
Prior to implementing this protocol at MSKCC, the protocol, informed consent form, HIPAA 
authorization and any other information pertaining to participants must be approved by the 
MSKCC Institutional Review Board/Privacy Board (IRB/PB). Prior to implementing this protocol at 
the participating sites, approval for the MSKCC IRB/PB approved protocol must be obtained from 
the participating site’s IRB. 
The following documents must be provided to MSKCC before the participating site can be initiated 
and begin enrolling participants: 
 
  Participating Site IRB approval(s) for the protocol, appendices, informed consent form and 
HIPAA authorization 
  Participating Site IRB approved consent form and HIPPA Authorization 
  Participating Site IRB membership list 
  Participating Site IRB’s Federal Wide Assurance number and OHRP Registration number 
  Curriculum vitae and medical license for each investigator and consenting professional 
  Documentation of Human Subject Research Certification training for investigators and key 
staff members at the Participating Site 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
  Documentation of Good Clinical Practice (GCP) training for the PI and co-PI at each 
participating site 
  Participating site laboratory certifications and normals 
 
Upon receipt of the required documents, MSKCC will formally contact the site and grant 
permission to proceed with enrollment. 
 
16.3.1 Ame ndments 
Protocol amendments 
Any amendment to this protocol must be agreed to by the Principal Investigator and reviewed by 
Celgene Corporation.  Protocol amendments should only be submitted to MSKCC IRB after 
consideration of Celgene review.  Written verification of MSKCC IRB approval will be obtained 
before any amendment is implemented. 
 
Each change to the protocol document must be organized and documented by MSKCC and first 
approved by the MSKCC IRB/PB. Upon receipt of MSKCC IRB/PB approval, MSKCC will 
immediately distribute all non expedited amendments to the participating sites, for submission to 
their local IRBs. 
Participating sites must obtain approval for all non expedited amendments from their IRB within 
90 calendar days of MSKCC IRB/PB approval. If the amendment is the result of a safety issue, or 
makes eligibility criteria more restrictive, sites will not be permitted to continuing enrolling new 
participants until the participating site IRB approval has been granted. 
 
The following documents must be provided to MSKCC for each amendment within the stated 
timelines: 
  Participating Site IRB approval 
  Participating Site IRB approved informed consent form and HIPAA  authorization 
 
 
16.3.2 Additional IRB Correspondence 
Continuing Review Approval 
The Continuing Review Approval letter from the participating site’s IRB and the most current 
approved version of the informed consent form should be submitted to MSKCC within 7 days of 
expiration. Failure to submit the re-approval in the stated timeline will result in suspension of study 
activities. 
 
Deviations and Violations 
 
A protocol deviation on this study is defined as a request to treat a research participant who does 
not meet all the eligibility criteria, pretreatment evaluation, or who requires alteration in their study 
plan. If a deviation from this protocol is proposed for a potential or existing participant at MSKCC 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
or a participating site, approval from the MSKCC IRB/PB is required prior to the action. 
Participating sites should contact the MSKCC PI who will in turn seek approval from the MSKCC 
IRB/PB. 
A protocol violation is anything that occurs with a participant, which deviated from the protocol 
without prior approval from the MSKCC IRB/PB. For protocol violations that are identified after 
they occur, the participating site should report to MSKCC as soon as possible. The MSKCC PI will 
in turn report the violation to the MSKCC IRB/PB. 
 
Participating sites should report deviations and violations to their institution’s IRBs as soon as 
possible per that site’s institutional guidelines. Approvals/acknowledgments from the participating 
site IRB for protocol deviations and violations should be submitted to MSKCC as received. 
Other correspondence 
 
Participating sites should submit other correspondence to their institution’s IRB according to local 
guidelines, and submit copies of that correspondence to MSKCC. 
 
16.3.3 Document maintenance 
 
The MSKCC PI and the Participating Site PI will maintain adequate and accurate records to 
enable the implementation of the protocol to be fully documented and the data to be subsequently 
verified. 
The participating sites will ensure that all participating site IRB correspondence (IRB approval 
letters referencing protocol version date and amendment number, IRB approved protocol, 
appendices, informed consent forms, deviations, violations, and approval of continuing reviews) is 
maintained in the regulatory binder on site and sent to MSKCC. 
 
A regulatory binder for each site will also be maintained at MSKCC; this binder may be paper or 
electronic. After study closure, the participating site will maintain all source documents, study 
related documents and CRFs for 3 years. 
16.4 Noncompliance 
 
If a participating site is noncompliant with the protocol document, accrual privileges may be 
suspended and/or contract payments may be withheld (if applicable), until the outstanding 
issues have been resolved. 
 
 
17.0  PROTECTION OF HUMAN SUBJECTS 
 
Participation in this trial is voluntary. All patients will be required to sign a statement of 
informed consent, which must conform to MSKCC and collaborating centers IRB guidelines. 
 
Patients will be eligible for this trial regardless of gender or racial/ethnic background.  All 
patients must follow the guidelines for pregnancy testing birth control and counseling related 
to the risk of fetal exposure to lenalidomide as outlined in Appendix B. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
 
The protocol for this study has been designed in accordance with the general ethical 
principles outlined in the Declaration of Helsinki.  The review of this protocol by the IRB and 
the performance of all aspects of the study, including the methods used for obtaining 
informed consent, must also be in accordance with principles enunciated in the declaration, 
as well as ICH Guidelines, Title 21 of the Code of Federal Regulations (CFR), Part 50 
Protection of Human Subjects and Part 56 Institutional Review Boards. 
Potential risks and benefits 
The potential risks of this therapy may outweigh the potential benefit in an individual patient. 
The potential risks to patients are related to drug induced adverse effects and are outlined in 
Section 11.0. Appropriate exclusion criteria for patients are listed in Section 6.0: Patient 
Eligibility. Appropriate exclusion of patients with significant organ dysfunction or infection will 
help avoid treatment-related toxicity. Careful monitoring of laboratory parameters and patient 
symptoms, along with serial assessment for disease recurrence, will be carried out routinely in 
order to minimize the risk of adverse effects during this study. 
 
Alternatives/Options for treatment 
Patients with newly diagnosed standard-risk multiple myeloma have many treatment options. 
Alternative therapy for patients who choose not to enroll on this study include standard 
chemotherapy, autologous or allogeneic stem cell transplant, thalidomide, steroids, bortezomib, 
lenalidomide, some combination of the above, other clinical trials, observation, or supportive 
care. 
 
Costs 
Patients will be responsible for all costs related to treatment and complications of treatment, 
including all hospitalizations.  Patients will not be responsible for the cost of lenalidomide, 
research blood tests and research bone marrow samples. 
 
 
17.1 Privacy 
 
MSKCC’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form.  The use and disclosure 
of protected health information will be limited to the individuals described in the Research 
Authorization form.  A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board. 
Celgene affirms the subject’s right to protection against invasion of privacy.  In compliance 
with United States federal regulations, Celgene requires the Investigator to permit their 
representatives and, when necessary, representatives of the FDA or other regulatory 
authorities to review and/or copy any medical records relevant to the study in accordance 
with local laws 
17.2 Serious Adverse Event (SAE) Reporting 
 
An adverse event is a new or unexpected event or a worsening of an existing condition in a 
subject that occurs during treatment and within the study period, whether or not considered to 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
be treatment-related. 
 
A serious adverse event is one that at any dose (including overdose): 
 
  Results in death 
 Is life-threatening: Life-threatening” means that the subject was at immediate risk of 
death at the time of the serious adverse event; it does not refer to a serious adverse 
event that hypothetically might have caused death if it were more severe. 
  Requires inpatient hospitalization or prolongation of existing hospitalization 
  Results in persistent or significant disability or incapacity:Persistent or significant 
disability or incapacity” means that there is a substantial disruption of a person’s ability 
to carry out normal life functions. 
  Is a congenital anomaly or birth defect 
  Is an important medical event. Medical and scientific judgment should be exercised in 
deciding whether expedited reporting is appropriate in situations where none of the 
outcomes listed above occurred.  Important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient or may 
require intervention to prevent one of the other outcomes listed in the definition above 
should also usually be considered serious.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development 
of drug dependency or drug abuse.  A new diagnosis of cancer during the course of a 
treatment should be considered as medically important. 
 
The following event must also be reported in an expedited manner: 
 
 Pregnancy (see section 17.4) 
 
 
Reporting SAE to IRB At MSKCC: 
 
Any SAE must be reported to the IRB/PB as soon as possible but no later than 5 calendar days. 
The IRB/PB requires a Clinical Research Database (CRDB) SAE report be submitted 
electronically to the SAE Office at sae@mskcc.org.  The report should contain the following 
information: 
 
 
Fields pop ulated from the CRDB: 
  Subject’s name (generate the report with only initials if it will be sent outside of 
MSKCC) 
  Medical record number 
  Disease/histology (if applicable) 
  Protocol number and title 


Amended:  04/14/15 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
 
 
Data needing to be entered: 
 
  The date the adverse event occurred 
  The adverse event 
  Relationship of the adverse event to the treatment (drug, device, or intervention) 
  If the AE was expected 
  The severity of the AE 
  The intervention 
  Detailed text that includes the following information: 
o An explanation of how the AE was handled 
o A description of the subject's condition 
o Indication if the subject remains on the study 
o If an amendment will need to be made to the protocol and/or consent form 
The PI’s signature and the date it was signed are required on the completed report. 
17.2.1  Reporting SAE to Study Supporter (Celgene Corporation) 
 
The investigator should first inform the MSKCC PI or designee of any SAE (regardless of 
causality) within 24 hours of being aware of the event. The MSKCC RSA will then inform Celgene 
and collaborating center of these SAEs.  The date of awareness should be noted on the report. 
This must be documented on a CRDB AE report or Celgene SAE Report Template. Either of these 
forms must be completed and supplied to Celgene within 24 hours of learning of the event by the 
MSKCC RSA.  If applicable, follow-up and resolution reports as described below must be reported 
to Celgene.  The Celgene tracking number (RV-MM-PI-641) and the institutional protocol number 
should be included on SAE reports (or on the fax cover 
letter) sent to Celgene.  A copy of the fax transmission confirmation of the SAE report to 
Celgene should be attached to the SAE and retained with the patient records. 
 
In addition to completing appropriate patient demographic and suspect medication information, 
the report should include the following information: 
  Treatment regimen (dosing frequency, combination therapy) 
  Protocol description (and number, if assigned) 
  Description of event, severity, treatment, and outcome if known 
  Supportive laboratory results and diagnostics 
  Investigator’s assessment of the relationship of the adverse event to each investigational 
product and suspect medication 
The investigator will determine which events are associated with the use of the study drugs. 
 
For reporting purposes, an AE should be regarded as possibly related to the use of the 
investigational product if the investigator believes: 
  There is a clinically plausible time sequence between onset of the AE and study drug 
administration; and/or 


Amended:  04/14/15 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
 
 
  There is a biologically plausible mechanism for the study drug causing or contributing to 
the AE; and 
  The AE cannot be attributed solely to concurrent/underlying illness, other drugs, or 
procedures. 
 
The initial report must be as complete as possible, including details of the current illness and 
(serious) adverse event, and an assessment of the causal relationship between the event and the 
investigational product(s).  Information not available at the time of the initial report (e.g., an end 
date for the adverse event or laboratory values received after the report) must be documented on 
a follow-up report.  A final report to document resolution of the SAE is required. 
 
Follow-up information may be added to a previously submitted report by any of the following 
methods: 
  Adding to the original report and submitting it as follow-up 
  Adding supplemental summary information and submitting it as follow-up with the 
original form 
  Summarizing new information and faxing it with a cover letter including subject identifiers 
(i.e. D.O.B. initial, subject number), protocol description and number, if assigned, 
suspect drug, brief adverse event description, and notation that additional or follow-up 
information is being submitted  (The patient identifiers are important so that the new 
information is added to the correct initial report) 
 
17.3 Serious Adverse Event (SAE) Reporting for Participating Sites 
 
Responsibility of Participating Sites 
  Participating sites are responsible for reporting all SAEs to their local IRB per local 
guidelines. Local IRB SAE approvals/acknowledgements must be sent to MSK upon 
receipt. 
  Participating sites are responsible for reporting all SAEs to the MSKCC PI via fax or 
e-mail within  24 hours of learning of the event. 
  Participating sites should notify the MSKCC PI of any grade 5 event immediately. 
  Participating sites should use the SAE Report Template to report SAEs to MSK. 
SAE contact information for the Coordinating Center is listed below: 
FAX: (646) 227-2482 to the attention of the MSKCC MCT Core/Clinical Trials Office Research 
Staff 
 
EMAIL: Hani Hassoun, MD (hassounh@mskcc.org) 
 
Responsibility of MSKCC 
 
  The MSKCC Research Staff is responsible for submitting all SAEs to the MSKCC IRB/PB 
as specified in 17.2 and to the Celgene Corporation as described in 17.2.1. 


Amended:  04/14/15 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
 
 
  The MSKCC PI is responsible for informing all participating sites about all unexpected 
SAEs that are either possibly, probably or definitely related to the study intervention 
within 30 days of receiving the stamped SAE from the MSKCC IRB/PB. 
  Any report pertaining to a grade 5 event will be distributed to the participating sites as soon 
as possible. 
17.4 Safety Reports 
 
  MSKCC will distribute outside safety reports to the participating sites immediately upon 
receipt. 
  MSKCC must submit safety reports to the MSKCC IRB/PB according to 
institutional guidelines. 
  Participating sites must submit safety reports to their institution’s IRBs within 30 
days of receipt from MSKCC or per the local IRB institutional guidelines. 
 
Adverse Drug Reaction Reporting 
 
Toxicity will be scored using CTCAE Version 4.0 for toxicity and adverse event reporting.  A 
copy of the CTCAE Version 4.0 can be downloaded from the CTEP homepage 
(http://ctep.info.n ih.gov).  All appropriate treatment areas should have access to a copy of the 
CTCAE Version 4.0.  All adverse clinical experiences, whether observed by the investigator or 
reported by the patient, must be recorded, with details about the duration and intensity of each 
episode, the action taken with respect to the test drug, and the patient’s outcome.  The 
investigator must evaluate each adverse experience for its relationship to the test drug and for 
its seriousness. 
 
The investigator must appraise all abnormal laboratory results for their clinical significance.  If 
any abnormal laboratory result is considered clinically significant, the investigator must provide 
details about the action taken with respect to the test drug and about the patient’s outcome. 
 
Pre gnancy Reporting 
 
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on lenalidomide, or within  28 days 
of the subject’s last dose of lenalidomide, are considered immediately reportable events. 
Lenalidomide  is to be discontinued immediately. The pregnancy, suspected pregnancy, or 
positive pregnancy test must be reported to Celgene Drug Safety immediately by facsimile or email 
using the Pregnancy Initial Report Form. The female subject should be referred to an obstetrician-
gynecologist, preferably one experienced in reproductive toxicity for further evaluation and 
counseling. 
 
The Investigator will follow the female subject until completion of the pregnancy, and must notify 
Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or abnormal 
outcome) using the Pregnancy Follow-up Report Form.  If the outcome of the pregnancy was 
abnormal (e.g., spontaneous or therapeutic abortion), the Investigator should report the abnormal 
outcome as an AE. If the abnormal outcome meets any of the serious criteria, it must be reported 


Amended:  04/14/15 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
 
 
as an SAE to Celgene Drug Safety immediately by facsimile, or other appropriate method, within 
24 hours of the Investigator’s knowledge of the event using the SAE Report Form. 
 
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 the IP should also be reported to Celgene Drug Safety 
immediately by facsimile, or other appropriate method, within 24 hours of the Investigator’s 
knowledge of the event using the SAE Report Form. 
 
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 their healthcare provider immediately. 
Celgene Drug Safety Contact Information: 
 
Ce lgene Corporation 
Global Drug Safety and Risk Manage ment 
Connell Corporate Pa rk 
300 Connell Dr. Suite 6000 
Berke ley He ights, NJ  07922 
Fax: ( 908) 673-9115 
E-mail:  drugsafety@celgene.com 
 
 
Adverse event updates/IND safety reports 
 
Celgene shall notify the Investigator via an IND Safety Report of the following information: 
 
  Any AE associated with the use of study drug in this study or in other studies that is both 
serious and unexpected. 
  Any finding from tests in laboratory animals that suggests a significant risk for human 
subjects including reports of mutagenicity, teratogenicity, or carcinogenicity. 
 
The Investigator shall notify his/her IRB promptly of these new serious and unexpected AE(s) or 
significant risks to subjects. 
 
The Investigator must keep copies of all AE information, including correspondence with Celgene 
and the IRB, on file. 
Annual Reports to Celgene 
 
This study meets requirements for IND exemption. Annual report must be submitted to Celgene 
for review/approval: 
 
Celgene Corporation 
Attn: Medical Development 


Amended:  04/14/15 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
 
 
86 Morris Avenue 
Summit, NJ  07901 
Tel: (908) 673-9000 
 
All adverse experience reports must include the patient number, age, sex, weight, severity of 
reaction (mild, moderate, severe), relationship to study drug (probably related, unknown 
relationship, definitely not related), date and time of administration of test medications and all 
concomitant medications, and medical treatment provided.   The investigator is responsible for 
evaluating all adverse events to determine whether criteria for “serious” and as defined above 
are present.  The investigator is responsible for reporting adverse events to Celgene as 
described below. 
 
 
18.1 INFORMED CONSENT PROCEDURES 
Before protocol-specified procedures are carried out, consenting professionals will explain full 
details of the protocol and study procedures as well as the risks involved to participants prior to  
their inclusion in the study. Participants will also be informed that they are free to withdraw from the 
study at any time. All participants must sign an IRB/PB-approved consent form indicating their 
consent to participate. This consent form meets the requirements of the Code of Federal 
Regulations and the Institutional Review Board/Privacy Board of this Center. The consent form will 
include the following: 
 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and investigational 
therapies. In addition, patients will be offered an option of supportive care for therapeutic 
studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
 
Before any protocol-specific procedures can be carried out, the consenting professional will fully 
explain the aspects of patient privacy concerning research specific information.  In addition to 
signing the IRB Informed Consent, all patients must agree to the Research Authorization 
component of the informed consent form. 
 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
18.1 FOR PARTICIPATING SITES 
 
The investigators listed on the protocol cover page and their qualified designees at each 
participating site may obtain informed consent and care for the participants according to good 
clinical practice and protocol guidelines. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
Signed copies of the informed consent should be distributed as follows: One copy will be given to 
the participant to be retained for their personal records. One copy will be maintained on file at the 
MSKCC. The third copy will be confidentially maintained by the participating institution. 
A note will be placed in the medical record documenting that informed consent was obtained for 
this study, and that the participant acknowledges the risk of participation. 
 
 
19.1 REFERENCES 
 
1. 
Smith A, Wisloff F, Samson D: Guidelines on the diagnosis and management of 
multiple myeloma 2005. Br J Haematol 132:410-51, 2006 
2. 
Jemal A, Murray T, Ward E, et al: Cancer statistics, 2005. CA Cancer J Clin 
55:10-30, 2005 
3. 
Laubach J, Richardson P, Anderson K: Multiple myeloma. Annu Rev Med 
62:249-64, 2011 
4. 
Anderson KC, Alsina M, Bensinger W, et al: NCCN clinical practice guidelines in 
oncology: multiple myeloma. J Natl Compr Canc Netw 7:908-42, 2009 
5. 
Barlogie B, Shaughnessy J, Tricot G, et al: Treatment of multiple myeloma. Blood 
103:20-32, 2004 
6. 
Fermand JP, Katsahian S, Divine M, et al: High-dose therapy and autologous 
blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 
55 to 65 years: long-term results of a randomized control trial from the Group Myelome- 
Autogreffe. J Clin Oncol 23:9227-33, 2005 
7. 
Jagannath S, Durie BG, Wolf J, et al: Bortezomib therapy alone and in 
combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J 
Haematol 129:776-83, 2005 
8. 
Richardson P, Chanan-Khan, A, Schlossman, R, Munshi, N, Oaklander,A.L., 
Heffner, L., Hassoun, H. Avigan, D. Amato,A. Anderson, K: Multicenter Phase 2 Study of 
Bortezomib in Previously Untreated Multiple Myeloma (MM); Encouraging Single-agent Activity 
and Tolerability Despite High Rates of Baseline Peripheral Neuropathy. Blood 106, 2005 
9. 
Dispenzieri A, Blood, E., Vesole, D., Fonseca, R., Callender, N., Pr, G.,  : A  
phase II study of PS-341 for patients with high risk, newly diagnosed multiple myeloma: A trial of 
the ECOG group (E2A02). Blood 106, 2005 
10. 
Harousseau JL, Attal M, Leleu X, et al: Bortezomib plus dexamethasone as 
induction treatment prior to autologous stem cell transplantation in patients with newly 
diagnosed multiple myeloma: results of an IFM phase II study. Haematologica 91:1498-505, 
2006 
11. 
Wang M, Giralt S, Delasalle K, et al: Bortezomib in combination with thalidomide- 
dexamethasone for previously untreated multiple myeloma. Hematology 12:235-9, 2007 
12. 
Wang M, Weber DM, Delasalle K, et al: Thalidomide-dexamethasone as primary 
therapy for advanced multiple myeloma. Am J Hematol 79:194-7, 2005 
13. 
Mateos MV, Hernandez JM, Hernandez MT, et al: Bortezomib plus melphalan 
and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter 
phase 1/2 study. Blood 108:2165-72, 2006 
14. 
Mateos MV, Hernandez JM, Hernandez MT, et al: Bortezomib plus melphalan 
and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events 
results and prognostic factors for time to progression. Haematologica 93:560-5, 2008 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
15. 
Oakervee HE, Popat R, Curry N, et al: PAD combination therapy (PS- 
341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple 
myeloma. Br J Haematol 129:755-62, 2005 
16. 
Popat R, Oakervee HE, Hallam S, et al: Bortezomib, doxorubicin and 
dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term 
follow-up. Br J Haematol 141:512-6, 2008 
17. 
Attal M, Harousseau JL, Stoppa AM, et al: A prospective, randomized trial of 
autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe 
Francais du Myelome. N Engl J Med 335:91-7., 1996 
18. 
Child JA, Morgan GJ, Davies FE, et al: High-dose chemotherapy with 
hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348:1875-83, 2003 
19. 
Lenhoff S, Hjorth M, Holmberg E, et al: Impact on survival of high-dose therapy 
with autologous stem cell support in patients younger than 60 years with newly diagnosed 
multiple myeloma: a population-based study. Nordic Myeloma Study Group. Blood 95:7-11., 
2000 
20. 
Palumbo A, Triolo S, Argentino C, et al: Dose-intensive melphalan with stem cell 
support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 94:1248- 
53., 1999 
21. 
Koreth J, Cutler CS, Djulbegovic B, et al: High-dose therapy with single 
autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A 
systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow 
Transplant 13:183-96, 2007 
22. 
Ladetto M, Pagliano G, Ferrero S, et al: Major tumor shrinking and persistent 
molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in 
patients with autografted myeloma. J Clin Oncol 28:2077-84, 2010 
23. 
Ludwig H, Adam Z, Tothova E, et al: Thalidomide maintenance treatment 
increases progression-free but not overall survival in elderly patients with myeloma. 
Haematologica 95:1548-54, 2010 
24. 
Brinker BT, Waller EK, Leong T, et al: Maintenance therapy with thalidomide 
improves overall survival after autologous hematopoietic progenitor cell transplantation for 
multiple myeloma. Cancer 106:2171-80, 2006 
25. 
Cavo M, Pantani L, Tacchetti P, et al: Thalidomide maintenance in multiple 
myeloma: certainties and controversies. J Clin Oncol 27:e186-7; author reply e188, 2009 
26. 
Berenson JR, Crowley JJ, Grogan TM, et al: Maintenance therapy with alternate- 
day prednisone improves survival in multiple myeloma patients. Blood 99:3163-8, 2002 
27. 
Attal M, Harousseau JL, Leyvraz S, et al: Maintenance therapy with thalidomide 
improves survival in patients with multiple myeloma. Blood 108:3289-94, 2006 
28. 
Zonder JA, Crowley J, Hussein MA, et al: Lenalidomide and high-dose 
dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a 
randomized Southwest Oncology Group trial (S0232). Blood 116:5838-41, 2010 
29. 
Rajkumar SV, Jacobus S, Callander NS, et al: Lenalidomide plus high-dose 
dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly 
diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11:29-37, 
2010 
30. 
McCarthy PL, Owzar K, Stadtmauer EA, et al: Phase III Intergroup Study of 
Lenalidomide (CC-5013) Versus Placebo Maintenance Therapy Following Single Autologous 
Stem Cell Transplant for Multiple Myeloma (CALGB 100104): Initial Report of Patient Accrual 
and Adverse Events. ASH Annual Meeting Abstracts 114:3416-, 2009 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
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IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
31. 
Attal M, Harousseau JL, Marit G, et al: Lenalidomide After Autologous 
Transplantation for Myeloma: First Analysis of a Prospective, Randomized Study of the 
Intergroupe Francophone Du Myelome (IFM 2005 02). ASH Annual Meeting Abstracts 114:529-, 
2009 
32. 
Richardson PG, Weller E, Jagannath S, et al: Multicenter, phase I, dose- 
escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple 
myeloma. J Clin Oncol 27:5713-9, 2009 
33. 
Richardson P, Jagannath S, Schlossman RL, et al: Multicenter, randomized, 
phase II study to evaluate the efficacy and safety of two CC-5013 dose regimens when used 
alone or in combination with dexamethasone for the treatment of relapsed or refractory multiple 
myeloma (MM). Blood 100:104a, 2002 
34. 
Alegre A, Granda A, Martinez-Chamorro C, et al: Different patterns of relapse 
after autologous peripheral blood stem cell transplantation in multiple myeloma: clinical results 
of 280 cases from the Spanish Registry. Haematologica 87:609-14, 2002 
35. 
Lenhoff S, Hjorth M, Turesson I, et al: Intensive therapy for multiple myeloma in 
patients younger than 60 years. Long-term results focusing on the effect of the degree of 
response on survival and relapse pattern after transplantation. Haematologica 91:1228-33, 2006 
36. 
Kumar S, Mahmood ST, Lacy MQ, et al: Impact of early relapse after auto-SCT 
for multiple myeloma. Bone Marrow Transplant 42:413-20, 2008 
37. 
Kumar SK, Rajkumar SV, Dispenzieri A, et al: Improved survival in multiple 
myeloma and the impact of novel therapies. Blood 111:2516-20, 2008 
38. 
Webber,DM, Chen, C, Niesvizky,R, et al: Lenalidomide plus 
dexamethasone for relapsed multiple myeloma in North America. New Engl Jour. Med 
357:2133, 2007 
39. 
Dimopoulos M, Spencer, A, Attal M, et al: Lenalidomide plus 
dexamethasone for relapse or refractory multiple myeloma.  New Engl Jour. Med 
357:2123, 2007 
 
 
20.0 
APPENDICES 
 
Appendix A: Criteria For Symptomatic Relapse And Progression Of Multiple Myeloma 
 
Appendix B: Lenalidomide Risks Of Fetal Exposure, Pregnancy Testing Guidelines And 
Acceptable Birth Control Methods 
 
Appendix C: Cockcroft-Gault Estimation Of Crcl 
 
Appendix D: Medication Diary/Log For Lenalidomide And Dexamethasone 
 
Appendix E: ECOG Performance Status 
 
 
 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
APPENDIX A: CRITERIA FOR SYMPTOMATIC AND 
ASYMPTMATIC RELAPSE AND PROGRESSION OF MULTIPLE 
MYELOMA 
 
 
Patients will be considered as having symptomatic relapse/progression of disease if the y show 
evidence of disease relapse or progression by serum or urine studies according to consensus 
criteria, AND present any of the following organ dysfunctions that are deemed to be related to 
disease progression: 
[C] Calcium elevation in the blood (serum calc ium > 10.5 mg/l or upper limit of 
normal) 
[R] Progressive renal insuffic iency (serum creatinine > 2mg/dl) 
[A] Progressive anemia with hemoglobin < 9 g/dl 
[B] New lytic lesion by skeletal survey 
 
 
Patients will be considered as having asymptomatic relapse/progression if they show evidence of 
disease relapse or progression by serum or urine studies according to consensus criteria without 
evidence of organ damage as defined above. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
APPENDIX B: LENALIDOMIDE RISKS OF FETAL EXPOSURE, 
PREGNANCY TESTING GUIDELINES AND ACCEPTABLE 
BIRTH CONTROL METHODS 
 
Risks Associate d with Pre gnancy 
 
The use of lena lidomide in pregnant females and nursing mothers has not been studied nor has the 
effect of the lenalidomide on human eggs and sperm.  Lenalidomide is structura lly related to 
thalidomide.  Thalidomide is a known human teratogenic active substance that causes severe life- 
threatening birth defects.  An embryofeta l deve lopme nt study in anima ls indicates that lena lidomide 
produced malformations in the offspring of female monkeys who received the drug during 
pregnancy.  The teratoge nic effect of lenalidomide in huma ns cannot be ruled out.  Therefore, a risk 
minimization plan to preve nt pregnancy must be observed. 
 
All study participants must be registered into the ma ndatory Revlimid REMS™ program, and be 
willing and able to comply with the requirements of Revlimid REMS™. 
 
Crite ria fo r fe male s of childbe aring pote ntial (FCB P) 
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 
for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive 
months). 
 
The investigator mus t e ns ure that: 
• Females of childbearing potentia l comply with the conditions for pregnancy risk 
minimization, inc luding confirmation that she has an adequate leve l of understanding 
• Females NOT of childbearing pote ntia l acknowledge that she understands the ha zards and 
necessary precautions assoc iated with the use of lena lidomide 
• Male patients taking le nalidomide acknowledge that he understands that traces of 
lena lidomide have been found in semen, that he understands the potentia l teratogenic risk if 
engaged in sexual activity with a female of childbearing pote ntia l or pregnant female, and 
that he understands the need for the use of a condom even if he has had a vasectomy, if 
engaged in sexual activity with a female of childbearing pote ntia l or pregnant female. 
• 
Contrace ption 
Females of childbearing potentia l (FCBP) enrolle d in this protocol must agree to use two reliable 
forms of contraception simultaneously or to practice complete abstine nce from heterosexua l 
intercourse during the following time periods related to this study: 1) for at least 28 days before 
starting lena lidomide; 2) throughout the entire duration of lena lidomide treatment; 3) during dose 
interruptions; and 4) for at least 28 days after lena lidomide discontinuation. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
The two methods of reliable contraception must inc lude one highly effective method and one 
additiona l effective (barrier) method. FCBP must be referred to a qualifie d provider of contraceptive 
methods if needed. The following are examples of highly effective and additiona l effective methods 
of contraception: 
o Highly effective methods: 
▪ Intrauterine device (IUD) 
▪ Hormona l (birth control pills, injections, impla nts) 
▪ Tuba l ligation 
▪ Partner’s vasectomy 
o Additiona l effective methods: 
▪ Male condom 
▪ Diaphragm 
▪ Cervical Cap 
Because of the increased risk of ve nous thromboembolism in patients with multiple mye loma taking 
lena lidomide and dexamethasone , combine d ora l contraceptive pills are not recommended. If a 
patie nt is currently using combine d ora l contraception the patie nt should switch to one of the 
effective method listed above. The risk of venous thromboembolism continues for 4−6 weeks after 
discontinuing combine d ora l contraception. The efficacy of contraceptive steroids may be reduced 
during co-treatme nt with dexamethasone. 
Implants and levonorgestrel-re leasing intrauterine systems are associated with an increased risk of 
infection at the time of insertion and irregular vagina l bleeding. Prophylactic antibiotics should be 
considered particularly in patients with ne utropenia. 
 
Pre gnancy tes ting 
Medically supervised pregnancy tests with a minimum sensitivity of 50 mIU/mL must be performed 
for females of childbearing potentia l, inc luding females of childbearing potentia l who commit to 
complete abstinence, as outlined below. 
 
Before starting le nalidomide 
 
Female Patients: 
FCBP must have two negative pregna ncy tests (sensitivity of at least 50 mIU/mL) prior to 
prescribing le nalidomide.  The first pregnancy test must be performed within 10-14 days prior to 
prescribing le nalidomide and the second pregnanc y test must be performed within 24 hours prior to 
prescribing le nalidomide.  The patie nt may not receive lena lidomide until the Investigator has 
verified that the results of these pregnancy tests are negative. 
 
Male Patients: 
Must agree to practice complete abstinence or agree to use a condom during sexual contact with 
pregnant females or females of childbearing pote ntia l throughout the entire duration of lena lidomide 
treatment, during dose interruptions and for at least 28 da ys following le nalidomide discontinuation, 
even if he has undergone a successful vasectomy. 
 
During study partic ipation and for 28 days following lena lidomide disc ontinuation 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
Female Patients: 
• FCBP with regular or no menstrua l cyc les must agree to have pregnancy tests weekly for the 
first 28 days of lena lidomide treatment, inc luding dose interruptions and the n every 28 days 
throughout the remaining duration of le nalidomide treatment, inc luding dose interruptions, at 
lena lidomide discontinuation, and at Day 28 following lena lidomide discontinuation.  If 
menstrua l cyc les are irregular, the pregnancy testing must occur weekly for the first 28 days 
of le nalidomide treatment, inc luding dose interruptions, and then every 14 days throughout 
the remaining duration of lena lidomide treatment, inc luding dose interruptions, at 
lena lidomide discontinuation, and at Day 14 and Day 28 following lena lidomide 
discontinuation. 
• At each visit, the Investigator must confirm with the FCBP that she is continuing to use two 
reliable methods of birth control at each visit during the time that birth control is required. 
• If pregnancy or a positive pre gnancy test does occur in a study patient, lena lidomide must be 
immediately discontinued. 
• Pregnancy testing and counse ling must be performed if a patient misses her period or if her 
pregnancy test or her menstrua l bleeding is abnorma l.  Lenalidomide treatment must be 
temporarily discontinued during this evaluation. 
• Females must agree to abstain from breastfeeding during study participation and for at least 
28 days after le nalidomide discontinuation. 
Male Patients: 
• Must practice complete abstine nce or use a condom during sexua l contact with pregnant 
females or females of childbearing potentia l throughout the entire duration of lena lidomide 
treatment, during dose interruptions and for at least 28 da ys following le nalidomide 
discontinuation, even if he has undergone a successful vasectomy. 
• If pregnancy or a positive pre gnancy test does occur in the partner of a male study patient 
during study participation, the investigator must be notifie d immediately. 
• Male patients should not donate semen or sperm during therapy or for at least 28 days 
following discontinuation of lena lidomide. 
• 
Additional pre cautions 
• Patients should be instructed never to give lena lidomide to another person. 
• Patients should not donate blood during therapy and for at least 28 days following 
discontinuation of lena lidomide. 
• Only enough lena lidomide for one cycle of therapy may be prescribed with each cycle of 
therapy. 
• Any unused lena lidomide must be returned as instructed through Revlimid REMS™. 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
IRB#: 11-107A(12) 
Amended:  04/14/15 
 
 
A P P END I X C : Cockcroft-Gault estimation of CrCl: 
 
 
Cockcroft-Gault estimation of creatinine clearance (CrCl): 
(Cockcroft, 1976; Luke 1990) 
 
CrCl (mL/min) = 
(140 –age) x (weight , kg)  
 
(Males) 
72 x (serum creatinine, mg/dL) 
 
CrCl (mL/min) = 
(140 –age) x (weight , kg)_    x 0.85 
(Females) 
72 
x 
(serum 
creatinine , 
mg/dL) 


Amended:  04/14/15 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
 
 
 
APPENDIX D: Pill Diary for IRB #11-107 
 
Number of Pills Given:_  
 
 
 
 
Pill Bottle(s) returned: Circle Yes or No 
IRB#: 11-107A(12) 
Total Daily Dose: 
_ 
Number of Pills returned:_  
 
(To be Completed by RN) 
 
PLEASE FILL OUT AND BRING THIS SHEET AT YOUR NEXT VISIT. This lo g should be completed each time you 
take the study medication at home, and returned at the end of each cycle. If you miss a dose, please indicate in the table 
below. 
CYCLE #: _  
 # of WEEKS_  
 
 
Day 
Date 
Number of Lenalidomide 
capsules taken (please indicate 
time) 
Dexamethasone tablets taken 
(please indicate time) 
EXAMPLE 
1/1/2011 
2, 4:00 PM 
1, 3:00 PM 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
Patient Signature:   
 
Date: __  
 
Consenting Professional/Research RN Signature: __________________ 
Date:    _   
Consenting Professional/Research RN 
Comments: 
_ 
_  
 


MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
 
 
APPENDIX E: ECOG Performance Status 
IRB#: 11-107A(12) 
 
Grade 
Description 
0 
Normal activity, fully active, able to carry on all pre-disease performance 
without restriction 
1 
Symptoms, but fully ambulatory, restricted in physica lly strenuous activity 
but ambulatory and able to carry out work of a light or sedentary nature (e.g. 
light housework, office work) 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about more than 50% of waking hours. 
3 
Capable of only limited self-care, Confined to bed or cha ir more than 50% of 
waking hours. 
4 
Complete ly disabled.  Cannot carry on any self-care.  Totally confined to bed 
or chair. 
5 
Death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amended:  04/14/15