Clinical trial NCT01891643
Conditions: Newly Diagnosed, Previously Untreated Multiple Myeloma
Sponsor: Bristol-Myers Squibb
Start date: 2013-09-30; Completion date: 2020-06-25
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to look at subjects who receive Lenalidomide, Dexamethasone, and Elotuzumab and determine if they will have lower surface CS1 expression on malignant plasma cells at the time of progression than those who receive Lenalidomide and Dexamethasone without Elotuzumab

Detailed description:

Arms: arm 1: Lenalidomide 25 mg capsules by mouth once daily (on Days 1-21), repeat every 28 days until subject meets criteria for discontinuation of study drug

Dexamethasone 40 mg tablets by mouth weekly (on Days 1, 8, 15, 22), repeat every 28 days until subject meets criteria for discontinuation of study drug arm 2: Lenalidomide 25 mg capsules by mouth once daily (Days 1-21)

Dexamethasone 28 mg tablets by mouth once daily \[Days 1, 8, 15, 22 (cycles 1 \& 2); Days 1 \& 15(cycles 3-18); Day 1 (cycle 19 \& beyond)\]

Dexamethasone 40 mg tablets by mouth once daily \[Days 8 \& 22 (cycles 3-18); Days 8, 15, 22 (cycle 19 \& beyond)\]

Dexamethasone 8 mg IV (intravenous) solution once daily \[Days 1, 8, 15, 22 (cycles 1 \& 2); Days 1 \& 15 (cycles 3-18); Day 1 (cycle 19 \& beyond)\]

Elotuzumab 10 mg/kg IV solution weekly \[Days 1, 8, 15, 22 (cycles 1 \& 2); Days 1 \& 15 (cycles 3-18)\]

Elotuzumab 20 mg/kg IV solution on Day 1 (cycle 19 \& beyond)

Repeat above-mentioned dose cycles every 28 days until subject meets criteria for discontinuation of study drug
Interventions: intervention 1: Lenalidomide intervention 2: Dexamethasone intervention 3: Elotuzumab
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_000.pdf: 
Page:
1
Protocol Number:
CA204006
IND Number:
IND 100,043
EUDRACT Number
2010-022445-20
Date:
19-Feb-2013
Protocol CA204006: A Phase 3, Randomized, Open Label Trial of 
Lenalidomide/dexamethasone With or Without Elotuzumab in Subjects with Previously 
Untreated Multiple Myeloma
Amendment Number 03 - Substudy
Site Number: All
Study Director/Central Medical Monitor
Jessica Katz, MD PhD
This protocol amendment contains information that is confidential and proprietary to 
Bristol-Myers Squibb (BMS). 
This amendment must be maintained with the referenced protocol.
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TABLE OF CONTENTS
TABLE OF CONTENTS.................................................................................................................2
1
AMENDMENT INTRODUCTION AND RATIONALE............................................3
1.2
Research Hypothesis.....................................................................................................4
2
OBJECTIVES...............................................................................................................4
2.1
Primary Objective.........................................................................................................4
2.2
Secondary Objectives ...................................................................................................4
3
STUDY SITES .............................................................................................................4
4
SUBJECT SELECTION CRITERIA ...........................................................................5
5
PROCEDURES ............................................................................................................5
7
CONFIDENTIALITY ..................................................................................................6
8
SUBJECT RIGHTS......................................................................................................6
8.1
Record Retention ..........................................................................................................6
9
WITHDRAWAL OF SUBJECTS FROM CORRELATIVE RESEARCH.................7
10
DESTRUCTION OF BONE MARROW SAMPLE AND RELATED 
MATERIAL..................................................................................................................7
11
FLOW CHART/TIME AND EVENTS SCHEDULE..................................................8
12
SAMPLE COLLECTION AND PROCESSING .........................................................8
13
INFORMED CONSENT..............................................................................................8
13.1
Informed Consent Procedures.......................................................................................9
14
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS 
COMMITTEE (IRB/IEC).............................................................................................9
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1
AMENDMENT INTRODUCTION AND RATIONALE
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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1.2
Research Hypothesis
At the time of progression the surface CS1 expression in the elotuzumab, lenalidomide, 
dexamethasone arm will be lower than at baseline.
2
OBJECTIVES
2.1
Primary Objective

To describe the change from baseline to progression of the cell surface expression of CS1 
from bone marrow-derived MM cells in both treatment arms.
2.2
Secondary Objectives

To describe the level of cell surface CS1 from bone marrow-derived MM cells at the time of 
progression in both treatment arms.

To describe sCS1 levels in serum and to evaluate change from baseline during therapy and at 
progression in both treatment arms.

To describe the presence, and the change from baseline, on therapy, and at progression, of 
circulating MM cell numbers and their CS1 cell surface expression in both treatment arms.

To describe the cell number and CS1 expression patterns between matched samples of bone 
marrow-derived MM cells and circulating MM cells at baseline and at progression in both 
treatment arms.
 
 
 
 
 
 
3
STUDY SITES
This study is a multi-center, non-randomized, correlative exploratory study that will be 
performed at approximately 15 North American and European sites that permit correlative 
exploratory studies to be conducted in compliance with all applicable laws, rules, and 
regulations. 
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4
SUBJECT SELECTION CRITERIA
To participate in this Correlative Sub-study Amendment, subjects will be asked to read, 
understand, and sign an informed consent form designed for the purpose of collecting samples 
for research purposes. Subjects must have consented to participate in the main clinical trial 
CA204006. There is no pre-determined enrollment goal for this study; participation in this 
substudy is strictly voluntary. Subjects will be informed that they will not be excluded from 
the main clinical trial CA204006 if they do not wish to participate in the Correlative 
Sub-study Amendment.
5
PROCEDURES
Subjects who consent to participate in this study and who voluntarily give written informed 
consent for collection of samples will have a bone marrow aspirate collected at screening 
(baseline) and again at time of progression. For each subject, approximately 10 mL of bone 
marrow aspirate will be collected at each time point; this is in addition to the volume required for 
the main study (1.5 mls -2.5 mls required for cytogenetic analysis, and approximately 1.5 -2.5
mls for creation of 10 slides [4 for ICON CL and 6 for FISH analysis]). A minimum of 3 mL is 
needed to conduct the procedures associated with the primary and secondary objectives. 
Additionally, peripheral blood will be collected allowing preparation of serum samples at 
matched time points (screening and at time of progression) and evaluation of secondary and 
exploratory objectives. The collected samples will be delivered to designated laboratories for 
completion of the biomarker analyses and the isolation of CD138+ plasma cells, which will be 
frozen and stored for exploratory analysis at a later date.
 
 
 
 
 
 
 
 
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7
CONFIDENTIALITY
Bristol Myers Squibb will work to protect the confidentiality of research subjects who volunteer 
to participate in this correlative sub-study and to ensure that the analyses are conducted in 
compliance with all applicable laws, rules and regulations.
All samples are stored in a de-identified fashion; they are labeled only with a randomly
generated bar code number.2 The link between this bar code number and the coded identification 
number assigned to the study subject is maintained in a secure Bristol-Myers Squibb database 
and is not shared with either the laboratories, or the researchers, that analyze the samples.
Bristol-Myers Squibb does not receive subject’s’ names, phone numbers, addresses or National 
ID Numbers, such as an identity card numbers, passport numbers or US social security numbers, 
when collecting data from the clinical trial, and, cannot link the identity of subjects to the 
research analyses. Therefore, any data from the analyses that might be released into the public 
domain will be predominately aggregate data. For example, a scientific research publication or a 
presentation at a scientific meeting will not contain any information that would allow a person 
reading the article or attending the presentation to identify individual participants. This will 
minimize the chance that any information will be used as a basis for discrimination (e.g., when 
the subject applies for life or medical insurance).
8
SUBJECT RIGHTS
Study subjects can withdraw their consent to participate in the Correlative Sub-study 
Amendment at any time, and even after the sample has been shipped to the analysis lab. As long 
as the Investigator or Investigator’s designee retains the clinical trial records, a study subject will 
be able to contact his/her Investigator or the Investigator’s designee and ask for his/her sample to 
be withdrawn from the sub study and destroyed.
8.1
Record Retention
The Investigator must retain essential documents for the maximum period required by applicable 
regulations and guidelines.7 or Institutional procedures, or for the period specified by the 
sponsor, whichever is longer. The Investigator must contact Bristol-Myers Squibb prior to 
destroying any records associated with the study. 
Bristol-Myers Squibb will notify the Investigator when the trial records are no longer needed.
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If the Investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another Investigator, IRB). Notice of such a 
transfer will be given in writing to Bristol-Myers Squibb.
9
WITHDRAWAL OF SUBJECTS FROM CORRELATIVE RESEARCH
Subjects have, at any time, the option to withdraw consent for participation from:
1. Only the Correlative Sub-study Amendment independent of the main clinical trial 
(CA204006);
OR
2. Both the main clinical trial (CA204006) and Correlative Sub-study Amendment.
Subjects who wish to withdraw their consent from the Correlative Sub-study Amendment 
(ie, have their samples destroyed) should contact the Investigator. 
It is possible that subjects may decide to withdraw consent from the main clinical trial 
(CA204006) but continue with their consent for the Correlative Sub-study Amendment. In 
such cases the Investigator should inform subjects that their sample may be used for 
research. 
If a subject requests to withdraw consent for the Correlative Sub-study Amendment after the 
time the Investigator is legally required to maintain the records linking the subject’s sample and 
coded health information to their identity, and the records have been destroyed, the sample will 
become anonymous and unable to be withdrawn. 
10
DESTRUCTION OF BONE MARROW SAMPLE AND RELATED
MATERIAL
In the case of subjects who have withdrawn their consent for participation in the Correlative 
Sub-study Amendment the Investigator will notify Bristol-Myers Squibb Sample Bank. 
Bristol-Myers Squibb Sample Bank will destroy any remaining sample and any material obtained 
from the sample in accordance with BMS procedure for Sample Destruction. In the case of 
samples that have been partially analyzed, the remaining sample will be destroyed but 
Bristol-Myers Squibb shall be entitled to retain and use any research results obtained prior to the 
withdrawal of consent. 
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11
FLOW CHART/TIME AND EVENTS SCHEDULE
Table 11-1:
Time and Event Schedule
Procedure
Visit Day: Screening
Visit Day: Cycle 3, Day 1
Visit Day: Time of 
Progression
Sub study Informed 
Consent
Xa
Bone Marrow Sample 
Collection
Xb
Xc
Serum Collection
Xb
X
Xc
Peripheral Blood 
Collection
Xb
X
Xc
a Informed consent for testing may be obtained at any time during the trial PRIOR to the collection of the sample.
b The sample can be collected up to 30 days prior to receiving first scheduled dose of drugs (Cycle 1/Day 1), 
regardless of study arm.
c The sample can be collected up to the start of new therapy.
12
SAMPLE COLLECTION AND PROCESSING
Following collection, the bone marrow aspirate sample will be shipped immediately at room 
temperature to the designated central laboratory Samples need to be received by the designated 
laboratory within 48 hours after collection to allow for completion of qualified assays and valid 
interpretation of results. The first 3mL of the collected sample will be used to conduct assays that 
comprise the primary, secondary objectives 
 
 The remainder of the sample will be processed by magnetic separation to isolate 
CD138+ plasma cells that will be immediately frozen and stored for future use to address the 
exploratory objectives. Peripheral blood will be collected and sent to two central laboratories to 
address objectives outlined in secondary and exploratory objectives. Serum collected will be 
prepared, frozen, and sent to BMS laboratories for evaluation of soluble proteins (including 
sCS1) as outlined in secondary objectives.  Details for collection, processing, storing and 
shipping these samples will be provided in a separate procedure manual.
13
INFORMED CONSENT
Investigators must ensure that subjects, or, in those situations where consent cannot be given by 
subjects, their legally acceptable representative are clearly and fully informed about the purpose, 
potential risks and other critical issues regarding clinical studies in which they volunteer to 
participate. Freely given written informed consent must be obtained from every subject or, in 
those situations where consent cannot be given by subjects, their legally acceptable 
representative, prior to study participation.
The rights, safety, well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
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The following section contains Bristol-Myers Squibb procedures on obtaining informed consent 
from subjects or their legally acceptable representative prior to participating in a clinical trial. 
Procedures are described for all subjects including those who are unable to give informed 
consent. The relevant procedures must be used whenever they are applicable.
A separate informed consent will be obtained from study subjects who voluntarily agree to 
participate in the correlative sub study Amendment. The informed consent form for correlative 
sample collection reflecting this Amendment will be submitted for review and approval to the 
IRB/Ethics Committee charged with this responsibility.
13.1
Informed Consent Procedures
Preparation of the consent form is the responsibility of the Investigator and must include all 
elements required by ICH, GCP and applicable regulatory requirements, and must adhere to GCP 
and to the ethical principles that have their origin in the Declaration of Helsinki. The consent 
form must also include a statement that Bristol-Myers Squibb and regulatory authorities have 
direct access to subject records. Prior to the beginning of the study, the Investigator must have 
the IRB/IEC’s written approval/favorable opinion of the written informed consent form and any 
other information to be provided to the subjects.
The Investigator must provide the subject or legally acceptable representative with a copy of the 
informed consent form and written information about the study in the language in which the 
subject is most proficient. The language must be non-technical and easily understood. The 
Investigator should allow time necessary for subject or subject’s legally acceptable 
representative to inquire about the details of the study, then informed consent must be signed and 
personally dated by the subject or the subject’s legally acceptable representative and by the 
person who conducted the informed consent discussion. The subject or legally acceptable 
representative should receive a copy of the signed informed consent and any other written 
information provided to study subjects prior to subject’s participation in the trial
14
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE 
(IRB/IEC)
This amendment, the informed consent form for correlative sample collection and any 
advertisement for subject recruitment will be submitted for review and approval to the 
IRB/Ethics Committee charged with this responsibility. The investigator must have on file 
written and dated approval/favorable for this amendment from the IRB/Ethics Committee before 
this sample is collected.
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AMENDMENT ACKNOWLEDGEMENT
I have read this Amendment and agree that it contains all necessary details for carrying out the 
changes described. I understand that it must be reviewed by the Institutional Review 
Board/Ethics Committee overseeing the conduct of the study and approved or given favorable 
opinion before implementation unless to eliminate an immediate hazard to subjects.
If this Amendment substantially alters the study design or increases potential risk to subjects, the 
consent form will be revised and submitted to the Institutional Review Board/Independent Ethics 
Committee for approval/positive opinion. I will use the new consent form for any new subjects 
prior to enrollment, and for subjects currently enrolled in the study if they are affected by the 
Amendment.
___________________________________
_______________
Investigator's printed name and signature
Date
___________________________________
_______________
Medical Monitor/Study Director
Date
(If required by applicable regulations and guidelines.)
Protocol Number: CA204006
Site Specific
Amendment Number: 03
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SAP_001.pdf: 
Official Title of Study: 
PH III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Previously 
Untreated Multiple Myeloma (ELO 1 Substudy) 
 
NCT Number: NCT01891643 
 
 
Document Date (Date in which document was last revised): February 19, 2013 


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6
STATISTICAL ANALYSIS
CS1 level on the cell surface is measured by mean fluorescent intensity.
The level of CS1 protein expression on the surface of bone marrow-myeloma cells and
peripheral blood myeloma cells at baseline and at progression, and the change in CS1 level, from 
baseline to progression, will be summarized, by arm, via descriptive statistics, including the 
mean, standard deviation, median, inter-quartile range, minimum and maximum. The level of 
CS1 on the surface of bone marrow-derived myeloma cells and circulating myeloma cells at 
progression will be regressed on treatment, baseline CS1 level, and treatment by baseline CS1 
level interaction to determine whether treatment affects CS1 level at progression, and, if so, 
whether the magnitude of the effect differs by baseline CS1 level. More complex modeling 
techniques may be employed, if necessary, such as adding higher order terms for baseline CS1 
expression or doing regression on log-transformed CS1 expression.
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