Clinical trial NCT03834623
Conditions: Melanoma
Keywords: melanoma skin
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Start date: 2019-05-14; Completion date: 2021-08-04
Enrollment: 23 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is to find out if the combination of CC-122 (an investigational agent) and Nivolumab will enhance the anti-cancer activity and prevent T-cell exhaustion (T-cells are responsible for maintaining the body's immune response).

Detailed description:

Arms: arm 1: Participants will take CC-122 orally at 2mg daily for 5 consecutive days every 7 days, with intravenous nivolumab (240mg) in days 1 and 15 within a 28-day cycle.
Interventions: intervention 1: CC-122 intervention 2: Nivolumab
Intervention descriptions: intervention 1: Oral CC-122 at 2 mg daily, 5 days out of 7 intervention 2: 240 mg Nivolumab intravenously days 1 and 15 in each 28 day cycle

Protocol documents:
ICF_002.pdf: 
A Phase II Biomarker Trial of Avadomide (CC-122) in 
combination with Nivolumab in Advanced Melanoma 
 
 
NCT03834623 
ICF Version 3 Dated 12/06/2019 


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CONSENT TO TAKE PART IN A CLINICAL RESEARCH STUDY 
AND 
AUTHORIZATION TO DISCLOSE HEALTH INFORMATION 
 
Study Title: 
  
A Phase II Biomarker Trial of Avadomide (CC-122) in 
combination with Nivolumab in Advanced Melanoma 
 
Protocol Number: 
 
Sponsor: 
MCC 19706 
 
Moffitt Cancer Center 
 
Principal Investigator: 
(Study Doctor) 
 
Nikhil Khushalani, MD 
 
 
Telephone: 
(24 hour number) 
(813) 745-3437 
(800) 456-3434 
Address: 
Moffitt Cancer Center McKinley 
10920 N. McKinley 
Tampa, FL 33612 
 
Moffitt Cancer Center 
12902 Magnolia Drive 
Tampa, FL 33612 
 
 
 
This consent and authorization form explains why this research study is being done and what 
your role will be if you choose to take part. You may choose not to take part in this study.  
The purpose of this study is to find out if the combination of Avadomide (CC-122, an 
investigational agent) and Nivolumab will result in improved anti-cancer activity and prevent T-
cell exhaustion (T-cells are responsible for maintaining your body immune response) in your 
advanced melanoma condition. This is a type of skin cancer, but this has now spread to other 
organs, and cannot be removed by surgery. 
The researchers will look for early signals that the study treatment is working (for example, 
tumor shrinkage, survival rate) and want to learn about the tolerability and toxicity of this 
combination. 
Another purpose of the study is to learn more about how the compounds work in combination, to 
get an early picture of what they do to biomarkers (for example, proteins) in the blood and 
tumor, and if these biomarkers in blood and tumor change over the course of the study. 
Biomarkers are substances in the body that increase or decrease in expected ways following 
study treatment. Studying these biomarkers while you are receiving study drugs may show 


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whether or not the study drugs are affecting your tumor. The relationship between the amount of 
study drug in your body and the effect of the biomarkers on your disease when the study drugs 
are given as pairs will also be studied. 
Your total participation in this study from the time you sign and date the informed consent form 
through your last visit may be up to about 36 months, depending on how your cancer responds 
to the study treatment and depending on your test results. 
Before you can start the study, the study doctor or study staff will talk to you about the study.  If 
you agree to participate, you have to sign and date this form before the study doctor or study 
staff can begin the first part of the study called a screening period (for a period of up to 28 days) 
to see if you qualify to be in the main part of the study. Your study doctor will determine your 
eligibility to participate in the study. If you qualify to continue in the study you will undergo a 
study treatment visit. This will involve administration of the investigational drug along with other 
study procedures which are later described in detail in this document. Post-study treatment visit, 
you will have an end of study treatment/follow-up visit which involves evaluating your health 
condition by routine clinic examination and procedures, later described in detail. Your regular 
medical care might include some of the study tests and procedures.  The study doctor or a 
member of the study staff can answer any questions you may have about which tests and 
procedures are not part of your regular medical care 
We anticipate enrolling between 44 to 66 participants in this study at Moffitt Cancer Center. 
Your participation is voluntary, and you may stop your participation at any time.  There will be no 
penalties or loss of benefits or opportunities if you do not participate or decide to stop once you 
start. 
Alternatives to participating in the study include – getting treatment or care for your cancer 
without being in a study (typically called standard of care treatment), taking part in another study 
of an investigational drug, and getting no treatment.  
If you decide that you don’t want any more active treatment, one of your options is called 
“comfort care”, also called palliative care. This type of care aims to help reduce pain, tiredness, 
appetite problems and other problems caused by the cancer. It does not treat the cancer 
directly, but instead tries to improve how you feel. Comfort care tries to keep you as active and 
comfortable as possible. If you think you might prefer comfort care, please discuss this with your 
family, friends and your study doctor. Talk to your study doctor about your choices and the risks 
and benefits before you decide if you will take part in this study.  
We do not know if you will receive any benefit from your participation. You will not be 
compensated for your participation.   
The most common and most serious risks that may be related to Avadomide includes fatigue, 
weakness, low blood counts, decreased appetite, nausea, vomiting, diarrhea, constipation, rash, 
fever, infection. The most common risks due to Nivolumab include diarrhea, fatigue, itching and 
rash. The other risks and side-effects due to use of investigational drug and risks associated 
with other study procedures are described later in this consent form. 
Any new important information that is discovered during the study and which may influence your 
willingness to continue participation in the study will be provided to you. 
Even if we publish the findings from this study, we will keep your study information private and 
confidential.  Anyone with the authority to look at your records must keep them confidential. 


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If you are interested in learning more about this study, please continue reading the information 
below: 
WHAT IS THIS STUDY ABOUT? 
We are asking you to take part in this research study because you have been diagnosed with 
‘unresectable or metastatic melanoma’ (one of the types of skin cancer). This disease condition 
means that your skin cancer has spread locally or to other organs and cannot be removed or is 
unresponsive to surgical treatment.  
Your study doctor considered you as a potential participant because you are treatment naïve for 
the present stage of your cancer (meaning you would be receiving study treatment for the first 
time) or you were treated with the study drug in the past and then your symptoms returned 
during therapy or after discontinuation of study drug.  
In this study, you will be treated with an investigational drug called Avadomide. The use of 
Avadomide is experimental. An “investigational drug” is a drug that is being tested and is not 
approved for sale in the United States by the U.S. Food and Drug Administration (FDA).  
Avadomide (CC-122) is manufactured by Celgene Corporation. It is a drug that has not been 
approved in any country for the treatment of any medical condition and is investigational (being 
tested) in this study. It is a “pleiotropic pathway modulator” that may affect cancer in many ways. 
Pleiotropy refers to a case where one target may influence several other characteristics or may 
have multiple effects in numerous tissues such as tumor, blood vessels and cells of the immune 
system. Avadomide comes in capsules that are taken by mouth and swallowed with water. It is 
being studied as a possible treatment for advanced solid (organ) tumors, non-Hodgkin’s 
lymphoma, chronic lymphocytic leukemia, and multiple myeloma (a type of blood cancer).  
Nivolumab (Anti PD-1) (OPDIVO®) is an antibody (a type of human protein) already approved 
by the FDA for the treatment of melanoma and several other cancers including metastatic 
kidney carcinoma, urothelial carcinoma, non-small cell and small cell lung cancer, squamous 
cell carcinoma of the head and neck, hepatocellular (liver) carcinoma, Hodgkin’s lymphoma, 
selected colon cancers, and cancers with high microsatellite instability (MSI-H). Nivolumab 
(Anti-PD-1 inhibitor) is effective in reducing the tumor induced immune suppression and can be 
given by itself or in combination with another drug called ipilimumab for the treatment of 
advanced melanoma based on current approval by the FDA in the United States. In melanoma, 
it is also approved after surgery to reduce the risk of recurrence in patients with stage III (lymph 
node involvement) or stage IV disease who have had all their cancer removed by surgery.  
WHAT WILL HAPPEN DURING THIS STUDY? 
Your study participation is divided into a Screening period, a Study Treatment period (each 
cycle for 28 days with Day 1 and Day 15 visits at the study doctor’s office for Nivolumab 
administration and other study procedures), and End of Study Treatment period.  
Screening Period 
Before you begin any part of this study, you must sign and date this consent form. You must be 
honest with your study doctor about your health history and medication use or it may not be safe 
for you to be in this study. If you decide to take part in the study, your study doctor must be sure 
that you are well enough to undergo the study treatment. This screening examination will 
involve: 


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• 
Physical Exam including your height and weight  
• 
Medical History/Oncology History – including questions regarding tobacco and alcohol 
use  
• 
Vital Signs (blood pressure, heart rate, and temperature)  
• 
Pregnancy Test - blood (only for women who are able to get pregnant)  
• 
Hormonal blood tests to assess your thyroid and adrenal gland function 
• 
Testosterone Test – blood (only for men) 
• 
Blood tests to monitor your general health  
• 
Performance status evaluation (what type of daily activities you can do)  
• 
Blood for biomarker testing and other study procedures. 
• 
If you are eligible to participate in this study, you will undergo one or more of the study 
procedures described in this form at each study visit 
Study Treatment Period 
Each study treatment cycle is 28 days long. When you complete the study treatment or stop the 
study treatment for any reason, you will have an end of study treatment visit before entering the 
follow-up period. 
When you return for your Cycle 1 Day 1 visit, you will have the following procedures: 
• 
Physical Exam 
• 
Weight 
• 
Vital Signs (blood pressure, heart rate, and temperature) 
• 
Pregnancy test: blood (only for females who are able to get pregnant 
• 
Demographic and medical history 
• 
Blood tests to monitor your health 
• 
Performance status evaluation 
• 
Blood for biomarker testing and other study procedures. 
On Day 1 of each study treatment cycle, during your study doctor visit, you will first receive 
Avadomide to take by mouth.  You will receive a fixed dose of Nivolumab by a needle inserted 
into your vein (IV).  On Day 2 through Day 5 of the study treatment cycle, you will take 
Avadomide at home. Try to take it in the morning and at about the same time that you took them 
on Day 1. On Day 6 through Day 7 of the study treatment cycle, no study drug will be taken. On 
Day 8 through Day 12 of the study treatment cycle, you will only take Avadomide capsule(s) at 
home. On Day 13 through Day 14 of the study treatment cycle, no study drug will be taken. On 
Day 15, you will return to your study doctors’ office for the Cycle 1 Day 15 visit.  
On the Cycle 1 Day 15 Visit, the following set of procedures will be performed: 
• 
Physical Exam 
• 
Weight 
• 
Vital Signs (blood pressure, heart rate, and temperature) 
• 
Pregnancy test: blood (only for women who are able to get pregnant) 
• 
Demographic and medical history 
• 
Blood tests to monitor your health 
• 
Performance status evaluation 
• 
Receive another 240mg IV infusion of Nivolumab  
• 
Blood for biomarker testing and other study procedures 


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On Day 15 through Day 19 of the study treatment cycle, you will only take Avadomide 
capsule(s) at home. On Day 20 through Day 21 of the study treatment cycle, no study drug will 
be taken. On Day 22 through Day 26 of the study treatment cycle, you will only take Avadomide 
capsule(s) at home. On Day 27 through Day 28 of the study treatment cycle, no study drug will 
be taken. Your study doctor or his/her study staff will give you clear instructions for taking study 
drugs. This way you will complete your Cycle 1 (28 days). 
Between Days 22 and 29, a tumor biopsy will be repeated from the same site where the pre-
study treatment biopsy was taken.   
After completing 28 days in your Cycle 1, you will return to study doctor for your Cycle 2 Day 1 
and other subsequent study treatment visit which will follow the same 28-day cycle. You can 
refer the ‘Schedule of events’ calendar included in this document and discuss with your study 
doctors and study staff for any questions about study related procedures. 
End of Study Treatment Period 
This visit starts when your study treatment is completed, changed or discontinued for any 
reason. The visit will be within 30 days after you complete or stop the study treatment. 
• 
Medical History  
• 
Weight 
• 
Physical Examination 
• 
Tumor Measurement 
• 
Vital Signs (blood pressure, heart rate, and temperature) 
• 
Demographic and medical history 
• 
Blood tests to monitor your health 
• 
Performance status evaluation 
• 
Blood for biomarker testing and other study procedures 
• 
Optional tumor biopsy 
If your study discontinuation is due to some study related toxicity or adverse event (bad side 
effect), you will be followed up until the adverse event is resolved.  
If you discontinue the study treatment for a reason other than disease progression or disease-
related toxicity, your study doctor will assess your condition every 12 weeks by radiology 
imaging techniques (computed tomography [CT] scan, magnetic resonance imaging [MRI] scan, 
positron emission tomography [PET] scan) to monitor your condition for up to 24 months.  
If your melanoma responds well to the study treatment, your study doctor will use these follow-
up visits to make sure it continues to do well. If the study treatment does not work as expected 
or stops working, your study doctor will use future follow-up visits to ask some questions about 
how you are doing and what other treatments you are receiving for melanoma. These questions 
can be asked over the telephone and you will not need to come to the study doctor’s office for a 
visit.  
The maximum time you will be in the study depends on many factors like how your melanoma 
responds to the study treatment, and how long the study has been open when you join.  
The study doctor or study staff will do the things listed below when you come in for study visits.  
If you would like more information about which tests and procedures will be done at each study 
visit, ask the study doctor or study staff. 


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Medical History:  Will be checked on screening visit, Cycle 1 Day 1, Cycle Day 15, Cycle 2 Day 
1, Cycle 2 Day 15, Cycle 3, other subsequent visits and the end of study treatment visit. The 
study doctor will ask you about past/present diseases and surgeries. The questions may also 
include any allergies, birth control procedures and medicines.  Any other studies you were in 
may also be asked. Other questions may include any medical conditions or side effects which 
may occur during the study. 
Vital Signs, Height and Weight: Will be checked on screening visit, Cycle 1 Day 1, Cycle Day 
15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3, other subsequent visits and the end of study 
treatment visit. Check your blood pressure by putting a band around your arm (this will squeeze 
your arm for about a minute), check your pulse, listen to you breathe in and out, and take your 
temperature. Body weight is also recorded to see how much you weigh.  
Demographic Data: At Screening, demographic information like your year of birth, gender, and 
ethnic origin will be collected if permitted by local regulations.  
Physical examination: Including symptoms of your disease will be performed at Screening, 
prior to receiving study treatment on Day 1 and Day 15 of each study treatment cycle, at the end 
of study treatment visit and at each follow-up assessment. 
Concomitant Medication: You will be asked about the medications you take currently and any 
medication prohibited taking while on the study. This will be asked at Screening, and on Day 1 
of each study treatment cycle. 
ECOG (Eastern Cooperative Oncology Group) Performance Status: This is a scale used by 
doctors to describe how well a cancer patient is able to function.  It assesses the patient’s ability 
to do daily activities like bathing and getting around.  Your ECOG performance status will be 
assessed at Screening, on Day 1 of each study treatment cycle, at the end of study treatment 
and at the 28-day follow-up visit. 
Study Diary: You will be given a study diary to assess compliance with Avadomide therapy. 
You will be asked to mark on a paper ‘diary card’ each time you take your doses of Avadomide.  
You will bring the diary card with you to your next study doctor’s visit. You must bring your bottle 
of study drug (even if empty) with your diary to all your scheduled study doctor visits.  
Tumor Biopsy/Core Needle Biopsy: Tumor biopsies will be done before study treatment 
during the screening period, between Day 22 and Day 29 of Cycle 1, and in some cases at the 
end of study treatment visit (if your cancer is no longer responding to the study treatment; your 
study doctor will discuss this with you to see if you are willing to participate in this). These 
biopsies will be either core needle biopsies (or punch biopsies if skin lesions) depending on 
which type your study doctor thinks will be possible on your tumor. Additional optional biopsies 
may be done with your permission. 
Echocardiogram (ECHO) or multiple gated acquisition scan (MUGA): This shows how well 
your heart is beating and pumping blood and if there are abnormalities present. This will be 
performed at Screening visit and Day 1 of Cycle 3. This test is a study requirement and usually 
not part of your routine cancer care.  
Pregnancy Testing: You will have either a blood pregnancy test (1 teaspoon or 5 milliliters) 
during the screening period prior to beginning the study treatment and on Day 1 of each cycle of 
study treatment. Women who are able to become pregnant must agree to use two effective birth 
control methods (for example: birth control pills, condoms) at the same time or practice 


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complete abstinence from sexual contact with a man beginning 28 days before starting study 
treatment, throughout the entire duration of study treatment including, during any dose 
interruptions, and for at least 28 days after the end of study treatment with Avadomide. Please 
see risk section below for additional birth control requirements.  
Testosterone testing: For male participants only, will be done only at Screening. 
Tumor Measurement: Your tumor will be measured every 12 weeks unless your disease 
shows progression and you are taken off study based on standard imaging criteria. The imaging 
is considered standard of care. 
• 
Computed tomography (CT) scan – is a type of X-ray scan.  Several X-rays from 
different angles are sent through the body at one time.  A computer processes the 
results to give a better picture than a standard, single X-ray scan.  Also, a special dye is 
used to help improve the picture quality. The dye that is injected into your body may 
cause you to get a metallic taste in your mouth and to feel warm.  Rarely, it causes 
nausea and vomiting.  The dye can also cause damage to the kidneys, which may lead 
to kidney failure.  This is a concern if you have poor kidney function.  Rarely, the dye can 
cause a life threatening reaction. The results are shown as a flat picture (length and 
width) displayed on a computer screen.  Your neck, chest, stomach area, and pelvic/hip 
area will be scanned.  A small amount of dye is inserted into your vein just before the 
pictures are taken. CT scans will be performed at Screening and every 12 weeks. This is 
the preferred method to follow the progress of your cancer. 
• 
Positron emission tomography (PET) scan – is a type of X-ray scan that uses a 
radiotracer called fludeoxyglucose (FDG).  The tracer is a sugar that carries a small 
amount of radiation and helps improve the picture quality.  Importantly, the FDG tracer 
shows how fast a tumor is growing.  The results are shown as a 3D picture (length, 
width, and depth) displayed on a computer screen.  Your neck, chest, stomach area, and 
pelvic/hip area will be scanned.  A small amount of tracer is inserted into your vein just 
before the pictures are taken.  PET will be done at Screening and every 12 weeks. This 
will be done only if you have specific reasons not to undergo a contrast CT scan to 
follow the progress of your cancer. 
• 
Magnetic resonance imaging (MRI) scan: An MRI machine or scanner uses a strong 
magnet and radio waves connected to a computer to create pictures of parts of the body. 
In this study, you will have an MRI of your brain. The MRI unit is a large magnet that 
looks like a donut. A sliding table is in the opening. You will lie on the table and be 
comfortably positioned. In many cases, an extra piece of imaging equipment called a coil 
will be placed over the area of your body that is being imaged. The table will move into 
the opening. The technologist will be just outside the scanner room, but can see, hear, 
and speak to you at all times. During the exam, you will need to remain very still.  Being 
in a tight enclosed space may make you feel anxious. 
Blood samples: To check your blood cell counts, heart, liver, and kidney function and other 
standard safety tests during study treatment. About 2 to 4 tablespoons or 30 to 60 milliliters of 
blood will be taken per test day. Blood samples are taken at Screening, on Day 1 and Day 15 of 
each study treatment cycle and at the end of study treatment.  


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Thyroid Stimulating Hormone (TSH) test: To check the function of your thyroid gland during 
study treatment. Blood samples are taken at Screening, and on Day 1 of Cycle 2 and Cycle 3 
study treatment. 
Troponin and Brain Natriuretic Peptide (BNP) test: To monitor for possible early signs of 
damage to your heart. Test will be performed at Screening and on Day 1 of every study 
treatment cycle. 
Biomarker Sampling: To check the effect of study treatment, blood will be taken for biomarker 
testing. The blood samples will be taken for biomarker analysis on the following days: 
Screening, Day 1 and Day 15 of Cycles 1 and 2, and at selected time points thereafter.  
Study Treatments 
If you meet eligibility criteria, you will be assigned to receive Avadomide (CC-122) and 
Nivolumab during this study.  
Nivolumab (240mg IV): This drug is administered by intravenous (IV) infusion, meaning the 
study drug is a solution given through a vein. A pump will be used to ensure correct amount of 
study is given over the proper amount of time. The infusions can take about 30 minutes per visit.  
Study Drug 
Infusion Time 
Frequency 
Study Treatment 
Duration 
Nivolumab (240 mg) 
30 minutes 
Every 2 weeks (Day 
1 and Day 15 of each 
cycle) 
Up to 52 weeks 
(about 26 doses) 
If your cancer is continuing to show improvement at the 52-week mark, you will be given the 
option of continuing study treatment. 
Avadomide (CC-122): Avadomide comes in capsules that should be stored as directed on the 
label. In this study, this study will be available in 3 different doses. You drug dose will be 
adjusted if you experience any toxicity at the given dose, and your study doctor will make that 
determination 
Avadomide 
Dose and schedule: 5 days on, 2 days off 
Starting dose 
2 mg 
1st Dose Reduction 
1.5mg 
2nd Dose Reduction 
1 mg 
On Day 1 of each 28-day study treatment cycle, you will receive 2mg of Avadomide while you 
are at the study doctor’s office, before receiving Nivolumab. Avadomide is taken for 5 days each 
week, followed by 2 days without taking Avadomide (5/7 days). Your study doctor or his/her 
study staff will give you clear instructions for taking Avadomide.  
On most days, you will take your dose of Avadomide at home.  You will be asked to mark on a 
paper ‘diary card’ each time you take your dose of Avadomide. You will bring the diary card with 
you to your next study doctor’s visit. Once at home, you should take Avadomide with plenty of 
water at about the same time on every dosing day.  If you forget to take a dose of Avadomide 
you can take it up to 12 hours later on the same day.  If you are late by more than 12 hours, you 
should not take Avadomide that day, and take your next dose as planned.  If you ever have 
questions about how to take your study drug, you should call your study doctor.   


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You must bring your bottle of study drug (even if empty) with you to all your scheduled study 
doctor visits. 
You may continue taking Avadomide until: 
• 
You have completed study treatment, 
• 
Your disease gets worse, 
• 
You have a serious side effect that is not tolerated, or 
• 
You or your study doctor decides to stop study treatment for any reason. 
Schedule of Event Calendar 
WHO IS PAYING FOR THIS STUDY? 
A company called Celgene Corporation, the sponsor of the study, is paying for this research 
study.  Avadomide is manufactured by Celgene and will be provided by them to you at no cost. 
 
 
Pre-
study/Screening 
 
C1D1 
 
C1D15 
 
C2D1 
 
C2D15 
 
C3 and 
beyond 
 
End of 
Study 
Treatment 
Informed consent 
X 
 
 
 
 
 
 
Medical history  
X 
X 
X 
X 
X 
X 
X 
Demographics 
X 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance 
status 
X 
X 
 
X 
 
X 
X 
Concomitant 
medications 
X 
X 
 
X 
 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
Tumor measurement 
X 
 
 
 
 
X 
X 
Blood samples 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test 
X 
X 
 
X 
 
X 
 
TSH 
X 
 
 
X 
 
X 
 
Testosterone (men 
only) 
X 
 
 
 
 
 
 
Troponin & BNP 
X 
 
 
X 
 
X 
 
Echo / MUGA 
X 
 
 
 
 
X 
 
Blood for Biomarker 
Analysis 
X 
X 
X 
X 
X 
X 
X 
Nivolumab (240mg IV) 
 
X 
X 
X 
 
 
 
Avadomide (CC-122) 
 
X 
 
X 
 
X 
 
Tissue Biopsy 
X 
 
 
X 
 
 
X 


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INSTITUTIONAL CONFLICT OF INTEREST MANAGEMENT PLAN 
Moffitt Cancer Center, sponsor of this study has a license agreement with Celgene Corporation, 
company supplying study drug. Payments have been distributed to the Moffitt Cancer Center 
and Moffitt Cancer Center inventors of the licensed technology which is not a part of this study. 
The Moffitt Cancer Center and those inventors are also entitled to receive additional payments 
related to the licensed technology. This study has been carefully reviewed to help assure that 
the professional judgement of the Moffitt Cancer Center doctors and staff will not be 
compromised. The study will be monitored for your safety and to ensure the proper analysis of 
data. Any questions you might have about this study will be answered by Dr. Nikhil Khushalani, 
the Principal Investigator (the person in charge of this research study), at the telephone number 
listed on the first page of this document or the Moffitt Cancer Center Compliance Office at (813) 
745-1869. Dr. Khushalani does not have a financial relationship with Celgene. 
WILL IT COST ANYTHING TO BE IN THIS STUDY? 
You and/or your insurance company will be financially responsible for hospital inpatient, 
outpatient and follow-up visits that would normally or routinely occur in the management of your 
disease.  Inpatient and outpatient visits could include charges for treatments, medications, 
physician visits, laboratory tests and procedures.   You and /or your insurance company will be 
responsible for paying for the charges which are considered routine, since you would have 
received these services even if you were not participating in this study.   You will be responsible 
for any costs not covered by your insurance company, including deductibles, co-payments and 
all out-of-pocket expenses. Before you agree to be in this study, you should contact your health 
insurer to see if your plan will cover the costs required as part of your participation.   
You and/or your insurance company will not be responsible for paying for study related items 
and services that are specifically required for this research study and are not considered part of 
the routine management of your disease, if these procedures are performed at Moffitt Cancer 
Center.   
During your participation in this study, the study sponsor will be responsible for providing the 
study drug, CC-122, at no additional charge to you.  
You and/or your insurance company will be responsible for the drug nivolumab that is 
commercially available.  You and/or your insurance company will be responsible for the charges 
related to the administration of the commercially available drugs. 
If you would like more information on the costs of being on this study or have other insurance 
related questions then please let your clinical trial coordinator know or contact our Business 
Office at 813-745-8422. 
WILL BEING IN THIS STUDY HELP ME? 
If you agree to take part in this study, there may or may not be direct medical benefit to you. 
Your condition may stay the same or it may get worse during the study. The information 
collected during this study will help researchers learn more about the study drug combination 
and may benefit you and other people with melanoma in the future. However, there is no 
guarantee that this will happen. 
 


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ARE THERE RISKS TO ME IF I AM IN THIS STUDY? 
Right now, we do not know for sure if combination of Avadomide and Nivolumab will help.  If it 
does not help, your condition/disease may get worse. 
You may have problems because of the drugs used in this study. These problems are called 
side effects. Some side effects are just bothersome. Others could harm you. There may be 
some side effects that we do not know about yet. The research might involve risks to you that 
are currently unforeseeable. Your study doctor may give you medicines to help lessen side 
effects. Many side effects go away soon after you stop taking the study drug. In some cases, 
side effects can be serious, long lasting, or may never go away. There may also be the risk of 
death. 
HERE ARE THE KNOWN SIDE EFFECTS THAT COULD HAPPEN WITH AVADOMIDE: 
Avadomide has been given to people with cancer. The side effects reported by people who 
have taken Avadomide are listed below according to how frequently they were reported. 
Very common side effects (greater than a 10% chance this will happen) 
• 
Fatigue (tiredness) and weakness 
• 
Anemia (decreased counts of red blood cells, a type of blood cell that carries oxygen) 
• 
Neutropenia (decreased counts of neutrophils, a type of white blood cell that helps to 
fight infection) 
• 
Thrombocytopenia (decreased counts of platelets, a type of blood cell that helps the 
blood to clot) 
• 
Decreased appetite 
• 
Nausea 
• 
Vomiting 
• 
Diarrhea 
• 
Constipation 
• 
Rash 
• 
Fever 
• 
Infections, including respiratory tract infection and pneumonia (lung infection)  
Common side effects (between 1% and 10% chance this will happen) 
• 
Febrile neutropenia (decreased white blood cells that help to fight infection with fever), 
requiring hospitalization and additional treatment 
• 
Severe infections including , urinary tract infection, and sepsis (blood stream infection) 
that could result in death. 
• 
Swelling of disease-affected lymph nodes and tumor sites causing pain, fever, and/or 
abnormal laboratory values. This is called tumor flare and usually occurs in the first cycle 
of treatment. Most participants who developed swelling of disease-affected lymph nodes 
and tumor sites had mild to moderate symptoms and recovered; however, one event of 
tumor flare reaction was fatal. 
 
Less Common but Serious: 
Other events reported in participants with cancer which may or may not be related to the study 
drug included:  


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• 
Blood clots (in the legs, lungs, or brain) 
• 
Inflammation of the lungs (making it difficult to breathe) 
• 
Development or worsening of pain and changes in sensations in nerves (tingling, 
burning) and decreased sense of touch (neuropathy) 
• 
Elevated liver laboratory test results (showing abnormal liver function) 
• 
Elevated kidney laboratory test results (showing abnormal kidney function). This can 
also occur as part of tumor lysis syndrome which refers to metabolic abnormalities 
arising from rapid destruction of cancer cells.  This is rare and was seen in diseases like 
acute leukemia and high-grade lymphomas. 
Some people with cancer taking Avadomine have reported later developing other cancers 
(second new cancers that are diagnosed in participants following a prior diagnosis of a first 
cancer). 
Severe allergic reaction (angioedema) was reported in one study participant, who developed 
face and airway swelling, requiring admission to the hospital and intensive treatment followed by 
full recovery. 
Laboratory tests in a few participants showed increased troponin (a test showing possible 
effects on heart muscle); however, other heart tests (ECG and ECHO/MUGA) in these 
participants were normal and they had no symptoms.  Troponin decreased when study drug 
was interrupted. Updated safety data suggests no causal relation of heart dysfunction with 
avadomide. 
Avadomide has been given to animals to find out what side effects might be seen in people.  
The most frequent side effects seen in animals include:  
• 
Decreased appetite 
• 
Weight changes 
• 
Dehydration 
• 
Inflammation of the lining of the stomach and intestine 
• 
Effects on eyes, including red eyes and swelling of the middle layer of the eye, which 
could result in impaired vision 
• 
Increased blood creatinine and urea (blood tests showing bad effects on the kidneys) 
To prevent possible effects on kidneys, good hydration is recommended (participants are 
advised to drink plenty of fluids).  Effects to heart muscle have been detected in two animals 
that received the highest dose of the study drug, but not seen in any other study animals. 
Pre-clinical studies show that Avadomide absorbs UV light. It is not yet known if Avadomide 
may make your skin or eyes more sensitive to sunlight.  As a precaution, participants are 
advised to avoid prolonged exposure to natural or artificial sunlight (UVA/B) while taking 
Avadomide by wearing sun-protective clothes, applying effective sunblock to your skin, and by 
wearing sunglasses. 
Please let your study doctor know all of your present and past diseases and allergies and any 
medication you may be taking including over-the-counter medications, vitamins, herbal, 
homeopathic or holistic medications or treatments, as well as foods and beverages containing 
grapefruit. This is important because a possible interaction with some medications, vitamins, 
and remedies may cause serious side effects, and/or may still be unknown. 


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Your study doctor will tell you if any additional measures are needed.  All participants taking part 
in the study will be watched carefully for any side effects and you should report any changes in 
the way you feel or your health to your study doctor. 
Other things may happen as well from taking the study drug that your study doctor can tell you 
about. The study doctor may give you something to make the sick feeling go away, or may stop 
giving you the study drug. 
Risks Associated with Pregnancy  
Avadomide has some similarities to thalidomide. Thalidomide is known to cause severe life- 
threatening human birth defects. Avadomide is therefore considered to have the potential to 
cause birth defects in humans. If Avadomide is taken during pregnancy, it may cause birth 
defects or death to an unborn baby. Women must not become pregnant while taking 
Avadomide. 
In an animal study, the tubes in the testicles where sperm is made were affected in some male 
rats after 3 months of receiving Avadomide and it is not currently known if this effect is 
reversible. The female animals were not affected and these changes were also not found in 
males of the other animal species tested. For male participants, the short- and long-term effects 
of Avadomide on the ability to make sperm and get a woman pregnant are currently unknown 
and, normally, it can take approximately 2-3 months to make new sperm. The effects of 
Avadomide on human fertility are currently not known, therefore all family planning options 
and/or alternatives should be thoroughly discussed with your study doctor prior to participating 
in this study. 
Prior to signing and dating this consent form, there is important information for you to know 
about the pregnancy risk precautions for this study, that a woman of childbearing potential must 
use two effective birth control methods (for example: birth control pills, condoms) at the same 
time or practice complete abstinence from sexual contact with a man beginning 28 days before 
starting study treatment, throughout the entire duration of study treatment including, during any 
dose interruptions, and for at least 28 days after the end of study treatment with Avadomide. 
All male participants must practice complete abstinence from sexual contact or use a condom 
during sexual contact with a pregnant woman or a woman of childbearing potential throughout 
the entire duration of study treatment including during dose interruptions, and for at least 3 
months after the end of study treatment with Avadomide, even if you have undergone a 
vasectomy. 
Before you consent to participating in this study, you will be counseled on the full requirements 
of the pregnancy precautions within the Avadomide Information Sheet that you have received 
and must agree to follow. 
Other than the participant, women who are able to become pregnant and men who are able to 
father a child should not touch or handle the Avadomide capsules or the powder they contain 
unless they are wearing gloves. 
You must never share your study drugs with others.  You must not breastfeed or donate blood 
while you are participating in this study, and for at least 28 days after the last dose of study 
drugs. You must not donate sperm or semen while you are participating in this study, and for at 
least 3 months after the last dose of study drugs. 
 


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HERE ARE THE KNOWN SIDE EFFECTS THAT COULD HAPPEN WITH NIVOLUMAB: 
Nivolumab may cause one or more of the side effects listed below. This information is based on 
data from cancer participants in other clinical trials with nivolumab. In addition, there may be 
side effects that are not yet known that may occur. You should tell your study doctor or study 
nurse right away about any possible side-effects you experience.  
Very common side effects of nivolumab [greater than or equal to 1/10 or greater than or equal to 
10%] are:  
• 
Diarrhea  
• 
Fatigue  
• 
Itching  
• 
Rash  
Common side effects of nivolumab [greater than or equal to 1/100 to less than 1/10 or greater 
than or equal to 1% to less than 10%] include:  
• 
Abdominal pain  
• 
Alkaline phosphatase increased: lab test result associated with liver or bone 
abnormalities  
• 
ALT increased: lab test result associated with abnormal liver function  
• 
Amylase increased: lab test result associated with pancreas inflammation  
• 
AST increased: lab test result associated with abnormal liver function  
• 
Chills  
• 
Constipation  
• 
Cough  
• 
Creatinine increased: lab test result associated with decreased kidney function  
• 
Decreased appetite  
• 
Dizziness  
• 
Dry mouth  
• 
Dry skin  
• 
Fever  
• 
Headache  
• 
Increased blood sugar  
• 
Inflammation of the colon 
• 
Inflammation of the mouth 
• 
Infusion related reaction 
• 
Lipase increased: lab test result associated with pancreas inflammation 
• 
Joint pain or stiffness 
• 
Loss of color (pigment) from areas of skin 
• 
Lung inflammation (pneumonitis – see details below) 
• 
Musculoskeletal pain 
• 
Nausea 
• 
Redness 
• 
Shortness of breath 
• 
Sodium levels in the blood are low 
• 
Swelling, including face, arms, and legs 


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• 
Thyroid gland function decreased 
• 
Thyroid gland function increased 
• 
Thyroid stimulating hormone increased: lab test result associated with abnormal thyroid 
function 
• 
Tingling, burning, numbness or weakness, possibly in arms, legs, hands and feet 
• 
Vomiting 
Uncommon side effects of nivolumab [ greater than or equal to 0.1% to less than 1%] include:  
• 
Adrenal gland function decreased 
• 
Allergic reaction/hypersensitivity 
• 
Bilirubin (liver function blood test) increased 
• 
Bronchitis (inflammation of the tubes that carry air to and from the lungs) 
• 
Cranial nerve disorder (caused by damage or inflammation to certain nerves in the brain 
and may cause eye problems/disorders and/or palsy) 
• 
Diabetes 
• 
Dry eye 
• 
Hair loss 
• 
Heart rate increased 
• 
Heart rhythm abnormal 
• 
High blood pressure 
• 
Hives 
• 
Inflammation of the eye 
• 
Inflammation of the kidney 
• 
Inflammation of the pancreas 
• 
Inflammation of the pituitary gland 
• 
Inflammation of the stomach 
• 
Inflammation of the thyroid gland 
• 
Liver inflammation 
• 
Low blood pressure 
• 
Lung infiltrates, associated with infection or inflammation 
• 
Pituitary gland function decreased 
• 
Psoriasis (characterized by patches of abnormal, scaly skin) 
• 
Renal failure 
• 
Respiratory failure 
• 
Upper respiratory tract infection 
• 
Vertigo (feeling off balance which can lead to dizziness) 
• 
Vision blurred 
Rare side effects of nivolumab [greater than or equal to 1/10,000 to less than 1/1,000 or greater 
than or equal to 0.01% to less than 0.1%] include: 
• 
Anaphylactic reaction (severe allergic reaction) 
• 
Damage to the protective covering of the nerves in the brain and spinal cord 
• 
Diabetes complications resulting in excess blood acids and diabetic coma 
• 
Erythema multiforme: skin inflammatory reaction 
• 
Guillain-Barre syndrome, an autoimmune disorder associated with progressive muscle 
weakness or paralysis 


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• 
Inflammation of blood vessels 
• 
Inflammation of the brain, potentially life-threatening or fatal 
• 
Inflammation of the heart 
• 
Muscle inflammation 
• 
Myasthenic syndrome (neurologic syndrome characterized by muscle weakness) 
including myasthenia gravis, a nerve disease that may cause weakness of eye, face, 
breathing, and swallowing muscles. 
• 
Polymyalgia rheumatica, an inflammatory disorder causing muscle pain and stiffness 
• 
Rhabdomyolysis: muscle fiber released into the blood stream which could damage your 
kidneys 
• 
Rosacea: acne-like skin condition resulting in redness of face 
• 
Sarcoidosis, a disease involving abnormal collections of inflammatory cells (granulomas) 
in organs such as lungs, skin, and lymph nodes 
• 
Stevens Johnson syndrome: a serious and potentially life-threatening inflammatory 
disorder of skin and mucous membranes, resulting in blistering and shedding of skin 
• 
Toxic epidermal necrolysis: a serious and potentially fatal disease characterized by 
blistering and peeling of the top layer of skin resembling a severe burn 
• 
Histiocytic necrotizing lymphadenitis or Kikuchi lymphadenitis: disorder of the lymph 
nodes which causes the lymph nodes to become enlarged, inflamed and painful, 
commonly affecting lymph nodes of the neck and possibly associated with fever or 
muscle and joint pains. 
• 
Vogt Koyanagi Harada syndrome; a disease that affects the pigmented tissue; this 
may affect the eye leading to swelling, pain and/or blurred vision; the ear leading to 
hearing loss, ringing in the ears and/or the skin leading to loss of skin color. 
Lung Inflammation (pneumonitis): It is possible that nivolumab may cause inflammation of the 
tissues of the lung. This adverse effect has been reported in participants treated with nivolumab. 
While many participants with x-ray or CT abnormalities have not developed any symptoms, 
some participants have developed mild to severe symptoms and in rare cases, death has 
occurred as a result of their lung inflammation. Signs and symptoms of lung inflammation may 
include:  
• 
Difficulty breathing 
• 
Pain or discomfort while breathing 
• 
Chest pain 
• 
Cough 
• 
Shortness of breath 
• 
Increased rate of breathing 
• 
Fever 
• 
Low blood oxygen levels 
• 
Fatigue 
Your study doctor and study nurse will watch you closely for changes in your ability to breathe 
and for other signs or symptoms that might show you are developing this type of lung 
inflammation and will perform regular tests including physical exams, measurement of oxygen 
levels through non-invasive testing (for example, pulse oximeter), blood tests, chest x-rays 
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Complications, including fatal events, have occurred in participants who received allogenic 
hematopoietic stem cell transplantation (HSCT) after nivolumab.  
Please inform your study doctor or study nurse AT ONCE if you experience any of the 
following:  
• 
Any new or increased shortness of breath;  
• 
Any new or increased chest pain;  
• 
Any new or increased pain/difficulty while breathing;  
• 
Any new or increased cough or any significant change in your type of cough; for 
example, any new or increased mucous or blood in your cough;  
• 
Any change in the amount of oxygen you require;  
• 
Any fever, fatigue, or other symptoms that occur at the same time as any changes to 
your breathing or other lung symptoms.  
If you start to develop symptoms, your study doctor will ask you to return to the clinic for 
additional tests, which could include a physical exam, measurement of oxygen levels, blood 
tests, chest x-rays, and/or CT scans. You will be monitored very closely for changes in your 
overall lung symptoms; monitoring may require hospitalization. You may require specific 
treatment in order to control pneumonitis. You may also be seen by a special doctor called a 
pulmonologist, who has special training to be an expert in how lungs work.  
Prolonged treatment with medicines that suppress inflammation, sometimes needed to manage 
the side effects of nivolumab, may lower your body’s ability to fight off certain infections (such as 
opportunistic infections). These infections may require treatment with antibiotic or antifungal 
medications and may be fatal. 
Ask the study doctor or study staff if you have questions about the signs or symptoms of any 
side-effects you read about in this consent form. 
RISKS ASSOCIATED WITH STANDARD OF CARE OR ALTERNATIVE TREATMENT: 
As with any medication there may be risks, known and unknown. 
A more complete listing of side effects for other therapies may be available for you to review if 
you wish.  Please talk with your study doctor about the risks of both these study drugs and any 
alternative methods of treatment that are available. 
WHAT CAN HAPPEN IF I GET INJECTIONS OR INFUSIONS? 
You will receive Nivolumab as an intravenous (IV) infusion, which means you will receive it 
directly into your vein. This may cause the following problems:  
• 
Irritation of the vein; your skin near the vein could become warm, swell, hurt, or get red  
• 
Damage to your vein  
• 
Damage to the skin or tissue around the injection site  
• 
A blood clot or an air bubble could form, which could block a blood vessel in another 
part of your body  
 
Some of these problems could be very serious.  


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Over time, getting a lot of injections can cause a vein to become hard or scar, which can make it 
difficult to put a needle into the vein to give you a shot or take blood. 
COULD I HAVE AN ALLERGIC REACTION? 
Sometimes people have allergic reactions to drugs (which includes the iodine dyes often used 
with CT scans).  If you have a very bad allergic reaction, you could die.  Some things that 
happen during an allergic reaction are: 
• 
Rash 
• 
Having a hard time breathing 
• 
Wheezing when you breathe 
• 
Sudden drop in blood pressure 
• 
Swelling around the mouth, throat, or eyes 
• 
Fast pulse 
• 
Sweating 
You should get medical help and contact the study doctor or study staff if you have any of these 
or any other side effects during the study. 
IS THERE ANY RISK TO YOUR UNBORN CHILDREN IF YOU TAKE PART IN THIS STUDY? 
For Women:  
If you are pregnant, you cannot participate in this study because there may be risks to you and 
your unborn baby that are currently unforeseeable, risks that we do not know about yet. 
Breastfeeding (nursing) mothers will not be included in this study since it is not known whether 
the drugs in this study will be passed on to the baby in mother’s milk. If you are currently 
breastfeeding and wish to continue breastfeeding, your study doctor may recommend another 
treatment. The study doctor will perform a blood pregnancy test before the start of the study for 
women who are able to have a baby.  
Tell the study doctor right away if:  
• 
You are pregnant.  
• 
You become pregnant.  
• 
You are planning to become pregnant  
• 
You are breastfeeding.  
For Men and Women: 
Whether you are a man or a woman, there may be risks to your unborn children. If you take part 
in this study, you must agree to use an effective method of birth control as discussed with your 
study doctor during the time that you are on this study and through 28 days after last dose of 
CC-122 or 5 months after the last dose of nivolumab; whichever is longer  (for women) and 
through 3 months after the last dose of CC-122 or 7 months after last dose of nivolumab; 
whichever is longer (for men).  
Examples of effective birth control methods include:  
• 
Barrier methods (diaphragm, condoms, spermicidal)  
• 
Hormonal methods (oral birth control pills, birth control patch, shots or injections) 
• 
Implanted devices (devices such as the copper intrauterine device (IUD)) 


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• 
Surgical sterilization (tubal ligation or vasectomy) 
• 
Abstinence (no sexual intercourse)  
Examples of non-effective birth control methods include: 
• 
IUD progesterone T 
• 
Progesterone-only “minipill” 
• 
Female condom 
• 
Natural family planning (rhythm method) or breastfeeding 
• 
Fertility awareness 
• 
Withdrawal 
• 
Cervical shield  
You should discuss the method of birth control which is best for you to use both during study 
treatment and for a period of time after study treatment. 
Whether you are a woman or a man, you should tell your study doctor immediately if you 
become pregnant or if your partner becomes pregnant.  Women who become pregnant during 
the study will have to leave the study.  The study doctor or study staff may ask for information 
about the pregnancy and the birth of the baby.  The study doctor or study staff may share this 
information with the sponsor and Advarra IRB (a group of people who review research studies 
to protect the rights and welfare of research participants). 
Cancer treatment can affect fertility in both men and women, and it is important to understand 
the risks before starting therapy.  Ask your study staff about fertility preservation before you 
begin study treatment.  However, once you have started study treatment you should not donate 
or sell your eggs or sperm. 
COULD I HAVE ANY OTHER PROBLEMS WITH MY HEALTH IF I DO THIS RESEARCH 
STUDY? 
It is possible that you could have problems and side effects of Nivolumab and Avadomide that 
nobody knows about yet, which include your melanoma condition getting worse or even death.  
If the study doctor learns any new information about these study drugs that might change your 
mind about continuing in the study, the study doctor or study staff will tell you about it.  The 
study doctor will also tell you if new treatments become available for your condition. 
What are the risks of giving blood for this study? 
Needle sticks carry some risks such as fainting, bleeding, bruising, discomfort, dizziness, 
infection and/or pain at the puncture site. 
What are the risks of having a biopsy done for this study? 
Risks include pain, discomfort, soreness, redness, swelling, bleeding, bruising, and/or drainage 
at the biopsy site, abnormal wound healing, fever, infection, allergic reaction to the medication 
used to numb the skin over the biopsy site, and missed abnormal tissue requiring the need for 
another biopsy. 
A biopsy procedure will involve removing a part of your tumor.  A core needle biopsy is a 
percutaneous (“through the skin”) procedure that involves removing small samples of tumor 
tissue using a hollow “core” needle.  An “excisional” biopsy is a surgical procedure where an 
entire mass or abnormal area is removed.  In all procedures, the area around the tumor will be 


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anesthetized with an injection to help ease the pain and a sample will be removed either by 
cutting it out or removing tissue through a hollow “core” needle.  There may be some bruising, 
bleeding, and soreness.  There is a risk of the biopsy site getting infected.  You may also be 
given medicine to make you sleepy. 
What are the risks of other invasive study procedures? 
MRI 
Magnetic resonance imaging (MRI) uses a magnet and radio waves to make diagnostic medical 
images of the body.  There have been no ill effects reported from exposure to the magnetism or 
radio waves used in this test.  However, it is possible that harmful effects could be recognized in 
the future.  A known risk is that the magnet could attract certain kinds of metal.  Therefore, we 
will carefully ask you about metal within your body, including medical implants, devices such as 
pacemakers and internal defibrillators, or certain dyes found in tattoos.  We will also keep the 
examining room locked so that no one carrying metal objects can enter while you are in the 
scanner. 
If there is any question about potentially hazardous metal within your body, you will not undergo 
the MRI.  This may exclude you from participation in this research study.  The MRI involves 
entering a large room in which a magnet is present.  You will be placed on a narrow bed and 
then slid into a small tunnel approximately 6 feet in length and 25 inches in diameter.  You will 
be asked to lie still for about one hour on this bed.  You will hear a loud machine-like noise.  You 
may be asked to have a harmless monitoring device applied during the MRI.  During the MRI, 
you can have voice contact and physical contact with someone in attendance if you desire.  Let 
the study doctor know if you have a fear of enclosed spaces. 
CT Scan 
Computed Tomography (CT) is a way to make x-ray images of the inside of the body.  The CT 
scanner is a doughnut-shaped machine that uses x-rays to create computer pictures that show 
structures inside your body more clearly than regular x-ray pictures.  During the procedure, a 
technologist will take you into the CT scan room where you will lie down on the patient table 
(usually on your back) inside of the CT machine.  You should get comfortable because it is very 
important that you not move during certain parts of the test. 
CT examinations differ depending on the part of your body being studied.  For example, if your 
abdomen is being studied, a series of pictures will be taken from your lower chest to your lower 
pelvis.  During the study, you will be asked to hold your breath so that the pictures will not be 
blurred.  The machine will make some noise, and the table will move during the scan.  Also, you 
may receive signals from the technologist or from the machine about your breathing.  Before or 
during the study, you may be given an injection of a contrast liquid in your vein to allow the 
radiologist to obtain clearer images of your organs.  If you have any discomfort during the test or 
after the injection, be sure to tell the technologist. 
FDG-PET scans 
There is a chance that you may experience discomfort, pain, or swelling at the site where the 
radiotracer (FDG) is injected. There is a slight risk of having an allergic reaction to the 
radiotracer. The amount of radiation from the radiotracer is small and will be gone from your 
body in a few hours. 


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You will be exposed to radiation from x-rays used for PET scans in this trial, and from the FDG, 
itself. The amount of radiation to your body from FDG is small and will be gone from your body 
in a few hours. There is always a risk of developing a new cancer from being exposed to any 
radiation, including the low levels of x-rays used for a PET scan. The risk is thought to be low 
compared to the benefit the test can provide about your disease. Radiation from each PET scan 
you receive is equivalent to about 3 years of normal background radiation. 
Whether or not you are in this clinical trial, you will probably have CT scans and/or PET scans to 
help your regular doctor treat your melanoma condition. If you participate in this clinical trial, you 
may have more CT scans and/or PET scans than you would if you were not in a clinical trial. 
ECHO or MUGA 
If you have an ECHO, electrodes will be placed on your chest. You may feel some discomfort 
similar to pulling off an adhesive bandage when the technician removes the electrodes after the 
procedure. During a MUGA, a small amount of a radioactive chemical will be injected into your 
veins. The radiation exposure from this is considered small and is not likely to adversely affect 
you or your disease. 
Confidentiality 
There is a risk of loss of confidentiality of your information.  You will read more about the 
protection of your information later in this form.  Please ask the study doctor or study staff if you 
would like to know more about how your information will be protected while you are in this study. 
WHAT IF I GET HURT OR SICK WHILE I AM IN THIS STUDY? 
If you need emergency care: 
• 
Call 911 or go to your nearest emergency room right away. Moffitt Cancer Center does 
not have an emergency room or the facilities to provide emergency care. 
If you do NOT need emergency care: 
• 
Call or go to your regular doctor.  It is important that you tell your regular doctor that you 
are participating in a research study.  If possible, take a copy of this consent form with 
you when you go. 
If you experience a side effect or a change in the way that you feel, call the study doctor at the 
telephone number listed on the first page of this form. 
By signing this informed consent and research authorization form, you have not given up any 
legal rights to seek compensation for injuries from the sponsor. 
MOFFITT CANCER CENTER INJURY STATEMENT 
If you believe you have been injured as a result of your participation in this study or if you have 
questions about your rights as a person who is taking part in a research study, you may call the 
Moffitt Cancer Center Risk Manager at 813-745-7882.  Moffitt Cancer Center and its 
investigators have made no provision for monetary compensation in the event of physical illness 
or injury resulting from this study.  Likewise, Moffitt Cancer Center and its investigators have 
made no provision for payment of lost wages, disability, or discomfort in the event of physical 
illness or injury resulting from this study.  Florida law (Statute 768.28) limits the liability of Moffitt 
Cancer Center.  This statute provides that damages are available only to the extent that 


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negligent conduct of a Moffitt Cancer Center employee caused your injuries, and are limited by 
law. A copy of this statute is available upon request at 813-745-1869. 
WILL I GET PAID? 
You will not be paid for taking part in this research study. You have no rights to and will not 
receive payments of any kind for discoveries, patents or products that may be developed from 
this study. 
WHILE YOU ARE IN THE STUDY, YOU MUST: 
• 
Follow the instructions you are given. 
• 
Come to the study center for all visits with the study doctor. 
• 
Give correct and accurate information about your medical history and current medical 
condition. 
• 
Tell the study doctor about any health problems you have during the study. 
• 
Tell the study doctor about any new medicine or drug you take during the study. 
• 
Not take any other drugs or remedies unless the study doctor has approved them 
beforehand.  This includes prescription drugs and over the counter medicine (including 
vitamins and herbal remedies) that you buy without a prescription. 
• 
Not participate in other medical research studies. 
• 
Not get pregnant or cause your partner to become pregnant. 
• 
Tell the study doctor or study staff if you want to stop being in the study at any time. 
DO I HAVE TO REMAIN ON THIS STUDY ONCE I JOIN? 
Your participation in this study is voluntary and you do not have to participate. If you decide to 
take part in this study, you may leave the study at any time. No matter what decision you make, 
there will be no penalty to you and you will not lose any of your regular benefits. Leaving the 
study will not affect your medical care. You can still get your medical care from our institution.  
Tell the study doctor if you are thinking about stopping or deciding to stop. If you do decide to 
stop your participation in the study, your study doctor will tell you how to stop safely and will 
discuss with you what follow-up care or testing would be helpful to you. The study doctor may 
stop you from taking part in this study at any time if he/she believes it is in your best interest, if 
you do not follow the study rules, or if the study is stopped 
ARE THERE REASONS THE STUDY DOCTOR OR SPONSOR MIGHT TAKE ME OUT OF 
THE STUDY LATER? 
Even if you want to stay in the study, there may be reasons the study doctor or study staff will 
need to take you out of it.  Your study doctor has the right to take you out of the study at any 
time with or without your agreement.  Your participation may be ended without your consent for 
different reasons, including the following: 
• 
If the study doctor believes, for any reason, that it is in your best interest. 
• 
If at any time while you are taking the study drug the study doctor discovers that your 
disease has worsened. 
• 
If you develop side effects that the study doctor considers unacceptable. 


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• 
If you refuse to take the study drug or return for follow-up as recommended by your 
study doctor, or do not follow the study doctor’s instructions. 
• 
If you refuse to have tests that are needed to determine whether the study drug is safe 
and effective. 
• 
If you require treatment with drugs that are not allowed on this study. 
• 
If other causes prevent you from continuing in this study. 
• 
If the Sponsor decides to end the study. 
HOW WILL MY INFORMATION BE KEPT CONFIDENTIAL? 
We understand that information about you and your health is personal, and we are committed to 
protecting the privacy of that information.  Because of this commitment and because of federal 
law, we must obtain your written authorization before we use or disclose your information for 
this study. 
By signing this form, you are permitting researchers at Moffitt Cancer Center to use personal 
health information for research purposes within its organized health care arrangements. You are 
also allowing the Moffitt Cancer Center to disclose your personal health information to outside 
organizations or individuals that participate in this study.  We may publish what we find out from 
this study.  If we do, we will not let anyone know your name.  We will not publish anything that 
would directly let people know who you are. 
WHO WILL DISCLOSE, RECEIVE, AND/OR USE YOUR INFORMATION? 
Your records are confidential and they will be kept in a secure environment and protected to the 
full extent of the law. 
To do this research, the following people and/or organization(s) will be allowed to disclose, use, 
and receive your information, but they may only use and disclose the information to the other 
parties on this list, to you or your personal representative, or as permitted by law: 
• 
Every research site for this study, including the Moffitt Cancer Center, and each site’s 
study team, research staff and medical staff. 
• 
Any person who provides services or oversight responsibilities in connection with this 
study. 
• 
Every member of the Moffitt Cancer Center workforce who provides services in 
connection with this study. 
• 
The person who is responsible for the study nationwide or worldwide (study 
chairperson). 
• 
Any laboratories, individuals, and organizations that use your health information in 
connection with this study. 
• 
Any sponsor of the study, including the following sponsors: Moffitt Cancer Center, 
Celgene (funding the study), Bristol Myers Squibb (supplying study drug). 
• 
Any federal, state, or local governmental agency that regulates the study (such as the 
U.S. Food and Drug Administration (FDA) and Florida Department of Health (FDH). The 
U.S. Department of Health & Human Services (DHHS), Office for Human Research 
Protections (OHRP). 
• 
Other government agencies in this or other countries. 


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• 
The designated Protocol Review and Monitoring Committees, Institutional Review 
Boards such as Advarra IRB, Privacy Boards, Data and Safety Monitoring Board and 
their related staff that have oversight responsibilities for this study. 
• 
The National Cancer Institute in evaluating the ongoing research of the Moffitt Cancer 
Center as a Comprehensive Cancer Center. 
The organizations and people listed above may employ or pay various consultants and 
companies to help them understand, analyze and conduct this study.  All of these people may 
not be known now, but if you would like to have more specific information about this at any time 
during the study, you may ask the study doctor and your questions will be answered. 
Moffitt Cancer Center cannot guarantee the privacy of your information, or block further use or 
distribution, after the information has left the Moffitt Cancer Center.  Others listed above may 
further disclose your information, and it may no longer be covered by federal privacy 
regulations.  If all information that does or can identify you is removed from your records, the 
remaining information will no longer be subject to this authorization and may be used or shared 
for other purposes.  You might have the right to see and copy your health records related to this 
research.  You might not be able to see or copy some of your records until after all participants 
finish the study.  If it is necessary for your care, your records will be provided to you or your 
regular doctor. 
WHAT INFORMATION WILL BE USED OR DISCLOSED? 
By signing below, you authorize the use and disclosure of your entire study record and any 
medical or other records held by Moffitt Cancer Center, including, but not limited to, HIV/AIDS, 
mental health, substance abuse or genetic information.  The purpose for the uses and 
disclosures you are authorizing is to conduct the study explained to you during the informed 
consent and research authorization process and to ensure that the information relating to that 
study is available to all parties who may need it for research purposes. 
Your authorization to use your health information will never expire unless and until you 
expressly revoke it in writing to the study doctor listed on the first page of this form. 
Any data collected before your letter will continue to be used as necessary to preserve the 
integrity of the study, however no additional information will be collected after you withdraw your 
authorization. 
You will receive a signed and dated copy of this form. 
WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study, please contact the Investigator at the 
telephone number listed on the first page of this consent document.  If you seek emergency 
care, or hospitalization is required, alert the treating physician that you are participating in this 
research study. 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research participants.  If you have any questions about your rights as a research 
participant, and/or concerns or complaints regarding this research study, contact: 


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• 
By mail: 
Study Participant Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• 
or call toll free: 
877-992-4724 
• 
or by email: 
adviser@advarra.com 
Please reference the following number when contacting the Study Participant Adviser: 
Pro00032422. 
WHERE CAN I GET MORE INFORMATION? 
You may call the National Cancer Institute’s (NCI) Information Service at: 
 
1-800-4-CANCER (1-800-422-6237). 
Visit the NCI’s Websites at: 
• 
CancerTrials: comprehensive clinical trial information at: http://cancertrials.nci.nih.gov 
• 
CancerNet: accurate cancer information including PDQ at:  http://cancernet.nci.nih.gov 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law.  This Web site will not include information that can identify you.  At most, the Web site 
will include a summary of the results.  You can search this Web site at any time. 
 
 


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STATEMENT OF CONSENT 
I have read this form and its contents were explained to me.  I agree to be in this research study 
for the purposes listed above.  All of my questions were answered to my satisfaction.  I will 
receive a signed and dated copy of this form for my records. 
 
 
 
Printed Name of Participant 
 
 
 
 
 
Signature of Participant  
 
Date / Time 
STATEMENT OF PERSON OBTAINING INFORMED CONSENT / RESEARCH 
AUTHORIZATION 
I attest that the participant named above had enough time to consider this information, had an 
opportunity to ask questions, and voluntarily agreed to be in this study. 
 
 
 
Printed Name of Person Explaining Consent 
 
 
 
 
 
 
Signature of Person Explaining Consent 
 
Date / Time 
 
 
 
 

Prot_SAP_000.pdf: 
 
 
 
A Phase II Biomarker Trial of Avadomide (CC-122) in Combination with 
Nivolumab in Advanced Melanoma 
 
NCT03834623 
 
Version 3.7 
November 22, 2019 


 
 
 
 
 
A Phase II Biomarker Trial of Avadomide (CC-122) in 
Combination with Nivolumab in Advanced 
Melanoma 
 
Protocol Identifying Number: 
 
 Principal Investigator: 
  
Statistician: 
 
IND/IDE Sponsor: Moffitt Cancer Center 
Funded by: Celgene Corporation   
 
 


 
 
TABLE OF CONTENTS 
  
List of Abbreviations ---------------------------------------------------------------------------------------------------------- 
5 
Statement of Compliance --------------------------------------------------------------------------------------------------- 
6 
Protocol Summary ------------------------------------------------------------------------------------------------------------- 
7 
Schematic of Study Design -------------------------------------------------------------------------------------------------- 
8 
1 Key Roles ------------------------------------------------------------------------------------------------------------------------ 
9 
2 Introduction: Background Information and Scientific Rationale ------------------------------------------- 
9 
     2.1 Background Information ------------------------------------------------------------------------------------------- 
9 
     2.2 Rationale ----------------------------------------------------------------------------------------------------------------- 
10 
     2.3 CC-122: Pre-Clinical and Clinical Studies --------------------------------------------------------------------- 
11 
     2.4 Rationale for CC-122 Plus Nivolumab in Melanoma ----------------------------------------------------- 
18 
3 Objectives and Purpose --------------------------------------------------------------------------------------------------- 
22 
4 Study Design and Endpoints --------------------------------------------------------------------------------------------- 
22 
     4.1 Description of the Study Design --------------------------------------------------------------------------------- 
22 
     4.2 Study Endpoints ------------------------------------------------------------------------------------------------------- 
22 
5 Study Enrollment and Withdrawal ------------------------------------------------------------------------------------ 
23 
     5.1 Participant Inclusion Criteria ------------------------------------------------------------------------------------- 
23 
     5.2 Participant Exclusion Criteria ------------------------------------------------------------------------------------- 
23 
     5.3 Strategies for Recruitment and Retention ------------------------------------------------------------------- 
24 
     5.4 Participant Withdrawal or Termination ---------------------------------------------------------------------- 
25 
            5.4.1 Reasons for Withdrawal or Termination ------------------------------------------------------------- 
25 
     5.5 Permanent Termination or Suspension of Study ---------------------------------------------------------- 
25 
6 Study Agent -------------------------------------------------------------------------------------------------------------------- 
26 
     6.1 Study Agent(s) and Control Description ---------------------------------------------------------------------- 
26 
            6.1.1 Dosing and Administration -------------------------------------------------------------------------------- 
26 
            6.1.2 Duration of Therapy ----------------------------------------------------------------------------------------- 
26 
            6.1.3 Dose Modifications ------------------------------------------------------------------------------------------ 
27 
     6.2 Study Agent Accountability Procedures ---------------------------------------------------------------------- 
34 
7 Study Procedures and Schedule ---------------------------------------------------------------------------------------- 
34 
     7.1 Study Procedures/Evaluations ----------------------------------------------------------------------------------- 
34 
     7.2 Schedule of Events Table ------------------------------------------------------------------------------------------- 
33 
     7.3 Concomitant Medications, Treatments, and Procedures ---------------------------------------------- 
38 
     7.4 Justification for Sensitive Procedures ------------------------------------------------------------------------- 
38 
     7.5 Precautionary Medications, Treatments, and Procedures -------------------------------------------- 
38 
     7.6 Prohibited Medications, Treatments, and Procedures -------------------------------------------------- 
39 
     7.7 Prophylactic Medications, Treatments, and Procedures ----------------------------------------------- 
39 
8 Assessment of Safety ------------------------------------------------------------------------------------------------------- 
39 
     8.1 Specification of Safety Parameters ----------------------------------------------------------------------------- 
39 
            8.1.1 Definition of Adverse Events (AE) ---------------------------------------------------------------------- 
39 
            8.1.2 Definition of Serious Adverse Events (SAE) --------------------------------------------------------- 
39 
            8.1.3 Definition of Unanticipated Problems ---------------------------------------------------------------- 
40 
     8.2 Classification of an Adverse Event ------------------------------------------------------------------------------ 
34 
            8.2.1 Severity of Event ---------------------------------------------------------------------------------------------- 
40 
            8.2.2 Relationship to Study Agent ------------------------------------------------------------------------------ 
40 
            8.2.3 Expectedness --------------------------------------------------------------------------------------------------- 
41 
     8.3 Time Period and Frequency for Event Assessment and Follow-Up --------------------------------- 
41 
     8.4 Reporting Procedures ----------------------------------------------------------------------------------------------- 
42 


 
 
TABLE OF CONTENTS 
 
 
 
 
 
            8.4.1 Adverse Event Reporting ---------------------------------------------------------------------------------- 
42 
            8.4.2 Serious Adverse Event Reporting ----------------------------------------------------------------------- 
42 
            8.4.3 Unanticipated Problem Reporting --------------------------------------------------------------------- 
42 
            8.4.4 Events of Special Interest ---------------------------------------------------------------------------------- 
43 
            8.4.5 Reporting of Pregnancy ------------------------------------------------------------------------------------ 
43 
  9 Clinical Monitoring -------------------------------------------------------------------------------------------------------- 
44 
10 Statistical Consideration ------------------------------------------------------------------------------------------------- 44 
     10.1 Statistical and Analytical Plans --------------------------------------------------------------------------------- 
44 
     10.2 Analysis of the Secondary Endpoints (S) -------------------------------------------------------------------- 
44 
     10.3 Efficacy Analysis ----------------------------------------------------------------------------------------------------- 
45 
     10.4 Planned Interim Analyses ---------------------------------------------------------------------------------------- 
46 
            10.4.1 Exploratory Analyses -------------------------------------------------------------------------------------- 
46 
     10.5 Sample Size ------------------------------------------------------------------------------------------------------------ 
48 
 
 
11 Source Documents and Access to Source Data/Documents ----------------------------------------------- 
48 
12 Quality Assurance and Quality Control ---------------------------------------------------------------------------- 
48 
13 Ethics/Protection of Human Subjects ------------------------------------------------------------------------------ 
49 
     13.1 Ethical Standard ----------------------------------------------------------------------------------------------------- 
49 
     13.2 Institutional Review Board -------------------------------------------------------------------------------------- 
49 
     13.3 Informed Consent Process --------------------------------------------------------------------------------------- 
49 
            13.3.1 Consent/Assent and Other Informational Documents Provided to Participants ---- 
49 
            13.3.2 Consent Procedures and Documentation --------------------------------------------------------- 
49 
     13.4 Participant and Data Confidentiality ------------------------------------------------------------------------- 
50 
            13.4.1 Research Use of Stored Human Samples, Specimens or Data ----------------------------- 
50 
     13.5 Future Use of Stored Specimens ------------------------------------------------------------------------------ 
50 
14 Data Handling and Record Keeping --------------------------------------------------------------------------------- 
51 
     14.1 Data Collection and Management Responsibilities ----------------------------------------------------- 
51 
     14.2 Study Records Retention ----------------------------------------------------------------------------------------- 
52 
     14.3 Protocol Deviations ------------------------------------------------------------------------------------------------ 
52 
     14.4 Publication and Data Sharing Policy -------------------------------------------------------------------------- 
53 
15 Study Administration ----------------------------------------------------------------------------------------------------- 
53 
     15.1 Study Leadership ---------------------------------------------------------------------------------------------------- 
53 
16 Conflict of Interest Policy ----------------------------------------------------------------------------------------------- 
54 
17 Literature References ---------------------------------------------------------------------------------------------------- 
55 
Appendix A 
58 
Appendix B 
59 
Appendix C 
60 
Appendix D 
61 


LIST OF ABBREVIATIONS 
5 
 
 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Science 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
CMS 
Centers for Medicare and Medicaid Services 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICH E6 
International Conference on Harmonisation Guidance for Industry, Good Clinical Practice: 
Consolidated Guidance 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Investigational Review Board 
ISO 
International Organization for Standardization 
LSMEANS 
Least Squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute & Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 


6 
STATEMENT OF COMPLIANCE 
 
 
 
The trial will be conducted in accordance with the ICH E6, the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46), and the <NIH IC> Terms of Award. The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place without prior 
agreement from the sponsor and documented approval from the Institutional Review Board, except 
where necessary to eliminate an immediate hazard(s) to the trial participants. All personnel involved in 
the conduct of this study have completed Human Subjects Protection Training. 
 
I agree to ensure that all staff members involved in the conduct of this study are informed of their 
obligation to meet the above commitments. 
 
 
Principal Investigator: 
  
 
 
Print/Type Name 
 
 
Signed: 
   
 Date: 
 


PROTOCOL SUMMARY 
7 
Avadomide plus Nivolumab 
November 22, 2019 
 
 
 
 
A Phase II Biomarker Trial of CC-122 in Combination with Nivolumab in Advanced Melanoma 
 
Précis: 
Preliminary pre-clinical data suggest that the novel immunomodulatory agent CC-122 can restore metabolic 
function of T-cells and will increase immunosurveillance in melanoma. The synergy of the combination of 
CC-122 and the anti-PD1 agent nivolumab will enhance reversal of T-cell exhaustion and improve anti-tumor 
immunity in patients with advanced melanoma.  Our goal is to link pharmacodynamic markers to immune 
mechanism of action and efficacy.  In addition, we seek to define sub-populations that may be enriched for 
response to CC-122 plus nivolumab in melanoma.    
 
Objectives: 
Primary: To determine the response rate to combination CC-122 plus nivolumab in both anti-PD1 naïve and 
anti-PD1 refractory advanced melanoma. 
Secondary: (1) To assess the toxicity of this combination. (2) To determine the progression-free survival 
and overall survival with this combination. (3) Examine blood and tissue-based biomarkers that will further 
our understanding of the complex interplay between the metabolic needs/changes in the tumor and the 
immune microenvironment. 
 
 
Population: 
Adults with advanced melanoma who are appropriate for treatment with anti-PD1 therapy or who are 
appropriate to resume anti-PD1 therapy after prior progression on anti-PD1 therapy with the goal of 
reversing resistance. 
 
      
Number of Sites 
 
This study will be conducted at the Moffitt Cancer Center 
      
Study Agent(s) and Administration: 
Oral CC-122 at 2mg daily for 5 consecutive days every 7 days, with intravenous nivolumab (240mg) in days 
1 and 15 within a 28-day cycle.   
 
 
Study Duration:  
Subjects will receive up to 52 weeks of therapy.  Decision to continue beyond this will be made based on 
response at that time. Based on planned futility analyses and enrollment across cohorts, the total number of 
subjects is anticipated to be 44-66.  
 
 
Participant Duration: 
Participants to be followed for up to 24 months following completion of study therapy. 
 
 




























CC-122 + Nivolumab
Version 3.7
21 
 
 












CC-122 + Nivolumab
Version 3.7
Nov 22, 2019
27 
 
 
cycle.  While regulatory approval for dosing at 480mg IV every 28 days was also recently obtained, we will 
maintain the approved biweekly dosing schedule in this trial based on the safety data from Study CC-122-
HC-002 in hepatocellular carcinoma.  Dose administration of +/- 2 days is permissible and will not constitute 
a deviation. There will be no dose adjustments for nivolumab.  Please refer to the OPDIVO Package Insert 
(November-2018) for full prescribing information.  
 
 
 
 
In the absence of progression or intolerable toxicity, therapy will continue up to a maximum of 52 weeks (13 
cycles).  For those patients who demonstrate continued improvement in radiographic response at scheduled 
restaging (anticipated around week 48) performed prior to reaching this landmark will be given the option of 
continuation of therapy.  This provision is based on the recently reported analysis of advanced melanoma 
patients who achieved a complete response to pembrolizumab on KEYNOTE-001 where the median time to 
achieve CR was 12 months (range, 3-36).44 For these subjects, therapy will continue for 1 cycle beyond CR 
(should they achieve this) or until 2 consecutive staging studies demonstrate a plateau in response.  For 
those patients achieving CR as best response prior to 52 weeks, therapy can be discontinued provided they 
have completed at least 26 weeks of treatment. 
 
If either CC-122 or nivolumab require discontinuation due to toxicity attributed exclusively to that agent 
(e.g., neutropenia secondary to CC-122), the second drug can continue for the duration as outlined above. 
 
 
 
Dose delay criteria apply for all drug-related adverse events regardless of whether or not the event is 
attributed to nivolumab, CC-122, or both unless it is explicitly clear that the toxicity is exclusive to one 
drug alone. All study drugs must be delayed until treatment can resume, unless in the judgement of the 
clinical investigator (with discussion with the PI), there is compelling evidence to continue one of the agents 
without the other. 
 
Causality should be assessed and provided individually for each study drug (CC-122 and nivolumab) for 
every AE/SAE based on currently available information.  Causality is to be reassessed and provided as 
additional information becomes available. 
 
6.1.3.1 
CC-122 Dose Delay and/or Modifications: 
 
The criteria for dose reduction and/or interruption for non-hematological toxicities attributed to CC-122 
are listed in the following table.  Chronic Grade 2 toxicity attributed to CC-122 may warrant dose reduction 
of CC-122. If necessary, the PI may reach out to the appropriate medical personnel at Celgene to discuss 
this further. 
  
Toxicity 
Action 
Any Grade 4 including LFT elevation 
(exceptions include lymphopenia, 
asymptomatic amylase and lipase) 
• 
Discontinue CC-122 
Grade 3 or 4 clinical liver failure 
• 
Discontinue CC-122 
6.1.2 DURATION OF THERAPY 
6.1.3 DOSE MODIFICATIONS 


CC-122 + Nivolumab
Version 3.7
Nov 22, 2019
28 
 
 
If recurrence of Grade 3 event after 
dose-reduction 
• 
Reduce dose to the next lower dose level; if available –
If none available, CC-122 should be discontinued. 
If recurrence of Grade 4 event after 
dose reduction 
• 
Discontinue CC-122 
Any non-hematological toxicity 
requiring interruption for > 4 
weeks  
• 
Discontinue CC-122 
Troponin-T/I > ULN with 
associated significant elevation in 
BNP or with cardiac symptoms or 
significant changes in ECG or 
LVEF1 
• 
Hold CC-122 
• 
Consider cardiology evaluation 
• 
Follow troponin-T/I, BNP, and ECG at least every 7 days 
• 
If troponin-T/I returns to normal levels in < 7 days 
and there are no other significant cardiac findings, 
resume CC-122 at the next lower dose level 
• 
If troponin T/I level elevation persists > 7 days, or 
recurs upon re-challenge, discontinue CC-122 
Rash ≥ Grade 3 
 
  
• 
If Grade 3 hold CC-122 until recovery to grade ≤ 1; if AE 
resolution to Grade ≤ 1 occurs ≤ 8 days, reintroduce CC-
122 at the same dose level 
• 
If AE resolution to Grade ≤ 2 or > 7 days, reintroduce 
CC122 on lower level, if available 
• 
Discontinue CC-122 for 2nd occurrence of ≥ Grade 3 
rash 
• 
For desquamating (blistering) Grade 3 or any Grade 4 
rash, discontinue CC-122 
• 
For maculopapular, aceiform, or pustular rashes lasting 
≤ 7 days medical management is warranted including topical 
corticosteroids, anti-pruritic agents (if indicated).  If this 
does not improve, oral steroids may be used.  It is likely 
that this intervention will be utilized given the overlap of 
this toxicity with nivolumab (see appendix D) 
Peripheral Neuropathy 
(neuropathies which begin or 
worsen while on study) 
≥ Grade 3 
• 
Hold CC-122 
• 
When the toxicity resolves to ≤ Grade 2 or to baseline, 
restart CC-122 at the next lower dose level 
Allergic Reaction or 
Hypersensitivity 
≥ Grade 3 
• 
Discontinue CC-122 


CC-122 + Nivolumab
Version 3.7
Nov 22, 2019
29 
 
 
Venous Thrombosis / Embolism 
(VTE) 
≥ Grade 2; anticoagulation 
indicated 
• 
Hold CC-122 and start anticoagulation; restart CC-122 
(maintain dose level) once therapeutic anticoagulation 
achieved AND it is clinically appropriate to resume.2 
Pneumonitis / Interstitial Lung 
Disease3 
 
• 
Grade 1: continue CC-122 
• 
Grade 2: interrupt CC-122; can resume at one dose 
level lower once < grade 1 AND steroid taper 
completed.  If recurrent Grade 2 toxicity on re-
challenge, permanently discontinue CC-122 
• 
> Grade 3: permanently discontinue CC-122  
Other Grade 34 
• 
Hold one or both study drugs (based on 
attribution) 
• 
When the toxicity resolves to < Grade 2, restart CC-
122 at the next lower dose level 
       
 
1. For BNP, greater than 20% increase from baseline value is considered significant. Any new ST segment 
or T wave changes, new bundle branch block, or new atrial or ventricular arrhythmia while on 
treatment with CC-122 is considered clinically significant.  An absolute decrease in LVEF of > 10% from 
baseline (even if asymptomatic), or a decrease of estimated LVEF to < 45% would mandate holding 
further CC-122 for up to 4 weeks.  If improved LVEF (repeated 2-4 weeks after holding drug) to 
baseline value, resume CC-122 at next lower dose level, if available.  If the decrease in LVEF is > 20% 
(absolute decrease) from baseline or there is any evidence of symptomatic congestive heart failure, 
CC-122 will be permanently discontinued. 
2. There are no prospective data available on the need to interrupt immunomodulatory agents like 
thalidomide, lenalidomide, CC-122 at the time of diagnosis of the VTE event.  However as these drugs 
are prothrombotic, it is reasonable to hold CC-122 till therapeutic anticoagulation is achieved.  For 
anticoagulants that do not require monitoring (such as low molecular weight heparin), CC-122 will be 
restarted 7 days after the initial hold.  For drugs requiring monitoring (unfractionated heparin, 
warfarin), CC-122 will be resumed once the aPTT or INR are in the recommended therapeutic range for 
that individual agent, but no sooner than 7 days from the hold.  Prior to resuming CC-122, clinically 
significant symptoms or signs related to VTE (e.g., chest pain, dyspnea, etc.) should have resolved.  
Persistence of leg/arm swelling (in case of DVT) would not be a contra-indication to resume therapy.       
3. As pneumonitis is an expected toxicity with nivolumab, it may be difficult to ascertain the causality to 
one specific drug in this combination.  The management algorithm to be followed based on the grade 
of toxicity is outlined in Appendix D. 
4. Exceptions to this include lymphopenia, asymptomatic elevation in amylase or lipase, and isolated 
electrolyte imbalances/abnormalities that are not associated with clinical sequelae.  Isolated 
electrolyte aberrations (e.g., sodium, potassium, magnesium, etc.) may require appropriate exogenous 
supplementation, but repeat levels must meet criteria outlined in the table to resume therapy. 
 
 
 
 
 


C C -1 2 2 + Niv ol u m a b  
V ersi o n 3. 7  
N o v 2 2 , 2 0 1 9 
3 0  
 
 
 
 
 
 
 
 
 
G ui d eli n es f or h e m at ol o gic al t o xicit y attri b ut e d t o C C -1 2 2 : 
 
 
T oxicit y  
Acti o n  
Gr a d e 2 t hr o m b ocyt o p e ni a 
•  
N o  acti o n  
Gr a d e  3 t hr o m b ocyt o p e ni a 
•  
H ol d u ntil r es ol uti o n t o Gr a d e  1 
•  
F oll o w C B C at l e ast ev ery 7 d ays  
•  
If r es ol uti o n t o Gr a d e 1 occ urs  ≤ 8 d ays, r ei ntr o d uc e  
C C -1 2 2  at  t h e s a m e d os e  l ev el 
•  
If A E r es ol uti o n occ urs > 8 d ays, or ev e nt occ urs  
wit hi n t h e s a m e cycl e, r ei ntr o d uc e  C C -1 2 2  at  t h e 
l o w er d os e l ev el, if av ail a bl e 
Gr a d e  4 t hr o m b ocyt o p e ni a 
•  
H ol d C C -1 2 2 u ntil r ec ov ery t o Gr a d e  1 
•  
F oll o w C B C at l e ast ev ery 7 d ays  
•  
R ei ntr o d uc e C C -1 2 2  at t h e  l o w er d os e l ev el, if 
av ail a bl e  
Gr a d e  3 n e utr o p e ni a  
•  
H ol d u ntil r es ol uti o n t o Gr a d e  ≤ 1 
•  
F oll o w C B C at l e ast ev ery 7 d ays  
•  
If A E r es ol uti o n t o Gr a d e  ≤ 1 occ urs  ≤ 8 d a ys,  
r ei ntr o d uc e C C -1 2 2  at  t h e s a m e d os e  l ev el 
•  
If A E r es ol uti o n occ urs > 8 d ays, or ev e nt occ urs  
wit hi n t h e s a m e c ycl e, r ei ntr o d uc e C C -1 2 2  at  o n e  
d os e l ev el l o w er, if av ail a bl e  
Gr a d e  4 n e utr o p e ni a  
•  
Gr a d e 4:  H ol d C C -1 2 2 u ntil r ec ov ery t o Gr a d e  1.  
•  
F oll o w C B C at l e ast ev ery 7 d ays  
•  
R ei ntr o d uc e C C -1 2 2  at t h e  l o w er d os e l ev el, if 
av ail a bl e  
•  
Us e  of gr o wt h f act ors ( G -C SF,  G M -CS F)  is p er mitt e d  
at t h e discr eti o n of t h e I nv esti g at or * 
F e bril e  n e utr o p e ni a  
•  
H ol d f urt h er d osi n g u ntil  r ec ov ery t o Gr a d e  ≤ 1 t h e n 
r es u m e d osi n g at o n e  d os e  l ev el l o w er, if av ail a bl e  
•  
Us e  of gr o wt h f act ors ( G -C SF,  G M -CS F)  is p er mitt e d  
at t h e discr eti o n of t h e I nv esti g at or * 


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Any hematological toxicity requiring 
interruption for > 3 weeks 
• 
Discontinue CC-122 
*The use of myeloid growth factors (filgastrim, sargramostin, peg-filgastrim, or biosimilars), if considered 
should be in accordance with the 2015 American Society of Clinical Oncology guidelines for the use of WBC 
growth factors.45  This includes use in subjects with neutropenia and fever who are at high risk for infection-
related complications.  These high-risk features are sepsis, age > 65 years, pneumonia, invasive fungal 
infection, other clinically documented infections, profound neutropenia (< 0.1 X 109/L) and hospitalization at 
the time of neutropenia. The growth factor should be continued until the absolute neutrophil count (ANC) 
has improved to < grade 1 (equal to or greater than 1.5 X 109/L). If resumption of CC-122 in planned at a 
lower dose (if available), growth factors should have been discontinued at least 48 hours prior with 
reconfirmation of acceptable ANC on the day of planned resumption of treatment. 
 
Additional toxicity-related precautions with CC-122: 
 
CC-122 absorbs ultraviolet (UV) light between the frequencies of 290 and 700 nm and has been shown to 
distribute to the skin and eyes in nonclinical animal studies. As a precautionary measure, it is recommended 
that subjects avoid prolonged exposure to UV light, wear protective clothing and sunglasses, and use UV-
blocking topical preparations while taking CC-122.  This is outlined in the informed consent document. 
   
6.1.3.2  
Nivolumab Dose Delays and/or Modifications: 
 
Nivolumab administration should be delayed for the following: 
 
• 
Grade 2 non-skin, drug-related adverse event, with the exception of fatigue 
• 
Grade 2 drug-related creatinine, AST, ALT and/or Total Bilirubin abnormalities 
• 
Grade 3 skin, drug-related adverse event 
• 
Grade 3 drug-related laboratory abnormality, with the following exceptions: 
− Grade 3 lymphopenia or asymptomatic amylase or lipase does not require dose delay 
− Grade 3 AST, ALT, Total Bilirubin will require dose discontinuation 
• 
Any adverse event, laboratory abnormality, or inter-current illness, which in the judgment of the 
investigator warrants delaying the dose of study medication. 
 
Participants who require delay of study drug administration should be re-evaluated weekly or more 
frequently if clinically indicated and resume dosing when re-treatment criteria are met. 
 
Criteria to Resume Treatment with Nivolumab: 
 
Participants may resume treatment with study drug when the drug-related AE(s) resolve to Grade < 
1 or baseline value, with the following exceptions: 
• 
Participants may resume treatment in the presence of Grade 2 fatigue 
• 
Participants who have not experienced a Grade 3 drug-related skin AE may resume treatment in the 
presence of Grade 2 skin toxicity 
• 
For participants with Grade 2 AST, ALT and/or Total Bilirubin Abnormalities, dosing may resume when 
laboratory values return to baseline and management with corticosteroids, if needed, is complete. 
• 
Participants with combined Grade 2 AST/ALT AND total bilirubin values meeting discontinuation 
parameters should have treatment permanently discontinued. 
• 
Drug-related pulmonary toxicity, diarrhea or colitis must have resolved to baseline before treatment is 
resumed. Participants with persistent Grade 1 pneumonitis after completion of a steroid taper over at 
least 1 month may be eligible for retreatment if they are asymptomatic and with normal pulse oximetry 


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readings in the absence of oxygen supplementation.  
 
Participants with drug-related endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume treatment provided any symptoms attributed to this event have improved to 
baseline. If the criteria to resume treatment are met, the participant should restart treatment at the 
next scheduled time point per protocol. However, if the treatment is withheld past the window period of 
the next scheduled time point per protocol to ensure adequate recovery from the adverse event or 
tapering of immunosuppression, the next scheduled time point will be delayed until dosing resumes. 
If treatment is withheld > 6 weeks from the last dose, the participant must be permanently 
discontinued from study therapy. 
 
Treatment with Nivolumab should be permanently discontinued for the following: 
 
• 
Any Grade 2 drug-related uveitis, eye pain or blurred vision that does not respond to topical therapy and 
does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment 
 
• 
Any Grade 3 non-skin, drug-related adverse event lasting > 7 days, or recurs with the following 
exceptions for laboratory abnormalities, diarrhea, colitis, neurologic toxicity, drug- related uveitis, 
pneumonitis, bronchospasm, hypersensitivity reactions, infusion reactions, and endocrinopathies: 
− Grade 3 drug-related diarrhea, colitis, neurologic toxicity, uveitis, pneumonitis, bronchospasm, 
hypersensitivity reaction, or infusion reaction of any duration requires discontinuation 
− Grade 3 drug-related endocrinopathies, adequately controlled with only physiologic hormone 
replacement do not require discontinuation. Adrenal insufficiency requires discontinuation regardless of 
control with hormone replacement. 
− Grade 3 drug-related laboratory abnormalities do not require treatment discontinuation except: 
♦ Grade 3 drug-related thrombocytopenia > 7 days or associated with bleeding requires 
discontinuation 
♦ Any drug-related liver function  test  (LFT)  abnormality that  meets  the  following criteria 
require discontinuation: 
o Grade 3 drug-related AST, ALT or Total Bilirubin requires discontinuation 
o Concurrent AST or ALT > 3 x ULN and total bilirubin > 2x ULN 
 
• 
Any Grade 4 drug-related adverse event or laboratory abnormality (including but not limited to 
creatinine, AST, ALT, or Total Bilirubin), except for the following events which do not require 
discontinuation: 
− Grade 4 neutropenia < 7 days 
− Grade 4 lymphopenia or leukopenia or asymptomatic amylase or lipase 
− Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical sequelae 
and are corrected with supplementation/appropriate management within 72 hours of their onset 
− Grade 4 drug-related endocrinopathy adverse events, such as, hyper- or hypothyroidism, or 
glucose intolerance, which resolve or are adequately controlled with physiologic hormone 
replacement (corticosteroids, thyroid hormones) or glucose-controlling agents, respectively, may 
not require discontinuation of nivolumab. 
 
• 
Any event that leads to delay in dosing lasting > 6 weeks from the previous dose requires 
discontinuation, with the following exceptions: 
− Dosing delays to allow for prolonged steroid tapers to manage drug-related adverse events are 
allowed. 
 


C C -1 2 2 + Niv ol u m a b  
V ersi o n 3. 7  
N o v 2 2 , 2 0 1 9 
3 3  
 
 
T h e al g orit h ms f or m a n a g e m e nt of i m m u n e t oxicity attri b ut e d t o niv ol u m a b will f oll o w r ec o m m e n d ati o ns 
o utli n e d i n t h e O P DI V O p ack a g e i ns ert a n d l a b eli n g i nf or m ati o n ( N ov e m b er -2 0 1 8) pl us g e n er ally acc e pt e d 
g ui d eli n es f or cli nic al c ar e of I O t oxicity m a n a g e m e nt.  T h es e g ui d eli n es ar e s u m m ariz e d i n A p p e n dix D . 
 
T u m or  ass ess m e nts  s h o ul d c o nti n u e as  p er  pr ot oc ol  ev e n  if d osi n g  is d el a y e d. P eri o dic  st u dy visits t o 
ass ess  s af et y a n d  l a b or at or y st u di es s h o ul d als o  c o nti n u e e v er y 6 w e e ks  or  m or e  fr e q u e ntly if cli nic ally 
i n dic at e d d uri n g s uc h d osi n g d el ays. 
 
Tr e at m e nt of Ni v ol u m a b R el at e d I nf usi o n R e acti o ns:  
 
Si nc e  niv ol u m a b  c o nt ai ns o nl y  h u m a n  i m m u n o gl o b uli n pr ot ei n  s e q u e nc es, it is u nlik ely  t o b e  
i m m u n o g e nic a n d  i n d uc e i nf usi o n or  hy p ers e nsitivity  r e acti o ns. H o w ev er,  if s uc h  a r e acti o n w er e  t o 
occ ur,  it mi g ht  m a nif est  wit h  f ev er, c hills, ri g ors, h e a d ac h e,  r as h, pr uritis,  art hr al gi as,  hy p o - or  
hy p ert e nsi o n,  br o nc h os p as m,  or  ot h er  sy m pt o ms. I nf usi o n r e acti o ns s h o ul d b e  gr a d e d  acc or di n g  t o 
N ati o n al  C a nc er  I nstit ut e C o m m o n  T er mi n ol o gy  Crit eri a  f or A dv ers e  E v e nts  ( N CI C T C A E   [v ersi o n  5. 0]) 
g ui d eli n es.  
 
Tr e at m e nt  r ec o m m e n d ati o ns ar e  pr ovi d e d  b el o w  a n d  m ay  b e  m o difi e d  b as e d  o n  l oc al tr e at m e nt 
st a n d ar ds a n d g ui d eli n es as a p pr o pri at e: 
 
F or  Gr a d e   1 s y m pt o ms: ( Mil d r e acti o n; i nf usi o n i nt err u pti o n n ot  i n dic at e d; i nt erv e nti o n n ot  i n dic at e d) 
 
R e m ai n  at  b e dsi d e  a n d  m o nit or  p artici p a nt  u ntil  r ec ov ery fr o m sy m pt o ms. T h e  f oll o wi n g pr o p hyl actic  
pr e m e dic ati o ns  ar e  r ec o m m e n d e d f or f ut ur e i nf usi o ns: di p h e n hy dr a mi n e  5 0  m g  ( or e q uiv al e nt)  a n d/ or  
p ar ac et a m ol  3 2 5  t o 1 0 0 0  m g  ( ac et a mi n o p h e n) at  l e ast 3 0  mi n ut es  b ef or e  a d diti o n al  ni v ol u m a b  
a d mi nistr ati o ns.  
 
F or  Gr a d e  2 s y m pt o ms: ( M o d er at e r e acti o n r e q uir es t h er a py or  i nf usi o n i nt err u pti o n b ut  r es p o n ds 
pr o m ptly  t o s y m pt o m atic tr e at m e nt [ e g, a nti hist a mi n es,  n o n -st er oi d al a nti - i nfl a m m at or y dr u gs,  
n arc otics,  c ortic ost er oi ds, br o nc h o dil at ors,  I V fl ui ds]; pr o p hyl actic  m e dic ati o ns  i n dic at e d f or <2 4 h o urs).  
 
St o p  t h e niv ol u m a b  i nf usi o n, b e gi n  a n  I V i nf usi o n of  n or m al  s ali n e, a n d  tr e at t h e p artici p a nt  wit h  
di p h e n hy dr a mi n e  5 0  m g  I V ( or e q ui v al e nt)  a n d/ or  p ar ac et a m ol  3 2 5  t o 1 0 0 0  mg  ( ac et a mi n o p h e n); r e m ai n 
at  b e dsi d e  a n d  m o nit or  p artici p a nt  u ntil  r es ol uti o n of  s y m pt o ms. C ortic ost er oi d  or  br o nc h o dil at or  t h er a py 
m ay  als o  b e  a d mi nist er e d  as  a p pr o pri at e.  If t h e i nf usi o n is i nt err u pt e d, t h e n r est art t h e i nf usi o n at  
5 0 %  of  t h e ori gi n al  i nf usi o n r at e w h e n  sy m pt o ms r es olv e; if n o  f urt h er c o m plic ati o ns e ns u e  aft er  3 0  
mi n ut es,  t h e r at e m ay  b e  i ncr e as e d t o 1 0 0 %  of  t h e ori gi n al  i nf usi o n r at e. M o nit or  p artici p a nt  cl os ely. If 
s y m pt o ms r ec ur t h e n n o  f urt h er niv ol u m a b  will  b e  a d mi nist er e d  at  t h at visit. A d mi nist er  
di p h e n hy dr a mi n e  5 0  m g  I V, a n d  r e m ai n at  b e dsi d e a n d  m o nit or  t h e p artici p a nt  u ntil  r es ol uti o n of  
s y m pt o ms. T h e  a m o u nt  of  st u dy dr u g  i nf us e d m ust  b e  r ec or d e d o n  t h e el ectr o nic  c as e r e p ort f or m ( e C R F). 
T h e f oll o wi n g  pr o p hyl actic  pr e m e dic ati o ns  ar e  r ec o m m e n d e d f or f ut ur e i nf usi o ns: di p h e n hy dr a mi n e  5 0  
m g  ( or e q uiv al e nt)  a n d/ or  p ar ac et a m ol  3 2 5  t o 1 0 0 0  m g  ( ac et a mi n o p h e n) s h o ul d b e  a d mi nist er e d  at  l e ast 
3 0  mi n ut es  b ef or e  a d diti o n al  niv ol u m a b  a d mi nistr ati o ns.  If n ec ess ary,  c ortic ost er oi ds (r ec o m m e n d e d 
d os e:  u p  t o 2 5  m g  of  I V hy dr oc ortis o n e  or  e q ui v al e nt)  m ay  b e  us e d.  
 
F or  Gr a d e   3 or  Gr a d e   4 s y m pt o ms: ( S e v er e r e acti o n, Gr a d e  3:  pr ol o n g e d  [i e, n ot  r a pi dly r es p o nsiv e 
t o sy m pt o m atic m e dic ati o n  a n d/ or  bri ef  i nt err u pti o n of  i nf usi o n]; r ec urr e nc e of  sy m pt o ms f oll o wi n g 
i niti al i m pr ov e m e nt; h os pit aliz ati o n  i n dic at e d f or ot h er  cli nic al s e q u el a e [ e g, r e n al i m p air m e nt, 
p ul m o n ary  i nfiltr at es]). Gr a d e  4:  (lif e t hr e at e ni n g; pr ess or or  v e ntil at ory  s u p p ort i n dic at e d). 
 
I m m e di at el y disc o nti n u e  i nf usi o n of  niv ol u m a b . B e gi n  a n  I V i nf usi o n of  n or m al  s ali n e, a n d  tr e at t h e 




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• 
Confirm informed consent of potential participant has been obtained. 
• 
Review medical history to determine eligibility based on inclusion/exclusion criteria. 
• 
Review medications history to determine eligibility based on inclusion/exclusion criteria. 
• 
Perform medical examinations needed to determine eligibility based on inclusion/exclusion 
criteria. 
• 
Collect/schedule study specific laboratory/biomarker tests and other studies that are outlined in the 
Schedule of Events. 
• 
Schedule biopsy of appropriate metastatic (or appropriately accessible) tumor site for biomarker 
analysis. 
 
 
Baseline Visit (Cycle 1, Day 1) 
 
• 
Verify inclusion/exclusion criteria based on screening studies.  The specific eligibility is typically 
completed ahead of this visit through the Moffitt Internal Monitoring Core. 
• 
Obtain serum or urine pregnancy test for women of child-bearing age; this could have been 
completed and verified negative up to 72 hours prior to this visit. 
• 
Obtain demographic information, medical history, and medication history. 
• 
Record vital signs (including weight), results of examinations.  Recording of height is necessary only 
at screening or baseline visit 
• 
Collect study specific laboratory/biomarker tests and other studies that are outlined in the Schedule 
of Events. This also includes standard of care assessments. 
• 
Administer the study treatment (nivolumab plus CC-122; first dose of CC-122 to be administered in 
the Clinical Research Unit). 
• 
Collect blood for biomarker analysis at 5 hours post CC-122 administration. 
 
Follow-up Visit (Visit 2; C1 Day 15; +/- 2 days)  
 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Record vital signs, confirm medical history and perform physical examination 
• 
Collect blood for routine testing and biomarker analysis as specified. 
• 
Administer nivolumab per institutional standard. 
• 
Record participant’s adherence to treatment program. 
• 
Schedule/remind subject of follow-up tumor biopsy (same site as done at screening) to be done 
between days 22 and 29 of cycle 1. 
 
Follow-up Visit (Visit 3; Cycle 2, day 1, +/- 2 days)  
 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Record vital signs, confirm medical history and perform physical examination 
• 
Administer nivolumab and provide CC-122 for home use  
• 
Record participant’s adherence to treatment program. 
 
Subsequent Visits to follow the ‘Schedule of Events’ calendar: All scheduled visits have the same window of 
+/- 2 days.  If there is a need to schedule outside of this window, this may be done at the discretion of the 
principal investigator as long as there is no perceived jeopardy to the health of the participant. Tumor 
measurements by cross-sectional imaging will be performed every 12 weeks (+/- 7days) unless documented 
progression or subject taken off the clinical trial.  Adverse events as reported by the subject or observed by 
the investigator will be recorded at each visit.  


















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• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
 
• 
UPs that are SAEs will be reported to the IRB and to the DCC/study sponsor within <insert 
timeline in accordance with policy> of the investigator becoming aware of the event. 
• 
Any other UP will be reported to the IRB and to the DCC/study sponsor within <insert timeline in 
accordance with policy> of the investigator becoming aware of the problem. 
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and OHRP within 
 
 
 
 
Not applicable. 
 
 
 
Although pregnancy and lactation are not considered adverse events, it is the responsibility of investigators 
or their designees to report any pregnancy or lactation in a subject (spontaneously reported to them), 
including the pregnancy of a male subject's female partner that occurs during the trial or within 120 days of 
completing the trial or 30 days following cessation of treatment. All subjects and female partners of male 
subjects who become pregnant must be followed to the completion/termination of the pregnancy. Any 
subject who becomes pregnant during the study, must be promptly withdrawn from the study and 
discontinue further study treatment. Pregnancy outcomes of spontaneous abortion, missed abortion, 
benign hydatidiform mole, blighted ovum, fetal death, intrauterine death, congenital anomaly, ectopic 
pregnancy, miscarriage and stillbirth must be reported as serious events (Important Medical Events). If the 
pregnancy continues to term, the outcome (health of infant) must also be reported.  
Such events must be reported within 24 hours of their knowledge of the event to Celgene using the Serious 
Adverse Event Form. Because the effect of the Celgene medicinal product on sperm is unknown, 
pregnancies in partners of male subjects exposed to a Celgene medicinal product will be reported by the 
Investigator within 24 hours of their knowledge of the event using the Serious Adverse Event Form. 
Depending on local legislation, this may require prior consent of the partner. Follow-up information 
regarding the outcome of the pregnancy and any postnatal sequelae in the infant will be required. 
8.4.4 
EVENTS OF SPECIAL INTEREST 
8.4.5 REPORTING OF PREGNANCY 




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the time of data analysis will be censored. 
 
 
 
Objective response rate is the primary end point in this combination trial involving an immune checkpoint 
inhibitor in combination with an immunomodulatory agent. Response rates per RECIST 1.1 will be 
evaluated. 
 
RECIST as assessed by the investigator will be used as the primary response rate efficacy end-point and 
make treatment decisions. 
  
Immunotherapeutic agents such as nivolumab and pembrolizumab may produce antitumor effects by 
potentiating endogenous cancer-specific immune responses, which may be functionally anergic. The 
response patterns seen with such an approach may extend beyond the typical time course of 
responses seen with cytotoxic agents, and can manifest a clinical response after an initial increase in 
tumor burden or even the appearance of new lesions. Standard RECIST criteria may not provide a 
complete response assessment of immunotherapeutic agents such as nivolumab, therefore the 
irRECIST have been developed to encompass this.  This will also be assessed as a secondary end-point of 
efficacy. 
 
Broadly, irRECIST includes the concept of treatment beyond progression, if radiologic imaging shows 
PD, tumor assessment should be repeated ≥ 4 weeks later in order to confirm PD with the option of 
continuing treatment, while awaiting radiologic confirmation of progression.  If repeat imaging shows a 
reduction in the tumor burden compared to the initial scan demonstrating PD, treatment may be 
continued as per treatment calendar. If repeat imaging confirms progressive disease, subjects will be 
discontinued from trial therapy. In determining whether or not the tumor burden has increased or 
decreased, Investigators should consider all target lesions as well as non-target lesions. 
 
In subjects who have initial evidence of radiological PD, it is at the discretion of the treating 
physician whether to continue a subject on study treatment, until repeat imaging is obtained a minimum 
of 4 weeks later. This decision should be based on the clinical judgment of the subject’s overall 
clinical condition, including performance status, clinical symptoms, and laboratory data. Subjects may 
receive treatment while waiting for confirmation of PD if they are clinically stable as defined by the 
following criteria: 
• 
Absence of signs and symptoms indicating disease progression 
• 
No decline in ECOG performance status  
• 
Absence of rapid progression of disease 
• 
Absence of progressive tumor at critical anatomical sites (e.g., cord compression) requiring urgent 
alternative medical intervention 
 
When feasible, subjects should not be discontinued until progression is confirmed. This allowance to 
continue treatment despite initial radiologic progression takes into account the observation that some 
subjects can have a transient tumor flare in the first few months after the start of immunotherapy, but 
with subsequent disease response. Subjects that are deemed clinically unstable are not required to 
have repeat imaging for confirmation of progressive disease. 
 
Subjects who continue treatment beyond initial radiographic progression while awaiting confirmation 
imaging will need to be re-consented for their ongoing treatment with nivolumab and avadomide on the 
clinical trial.  All other elements of the main consent including description of reasonable foreseeable risks or 
discomfort, and other alternative therapy will still apply. 
10.3 EFFICACY ANALYSIS 
























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Seymour L, Bogaerts J, Perrone A, et al: iRECIST: guidelines for response criteria for use in 
trials testing immunotherapeutics. Lancet Oncol 18:e143-e152, 2017 
 
44. 
Robert C, Ribas A, Hamid O, et al: Durable Complete Response After Discontinuation of 
Pembrolizumab in Patients With Metastatic Melanoma. Journal of Clinical Oncology 0:JCO.2017.75.6270 
 
45. 
Smith TJ, Bohlke K, Lyman GH, et al: Recommendations for the Use of WBC Growth Factors: 
American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 33:3199-212, 2015 
 
46. 
Simon R: Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1-10, 


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1989 
 
47. 
Jung SH, Lee T, Kim K, et al: Admissible two-stage designs for phase II cancer clinical trials. 
Stat Med 23:561-9, 2004 
 
48. 
Bowyer S, Prithviraj P, Lorigan P, et al: Efficacy and toxicity of treatment with the anti-CTLA-4 
antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. Br J Cancer 
114:1084-9, 2016 
 
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Ivanova A, Qaqish BF, Schell MJ: Continuous toxicity monitoring in phase II trials in oncology. 
Biometrics 61:540-5, 2005 
 
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Nishino M, Giobbie-Hurder A, Gargano M, et al: Developing a common language for tumor 
response to immunotherapy: immune-related response criteria using unidimensional measurements. Clin 
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Appendix B: ECOG Performance Status 
 
Grade 
Description 
0 
Normal activity.  Fully active, able  to  carry  on  all  pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous activity, 
but ambulatory and able to carry out work of a light or sedentary 
nature (e.g., light housework, office work). 
2 
In bed <50% of the time. 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 
In bed >50% of the time. Capable of only limited self-care, confined to 
bed or chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self- care. 
Totally confined to bed or chair. 
5 
Dead. 
* As published in Am. J. Clin. Oncol.: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, 
T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern 
Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982. The Eastern Cooperative 
Oncology Group, Robert Comis M.D., Group Chair. 
 
 
 
 
 
 
 


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Appendix C:  iRECIST (immune Response Evaluation Criteria in Solid Tumors) 
 
Tumor response will be assessed by the RECIST 1.1 (primary) and iRECIST (secondary).43,50 The latter is a 
reconciliation of RECIST guidelines v1.1 with the original immune-related Response Criteria (irRC). The 
latter standard incorporated principles important for assessment of immune-checkpoint blocking 
immunotherapy for cancer, but fundamentally differed from RECIST in using 2-dimensional tumor 
assessment. In contrast, iRECIST is based on 1-dimensional tumor measurement, but it differs from 
RECIST guidelines v1.1 in the following key ways: 
 
• 
Under RECIST guidelines v1.1, the appearance of new lesions indicates PD. Under iRECIST, new 
measurable lesions are incorporated in the tumor burden, which is used to determine immune-related 
progressive disease (iPD), immune-related partial response (iPR), and immune-related complete 
response (iCR). New non-measurable lesions preclude iCR. 
 
• 
Under RECIST guidelines v1.1, there is no confirmation for PD. In addition, responses and iPDs must be 
confirmed by consecutive scans at least 4 weeks apart, assuming no clinical deterioration. 
 
The following sub-section describes iRECIST in detail. 
 
Tumor Burden: 
At baseline, the tumor burden is the sum of single diameters (short axis for nodal lesions, longest 
diameter for other lesions) for the target lesions. In subsequent scans, the diameters of new measurable 
lesions are added to the tumor burden. If a subject is retreated, then up to 5 target lesions (perhaps 
different from the original lesions) will be selected and a new baseline tumor burden will be 
established. 
 
Overall Response at a Single Time Point 
 
The table below outlines determination of disease response at a single assessment based on iRECIST. 
 
iRECIST: Overall Response 
 
Tumor Burden 
(Baseline and New) 
Non-Target Lesions 
(Baseline and New) 
Response 
Disappearance of non-nodal lesions. All 
pathologic lymph nodes < 10 mm (short 
axis) 
Disappearance of non-nodal lesions. All 
pathologic lymph nodes < 10 mm (short 
axis) 
irCRa 
≥ 30% decrease from baseline 
Any 
irPRa 
≥ 20% increase from nadir and at least 5 
mm 
Any 
irPDa 
Neither sufficient decrease to qualify for 
PR  nor sufficient increase to qualify for PD 
Any 
irSD 
Disappearance of all non-nodal lesions. All 
pathologic lymph nodes < 10 mm 
Any other than disappearance of all non- 
nodal lesions and reduction of pathologic 
lymph nodes < 10 mm 
irPRa 
 
 
 
a. Selection as best response requires confirmation by 2 consecutive measurements at least 4 weeks apart. 
b. If some lesions are measured, response may be inferred from available measurements. For example, growth in evaluated target lesions 
may be sufficient for irPD regardless of status of non-evaluated lesions. 
 
 
 
 
Not all evaluatedb 
Any 
irNE 


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Appendix D: Immune Adverse Events Management Algorithm 
 
The following section outlines general principles for the management of immune-related adverse events.  A 
general principle is that differential diagnoses should be diligently evaluated according to standard medical 
practice.  Non-inflammatory etiologies should be considered and appropriately treated.  The updated 
package insert for OPDIVO (nivolumab) will be concurrently followed to assist with clinical decision making. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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