Clinical trial NCT02728102
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma Lenalidomide Maintenance Therapy Hematologic Disorders Vaccine GM-CSF Transplant Anti-Myeloma Agents
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Start date: 2016-07-01; Completion date: 2022-12-09
Enrollment: 203 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study is designed as a Phase II, multicenter trial of vaccination with Dendritic cell/myeloma fusions with granulocyte macrophage colony-stimulating factor (GM-CSF) adjuvant plus lenalidomide maintenance therapy versus maintenance therapy alone or with GM-CSF following autologous transplant as part of upfront treatment of multiple myeloma (MM). It is hypothesized that the dendritic cell myeloma vaccine will result in improved response in patients with multiple myeloma after autologous Hematopoietic Cell Transplant (HCT).

Detailed description:
The study is a three-arm, phase II randomized, open-labeled clinical trial that randomizes patients to vaccination with Dendritic Cell (DC)/myeloma fusions/GM-CSF plus lenalidomide maintenance therapy or lenalidomide maintenance therapy with or without GM-CSF following autologous transplant as part of upfront treatment for patients diagnosed with multiple myeloma. Patients are randomized approximately 2 months post transplant and will begin maintenance lenalidomide between day 90 and 100. The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (defined as CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF.

Arms: arm 1: Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. arm 2: Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. arm 3: Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Interventions: intervention 1: Tumor Cell Collection intervention 2: Autologous Stem Cell Transplant intervention 3: Melphalan intervention 4: Leukapheresis intervention 5: Myeloma vaccine intervention 6: GM-CSF intervention 7: Lenalidomide
Intervention descriptions: intervention 1: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). intervention 2: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation. intervention 3: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices. intervention 4: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. intervention 5: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients who have \<3 x 10\^6 total fusion cells will not proceed with vaccination. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. Vaccine will be administered by subcutaneous injection in the upper thigh. intervention 6: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle. intervention 7: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.

Protocol documents:
ICF_002.pdf: 
BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
NCT02728102 
 
 
 
Version 4.0 dated July 24, 2018  
 
1 
Informed Consent to Participate in Research 
 
BMT CTN 1401 v4.0 
 
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant 
Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
 
 
 
 
Your Name:   
__________________________ 
 
 
Study Title:  
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma 
with or without Vaccination with Dendritic Cell /Myeloma Fusions  
 
Protocol:  
BMT CTN 1401 v4.0 
 
Principal  
Investigator:  
Insert local PI information  
 
Sponsor:  
The National Institutes of Health (NIH) is sponsoring this study by 
providing financial support for the coordination of this study through the 
Blood and Marrow Transplant Clinical Trials Network (BMT CTN).  
 
 
 
 


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1. 
Introduction  
We invite you to join this clinical trial, also known as a research study. You are being asked to 
join because: 
• You’re >18 and <71 years old 
• You have multiple myeloma (MM)  
• Your doctor thinks an autologous transplant is a possible treatment option for you. 
The standard of care for patients with MM is an autologous transplant and maintenance 
treatment. Maintenance treatment is chemotherapy after transplant. There’s no cure for MM, so 
patients get maintenance treatment to slow the return of MM after a transplant.   
We’re doing this study to learn if maintenance treatment works better alone or with a vaccine 
made from your own blood cells.   
This study will take at least 3 years and will include 203 participants. Your participation will 
last for a maximum of 4 years from when you are enrolled.  
 
This consent form will tell you about the purpose of the study, the possible risks and benefits, 
other options available to you, and your rights as a participant in the study.  
Everyone who takes part in research at [insert facility name] should know that: 
• Being in any research study is voluntary. 
• You may or may not benefit from being in the study. Knowledge we gain from this study 
may benefit others. 
• If you join the study, you can quit the study at any time.  
• If you decide to quit the study, it will not affect your care at [insert name of facility or 
institution]. 
• Please ask the study staff questions about anything that you do not understand, or if you 
would like to have more information. 
• You can ask questions now or any time during the study. 


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• Please take the time you need to talk about the study with your doctor, study staff, and your 
family and friends. It is your decision to be in the study. If you decide to join, please sign 
and date the end of the Consent Form.  
You and your doctor will discuss other treatment choices if you do not want to participate in this 
study. 
2. 
Study Background 
The National Institutes of Health (NIH), through the Blood and Marrow Transplant Clinical 
Trials Network (BMT CTN), are providing staff support and money for this research study. The 
BMT CTN and the NIH will make decisions about how to manage the study.  
For this study, you will receive an autologous transplant (transplant). An autologous transplant 
uses blood-forming cells that are collected from your blood stream. After they are collected and 
frozen, you will get a high dose of chemotherapy. Chemotherapy before a transplant is called the 
“conditioning regimen”.  
The goal of chemotherapy is to kill as many cancer cells in your body as possible. It also 
destroys most of the normal cells in your bone marrow. To restore your marrow, your frozen 
blood-forming cells are thawed and transplanted back into your blood stream. The cells find their 
way into the bone marrow where they start making healthy blood-forming cells. 
The standard of care for patients with MM is an autologous transplant and maintenance 
treatment. Maintenance treatment is chemotherapy after transplant. There’s no cure for MM, so 
patients get maintenance treatment to slow the return of MM after a transplant.  
Some patients may receive a vaccine, and/or GM-CSF (also known as Leukine) with their 
maintenance therapy. GM-CSF helps your body make new white blood cells after transplant. 
The vaccine is made from dendritic cells and MM tumor cells in a laboratory. We will collect a 
sample of your cells through your central line (or catheter). This process is called leukapheresis. 
If the vaccine is made successfully, it will be frozen and stored to give to you later. 
We’re doing this study to learn if maintenance treatment works better alone, or with a vaccine 
made from your own blood cells.  
 


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3. 
Study Purpose 
We are inviting you to take part in this study because you have multiple myeloma (MM) and an 
autologous transplant is a treatment option for you. We are doing this study to learn more about 
ways to prevent or slow the return of MM after transplant.  
We will use 3 treatments to see which one works best to prevent or slow the return of MM. See 
Table 1 for information on each treatment group.  
Table 1. Study Treatment Groups 
Treatment Group A 
(maintenance treatment with 
GM-CSF and vaccines) 
Treatment Group B 
(maintenance treatment with 
GM-CSF)  
Treatment Group C (only 
maintenance treatment) 
• 
Melphalan 
(chemotherapy 
drug) 
• 
Autologous transplant 
• 
Lenalidomide (maintenance 
treatment) 
• 
GM-CSF  
• 
Vaccine 
• 
Melphalan 
(chemotherapy drug) 
• 
Autologous transplant 
• 
Lenalidomide 
(maintenance treatment) 
• 
GM-CSF 
 
• Melphalan 
(chemotherapy 
drug) 
• Autologous transplant  
• Lenalidomide (maintenance 
treatment)  
•  
 
This study will help doctors make the best choice about treatment after transplant for patients 
with MM. See section 5: Study Tests and Treatments for information on how your treatment 
group will be determined and for information about the drugs listed in Table 1. 
4. 
Rights to Ask Questions and/or Withdraw  
You have the right to ask questions about the study at any time. If you have questions about your 
rights as a participant or you want to leave the study, please contact:  
[insert contact info] 


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Being in this study is voluntary. You can choose not to be in this study or leave this study at any 
time. If you choose not to take part or leave this study, it will not affect your regular medical care 
in any way.  
Your study doctor and study staff will be available to answer any questions that you may have 
about taking part in or leaving this study.  
5. 
Study Treatment and Tests  
We will check your health before you start treatment, during your treatment, and for 3 years after 
you begin your maintenance treatment.  
Before You Start Your Treatment  
You will need to have several check-ups and tests to see if you can be in the study. These check-
ups and tests are part of your regular cancer care and would be done even if you were not part of 
this study. These tests include: 
• Medical history and physical exam 
• Blood tests for cell counts 
• Liver and kidney function tests 
• Tests to measure your disease 
• Bone marrow tests  
• Skeletal survey 
• A pregnancy test (if you are a woman able to have children)  
During Your Treatment 
Tumor Cell Collection 
After you join the study, we will collect about 30mL (approximately 2 tablespoons) of bone 
marrow and 50mL (approximately 3 tablespoons) of blood. The bone marrow and blood samples 
will be frozen until it is determined if you will receive the vaccine as part of your treatment. This 
tumor cell collection is not part of your standard of care treatment 
If you are assigned to Treatment Group A after your transplant, your bone marrow will be 
thawed and used to make your vaccine. If you are assigned to Treatment Group B or C, your 


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bone marrow sample will not be used in this study. Your doctor may talk to you about other uses 
for your stored bone marrow samples not related to this study.   
We will also talk with you about giving extra blood and marrow samples for future research (see 
section 17: Blood and Marrow Samples for Future Research). The extra blood and marrow 
samples are also completely optional.  
Initial Treatment for Multiple Myeloma (MM) 
The first step (initial) is standard chemotherapy treatment (chemo). Chemo lowers the number of 
MM cells in your body. Different chemotherapy drugs can be used to treat MM. Your doctor will 
decide which drug or combination of drugs is best for you.  
You will be asked to sign a separate consent form that will explain the side effects of whichever 
drug your doctor chooses. This step may last several months.  
Blood-Forming Cell Collection 
Next, we’ll collect blood-forming cells from your blood stream. This is known as apheresis. 
These cells will be frozen and stored until your transplant day. 
Conditioning Regimen Before Transplant 
The third step is the conditioning regimen, or the chemotherapy, you will get before your 
transplant. The conditioning regimen helps the blood-forming cells start to grow and make new 
cells in your bone marrow (engraft). The regimen includes a chemo drug called melphalan, 
given by intravenous infusion (IV) in your arm.  
Your doctor will decide when you are ready to get melphalan. You will start this treatment step 
no more than 12 months after you start on this study. Melphalan works better for some patients 
than it does for others. If the drug does not work well for you, you may not be able to have a 
transplant. Your doctor will talk to you about other treatment options.  
Infusion of Blood Forming Cells (Transplant) 
On your transplant day (Day 0), your cells will be given to you through your catheter. The cells 
will travel to your bone marrow where they will start to make healthy, new blood cells (engraft).  
Your Treatment Group 
Approximately 2 months after transplant, we will check to see if you’re healthy enough to start 
maintenance treatment. If you are found healthy enough, we will randomize you to 1 of the 3 
treatment groups. “Randomize” means that you will be put in one or another group by chance, 
just like flipping a coin. We will use a computer program to assign you by chance to Treatment 


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Group A, B, or C. You won’t be able to choose your group. Once you are assigned to a group, 
you can’t change to another group. The study doctor can’t change your group either.  
Half of the patients on this study (about 66), will be assigned to Treatment Group A. One-fourth 
of the patients (about 33) will be assigned to Treatment Group B; and one-fourth of patients 
(about 33) will be assigned to Treatment Group C. See the section below, Your Maintenance 
Treatment After Transplant, for a description of the treatments. 
Once all these tests are done, you will be randomized to Treatment Group A, B or C. See Table 
2 for a schedule of these tests.   
If you’re not healthy enough after transplant, you won’t be randomized. If this happens, your 
Follow up on this study is complete 
Your Maintenance Treatment After Transplant 
You will start maintenance treatment about 3 months after your transplant.  
 Treatment Group A: Lenalidomide, Vaccine, and GM-CSF injections 
If you are assigned to Treatment Group A, you will get: lenalidomide, vaccines, and GM-CSF 
injections. 
We will collect extra blood samples to make the vaccine. We will insert a catheter into a large 
vein in your neck or chest. The catheter will collect some blood cells and the rest are returned to 
your body. This process is called leukapheresis. We will use the blood cells and the marrow that 
was collected and frozen to create your vaccine. The vaccine will be made in a laboratory and 
frozen until you’re ready for maintenance treatment. 
You will take lenalidomide as a pill every day for 2 years or until your disease returns. You will 
receive enough pills for 1 cycle (28 days in each cycle) at a time. It’s important to take the pill at 
the same time every day. Be sure to talk with your doctor to figure out a good time to take the 
pill every day.  
You will also receive 3 doses of the vaccine. This will be given to you on the first day of your 2nd, 
3rd, and 4th cycle of lenalidomide. The vaccine is the part of the treatment we are testing in this 
study. This is also called the research treatment.  
With each vaccine, you will also get an injection of GM-CSF in your upper thigh. GM-CSF helps 
to boost the effect of the vaccine. You will receive the GM-CSF injection on the day you get the 
vaccine and every day for 3 days after the vaccine.  This will either be given to you in the clinic 
or you will be taught to give the injections to yourself at home.  
See Table 2 for a timeline of the drugs for Treatment Group A. 


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Table 2: Treatment Group A 
 
 
Treatment 
Group A 
drugs: 
Amount: 
Timeline for Maintenance Treatment Drugs 
Cycle: 
(28 days 
in each 
cycle)  
1  
2 
3  
4 
6 
9  
12 
15 
18 
21 
24 
Lenalidomide 
1 dose every day for 
2 years 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vaccine 
3 doses total 
 
X 
X 
X 
 
 
 
 
 
 
 
GM-CSF 
12 doses total 
 
X (+3 
days) 
X   
(+3 
days) 
X   
(+3 
days) 
 
 
 
 
 
 
 
 
 Treatment Group B: Lenalidomide and GM-CSF 
If you are assigned to Treatment Group B, you will get: lenalidomide and GM-CSF injections.  
You will take lenalidomide every day for 2 years or until your disease returns. You will receive 
the enough pills for 1 cycle (28 days in each cycle) at a time. It’s important to take the pill at the 
same time every day. Be sure to talk with your doctor to figure out a good time to take the pill 
every day.  
You will also get an injection of GM-CSF in upper thigh. You will get the GM-CSF injection 
every day for 4 days starting the first day of cycles 2, 3 and 4. This will either be given to you in 
the clinic or you will be taught to give the injections to yourself at home.  
See Table 3 for a timeline of the drugs for Treatment Group B.  


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Table 3: Treatment Group B 
Treatment 
Group B 
drugs: 
Amount: 
Timeline for Maintenance Treatment Drugs 
 
Cycle: 
(28 days in 
each cycle) 
1  
2 
3  
4 
6 
9  
12 
15 
18 
21 
24 
Lenalidomide 
1 dose every day for 2 
years 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GM-CSF 
12 doses total  
 
X  
(+ 3 
days) 
X  
(+ 3 
days)   
X  
(+ 3 
days)    
 
 
 
 
 
 
 
 
 Treatment Group C: Lenalidomide  
If you are assigned to Treatment Group C, you will take lenalidomide every day for 2 years or 
until your disease returns. You will receive enough pills for 1 cycle (28 days in each cycle) at a 
time. It’s important to take the pill at the same time every day. Be sure to talk with your doctor to 
figure out a good time to take the pill every day.  
 
Maintenance treatment dose (All treatment groups)  
 
How We Will Give You Lenalidomide 
Lenalidomide is available only from a certified pharmacy through the Revlimid REMS® program.  
During maintenance therapy, only a 28-day supply (1 cycle) will be given to you at a time. 
If this is the first time you’ve taken lenalidomide, you’ll have to sign-up, or register, for the 
program. This will include a separate consent process, which calls out the reproductive risks of 
taking this medicine. You’ll have to give your name, address, phone number, birth date, and social 
security number to sign-up for the program. This information will be provided to Celgene 
Corporation and Biologics Incorporated to show you’re taking part in this study.   
After you’re registered, you’ll be counseled at the site or through the program: 
• When you’re first given the drug 
• At least every 28 days while you’re taking it, and 


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• When you stop taking it  
You will be counseled about: 
• Side effects 
• Not sharing lenalidomide (or other study drugs) 
• Risks of exposing a fetus (unborn baby) 
• Donating blood 
• How to take the pills  
We’ll give you the, “Lenalidomide Information Sheet for Patients Enrolled in Clinical Research 
Studies” with each new supply of lenalidomide to remind you of these safety issues. 
How to Take the Lenalidomide Pills 
• Swallow the whole lenalidomide pill with water at the same time each day.  Do not break, 
chew or open the capsules.   
• If you miss a dose, take it as soon as you remember on the same day. If you miss taking your 
dose for the entire day, take your regular dose the next scheduled day (do not take a double 
dose to make up for the missed dose).   
• If you take more than the prescribed dose you should seek emergency medical care if needed 
and contact study staff right away. 
• Women who can become pregnant that care for you should wear gloves whenever they need 
to touch the lenalidomide pills or bottles. 
Checking Your Health 
We will watch your health closely during your maintenance treatment, including how well your 
organs work. We will lower your dose if your organs don’t handle the treatment well.  
We won’t start a new cycle until your organs work well again. If we lower your dose and then 
your organs start working normally, we may raise your dose again.      
We will stop the maintenance treatment if you:  
• 
Have a serious side effect  


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• Have low blood cell counts  
• Are a woman and become pregnant, or there is a chance that you are pregnant 
• Go more than 56 days before starting a new maintenance treatment cycle  
• Don’t follow the study directions, or 
• Choose to leave the study. 
You will need to visit your clinic for several check-ups and tests during your maintenance 
treatment. These tests are shown in Table 4. These assessments are standard of care for 
patients receiving lenalidomide maintenance therapy.   
Table 4. Timeline of Tests Before and During Your Maintenance Treatment 
Tests 
Before 
you‘re 
Random
ized 
Timeline for Maintenance Treatment Tests (CYCLES) 
Timeline for 
Post-Transplant 
Tests (Months) 
1 
2 
3 
4 
6 
9 
12 
15 
8 
21 
24 
6T 
2T 
24T 
Physical 
exam, height, 
and weight 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tests for 
toxicities, and 
infections 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
 
 
Blood tests for 
cell counts, 
liver and 
kidney 
function 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Tests to see 
how much 
cancer you 
still have 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test 
(women able 
to have 
children) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 


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Blood and Bone Marrow Samples 
Throughout the study, we will collect blood and marrow samples to check if the treatments are 
working. These samples are being done as a part of the standard of care disease assessment.  In 
addition, blood and marrow samples are also collected as part of this research study to check 
your immune response to the vaccine and are not part of your standard of care. The maximum 
amount of blood we will collect for this study in one day is 70mL (approximately 4.5 
tablespoons). If more blood is required at a particular time, we will collect blood on 2 or more 
days spread out over 1-2 weeks.  
The maximum amount of bone marrow sample we will collect is 37mL (approximately 2.5 
tablespoons). Table 5 shows the timeline and amount of samples we may collect from you 
during the study. 
Table 5: Timeline and Sample Amount Collected during Study (in approximate tablespoons 
(Tbsp) or teaspoons (tsp)) 
 
6. 
Risks and Discomforts  
You may have side effects while on the study. Side effects can range from mild to serious. The 
risks and discomforts of autologous transplant are the same if you join this study, or if you don’t 
join this study.  
Sample 
When 
you join 
the 
study 
Before 
you’re  
randomized 
Maintenance Cycles 
1 
2 
2 
(day 7) 
3 
4 
4 
(day 7) 
9 
Bone marrow  
2.5 Tbsp 
1 tsp 
 
 
 
 
 
 
2 tsp 
Optional bone 
marrow 
samples for 
future research  
<1 tsp 
<1 tsp 
 
 
 
 
 
 
<1 tsp 
Blood-forming 
cells  
6.5 Tbsp 
*over 10 
days 
2 Tbsp 
4.5  
Tbsp 
4.5  
Tbsp 
4   
Tbsp 
4.5  
Tbsp 
4.5  
Tbsp 
4 Tbsp 
4.5  
Tbsp 
Optional blood 
samples for 
future research  
1.5 tsp 
1.5 tsp 
 
 
 
 
 
 
1.5 tsp 


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You might do better or worse than you would with a standard transplant. Your healthcare team 
may give you medicines to help with side effects like nausea (feeling sick to your stomach). In 
some cases, side effects can last a long time or may never go away.  
Risks of Making the Vaccine  
We will collect bone marrow samples on all patients. 
We will take the bone marrow samples from your hip bone with a large needle. This is called a 
bone marrow aspirate. After, you may feel pain and bleed at the site where the needle went in 
your hip. A small number of patients will have pain that runs down their legs, pain that lasts 
more than a few days, and/or get an infection.  
If you are assigned to Treatment Group A, we will collect blood and bone marrow samples to 
make the vaccine (see Table 5. Timeline and Sample Amount Collected during Study).  
We will also collect extra samples of blood through a catheter in your neck or chest 
(leukaphereis). The risks of leukapheresis include:   
• 
Bleeding 
• 
Punctured lung (hole in lung) 
• 
Infection  
• 
Low blood cell counts. 
Risks of Medications  
The risks of the chemotherapy and maintenance drugs you will get as part of the treatment are 
listed below.  
 


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Melphalan - Conditioning Regimen Drug (Before Transplant) 
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less than 20% of 
patients) 
Rare, but Serious  
(May happen in less than 2% of 
patients) 
• Loss of appetite 
• Constipation 
• Diarrhea 
• Nausea (feeling sick to 
your stomach) 
• Vomiting 
(throwing 
up) 
• Temporary hair loss 
• Sensitive skin 
• Infection 
• Low number of white 
blood cells 
 Low number of platelets 
in 
the 
blood 
with 
increased 
risk 
of 
bleeding  
• Anemia (low number 
of red blood cells) 
• Mouth sores 
• Sore throat (red with 
swelling) 
• Skin breakdown (if 
drug leaks from vein)   
• Changes in heart beat 
• Dizzy 
• Feeling faint  
• Shortness of breath 
• Hepatitis (swelling of the 
liver) 
• Kidney failure 
• Weight loss 
• Feeling weak 
• Allergic reaction 
• Lung infection 
• Scarring of lung tissue  
• Seizure 
• Vasculitis (inflammation of 
blood vessels)   
• Low blood pressure 
• Sweating too much 
• Sterility 
(unable 
to 
have 
children) 
• Liver damage 
• Heart stops beating 
• New cancer of bone marrow 
cells  
 
 
 


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Vaccine  
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less 
than 20% of patients) 
Rare, but Serious  
(May happen in less than 2% of patients) 
• Twitching 
(at 
injection site) 
• Itching (general or 
at injection site) 
• Discomfort 
(at 
injection site) 
• Swelling 
(at 
injection site) 
• Bruising 
at 
the 
injection 
site 
 
 
• Fluid 
retention 
(too much water 
in your body) 
• Fatigue  
• Muscle aches 
• Itching 
• Fever 
• Abnormal 
Antinuclear 
Antibody (ANA) 
blood test   
• Decreased white 
blood cell count 
(including 
neutrophils)  
• Headache 
• Diarrhea 
• Feeling 
light 
headed 
• Flu-like 
symptoms  
• Night sweats 
• Allergic reaction leading to rashes, 
joint pain, kidney, heart or lung 
damage, drop in blood counts  
• Tumor growth or the spread of your 
cancer  
• Infection at the vaccine site 
• Change in thyroid function (fatigue, 
weight gain, sensitivity to cold and 
lack of interest or emotion) 
• Pulmonary embolus (blood clot in 
the lungs)  


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Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less 
than 20% of patients) 
Rare, but Serious  
(May happen in less than 2% of patients) 
• Elevated 
TSH 
(TSH is a thyroid 
hormone) 
• Candida 
infection  
 
 


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GM-CSF (Leukine) 
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less than 20% 
of patients) 
Rare, but Serious  
(May happen in less than 
2% of patients) 
• Fever  
• Chills  
• Nausea 
• Vomiting  
• Diarrhea  
• Fatigue  
• Feeling weak  
• Headache 
• Loss of appetite 
• Flushed face (red or pink 
cheeks)  
• Bone and muscle pain in 
arms, legs and feet  
• Red skin, swelling, or 
itching at needle injection 
site 
• Low blood pressure  
• Shortness of Breath 
• Rapid, irregular heartbeats 
• Feeling 
lightheaded 
or 
dizzy 
• Allergic reaction 
• Fluid in lungs or around 
your heart  
• Changes in vision 
• Low blood cell counts 
• Infection 
at 
needle 
injection site 
 
• Blood clots  
 
 
 
 


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Lenalidomide- Maintenance Treatment Drug 
Likely  
(May happen in more 
than 10% of patients) 
Less Likely  
(May happen in less than 10% of 
patients) 
Rare, but Serious  
(May happen in less than 2% of 
patients) 
• Low number of 
white blood cells 
(with or without 
fever) 
• Anemia; Decrease 
in cells that help 
your blood clot  
• Vision Blurred 
• Diarrhea 
• Pain, Constipation 
• Indigestion 
•  Nausea 
•  Vomiting 
•  Feeling weak and 
unwell 
•  Tired  
• Swelling 
•  Fever 
• Chills  
• Pneumonia 
or 
other infections 
• Sore throat 
• Stuffy nose  
• Weight loss  
• Decreased appetite 
• High blood sugar  
• Abnormally low number of 
blood cells 
• Destruction of red blood cells 
•  Heart attack 
• Abnormal heart beats 
• Heart stops working 
• Low oxygen to heart tissue 
•  Dry mouth 
• Decreased action of intestine 
•  Bile flow from liver slowed or 
blocked 
• Gout 
• Fall 
• Bruise 
• Lowered 
level 
of 
consciousness 
with 
drowsiness, listlessness, and 
apathy 
• Abnormal liver lab tests 
•  Increase in liver protein that 
indicates 
inflammation 
in 
body 
• Loss of fluid 
• Diabetes 
• High uric acid in blood 
• Iron build up in body 
• Swelling of lungs 
 
• Over and underactive thyroid 
 
• 
Severe 
allergic 
conditions 
including: 
Swelling 
under 
skin; Severe skin reactions 
involving lining of the nose, 
mouth, stomach and intestines 
or 
rash 
leading 
to 
the 
separation of the top layer of 
skin  
 
• Tumor Lysis Syndrome (TLS) 
is caused by the sudden, rapid 
death of cancer cells in 
response to treatment. When 
cancer cells die they may spill 
their 
inner 
(intracellular) 
contents, which accumulate 
faster 
than 
they 
can 
be 
eliminated. This debris from 
the cancer cells can change the 
balance of the chemistry of the 
body, which can be dangerous. 
 


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You shouldn’t donate blood while you’re in the study and for 28 days after you stop taking 
lenalidomide. 
• Chemical 
imbalance in blood 
• Pain 
including 
muscles, 
joints, 
and 
non-cardiac 
chest pain 
•  Dizziness 
•  Altered sense of 
taste  
• Headache  
• Eye lens cloudy  
• Abnormal sense of 
touch 
• Pain and decreased 
sensation in nerves  
• Shaking 
• Cough  
• Shortness of breath 
•  Nosebleed  
• Blood clot in lower 
extremities, lungs, 
heart, brain, and 
other organs  
• Dry skin  
• Itching  
• Allergic reaction 
• Feeling sad  
• Not sleeping well 
 
• Muscle weakness 
• Cancer 
• Stroke 
• Tingling of skin 
•  Fainting 
• Moody 
• Kidney failure 
• Breathing disorder  
• Excessive sweating 
• Night sweats 
• Skin redness 
• Swelling of skin filled with 
blood 
• Swelling of blood vessels 
•  High or low blood pressure 
•  Blood 
not 
getting 
to 
extremities 
• Clot in vein 
• Sudden increase in tumor size 
• Rapid death of cancer cells 
where 
the 
accumulating 
contents of dying cancer cells 
cause an imbalance in the 
chemistry of the body which 
can lead to kidney damage 
•  Blood cancer that causes 
decreased number of red blood 
cells, white blood cells, and 
platelets because they do not 
develop normally. 
 


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Risk to the Unborn 
Lenalidomide can cause severe birth defects or death of a baby if the mother or the father is taking 
this medicine at the time of conception or during pregnancy. Because of this, it is extremely 
important that you don’t get pregnant while you’re taking lenalidomide. 
If you’re pregnant or nursing, you’re not eligible to take part in this study. Women who can become 
pregnant must use at least 2 forms of effective birth control while in the study or abstain from all 
reproductive sexual intercourse. Effective birth control is defined as the following:  
1. Refraining from all acts of vaginal sex (abstinence)  
2. Consistent use of birth control pills 
3. Injectable birth control methods (Depo-Provera, Norplant) 
4. Tubal sterilization or male partner who has undergone a vasectomy 
5. Placement of an IUD (intrauterine device) 
6. Use of a cervical cap or a diaphragm with contraceptive jelly and/or condoms with 
contraceptive foam every time you have sex. 
Females taking lenalidomide have blood clots more often. Because of this, you should talk to 
your doctor about birth control pills and hormone replacement therapy, and the risks and 
benefits. 
You do not need to use effective birth control only if you are a woman and cannot have children 
because you: 
 Had a hysterectomy (your ovaries and uterus were removed), OR 
 Had a bilateral oophorectomy (your ovaries were removed), OR 
 Went through menopause (post-menopausal). 
Reproductive Risks  
The drugs used in this research study may damage your reproductive organs, affect your ability to 
have children, or cause birth defects if you take them while you are pregnant or nursing.  
Both women who can become pregnant and their male partners should use birth control while on 
this study and for 28 days after maintenance treatment is stopped. If you or your partner 
becomes pregnant during this study, you must tell the study doctor immediately.  


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Your doctor will discuss the risks to your unborn child and options with you.  
It is important that females who aren’t pregnant or nursing don’t become pregnant while part of 
the study. If you are a woman and become pregnant while on this study, we will stop the 
maintenance treatment drug right away.  
Your study doctor will watch your health closely while you are pregnant and for 30 days after 
the pregnancy ends. 
 
Females who join the study 
If you are female and can become pregnant, you will need to take a pregnancy test before you 
start the study. You should discuss ways to prevent pregnancy while you’re in the study. Women 
who have gone through puberty might experience irregular menstrual cycles or their cycle might 
stop forever. This doesn’t mean that you can’t become pregnant. You must still use 2 effective 
forms of birth control during the study and continue with it for 28 days after you finish 
maintenance treatment.  
Be sure to talk with your doctor about options for fertility planning, like storing your eggs, 
before starting chemotherapy treatment. 
 
Males who join the study 
If you are male, your body may not be able to produce sperm (become sterile). Be sure to talk 
with your doctor about options for fertility planning, like banking your sperm, before starting 
chemotherapy treatment. 
Damage to the vital organs in your body 
Your vital organs include your heart, lungs, liver, intestines, kidneys, bladder and brain. The 
chemotherapy drugs may hurt these organs. You may develop lung problems from chemotherapy 
or an infection.  
Some patients can have veno-occlusive disease (VOD) of the liver. Patients with VOD become 
jaundiced (yellow skin), have problems with their liver, retain too much water (feel swollen and 
uncomfortable), and have stomach swelling and pain.  
If there is serious damage to your vital organs, you may have to stay in the hospital longer or 
return to the hospital after your transplant. Many patients get better, but these complications can 
cause permanent damage to your organs or death. 
Relapse (return) of disease or a new blood cancer 
Your disease may come back even if the transplant was successful at first.  


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We don’t know if new blood cancers are caused by lenalidomide or other drugs. Other research 
looked at the number of patients who got new blood cancers after taking lenalidomide for: 
 Diseases other than multiple myeloma, AND 
 Relapsed multiple myeloma. 
In these studies, no difference was shown in the number of patients who got new blood cancers. 
Researchers for other studies of lenalidomide are still watching patients to see if they get new 
blood cancers. We will give you any new information that we learn about new blood cancers.  
 
 
 


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All Patients Taking Lenalidomide 
 
In order to participate in this study you must register into and follow the requirements of 
the REVLIMID REMS™ program of Celgene Corporation.  This program provides 
education and counseling on the risks of fetal exposure, blood clots and reduced blood counts.  
You will be required to receive counseling every 28 days during treatment with lenalidomide, 
follow the pregnancy testing and birth control requirements of the program that are 
appropriate for you and take telephone surveys regarding your compliance with the 
program.    
 
You have been informed of the risk of birth defects.  If you are female, you agree not to become 
pregnant while taking lenalidomide. For this reason, lenalidomide is provided to patients under a 
special distribution program called REVLIMID REMS TM. 
 
. 
Other Information: 
 
There may be some unknown or unanticipated discomforts or risks associated with this treatment 
in addition to those specified above, but every precaution will be taken to assure your personal 
safety and to minimize discomforts. 
 
Throughout the study, the researchers will tell you of new information that might affect your 
decision to remain in the study. 
 
If you wish to discuss the information above or any other discomforts you may experience, you 
may ask questions now or call your doctor _______________________, the Principal Investigator 
or contact person listed on the front page of this form. 
 
Other Risks  
Serious infections 
It may take many months for your immune system to recover from the chemotherapy and 
maintenance therapy drugs. There is an increased risk of infection during this time when your 
body is healing. We will give you drugs to reduce the chance of infection, but they may not 
work. If you have an infection, you may have to stay in the hospital longer or return to the 
hospital after transplant. Many patients get better, but some infections can cause death. 
Unforeseen Risks  
Chemo drugs can damage your blood cells, which may cause a new blood cancer to grow. We 
know from other MM research studies, that more patients had a second cancer after chemo 
and/or autologous transplant with maintenance lenalidomide than those who didn’t get 
lenalidomide. We don’t know if taking lenalidomide for a long time raises the risk of having a 
second cancer.  


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Other new risks might appear at any time during the study. These risks might be different from 
what is listed in this Consent Form. There may be some unknown or unanticipated discomforts 
or risks associated with this treatment in addition to those specified above, but every precaution 
will be taken to assure your personal safety and to minimize discomforts. 
Other Treatments or Medicines 
Some medicines react with each other, and it is important that you tell the study doctor or staff 
about any other drugs, treatments, or medicines you are taking. This includes non-prescription or 
over-the-counter medicines, vitamins, and herbal treatments.  
It is also important that you tell the study staff about any changes to your medicines while you’re 
in the study. 
For more information about risks and side effects, ask your study doctor. 
7. 
Other Treatments 
Participation in this study is optional. If you choose not to take part, you may still receive non-
transplant treatments or an autologous or an allogeneic transplant to treat your disease. The 
treatment and evaluations you would receive could be very similar to what would receive if you 
join this study.  
Your study doctor will talk with you about your options. If you decide not to participate in this 
study, your medical care will not be affected in any way. 
Your other options may include: 
• Treatment with other drugs, radiation, or a combination of drugs and radiation without 
a transplant. 
• An allogeneic (donor) blood or marrow transplant that is not part of the study, or 
another type of transplant 
• Participation in another clinical trial, if available (check with your doctor) 
• No treatment for your blood cancer at this time 
• Comfort care 
Every treatment option has benefits and risks. Talk with your doctor about your treatment 
choices before you decide if you will take part in this study. 


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8. 
Possible Benefits 
Taking part in this study may or may not make your health better. The information from this 
study will help doctors learn more about drugs used to treat MM.  
This information could help people with multiple myeloma who may need a transplant in the 
future. 
9. 
New Information Available During the Study 
During this research study, the study doctors may learn about new information about the study 
drugs or the risks and benefits of the study. If this happens, they will tell you about the new 
information. The new information may mean that you can no longer participate in the study, or that 
you may not want to continue in the study.  
If this happens, the study doctor will stop your participation in the study and will offer you all 
available care to suit your needs and medical conditions. 
10. 
Privacy, Confidentiality and Use of Information  
Your privacy is very important to us.  The study doctors will make every effort to protect it.  The 
study doctors have a privacy permit to help protect your records if there is a court case.  However, 
some of your medical information may be given out if required by law.  If this should happen, the 
study doctors will do their best to make sure that any information that goes out to others will not 
identify who you are.  
 
Data regarding your clinical situation, including follow-up after 2 years, may be obtained from 
the CIBMTR, which captures information on all US transplants. 
All your medical and demographic information (such as race and ethnicity, gender and 
household income) will be kept private and confidential. (Name of Transplant Center) and the 
organizations listed below will not disclose your participation by any means of communication 
to any person or organization, except by your written request, or permission, or unless required 
by federal, state or local laws, or regulatory agencies.  
The individuals below will have access to your research and medical information. They may use 
this information for inspections or audits to study the outcomes of your treatment. By agreeing to 
participate, you consent to such inspections and to the copying of parts of your records, if 
required by these organizations. 


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We may give out your personal information if required by law. If information from this study is 
published or presented at scientific meetings, your name and other personal information will not 
be used.  
Information about your transplant from your original medical records may be seen or sent to 
national and international transplant registries, including:  
1. /Institution/ 
2. The Center for International Blood and Marrow Transplant Research (CIBMTR) 
3. The National Marrow Donor Program (NMDP) 
4. The Food and Drug Administration (FDA) 
5. The National Institutes of Health (NIH), which include the National Heart, Lung, and Blood 
Institute (NHLBI) and the National Cancer Institute (NCI) 
6. Data and Coordinating Center of the Blood and Marrow Transplant Clinical Trials Network 
(BMT CTN)  
7. Data and Safety Monitoring Board (DSMB), not part of /Institution/ 
8. Study investigators.   
9. Celgene, the manufacturer of lenalidomide 
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. For 
questions about access to your medical records, please contact /name/ at /number. 
11. 
Ending Your Participation 
The study doctor or the study sponsor may stop the study at any time, and we may ask you to 
leave the study. We may ask you to leave the study if you do not follow directions or if you 
suffer from side effects of the treatment. If we ask you to leave the study, the reasons will be 
discussed with you. Possible reasons to end your participation in this study include: 
1. You do not meet the study requirements.  
2. You need a medical treatment not allowed in this study. 
3. The study doctor decides that it would be harmful to you to stay in the study. 


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4. You are having serious side effects. 
5. You become pregnant. 
6. You cannot keep appointments or take study drugs as directed. 
7. The study is stopped for any reason. 
You could have serious health risks if you stop treatment during the conditioning process before 
you receive your transplant. If you stop taking the immune suppressing drugs (see Section 6: 
Risks and Discomforts) too soon after transplant, your body could reject the stem cells or you 
could develop serious complications and possibly die.  
We ask that you talk with the research doctor and your regular doctor before you leave the study. 
Your doctors will tell you how to stop safely and talk with you about other treatment choices.  
If you decide to leave this study after getting the study treatment, or are asked to leave by your 
doctor for medical reasons, you will need to come back to the doctor’s office for tests for your 
safety. Even if you leave the study, the information collected from your participation will be 
included in the study evaluation, unless you specifically ask that it not be included. 
12. 
Physical Injury as a Result of Participation  
It is important that you tell your doctor, __________________ [investigator's name(s)] or study 
staff if you feel that you have been injured because of taking part in this study.  You can tell the 
doctor in person or call him/her at __________________ [telephone number]. 
You will get all available medical treatment if you are injured from taking part in this study. You 
and/or your health plan will be charged for this treatment. There is no provision for free medical 
care or monetary compensation from the study sponsor, The National Institutes of Health or the 
study contributor, Celgene Corporation.  
In case you are injured in this study, you do not lose any of your legal rights to ask for or receive 
payment by signing this form. 
13. 
Compensation or Payment 
You will not be paid for your participation in this research study. You will not get compensation or 
reimbursement for any extra expenses (travel, meals, etc.) you may have through your participation 
on this trial.  
Taking part in this study might help researchers make products to sell. Celgene or others may 
profit from these products. You will not have any rights to the patents or discoveries that could 
happen from this research, and you will not receive any payments from it. 
 


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14. 
 Costs and Reimbursements 
Most of the visits for this research study are standard medical care for your autologous transplant 
and will be billed to your insurance company. You and/or your health plan/insurance company 
will need to pay for some or all of the costs of standard treatment in this study.    
 
You or your insurance will not be charged for blood and marrow samples for research on this study. 
You will not pay for any extra tests that are being done for the study. Lenalidomide will be provided 
to you for free for two years. After that your doctor will discuss what treatment is best for you.   
Some health plans will not pay these costs for people taking part in studies. Check with your 
health plan or insurance company to find out if they will pay. 
For questions about your costs, financial responsibilities, and/or medical insurance coverage for 
your transplant and this study, please contact /Center/ Financial Counselor at /Number/. 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage. You can 
print a copy of the “Clinical Trials and Insurance Coverage” information from this Web site. 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy. 
15. 
For More Information 
If you need more information about this study, or if you have problems while taking part in this 
study, you can contact the study doctor or his/her staff.  
They can be reached at the telephone numbers listed here: 
[Insert name and contact details] 
16. 
Contact Someone about Your Rights 
If you wish to speak to someone not directly involved in the study, or if you have any complaints 
about any aspect of the project, the way it is being conducted or any questions about your rights as a 
research participant, then you may contact:  
[Insert appropriate contact details] 
The ethical aspects of this study have been reviewed and approved by [name of IRB]. 


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17. 
Blood and Bone Marrow Samples for Future Research (Optional)  
This section of the informed consent form is about future research studies that will use blood and 
bone marrow samples from people who are taking part in the main study. You may choose to 
give samples for these future research studies if you want to. You can still be a part of the main 
study even if you say 'no' to give samples for future research studies. 
Researchers are trying to learn more about how the human body processes the drugs used for 
transplant and how the body recovers after transplant. This research is meant to gain knowledge 
that may help people in the future and make transplants even more successful.  
If you agree to provide blood and bone marrow samples, here is what will happen: 
• We will collect 3 extra blood samples at the same time you have routine blood tests done  
(Table 3):  
o Around the time of your enrollment 
o About 2 months after your transplant  
o Before the start of your 9th cycle of maintenance therapy  
• The amount of blood collected from you is about 1 teaspoon (6 ml) each time.  
• We will collect 3 bone marrow samples at the same time you have routine bone biopsies done. 
The amount of tissue collected from you is about a half of a teaspoon (3 mL) each time. We 
will collect samples at 3 different dates in the study (see Table 3): 
o Around the time of your enrollment 
o About 2 months after your transplant  
o Before the start of your 9th cycle of maintenance therapy.  
• The blood and bone marrow samples will be sent to the BMT CTN Repository for processing 
and storage. A repository is a place that protects, stores and sends out samples for approved 
research studies. All research samples will be given a bar code that cannot be linked to you by 
future researchers testing your samples. 
• Materials stored in the Repository will be used mainly by clinicians and researchers in the 
BMT CTN network. In the future, the unused research samples and clinical data will be made 
available outside of this network.  


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• Researchers can apply to study the materials stored in the Repository. The BMT CTN Steering 
Committee and/or the BMT CTN Executive Committee must approve each request before they 
will share samples or information with researchers. This is to make sure that the investigators 
requesting the samples are qualified, and that the research is of high quality. 
• DNA from your stored blood samples might be used in genome-wide association (GWA) 
studies for a future project either done or supported by the National Institutes of Health (NIH). 
Genome-wide association studies are a way for scientists to find genes that have a role in 
human disease or treatment. Each study can look at hundreds of thousands of genetic changes 
at the same time. 
If your coded samples are used in such a study, the researcher is required to add your test 
results and sample information into a shared, public research database. This public 
database is called the NIH Genotype and Phenotype Database and it is managed by the 
National Center for Biotechnology Information (NCBI). The NCBI will never have any 
information that would identify you, or link you to your information or research samples.  
Some general things you should know about letting us store your blood samples for research are: 
1. We will only store samples from people who give us permission. 
2. Research is meant to gain knowledge that my help people in the future. You will not get any 
direct benefit from taking part. Additionally, you or your doctor will not be given results and 
they will not be added to your medical record. 
3. A possible risk is the loss of confidentiality about your medical information. We will use safety 
measures with both your samples and clinical information to make sure that your personal 
information will be kept private. The chance that this information will be given to someone 
else is extremely small.  
4. Your blood will be used only for research and will not be sold. The research done with your 
blood may help to develop new products in the future. You will not get paid for any samples 
or for any products that may be developed from current or future research. 
You can change your mind at any time about allowing us to use your samples and health 
information for research.  
We ask that you contact [Principal Investigator] in writing and let him/her know you do not 
want us to use your research samples or health information for research. His/her mailing address 
is on the first page of this form. However, samples and information that have already been shared 
with other researchers cannot be taken back or destroyed.  


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Making Your Choice  
Please read each sentence below and think about your choice. After reading each sentence, 
please indicate your choice below. If you have any questions, please talk to your doctor or nurse, 
or call our research review board at _[contact information].  
No matter what you decide to do, it will not affect your care. 
 
 


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Statement of Consent for Research Samples 
The purpose of storing blood and tissue samples, the procedures involved, and the risks and 
benefits have been explained to me. I have asked all the questions I have at this time and I have 
been told whom to contact if I have more questions. I have been told that I will be given a signed 
copy of this consent form to keep. 
I understand that I do not have to allow the use of my blood and tissue for research. If I decide to 
not let you store research samples now or in the future, it will not affect my medical care in any 
way. 
I voluntarily agree that my blood, tissue, and information can be stored indefinitely by the BMT 
CTN and/or NHLBI Repositories for research to learn about, prevent, or treat health problems. I 
also understand that my DNA and health information may or may not be used in genome-wide 
association studies. 
Blood 
 I agree to allow my blood samples to be stored for research. 
 I do not agree to allow my blood samples to be stored for research. 
Bone marrow 
 I agree to allow my bone marrow samples to be stored for research. 
 I do not agree to allow my bone marrow samples to be stored for research. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
 
 


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Health Insurance Portability and Accountability Act 1 (HIPAA1) Authorization to use and 
disclose individual health information for research purpose 
 
• Purpose: 
As a research participant, I authorize the Principal Investigators and the researcher’s staff to use 
and disclose my individual health information for the purpose of conducting the research study:  
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed 
by Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination with 
Dendritic Cell /Myeloma Fusions 
 
• Individual Health Information to be Used or Disclosed:  
My individual health information that may be used or disclosed to do this research includes:  
1. Demographic information (for example, date of birth, sex, weight).  
2. Medical history (for example, diagnosis, complications with prior treatment). 
3. Findings from physical exams. 
4. Laboratory test results obtained at the time of work up and after transplant (for example, blood 
tests, biopsy results).  
• Parties Who May Disclose My Individual Health Information:  
The researcher and the researcher’s staff may collect my individual health information from: 
[List hospitals, clinics or providers from which health care information can be requested]. 
• Parties Who May Receive or Use My Individual Health Information:  
The individual health information disclosed by parties listed in item c and information disclosed 
by me during the course of the research may be received and used by the following parties: 
1. Dr. David Avigan, Co-Principal Investigator  
2. Dr. Nina Shah, Co-Principal Investigator  
3. Dr. David Chung, Co-Principal Investigator 
 
1 HIPAA is the Health Insurance Portability and Accountability Act of 1996, a federal law related to privacy of health 
information 


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4. Celgene, its collaborators or designees 
5. National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute 
(NCI), both of the National Institutes of Health (NIH),  
6. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Data and 
Coordinating Center 
7. U.S. government agencies that are responsible for overseeing research such as the Food 
and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) 
8. U.S. government agencies that are responsible for overseeing public health concerns such 
as the Centers for Disease Control (CDC) and federal, state and local health departments. 
• Right to Refuse to Sign this Authorization:  
I do not have to sign this Authorization.  If I decide not to sign the Authorization, I will not be 
allowed to participate in this study or receive any treatment related to research that is provided 
through the study.   
My decision not to sign this authorization will not affect any other treatment, payment, or 
enrollment in health plans or eligibility for benefits.   
• Right to Revoke:   
I can change my mind and withdraw this authorization at any time by sending a written notice to 
the Principal Investigator to inform the researcher of my decision.  
If I withdraw this authorization, the researcher may only use and disclose the protected health 
information already collected for this research study.  No further health information about me 
will be collected by or disclosed to the researcher for this study. 
• Potential for Re-disclosure:  
My individual health information disclosed under this authorization may be subject to re-
disclosure outside the research study and no longer protected. 
Examples include potential disclosures for law enforcement purposes, mandated reporting or 
abuse or neglect, judicial proceedings, health oversight activities and public health measures. 
• Genetic Information Nondiscrimination Act (GINA)  
A new federal law (2009), called the Genetic Information Nondiscrimination Act (GINA) 
generally makes it illegal for health insurance companies, group health plans, and employers of 15 
or more persons to discriminate against you based on your genetic information.  


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Health insurance companies and group health plans may not request your genetic information that 
we get from this research. This means that they must not use your genetic information when 
making decisions regarding insurability. Be aware that this new federal law will not protect you 
against genetic discrimination by companies that sell life insurance, disability insurance, or long-
term care insurance. 
• This authorization does not have an expiration date. 
 
 


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TITLE: Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant 
Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
PROTOCOL NUMBER: BMT CTN #1401 
PRINCIPAL INVESTIGATOR:  
Name: 
Address: 
Email:  
Phone:  
 
 
 
 
 
 
 
 
 
 
 
Fax:  
I have read and understood this Consent Form. The nature and purpose of the research study has 
been explained to me. 
• I have had the chance to ask questions, and understand the answers I have been given. I 
understand that I may ask questions at any time during the study. 
• I freely agree to be a participant in the study. 
• I understand that I may not directly benefit from taking part in the study. 
• I understand that, while information gained during the study may be published, I will not be 
identified and my personal results will stay confidential. 
• I have had the chance to discuss my participation in this research study with a family member 
or friend. 
• I understand that I can leave this study at any time, and doing so will not affect my current care 
or prevent me from receiving future treatment. 
• I understand that I will be given a copy of this signed consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant Name 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
I certify that I have provided a verbal explanation of the details of the research study, including 
the procedures and risks. I believe the participant has understood the information provided. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Counseling Physician 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Counseling Physician 
 
    
 
 
 
Date 


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INFORMED CONSENT DOCUMENTS FOR BMT CTN 1401 OPTIONAL 
CORRELATIVE LABORATORY STUDY PARTICIPATION 
 
 


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Informed Consent to Participate in Research 
 
Optional Correlative Laboratory Study Participation for patients enrolled on BMT CTN 1401 
entitled “Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant 
Followed by Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination 
with Dendritic Cell /Myeloma Fusions” 
 
 
 
Your Name:   
__________________________ 
 
Study Title: 
Optional Correlative Laboratory Study Participation for patients enrolled on 
BMT CTN 1401 “Phase II Multicenter Trial of Single Autologous 
Hematopoietic Cell Transplant Followed by Lenalidomide Maintenance for 
Multiple Myeloma with or without Vaccination with Dendritic Cell 
/Myeloma Fusions” 
 
 
Parent Study Title:  Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma 
with or without Vaccination with Dendritic Cell /Myeloma Fusions  
 
Protocol:  
BMT CTN 1401 v4.0 
 
Principal  
Investigator:  
Insert local PI information  
 
Sponsor:  
The National Institutes of Health (NIH) is sponsoring this study by 
providing financial support for the coordination of this study through the 
Blood and Marrow Transplant Clinical Trials Network (BMT CTN).  
 
 
 
 


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1. 
Introduction  
We invite you to participate in one or both of the optional correlative laboratory studies associated 
with the BMT CTN 1401 trial.  You’re being asked to join these optional studies because you were 
enrolled on BMT CTN 1401 and are being evaluated for randomization. Participation in these 
studies will involve you agreeing to allow investigators to either use previously collected research 
samples required by the primary trial and/or provide additional blood and marrow samples during 
your participation on the primary BMT CTN 1401 trial.   
It is your choice to participate in these optional studies and to provide additional blood or bone 
marrow samples for this optional research. Even if you decide not to participate in these optional 
research studies, you can still participate on the primary BMT CTN 1401 study.  
This Consent Form will tell you about the purpose of the optional research studies, the clinical 
samples needed for this research, the possible risks and benefits, other options available to you, 
and your rights as a research participant. 
Everyone who takes part in research at [insert facility name] should know that: 
 Being in any research study is voluntary. 
 You will not directly benefit from being in the study. Knowledge we gain from this study may 
benefit others. 
 If you give blood and bone marrow samples for research, you can change your mind at any 
time. The blood and marrow samples that you already provided will be used for research but 
no further research will be done after you change your mind.  
 If you decide to quit the study, it will not affect your at [insert name of facility or institution]. 
 Please ask the study staff questions about anything that you do not understand, or if you would 
like to have more information. 
 You can ask questions now or any time during the study. 
 Please take the time you need to talk about the study with your doctor, study staff, and your 
family and friends. It is your decision to provide samples for research. If you decide to join, 
please sign and date the end of the Consent Form. 
 
2. 
Study Background 
The National Institutes of Health (NIH), through the Blood and Marrow Transplant Clinical Trials 
Network (BMT CTN), are providing staff support and money for this research study. The BMT 
CTN and the NIH will make decisions about how to manage the study.  


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For participation in one or both of these optional research studies, you will be asked to provide 
blood or bone marrow samples that will be shipped to a lab for further testing. Your doctor will 
discuss the research studies that are available to you as a part of this study.  
 
3. 
Study Purpose 
We are conducting these additional laboratory studies to further our understanding and knowledge 
about how the treatments you receive as part of the parent study (BMT CTN 1401) work.  
4. 
Rights to Ask Questions and/or Withdraw  
You have the right to ask questions about the study at any time. If you have questions about your 
rights as a participant or you want to leave the study, please contact:  
[insert contact info] 
Participating in either of these optional research studies is voluntary. You can choose not to be in 
these studies or leave either study at any time. However, some of the blood and bone marrow 
already donated may have already been used for research. If you choose not to take part or leave 
one of these studies, it will not affect your regular medical care in any way.  
Your study doctor and study staff will be available to answer any questions that you may have 
about taking part in or leaving these optional research studies.  
5. 
Study Treatment and Tests  
There are two different research studies associated with the primary parent trial (BMT CTN 1401) 
that you are participating in.  You doctor will explain which studies you are being asked to 
participate on at the end of this consent form and you will be presented with one or two more 
informed consent forms. These consent forms will go over the study tests in detail. The schedule 
of blood or bone marrow collections will depend on which studies you agree to participate in.  If 
you would like to participate in this optional research, you will be asked to sign this informed 
consent form along with the other consent form(s) associated with the optional research your 
doctor is asking you to be a part of.   
If you agree to participate on either of these research studies, your blood and or bone marrow will 
be shipped to laboratories at either Beth Israel Deaconess Medical Center and/or the University of 
Wisconsin. All research samples will be given a bar coded ID that cannot be linked to you by the 
researchers testing your samples. Samples will not be used for purposes other than those specified 
in this consent form.  


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6. 
Risks and Discomforts  
Information about your demographics, disease, and response to the treatments you receive as part 
of the main clinical study may be provided to the investigators listed in the privacy portion of this 
consent form. This information is used to help the investigators understand how the research 
samples correlate to your disease. There are no major risks to having your blood or bone marrow 
drawn. It can be uncomfortable to have your blood and bone marrow taken and it can sometimes 
leave a bruise. You might faint, but this is unlikely to happen. Only trained people will take your 
blood and bone marrow.  
A possible risk is the loss of confidentiality about your medical information. We will use safety 
measures with both your samples and clinical information to make sure that your personal 
information will be kept private. The chance that this information will be given to someone else is 
extremely small.  
For more information about risks and side effects, ask your study doctor. 
7. 
Other Treatments 
Participation in this study is optional. The alternative to participating on this research sample study, 
is not agreeing to provide blood or bone marrow samples. If you choose not to take part, your 
treatment on BMT CTN 1401 will not be affected 
This information could help people with multiple myeloma who may need a transplant in the future 
8. 
Possible Benefits 
Taking part in this study will not make your health better. You will not get any direct benefit from 
taking part in this study. The information from this study will help doctors and researchers learn 
more about how well unrelated transplant works as treatment for people with a blood disease. 
9. 
Privacy, Confidentiality and Use of Information  
Your privacy is very important to us.  The study doctors will make every effort to protect it.  The 
study doctors have a privacy permit to help protect your records if there is a court case.  However, 
some of your medical information may be given out if required by law.  If this should happen, the 
study doctors will do their best to make sure that any information that goes out to others will not 
identify who you are.  
 
Data regarding your clinical situation, including follow-up after 2 years, may be obtained from the 
CIBMTR, which captures information on all US transplants. 
All your medical and demographic information (such as race and ethnicity, gender and household 
income) will be kept private and confidential. (Name of Transplant Center) and the organizations 
listed below will not disclose your participation by any means of communication to any person or 


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organization, except by your written request, or permission, or unless required by federal, state or 
local laws, or regulatory agencies.  
The individuals below will have access to your research and medical information. They may use 
this information for inspections or audits to study the outcomes of your treatment. By agreeing to 
participate, you consent to such inspections and to the copying of parts of your records, if required 
by these organizations. 
We may give out your personal information if required by law. If information from this study is 
published or presented at scientific meetings, your name and other personal information will not 
be used.  
Information about your transplant, research samples, and treatment on BMT CTN 1401 from your 
original medical records may be seen or sent to national and international transplant registries, 
including:  
1. /Institution/ 
2. The Center for International Blood and Marrow Transplant Research (CIBMTR) 
3. The National Marrow Donor Program (NMDP) 
4. The Food and Drug Administration (FDA) 
5. The National Institutes of Health (NIH), which include the National Heart, Lung, and Blood 
Institute (NHLBI) and the National Cancer Institute (NCI) 
6. Data and Coordinating Center of the Blood and Marrow Transplant Clinical Trials Network 
(BMT CTN)  
7. Data and Safety Monitoring Board (DSMB), not part of /Institution/ 
8. Study investigators.   
9. Dr. David Avigan and laboratory staff at Beth Israel Deaconess Medical Center/Dana Farber 
Cancer Institute   
10. Dr. Fotis Asimakopoulos and laboratory staff at University of Wisconsin and at Medical 
College of Wisconsin.   
11. Celgene, the manufacturer of lenalidomide 
DNA from your blood samples might be used in genome-wide association (GWA) studies for a 
future project either done or supported by the National Institutes of Health (NIH). Genome-wide 


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association studies are a way for scientists to find genes that have a role in human disease or 
treatment. Each study can look at hundreds of thousands of genetic changes at the same time. 
If your coded samples are used in such a study, the researcher is required to add your test 
results and sample information into a shared, public research database. This public database is 
called the NIH Genotype and Phenotype Database and it is managed by the National Center 
for Biotechnology Information (NCBI). The NCBI will never have any information that would 
identify you, or link you to your information or research samples.  
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.  
For questions about access to your medical records, please contact /name/ at /number. 
10. 
Ending Your Participation 
The study doctor or the study sponsor may stop the study at any time, and we may ask you to leave 
the study. We may ask you to leave the study if you do not follow directions or if you suffer from 
side effects of the treatment. If we ask you to leave the study, the reasons will be discussed with 
you. Possible reasons to end your participation in this study include: 
1. You do not meet the study requirements.  
2. The study doctor decides that it would be harmful to you to stay in the study. 
3. You become unable to donate blood or bone marrow for any reason  
4. The study is stopped for any reason. 
Even if you leave the study, the information collected from your participation will be included in 
the study evaluation, unless you specifically ask that it not be included. 
11. 
Physical Injury as a Result of Participation  
It is important that you tell your doctor, __________________ [investigator's name(s)] or study 
staff if you feel that you have been injured because of taking part in this study.  You can tell the 
doctor in person or call him/her at __________________ [telephone number]. 
You will get all available medical treatment if you are injured from taking part in this study. You 
and/or your health plan will be charged for this treatment. There is no provision for free medical 
care or monetary compensation from the study sponsor, The National Institutes of Health or the 
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In case you are injured in this study, you do not lose any of your legal rights to ask for or receive 
payment by signing this form. 
12. 
Payment and Study Costs  
You will not be paid for donating your blood and/or bone marrow.. You will not be paid  or 
reimbursed for any extra expenses (travel, meals, etc.) you may have to donate blood and bone 
marrow. 
Your blood and marrow will be used only for research and will not be sold. The research done 
with your blood may help to develop new products in the future. You will not get paid for any 
samples or for any products that may be developed from current or future research. 
The visits for this research study are standard medical care for your autologous transplant and will 
be billed to your insurance company. You and/or your health plan/insurance company will need to 
pay for some or all of the costs of standard treatment in this study.  
 
For questions about your costs, financial responsibilities, and/or medical insurance coverage for 
your transplant and this study, please contact /Center/ Financial Counselor at /Number/. 
 
13. 
For More Information 
If you need more information about these studies, or if you have problems while taking part in either 
of these studies, you can contact the study doctor or his/her staff.  
They can be reached at the telephone numbers listed here: 
[Insert name and contact details] 
14. 
Contact Someone about Your Rights 
If you wish to speak to someone not directly involved in the study, or if you have any complaints 
about any aspect of the project, the way it is being conducted or any questions about your rights as a 
research participant, then you may contact:  
[Insert appropriate contact details] 
The ethical aspects of this study have been reviewed and approved by [name of IRB]. 
Health Insurance Portability and Accountability Act 1 (HIPAA2) Authorization to use and 
disclose individual health information for research purpose 
 
 
2 HIPAA is the Health Insurance Portability and Accountability Act of 1996, a federal law related to privacy of health 
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• Purpose: 
As a research participant, I authorize the Principal Investigators and the researcher’s staff to use 
and disclose my individual health information for the purpose of conducting either of the research 
studies described in this consent:  
Optional Correlative Laboratory Study Participation for patients enrolled on “Phase II 
Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed by 
Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination with Dendritic 
Cell /Myeloma Fusions” 
 
• Individual Health Information to be Used or Disclosed:  
My individual health information that may be used or disclosed to do this research includes:  
1. Demographic information (for example, date of birth, sex, weight).  
2. Medical history (for example, diagnosis, complications with prior treatment). 
3. Findings from physical exams. 
4. Laboratory test results obtained at the time of work up and after transplant (for example, blood 
tests, biopsy results).  
• Parties Who May Disclose My Individual Health Information:  
The researcher and the researcher’s staff may collect my individual health information from: 
[List hospitals, clinics or providers from which health care information can be requested]. 
• Parties Who May Receive or Use My Individual Health Information:  
The individual health information disclosed by parties listed in item c and information disclosed 
by me during the course of the research may be received and used by the following parties: 
1. Dr. David Avigan, Co-Principal Investigator  
2. Dr. Nina Shah, Co-Principal Investigator  
3. Dr. David Chung, Co-Principal Investigator 
4. Laboratory staff at Beth Israel Deaconess Medical Center/Dana Farber Cancer Institute   
5. Dr. Fotis Asimakopoulos and laboratory staff at University of Wisconsin and at Medical 
College of Wisconsin.   


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6. Celgene, its collaborators or designees 
7. National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute 
(NCI), both of the National Institutes of Health (NIH),  
8. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Data and 
Coordinating Center 
9. U.S. government agencies that are responsible for overseeing research such as the Food 
and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) 
10. U.S. government agencies that are responsible for overseeing public health concerns such 
as the Centers for Disease Control (CDC) and federal, state and local health departments. 
• Right to Refuse to Sign this Authorization:  
I do not have to sign this Authorization.  If I decide not to sign the Authorization, I will not be 
allowed to participate in this study. 
My decision not to sign this authorization will not affect any other treatment, payment, or 
enrollment in health plans or eligibility for benefits.   
• Right to Revoke:   
I can change my mind and withdraw this authorization at any time by sending a written notice to 
the Principal Investigator to inform the researcher of my decision.  
If I withdraw this authorization, the researcher may only use and disclose the protected health 
information already collected for this research study.  No further health information about me will 
be collected by or disclosed to the researcher for this study. 
• Potential for Re-disclosure:  
My individual health information disclosed under this authorization may be subject to re-
disclosure outside the research study and no longer protected. 
Examples include potential disclosures for law enforcement purposes, mandated reporting or abuse 
or neglect, judicial proceedings, health oversight activities and public health measures. 
• Genetic Information Nondiscrimination Act (GINA)  
A federal law (2009), called the Genetic Information Nondiscrimination Act (GINA) generally 
makes it illegal for health insurance companies, group health plans, and employers of 15 or more 
persons to discriminate against you based on your genetic information.  


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Health insurance companies and group health plans may not request your genetic information that 
we get from this research. This means that they must not use your genetic information when 
making decisions regarding insurability. Be aware that this federal law will not protect you against 
genetic discrimination by companies that sell life insurance, disability insurance, or long-term care 
insurance. 
• This authorization does not have an expiration date. 
 
 


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TITLE: Optional Correlative Laboratory Study Participation for Patients Enrolled on BMT 
CTN 1401 entitled, “Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions” 
PROTOCOL NUMBER: BMT CTN #1401 
PRINCIPAL INVESTIGATOR:  
Name: 
Address: 
Email:  
Phone:  
 
 
 
 
 
 
 
 
 
 
 
Fax:  
I have read and understood this Consent Form. The nature and purpose of the research study has 
been explained to me. 
• I have had the chance to ask questions, and understand the answers I have been given. I 
understand that I may ask questions at any time during the study. 
• I freely agree to be a participant in the study. 
• I understand that I may not directly benefit from taking part in the study. 
• I understand that, while information gained during the study may be published, I will not be 
identified and my personal results will stay confidential. 
• I have had the chance to discuss my participation in this research study with a family member 
or friend. 
• I understand that I can leave this study at any time, and doing so will not affect my current care 
or prevent me from receiving future treatment. 
• I understand that I will be given a copy of this signed consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant Name 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
 


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I certify that I have provided a verbal explanation of the details of the research study, including 
the procedures and risks. I believe the participant has understood the information provided. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Counseling Physician 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Counseling Physician 
 
    
 
 
 
Date 
 
 


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Supplemental Informed Consent Form to Participate in Research  
 
Study Title: Characterization of the T cell immune response and myeloma genomic signature as 
predictors of immunologic and clinical response 
 
Parent Study Title: Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
 
 
A. What is this Document?  
The purpose of this document is to give you more information on the specific research sample 
study your physician is asking for your consent to join. This document will explain further 
details of what samples are collected, why they are being collected, and where they are being 
sent. Details about risks, study participation, and your rights are explained in the primary 
informed consent form that your doctor already presented to you.  
B. Why am I here? 
You are being asked to participate in this study because you are participating on BMT CTN 
1401 and are approaching the randomization portion of the parent study.  
If you give us your permission, we would like to collect extra samples of your blood and 
marrow at several time points during your participation on the parent trial. 
C. Why are you doing this study? 
We are collecting samples to learn more about how your body responds to the treatment on the 
parent trial. We will collect samples on 60 patients across all treatment arms. Your 
participation on this study is expected to last up to 3 years.  
D. What will happen to me if I join the study? 
If you say you want to be in the study, we will ask you for the following samples:  
• Bone Marrow Aspirate Samples: About 1 teaspoon of bone marrow will be collected at the 
following timepoints:  
o Just before you are randomized on the parent trial (about 50-80 days after your bone 
marrow transplant). This is one teaspoon more of bone marrow being collected at 
the  time of a required bone marrow aspirate being performed as part of the primary 
trial.  
o Just before you start your 9th Cycle of Maintenance (about 1 year after your bone 
marrow transplant). This is one teaspoon more of bone  marrow being collected at 


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the time of a required bone marrow aspirate being performed as part of the primary 
trial.   
o If your disease comes back, an additional bone marrow aspirate sample will be 
collected at that time. This is an additional aspirate not required as part of the 
primary trial. 
• Blood Samples:  
o About 2 teaspoons of blood will be collected just before you start Cycles 1, 2, and 
4 of Maintenance Therapy. This is extra  blood being collected at the time of  a 
required blood sample collection being performed as part of the primary trial. 
o If your disease comes back, about 10 teaspoons of blood will be collected at that 
time. This is an additional collection not required as part of the primary trial.  
• We will also use a portion of the bone marrow aspirate sample that you already provided 
at the time of agreeing to participate on the BMT CTN 1401 study as part of this research 
sample  study.  
 
E. Where will my samples be sent? 
Your samples will be sent to a laboratory at Beth Israel Deaconess Medical Center.  
All research samples will be tied to a number. This number will not be linked to your name or 
other identifying information.  
 
 


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Statement of Consent for Research Samples  
The purpose of providing blood and bone marrow samples, the procedures involved, and the risks 
and benefits have been explained to me. I have asked all the questions I have at this time and I 
have been told whom to contact if I have more questions. I have been told that I will be given a 
signed copy of this consent form to keep. 
I understand that I do not have to allow the use of my blood and bone marrow for this research. If 
I decide to not let collect research samples now or in the future, it will not affect my medical care 
in any way. 
I voluntarily agree that my blood, bone marrow, and information can be used for the study entitled 
“Characterization of the T cell immune response and myeloma genomic signature as predictors 
of immunologic and clinical response”. I also understand that my DNA and health information 
may or may not be used in genome-wide association studies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
 
 


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Supplemental Informed Consent Form to Participate in Research  
 
Study Title: VCAN Proteolysis: Investigation of a Potential Novel Immune Biomarker in 
Myeloma 
 
Parent Study Title: Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
 
 
A. What is this Document?  
The purpose of this document is to give you more information on the bone marrow sample 
study your physician is asking for your consent to join. This document will explain further 
details of what samples are collected, why they are being collected, and where they are being 
sent. Details about risks, study participation, and your rights are explained in the primary 
informed consent form that your doctor already presented to you. If you want to participate in 
this research you will be asked to sign the primary informed consent form as well as this 
document.  
B. Why am I here? 
You are being asked to participate in this study because you are participating on BMT CTN 
1401 and are approaching the randomization portion of the parent study.  
If you give us your permission, we would like to send a portion of a clinical bone marrow  
sample to study investigators at the time of randomization. The sample we are asking for is 
part of a clinical sample collection procedure you will have already undergone as part of the 
parent trial. We will not collect any additional samples as part of this study. We are asking for 
your consent to ship a portion of this clinical bone marrow  sample to a different lab and study 
it for research purposes.  
C. Why are you doing this study? 
We are collecting bone marrow samples to learn more about how your body responds to the 
treatment on the parent trial. We will collect samples on 20 patients across all treatment arms. 
Your participation on this study is expected to last 1 month. We may use data collected on the 
parent trial for this study for up to 3 years after you are randomized on the parent trial.  
D. What will happen to me if I join the study? 
The bone marrow sample we are asking for is part of a procedure you will already undergo as 
part of the parent trial. We will not collect any additional samples as part of this study. We are 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
54 
asking for your consent to ship a portion of this bone marrow sample to a different lab and 
study it for research purposes.  
If you say you want to be in the study, we will not collect any additional samples. The clinical 
pathology lab at /Institution/ will cut a small piece of your bone marrow biopsy that you 
provided for the BMT CTN 1401 parent trial and ship it to investigators at University of 
Wisconsin. If the lab is not able to obtain enough sample from the bone marrow biopsy you 
provided for the parent trial (BMT CTN 1401), you will not be asked to provide additional 
samples and you will be removed from the study.  
E. Where will my samples be sent? 
Your samples will be sent to a laboratory at University of Wisconsin.  
All research samples will be tied to a number. This number will not be linked to your name or 
other identifying information.  


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
55 
Statement of Consent for Research Samples  
The purpose of providing bone marrow biopsy samples, the procedures involved, and the risks and 
benefits have been explained to me. I have asked all the questions I have at this time and I have 
been told whom to contact if I have more questions. I have been told that I will be given a signed 
copy of this consent form to keep. 
I understand that I do not have to allow the use of my bone marrow biopsy samples for this 
research. If I decide to not let collect research samples now or in the future, it will not affect my 
medical care in any way. It will also not affect my participation in the Parent Trial.  
I voluntarily agree that my bone marrow biopsy samples and information can be used for the study 
entitled “VCAN Proteolysis: Investigation of a Potential Novel Immune Biomarker in Myeloma”. 
I also understand that my DNA and health information may or may not be used in genome-wide 
association studies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
 

SAP_003.pdf: 
BMT CTN 1401/ Myeloma Vaccine 
 
         
    
 
 
 
          Version 1.0 
Statistical Analysis Plan 
 
07June2019 
THIS DOCUMENT IS CONFIDENTIAL AND PRIVILEGED 
 
 
 
 
 
 
BMT CTN 1401/ MYELOMA VACCINE 
PHASE II MULTICENTER TRIAL OF SINGLE AUTOLOGOUS HEMATOPOIETIC 
CELL TRANSPLANT FOLLOWED BY LENALIDOMIDE MAINTENANCE FOR 
MULTIPLE MYELOMA WITH OR WITHOUT VACCINATION WITH DENDRITIC 
CELL/MYELOMA FUSIONS 
 
NCT#: NCT02728102 
Statistical Analysis Plan  
Version 1.0 
June 07, 2019 
 
 
Sponsored by the National Institutes of Health 
National Heart, Lung, and Blood Institute 
National Cancer Institute 


NCT02728102


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Table of Contents 
 
1. 
General Review of Study Design and Process ................................................................... 3 
1.1 
Study Objectives ......................................................................................................................... 3 
1.1.1 
Primary Objective ................................................................................................................... 3 
1.1.2 
Secondary Objectives............................................................................................................ 3 
1.1.3 
Exploratory (immunologic) Objectives ................................................................................ 3 
1.2 
Study Design and Procedures .................................................................................................. 4 
1.2.1 
Primary Hypothesis and Primary Endpoint ........................................................................ 4 
1.2.2 
Accrual Plan and Randomization ......................................................................................... 4 
1.2.3 
Duration of Follow-up ............................................................................................................ 4 
1.3 
Inclusion/Exclusion Criteria and Treatment Description ....................................................... 5 
1.4 
Treatment Description ............................................................................................................... 5 
1.5 
Response Variables and Data Collection Time Points ......................................................... 6 
1.5.1 
Response Variables ............................................................................................................... 6 
1.5.2 
Timing of Assessments ......................................................................................................... 7 
2. 
General Statistical Considerations ...................................................................................... 8 
2.1 
Sample Size and Power Calculations ..................................................................................... 8 
2.2 
Handling Missing Data ............................................................................................................... 8 
2.3 
Multiple Comparisons ................................................................................................................ 9 
2.4 
Interim Analysis .......................................................................................................................... 9 
2.5 
Timing of Analysis .................................................................................................................... 10 
2.6 
Software ..................................................................................................................................... 11 
2.7 
Analysis Populations ................................................................................................................ 11 
2.7.1 
Enrolled Population .............................................................................................................. 11 
2.7.2 
Primary Analysis Population ............................................................................................... 11 
2.7.3 
Safety Analysis Population ................................................................................................. 11 
2.8 
General Analysis Guidelines ................................................................................................... 11 
2.9 
Demographics and Baseline Characteristics ....................................................................... 12 
2.10 
Participant Compliance ............................................................................................................ 12 
3. 
Analysis Plan ........................................................................................................................ 12 
3.1 
Analysis of the Primary Endpoint ........................................................................................... 12 
3.2 
Analysis of the Secondary Endpoints .................................................................................... 13 
3.3 
Analysis of the Immunologic Endpoints ................................................................................ 15 
3.3.1   Primary immunologic endpoint: Myeloma reactive T-cells .............................................. 15 
3.3.2   Secondary immunologic endpoints .................................................................................... 15 
4. 
Template of Proposed Table/Figure/Listing (TFL) Shells ................................................ 16 
5. 
References ............................................................................................................................ 16 
Appendix ....................................................................................................................................... 17 
EXHIBIT 1401-1:  Participant Disposition and Follow-Up ........................................................... 17 
EXHIBIT 1401-2:  Participant Demographics and Baseline Characteristics ............................ 18 


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EXHIBIT 1401-3:  Complete Response/Stringent Complete Response Rate at 1 Year Post 
Transplant .......................................................................................................................................... 20 
EXHIBIT 1401-4: Disease Response ............................................................................................. 22 
EXHIBIT 1401-5:  Cumulative Incidence of Relapse/Progression ............................................. 25 
EXHIBIT 1401-6:  Cumulative Incidence of Treatment-related Mortality (TRM) ...................... 27 
EXHIBIT 1401-7: Progression-Free Survival (PFS) ..................................................................... 29 
EXHIBIT 1401-8: Overall Survival (OS) ......................................................................................... 31 
EXHIBIT 1401-9:  Incidence of Toxicities Grade ≥ 3 per CTCAE Version 4.0 ......................... 32 
EXHIBIT 1401-10: Incidence of Infections .................................................................................... 34 
EXHIBIT 1401-11: Minimal Residual Disease Assessment........................................................ 37 
EXHIBIT 1401-12: Primary Immunologic Endpoint: Myeloma Reactive T Cells ...................... 38 
EXHIBIT 1401-13:  Secondary Immunologic Endpoints.............................................................. 40 
Supplemental Exhibit 1401-1:  Enrollment .................................................................................... 42 
Supplemental Exhibit 1401-2:  Significant Protocol Deviations .................................................. 42 
Supplemental Exhibit 1401-3:  Primary Cause of Death ............................................................. 42 
Supplemental Exhibit 1401-4:  Adverse Events ........................................................................... 42 
Supplemental Exhibit 1401-5:  Serious or Grades 3-5 Adverse Events ................................... 42 
Supplemental Exhibit 1401-6:  Safety Monitoring (Safety Endpoints) ....................................... 44 
 
 
 


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Protocol  
BMT CTN #1401 is titled “Phase II Multicenter Trial of Single Autologous Hematopoietic 
Cell Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or 
without Vaccination with Dendritic Cell/Myeloma Fusions”.  
1. General Review of Study Design and Process 
1.1 Study Objectives  
BMT CTN protocol #1401 is a three-arm, Phase II, open-labeled, multi-center trial 
designed to evaluate whether dendritic cell (DC)/myeloma fusion vaccine in combination 
with granulocyte macrophage colony-stimulating factor (GM-CSF) and standard 
immunomodulatory therapy, i.e. lenalidomide, can be used as an upfront cellular 
immunotherapy following autologous transplant for participants with multiple myeloma1. 
Primarily, the study aims to identify whether the combination of vaccine and 
maintenance therapy increases post-transplant clinical response compared to the non-
vaccine control groups (lenalidomide with and without GM-CSF). Furthermore, the study 
will assess the effect of the vaccine on the anti-myeloma immunity by isolating the effect 
of lenalidomide maintenance and/or GM-CSF adjuvant. 
1.1.1 
Primary Objective 
The primary objective of the study is to compare the percentage of participants alive and 
achieving complete response (CR) or stringent complete response (sCR) at one year 
post transplant (approximately 10 months post randomization) between participants 
randomized to the vaccine arm and participants randomized to the combined non-
vaccine arms (lenalidomide with/without GM-CSF). 
1.1.2 
Secondary Objectives 
The secondary objectives of the study include:   
• 
Myeloma response to treatment 
• 
Cumulative incidence of myeloma progression  
• 
Cumulative incidence of treatment-related mortality (TRM) 
• 
Progression-free survival (PFS) 
• 
Overall survival (OS) 
• 
Incidence of grade ≥ 3 toxicities per CTCAE version 4.0 
• 
Incidence of infection  
• 
Minimal residual disease assessment 
 
1.1.3 
Exploratory (immunologic) Objectives 
The exploratory (immunologic) objectives of the study are/include: 
• 
Myeloma-reactive T-cells 


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• 
Assessment of antigen-specific reactivity  
• 
Quantification of T-cell subsets 
• 
Assessment of effect on NK cell population  
• 
Assessment of humoral immune response 
1.2 Study Design and Procedures  
1.2.1 
Primary Hypothesis and Primary Endpoint 
The primary hypothesis of the study is that vaccination with DC/myeloma fusions/GM-
CSF in combination with lenalidomide maintenance therapy will increase the proportion 
of participants alive and in CR or sCR at one year post transplant compared to the 
combined non-vaccine groups. 
H0: PVACCINE/GMCSF +MAINT = PMAINT±GMCSF vs. Ha: PVACCINE/GMCSF +MAINT > PMAINT±GMCSF. 
The primary endpoint is the proportion of participants alive and in CR or sCR at one year 
post transplant (corresponding to approximately 10 months post randomization).  
1.2.2 
Accrual Plan and Randomization  
The study targets 132 randomized participants. Considering 30% of participants are 
expected to drop out between tumor cell collection and randomization, the study will 
target 188 participants for tumor cell collection. It was estimated that 36 months of 
accrual will be necessary to enroll the target sample size. 
Participants will be randomized to DC/myeloma vaccine/GM-CSF/lenalidomide, 
lenalidomide/GM-CSF, and lenalidomide alone in a 2:1:1 ratio using random block sizes. 
Randomization will be stratified based on disease response at time of randomization 
between stringent complete response/complete response and very good partial 
response/partial response/stable disease. 
A memorandum was issued on August 1, 2018 to the participating sites of this trial 
regarding the Accrual Continuation Plan that the study enrollment will remain open until 
enrollment reached 203 patients with tumor cell collection.  This change was intended to 
ensure sufficient patients proceed to randomization given a higher than expected drop-
off rate and the long period between tumor cell collection and randomization. The 
expanded accrual was noted in the Data and Safety Monitoring Board (DSMB) and FDA 
reports. 
1.2.3 
Duration of Follow-up 
Participants will be followed for approximately 3 years post maintenance initiation for AE 
(including SPM).   The primary endpoint is at 1 year post transplant. Secondary 
endpoints data are collected from Emmes end up to approximately 2 years (through 
cycle 24 of maintenance). 


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Data regarding study participants’ clinical situation, including follow-up after 2 years, may be 
obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR), 
which captures information on all US transplants. Such long-term follow-up data is NOT within 
the scope of this SAP and analysis on these long-term follow up data is not part of the primary 
analysis. 
1.3 Inclusion/Exclusion Criteria and Treatment Description 
Patients must be considered transplant eligible by treating physician at the time of study. 
Patients will be enrolled prior to tumor cell collection for vaccine manufacturing. Eligible 
patients are ≥18.00 and < 71.00 years of age with symptomatic multiple myeloma 
requiring treatment, without history of prior disease progression or prior HCT, Karnofsky 
performance score ≥70%, evidence of at least 20% plasma cells in a bone marrow 
differential within 60 days of enrollment and have received <1 cycle of systemic anti-
myeloma therapy. If patient receives anti-myeloma therapy treatment after bone marrow 
aspirate to assess eligibility and before bone marrow aspirate for tumor cell collection, a 
repeat bone marrow evaluation will be required to confirm > 20% plasma cells in the 
bone marrow aspirate differential prior to enrollment and tumor cell collection.  Patients 
with prior auto or allo transplant are not eligible. Patients with active autoimmune 
diseases will be excluded. More details for inclusion and exclusion criteria for study 
enrollment are outlined in Protocol Version 4.0 Chapter 2.3.2.  
Randomization eligibility will be evaluated prior to randomization among transplanted 
participants. In order to be randomized to study treatments (maintenance therapy), 
participants are required to have sufficient tumor cells and subsequent vaccine 
production with no evidence of disease progression within 10 days prior to 
randomization, a minimum of 75,000/mm3 for platelet count without transfusion in 
previous 7 days and a minimum of 1,500/mm3 for absolute neutrophil count without 
filgrastim administration within 7 days or pegfilgrastim within 14 days of measurement, 
and maintain adequate physical function measured by hepatic and renal assessments. 
Details are documented in Protocol Version 4.0 Chapter 2.3.3.  
Amendments to eligibility criteria since the first version of the protocol release Version 
1.0 were documented in the protocol amendment summary of changes.  
1.4 Treatment Description 
Eligible participants will undergo tumor cell collection after enrollment. Participants with 
bone marrow harvest that yields sufficient cell counts per BMT CTN 1401 Vaccine 
Product Release Criteria will be scheduled for an autologous hematopoietic cell 
transplant within 1 year of enrollment. Pre-transplant systemic anti-myeloma therapy will 
be administered per institutional practices. Transplant-eligible participants will receive an 
autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg with high-dose 
melphalan (200mg/m2).  
A disease response assessment will be done approximately 2 months post-transplant 
and participants who meet eligibility criteria will be randomized within 10 days of the 


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assessment to one of three treatment groups: vaccine/GM-CSF with lenalidomide, 
lenalidomide/GM-CSF, or lenalidomide alone.  
Participants start maintenance therapy between 90 and 100 days post-transplant 
(approximately 1 month post randomization). Lenalidomide will be administered at an 
initial dose of 10 mg per day starting Day 1 for 2 years (24 maintenance therapy cycles) 
until disease progression. One maintenance therapy cycle lasts for 28 days and 
participants will be only given a 28-day supply at a time. The dose modifications for 
lenalidomide are described in Protocol Version 4.0 Chapter 2.4.6. Participants who are 
randomized to the vaccine arm will receive 3 doses of the vaccine on the first day of 2nd, 
3rd, and 4th cycle of lenalidomide with an injection of GM-CSF on the same day and 
every day for 3 days after the vaccine to boost the effect of the vaccine. Participants who 
are randomized to the lenalidomide/GM-CSF arm will receive GM-CSF injection every 
day for 4 days starting the first day of 2nd, 3rd, and 4th cycle of lenalidomide.  
1.5 Response Variables and Data Collection Time Points 
1.5.1 
Response Variables 
The response variables for this study include the primary, secondary, safety and 
immunologic endpoints. The primary endpoint is the proportion of participants alive with 
CR/sCR at 1 year post transplant (approximately 10 month post maintenance initiation).  
Secondary endpoints include: 
• 
Disease response/myeloma response to treatment  
• 
Disease progression/myeloma progression  
• 
Treatment-related mortality 
• 
Progression-free survival 
• 
Overall survival 
• 
Minimal residual disease 
Immunologic endpoints include: 
• 
The percent of participants achieving at least a 2.4-fold increase in myeloma-
specific T cells from pre-therapy to peak post-treatment levels 
• 
The percent of participants achieving at least a 10-fold increase in myeloma-
reactive T-cells 
• 
Assessment of antigen specific reactivity in HLA-A2.1 participants by multichannel 
flow cytometry and intracellular staining 
• 
Quantification of T-cell subsets by multichannel flow cytometry 
• 
Assessment of effect of lenalidomide alone and in combination with vaccination on 
the phenotype and function of NK cell populations 


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• 
Assessment of humoral response targeting myeloma antigens in participants 
treated with lenalidomide alone and in combination with vaccination 
Safety endpoints included mortality, toxicity and adverse events. Safety monitoring will 
be conducted per protocol schedule. Adverse events will be reported per the BMT CTN 
Manual of Procedures (MOP).  
Definitions for each endpoint are described in detail in Protocol Version 4.0 Chapter 3 
and in Section 3 of this SAP. 
1.5.2 
Timing of Assessments 
Participants are evaluated for pre-enrollment assessments at study entry. Pre-enrollment 
evaluations must be determined within 8 weeks prior to enrollment. Bone marrow 
aspirate and biopsy are required to assess plasma cell involvement within 60 days of 
enrollment. Once participants enter the study, tumor cell collection will be done for 
vaccine production and randomization eligibility validation. Initiation of systemic anti-
myeloma therapy and transplant will be done within 1 year of enrollment to the study. 
Participants who are unable to have tumor cell collection or vaccine preparation done 
appropriately per BTM CTN 1401 manufacturing SOP may still receive initial anti-
myeloma therapy and transplant but will be dropped from the study and not proceed to 
transplant. 
Participants who undergo autologous hematopoietic cell transplant will be seen 14 days 
or less prior to randomization for pre-randomization evaluations, and disease response 
assessment must be performed within 10 days prior to randomization. Randomization 
occurs approximately 2 months post-transplant (from Day 53 to Day 90). Before starting 
the assigned maintenance therapy, participants need to complete pre-maintenance 
evaluations within 14 days prior to initiation of lenalidomide for eligibility. Post 
maintenance initiation assessments including toxicities, bone marrow evaluation, 
laboratory disease evaluation, and physical function occur monthly for the first 4 cycles, 
and then at cycles 6, 9, 12, 15, 18, 21, and 24. One maintenance cycle duration is 28 
days. Disease response will be assessed at 6 months, 1 year, and 2 years post-
transplant. Participants who stop maintenance therapy for any reason will still be 
followed on the study, unless they withdraw consent from the study.  
Sample collection for ancillary studies and for future research use are performed at 
enrollment, pre-randomization, and during maintenance. Death, relapse, infections, 
hospitalizations, and adverse events are reported on event-driven forms. Data on 
occurrence of these events are recorded per the BMT CTN MOP. 
Participant data related to primary and secondary endpoints are collected through 
AdvantageEDC up to 28 days after the last maintenance dose or 2-year post-transplant 
depending on participant’s compliance to the lenalidomide. The specimens collected for 
immunologic endpoints are being tracked in AdvantageEDC and Global Trace. Samples 
will be shipped to BMT CTN Biorepository or institutional laboratories based on the 
purpose of specimen. All unexpected grades 3-5 AEs unless a participant has protocol-


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defined progression, and second primary malignancies (SPM) regardless of progression 
are required to be reported using the expedited AE reporting system in AdvantageEDC 
through 3-year post maintenance. Other follow up data after 2 years post maintenance 
initiation until 3 years post maintenance initiation will be obtained from the CIBMTR.  
2. General Statistical Considerations 
2.1 Sample Size and Power Calculations 
The primary hypothesis testing will be done using a one-sided two-sample comparison 
of proportions between the vaccine arm and the combined non-vaccine arms. The prior 
studies suggest a 29% and 54% CR rate respectively at 100 days and 1 year post 
transplant for participants who undergo post-transplant vaccination in the absence of 
lenalidomide maintenance. Thus, it’s anticipated that 40% of study participants will 
achieve CR/sCR at 1 year post transplant following vaccination without lenalidomide 
maintenance. Considering lenalidomide maintenance therapy will boost the effects of 
vaccination and thus enhance vaccine efficacy2, we will consider vaccine/GM-CSF plus 
lenalidomide therapy to be promising if there is a 20% increase in CR rate at 1 year from 
40% to 60%. For the primary comparison between the vaccine and the combined non-
vaccine arms, 66 participants in each group is sufficient to maintain a one-sided type I 
error rate of 10% and provide 85% statistical power to detect a 20% improvement in the 
1 year CR rate using a two-sample proportions test. Furthermore, since randomization 
occurs after tumor cell collection and transplant, we expect a 30% drop-out rate and thus 
the study planned to enroll a total of 188 participants at the time of initial tumor collection 
(later expanded to 203 participants).  
In a secondary pairwise analysis that compares CR rate at 1 year post transplant 
between the vaccine arm versus either lenalidomide/GM-CSF arm or lenalidomide only 
arm, the sample size (66 in the vaccine arm, 33 in each non-vaccine arm) is also 
sufficient to detect a 23% increase while maintaining a 80% power under the same alpha 
level. Besides, a 26% increase between the two non-vaccine groups can also be 
detected with 80% power.  
Since this is a Phase II trial, the consideration on sample size and power calculation and 
study design of the trial is not intended to provide definitive results but rather to detect 
any promising difference in response rates between the vaccine arm and combined non-
vaccine arm by assessing vaccination plus maintenance therapy in a multi-center setting 
for future trials consideration. 
2.2 Handling Missing Data 
Comprehensive data quality assurance will be conducted to reconcile data issues 
including missing data.    
The primary endpoint will be evaluated at 1 year post-transplant (approximately 10 
months post randomization). An Endpoint Review Committee (ERC) will adjudicate the 
primary endpoint and resolve this endpoint for any participants with missing data using 


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available source documents provided by sites. Remaining participants with missing data 
will be considered not evaluable.  
For time-to-event variables, participants will be censored at the last observation for the 
endpoint if they have not had an event or competing risk event. Participants lost to 
follow-up will be censored at the time of last contact date captured in the 
AdvantageEDC.  
Since this is a phase II trial, all available data will be used in the analyses and no 
imputation will be done on missing data.    
2.3 Multiple Comparisons 
A one-sided significance level of 10% will be used for testing the primary endpoint 
between the vaccine group and combined non-vaccine groups. The same alpha level will 
be used for the secondary comparisons of CR rate between the vaccine versus either 
lenalidomide/GM-CSF or lenalidomide alone arm. All other secondary analyses will use 
a two-sided significance level of 5%.  The pairwise tests for treatment group difference 
that compare 2 groups at a time will use the 0.05 significance level, but these 
comparisons will only be considered significant if the multiple degree of freedom overall 
test among the three groups is significant. 
2.4 Interim Analysis 
No interim analyses for efficacy or futility were planned for the study.  
The key safety endpoint for interim monitoring is the treatment limiting toxicity (TLT) 
within the first month of the combined therapy. TLT will be monitored separately for the 
vaccine/GM-CSF arm and the combined non-vaccine groups (lenalidomide/GM-CSF 
arm and lenalidomide alone arm) under the same stopping rule using a truncated SPRT 
for binary outcomes. Each month, the null hypothesis that the 1 month TLT rate is 25% 
will be tested. At each interim analysis, the total number of participants enrolled and 
started combined therapy is plotted against the total number of participants who have 
experienced TLT. The continuation region of the SPRT3 is defined by two decision 
boundaries. Only the upper boundary will be used for monitoring the study to protect 
against high incidences of TLT. If the graph falls above the upper boundary, the SPRT 
rejects the null hypothesis, and concludes that the TLT incidence is higher than 
predicted by the observed number of participants enrolled on study. Otherwise, the 
SPRT continues until enrollment reaches the target goal. The SPRT for TLT was 
developed from the following SPRT: 
A SPRT contrasting 25% versus 40% 1 month incidence, with nominal type I and II 
errors of 12% and 15%, respectively, which results in decision boundaries with a 
common slope of 0.322 and an upper intercept of 2.824. 
The table illustrates the operating characteristics of the described truncated test based 
on a simulation study that assumed uniform accrual of 66 individuals over a three-year 


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time period. When the true 1 month incidence rate is 25%, 10% of the time we will reject 
the null hypothesis. When the true rate is 40%, there is an 84% chance of rejecting the 
null hypothesis.  
True 1 month Incidence 
25% 
35% 
40% 
45% 
Probability Reject Null  
0.100 
0.595 
0.836 
0.957 
Mean Month Stopped 
34.8 
25.0 
18.3 
13.5 
Mean # Endpoints in 1 month 
15.5 
15.4 
13.1 
10.6 
Mean # Participants Enrolled 
62.1 
43.8 
32.7 
23.7 
  
 
2.5 Timing of Analysis 
The first round of the analysis is the timing for the primary endpoint, which is when all 
participants complete one year follow-up post-transplant and the ERC completes the 
endpoint adjudications on the primary endpoint.  
A topline analysis will be conducted to include the primary clinical endpoint, primary 
immunologic endpoint and some secondary endpoints to facilitate abstract submission of 
the primary results. For the secondary endpoints, this topline analysis will only include 
descriptive analysis on the secondary endpoints with 1-year data but no formal 
comparison will be conducted in order to maintain planned statistical power when final 
data become available. Secondary endpoints in the topline analysis will only include 
disease response, disease progression, treatment-related mortality, progression-free 
survival, overall survival, and all these will only include data within 1 year. Study 
enrollment, patient demographics and baseline data will also be included in the topline 
analysis.  
A data freeze will be done upon the completion of ERC adjudication on the primary 
endpoint and completion of related data quality assurance. An ERC Charter will be in 
place to define the scope of ERC review as well as the timeline for the data adjudication.  
The second round of the analysis is the timing for all the secondary endpoints with 
complete 2-year follow-up. A comprehensive analysis report including 2-year data for 
primary endpoint and all secondary endpoints is planned when the last randomized 
participant finishes 2-year post maintenance assessment. The comprehensive analysis 
is conducted to facilitate the primary manuscript submission of the study. Correlative 
immunologic endpoints that defined in the protocol will be included in this 
comprehensive analysis report. Emmes will request data from study labs and run 
analyses per protocol.  
Analysis on the long-term follow up beyond 2-year post maintenance are not collected in 
AdvantageEDC Emmes data system and will be collected via the CIBMTR data system. 
This will be a separate publication and the analysis plan are not covered in this SAP. 


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The timing for the ancillary studies, the T Cell/Genomic Signature and the VCAN 
Proteolysis, are covered in separate protocols managed by the Beth Israel Deaconess 
Medical Center and University of Wisconsin-Madison respectively.  Analysis plans for 
these ancillary studies are not covered in this SAP. 
2.6 Software 
All analyses will be conducted using SAS 9.4 or higher software, or R version 3.4.4 or 
higher.  
2.7 Analysis Populations  
2.7.1 
Enrolled Population 
All participants who were enrolled to the study will be counted in the enrolled population. 
Participants who did not make it to randomization due to various reasons will be 
described.  
2.7.2 
 Primary Analysis Population 
All randomized participants will be included in the primary analysis population per intent-
to-treat (ITT) principle regardless of whether the assigned transplant was administered. 
This population will be applied to the primary endpoint and some secondary endpoints.  
It is clearly defined for each secondary endpoint whether or not this population will be 
used for analysis, as described in section 3.2 of this SAP. 
2.7.3 
Safety Analysis Population 
The reporting of serious adverse events will be consistent with standard BMT CTN 
procedures and compliant with additional requirements from Celgene Corporation who 
supplies lenalidomide for the study with the addition of any anticipated SAE related to 
the study drug or treatment/procedure. All reported serious adverse events potentially 
associated with study drug or treatment/procedure will be carefully examined with 
respect to the severity and relationship to study drug. The type and severity of adverse 
events will be described. Safety data will be summarized using Medical Dictionary for 
Regulatory Activities (MedDRA) Coding Version 20.0 or above. 
All secondary primary malignancies (SPMs), excluding non-melanoma skin cancers, 
experienced by participants from the time of enrollment until 3 years post maintenance 
initiation will also be reported. 
The safety analysis population will consist of participants according to treatment 
received and SPM analysis population will consist of all enrolled participants. 
2.8 General Analysis Guidelines 
Continuous variables will be described using mean, standard deviation, median, 
quartiles, minimum and maximum. Frequencies and percentages will be displayed for 
categorical data. The log transformation will be applied to immunological endpoints to 
induce normality in quantitative measurements. Between group comparisons will be 


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performed for continuous variables via a Kruskal-Wallis test and for categorical 
variables, via the chi-squared test.      
Any changes to the planned analyses and ad hoc analysis will be documented in the 
final analysis report with detailed justifications. If it is a change to analysis of an existing 
endpoint, the change should be clearly stated in the relevant exhibit. If it is a new 
endpoint or analysis performed, it should be included in a supplemental exhibit.  
Statistical consideration and analysis plan for the ancillary studies will be handled by 
separate study teams thus not covered in this SAP. 
2.9 Demographics and Baseline Characteristics  
Descriptive statistics for demographics and baseline characteristics will be presented by 
treatment group. Characteristics to be examined are: age, gender, race, ethnicity, 
performance status, pre-randomization disease response.    
2.10 Participant Compliance 
A consort diagram will be provided to illustrate study accrual and follow up. The enrolled 
participants who did not get to randomization, and those randomized but did not receive 
vaccination will be listed with reasons for non-adherence.  
A table listing significant protocol deviations/violations will be provided by treatment 
group (if applicable). Compliance with protocol interventions will be evaluated as 
appropriate. Premature withdrawals will be described for each case.  
In the tables/figures, the number of included participants will be provided/described for 
each analysis. 
The metrics of manufacture products will be explored, and to be assessed with the 
treatment group association, and center effect. Exploratory results will be displayed with 
available data. 
3. Analysis Plan  
3.1 Analysis of the Primary Endpoint 
Participant’s disease status will be evaluated based on the International Uniform 
Response Criteria4. Before disease progression, all disease classifications including 
stringent complete response (sCR), complete response (CR), very good partial 
remission (VGPR), partial response (PR), stable disease (SD) are relative to 
participant’s disease status at study entry. If participant develops disease progression, 
the disease classifications are relative to participant’s best response since time of study 
entry.  
The primary endpoint for the study is the proportion of participants alive and in complete 
response (CR) or stringent complete response (sCR) at one year post transplant, 
corresponding to approximately 10 months post randomization. The primary analysis will 
utilize the primary analysis population. The proportion of CR or sCR at one year post 
transplant will be estimated using frequencies in each group and compared between the 
treatment groups using a two-sample Z statistic for comparing two proportions. This test 


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will use the pooled proportion for the variance calculation under the null hypothesis, 
which is equivalent to the chi-squared test and has good asymptotic properties for the 
sample size and the expected proportions. A one-sided significance level of 0.10 will be 
used to assess whether the vaccine appears promising relative to control.  
A secondary analysis stratified on disease response prior to randomization will be 
conducted using a Cochran-Mantel-Haenszel test, and a stratified odds ratio along with 
80% confidence intervals will be estimated.   
A secondary pairwise analysis of CR rates comparing the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm will also be conducted. 
3.2 Analysis of the Secondary Endpoints 
All secondary analyses will use a two-sided significance level of 5%. 
3.2.1 Myeloma Response to Treatment 
The disease response categories, including sCR, CR, VGPR, PR, SD, PD, will be 
tabulated at each assessment period. The proportion of participants alive and with 
sCR/CR/VGPR will be compared between the vaccine and the combined non-vaccine 
arms at 6 months, 1 year, and 2 years post-transplant using a chi-squared test.  
A secondary pairwise analysis of response to treatment comparing the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm will also be conducted.  
Rates of conversion to CR will also be compared using a chi-square test among the 
subset of patients who are not in CR at the time of randomization.   
 
3.2.2 Myeloma Progression 
The event for this endpoint is defined as disease progression from CR/sCR or 
progressive disease for participants not in CR/sCR, or initiation of off protocol anti-
myeloma therapy. The incidence of myeloma progression will be compared between the 
vaccine arm and the combined non-vaccine arms using Gray’s test5 and treating death 
(without documentation of disease progression) as a competing risk. Participants alive 
without disease progression at last observation will be censored at the date of last 
contact. A secondary pairwise analysis will be comparing the cumulative incidence of 
myeloma progression between the vaccine arm, lenalidomide/GM-CSF arm and 
lenalidomide alone arm. 
3.2.3 Treatment-related Mortality (TRM) 
The incidence of TRM will be compared between the vaccine arm and the combined 
non-vaccine arm, treating disease progression as a competing risk. An event is death 
from causes other than disease relapse or progression. Participants alive without 
disease progression at last contact will be censored. Gray’s test will be used to compare 
the vaccine arm and the combined non-vaccine arms. A secondary pairwise analysis will 
be comparing the cumulative incidence of TRM between the vaccine arm, 
lenalidomide/GM-CSF arm and lenalidomide alone arm. 


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3.2.4 Progression-free Survival (PFS) 
Death or disease progression will be considered as events for this endpoint. The time to 
event will be calculated as time from randomization to disease progression, death, 
initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, 
whichever comes first. The Kaplan-Meier estimator will be constructed for each 
treatment arm. Progression-free survival will be compared between the vaccine and the 
combined non-vaccine arms using the log-rank test. The hazard ratios, along with 
confidence intervals, will be estimated from a Cox model with treatment group as a 
covariate.  
A secondary analysis of PFS will be conducted to compare the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm in pairwise comparison.  
3.2.5 Overall Survival (OS) 
Death from any cause will be considered as an event for this endpoint. The time to event 
will be calculated as time from randomization to death, loss to follow-up or the end of the 
study, whichever comes first. Participants alive at the time of last observation will be 
censored at the date of last contact. The Kaplan-Meier estimator will be constructed for 
each treatment arm. Overall survival will be compared between the vaccine and the 
combined non-vaccine arms using the log-rank test. The hazard ratios, along with 
confidence intervals, will be estimated from a Cox model with treatment group as a 
covariate.  
A secondary analysis of OS will be conducted to compare the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm in pairwise comparison.  
3.2.6 Incidence of Toxicities Grade ≥ 3 per CTCAE version 4.0 
Frequencies of grade 3 or higher toxicities based on NCI Common Terminology Criteria 
for Adverse Events (CTCAE) Version 4 will be tabulated by grade for each treatment 
arm, by toxicity type and by maximum grade at each time interval as well as the 
cumulative over time. Toxicity frequencies of participants developing Grade ≥ 3 will be 
compared between the vaccine and the combined non-vaccine arms using the Chi-
square test.    
3.2.7 Incidence of Infection 
Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, occurring after 
randomization will be reported. The number of infections and the number of patients 
experiencing infections will be tabulated by type of infection, severity, and time period 
after transplant. The cumulative incidence of infections post randomization, treating 
death as a competing risk, will be compared between the vaccine and the combined 
non-vaccine groups using the Gray’s test. 
A secondary pairwise analysis that compares incidence of infections between the 
vaccine arm, lenalidomide/GM-CSF arm and the lenalidomide alone arm will be 
conducted.  
3.2.8 Minimal Residual Disease Assessment 


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The proportions of participants with MRD present (MRD+) will be tabulated at 
randomization and after the completion of Cycle 9 of maintenance and compared 
between the vaccine and the combined non-vaccine groups using the Chi-square test. 
A secondary pairwise analysis that compares proportions of MRD+ between the vaccine 
arm, lenalidomide/GM-CSF arm and the lenalidomide along arm will be conducted.  
Data on MRD assessments will be retrieved from external lab and this data will be 
included in the primary manuscript. MRD analysis will not be included in the topline 
analysis.  
3.3 Analysis of the Immunologic Endpoints 
All analyses on immunologic endpoints will use a two-sided significance level of 5%. 
3.3.1   Primary immunologic endpoint: Myeloma reactive T-cells 
Log transformations will be used to induce normality in quantitative measurements, and 
if still non-normal, then nonparametric tests will be used.  The primary endpoint of log 10 
peak change in tumor reactive T cells from baseline will be compared across the 3 
groups using analysis of variance, and if significant then two-sample t-tests will be 
conducted for each pairwise comparison to determine which groups are different from 
one another.   
A secondary analysis of peak change in tumor reactive T cells will be done by comparing 
the proportions of patients who experience >10-fold increase in IFNγ expression, using a 
chi-squared test.  Myeloma reactive T-cell response profiles over time will be compared 
between the treatment groups using linear mixed models for repeated measures data.  
Peak immune response as well as most recent immune response will be compared 
between those in CR and those not in CR at each assessment, using a two-sample t-
test, to assess the relationship between immune response and clinical response.  Peak 
and most recent immune response will also be considered as time-dependent covariates 
in a Cox proportional hazards model to assess their impact on progression-free survival.  
3.3.2   Secondary immunologic endpoints 
Additional exploratory analyses will be conducted in a similar fashion to examine a 
number of secondary immunologic endpoints, including:  
1) antigen specific reactivity by tetramer analysis,  
2) quantification of T-cell subsets and PD-1 expressing lymphocytes by flow cytometry  
3) quantification of NK cell populations with inhibitor and activating markers,  
4) NK-cell cytotoxic function as measured by IFNγ and CD107a degranulation in 
response to ex vivo exposure to autologous MM cells,  
5) humoral response against autologous MM cells and myeloma associated antigens 
such as MUC1, and vaccine-induced myeloma-specific plasmablast responses.   
In each case, log transformations will be considered to induce normality, and if still non-
normal then nonparametric tests will be used. Profiles of these secondary immunologic 


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endpoints will be described at each time point for each group using summary statistics 
and compared between the groups using mixed models for repeated measures data.    
The correlation between the immune environment measures and the myeloma specific 
T-cell response will NOT be assessed. Instead, the correlation between the immune 
environment measures and the primary clinical outcome will be assessed and reported 
as exploratory analyses for the pooled treatment groups. 
4. Template of Proposed Table/Figure/Listing (TFL) Shells  
Table/Figure/Listing titles and layout are for illustration purposes only, and may not be 
the final layout or wording chosen for publications or presentations. Actual format of the 
tables and figures may differ and will be subject to change in the final analysis report 
and/or publication. See Appendix of this SAP for the exhibits title and shell. 
5. References  
1 Rosenblatt, J. et al. Vaccination with dendritic cell/tumor fusions following autologous 
stem cell transplant induces immunologic and clinical responses in multiple myeloma 
patients. Clin Cancer Res 19, 3640-3648, doi:10.1158/1078-0432.CCR-13-0282 (2013). 
2 Luptakova, K. et al. Lenalidomide enhances anti-myeloma cellular immunity. Cancer 
Immunol Immunother 62, 39-49, doi:10.1007/s00262-012-1308-3 (2013). 
3 BGM Durie et al. International uniform response criteria for multiple myeloma. Leukemia 
(2006) 1-7. 
4 Jennison C, Turnbull BW.  Group sequential methods with applications to clinical trials.  
Chapman and Hall/CRC, Boca Raton, 2000. 
5 Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a 
competing risk. Annals of Statistics 1988, 16: 1141-1154. 
 
 


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Appendix 
 
EXHIBIT 1401-1:  Participant Disposition and Follow-Up 
A consort diagram will be provided showing the number of participants enrolled to the 
study, dropped out, received transplant, randomized to the study treatment, and 
treatment compliance as applicable. A table will be provided with descriptive statistics on 
length of follow-up by assigned treatment arm. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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EXHIBIT 1401-2:  Participant Demographics and Baseline Characteristics 
Baseline characteristics and demographics will be described by frequencies and 
percentages for categorical covariates, and minimum, maximum, median, mean, and 
standard error for continuous covariates.  The following covariates may be included:  
• 
Treatment group assignment 
• 
Strata (Risk status at time of randomization or other stratification factors) 
• 
Gender 
• 
Ethnicity 
• 
Race  
• 
Participant age 
• 
Karnofsky performance score  
• 
Disease response 
Demographics for participants that did not make it to the randomization will also be 
described/summarized. 
 
 
Treatment Arm 
 
 
Vaccine/GM-
CSF/Lenalidomide 
(N=) 
N (%) 
Lenalidomide/GM
-CSF 
(N=) 
N (%) 
Lenalidomide 
alone 
(N=) 
N (%) 
Total 
(N=) 
N (%) 
Gender 
 
 
 
 
  Female 
 
 
 
 
  Male 
 
 
 
 
Ethnicity 
 
 
 
 
  Hispanic or Latino 
 
 
 
 
  Not Hispanic or Latino 
 
 
 
 
  Unknown 
 
 
 
 
  Not Answered 
 
 
 
 
Race 
 
 
 
 
  American Indian/Alaskan Native 
 
 
 
 
  Asian 
 
 
 
 
  Hawaiian/Pacific Islander 
 
 
 
 
  Black or African American 
 
 
 
 
  White 
 
 
 
 
  More than One Race 
 
 
 
 
  Other, Specify 
 
 
 
 
  Unknown 
 
 
 
 
  Not Answered 
 
 
 
 
Age, years 
 
 
 
 
  Mean (SD) 
 
 
 
 
  Median (Range) 
 
 
 
 
Karnofsky Performance Score 
 
 
 
 
 100 
 
 
 
 


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Treatment Arm 
 
 
Vaccine/GM-
CSF/Lenalidomide 
(N=) 
N (%) 
Lenalidomide/GM
-CSF 
(N=) 
N (%) 
Lenalidomide 
alone 
(N=) 
N (%) 
Total 
(N=) 
N (%) 
  90 
 
 
 
 
  80 
 
 
 
 
  70 
 
 
 
 
Disease Response at Randomization 
 
 
 
 
  Stringent Complete Response 
 
 
 
 
  Complete Response 
 
 
 
 
  Very Good Partial Response 
 
 
 
 
  Partial Response 
 
 
 
 
  Stable Response 
 
 
 
 
 
Time from enrollment to transplant and from transplant to randomization will be summarized in basic statistics including 
mean, standard deviation, range.  
 


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EXHIBIT 1401-3:  Complete Response/Stringent Complete Response Rate at 1 Year 
Post Transplant  
The primary endpoint is the proportion of patients alive and in CR or sCR at one year 
post transplant.  The proportion of patients alive and in CR/sCR at 1 year post transplant 
will be described in the vaccine and no vaccine groups with 80% confidence intervals 
and compared between groups using a two-sample Z test comparing binomial 
proportions.   
Proportion of Surviving Participants in CR/sCR at 1 Year Post Transplant 
Alive and in CR/sCR 
Vaccine 
(N=) 
N (%) 
Combined Non-
vaccine 
(N=) 
N (%) 
P-value 
YES  
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
NO 
XX (XX.X%) 
XX (XX.X%) 
        Alive and Not in CR/sCR 
XX (XX.X%) 
XX (XX.X%) 
        Dead  
XX (XX.X%) 
XX (XX.X%) 
        Not Evaluable1 
XX 
XX 
Note: 1 Participants that withdrew from the study or loss to follow up prior to the assessment time will be categorized into 
Not Evaluable. 
 
A secondary analysis of CR/sCR rate stratified on disease response prior to 
randomization will be conducted and the stratified odds ratio will be estimated.  
Stratum 1: sCR/CR at Randomization 
Alive and in CR/sCR 
Vaccine 
(N=) 
N (%) 
Combined Non-
vaccine 
(N=) 
N (%) 
P-value 
YES  
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
NO 
XX (XX.X%) 
XX (XX.X%) 
        Alive and Not in CR/sCR 
XX (XX.X%) 
XX (XX.X%) 
        Dead  
XX (XX.X%) 
XX (XX.X%) 
        Not Evaluable 
XX 
XX 
 
Stratum 2: VGPR/PR/SD at Randomization 
Alive and in CR/sCR 
Vaccine 
(N=) 
N (%) 
Combined Non-
vaccine 
(N=) 
N (%) 
P-value 
YES  
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
NO 
XX (XX.X%) 
XX (XX.X%) 


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        Alive and Not in CR/sCR 
XX (XX.X%) 
XX (XX.X%) 
        Dead  
XX (XX.X%) 
XX (XX.X%) 
        Not Evaluable 
XX 
XX 
 
 
Cochran-Mantel-Haenszel Test for Stratification 
Strata 
Stratified Odds Ratio 
80% Confidence 
Interval 
Vaccine vs Combined Non-Vaccine 
X.XX 
X.XX, X.XX 
             *Note: P-value from heterogeneity test  
 
A secondary pairwise analysis for CR/sCR rate will be conducted between vaccine and 
each non-vaccine group. Tabulation formats will be similar for each pair of group 
comparison.  
 
Alive and in CR/sCR 
Vaccine 
(N=) 
N (%) 
Non-vaccine Group 1: 
Lenalidomide/GM-CSF 
(N=) 
N (%) 
P-value 
YES  
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
NO 
XX (XX.X%) 
XX (XX.X%) 
        Alive and Not in CR/sCR 
XX (XX.X%) 
XX (XX.X%) 
        Dead  
XX (XX.X%) 
XX (XX.X%) 
        Not Evaluable 
XX 
XX 
 
Alive and in CR/sCR 
Vaccine 
(N=) 
N (%) 
Non-vaccine Group 2: 
Lenalidomide Alone 
(N=) 
N (%) 
P-value 
YES  
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
NO 
XX (XX.X%) 
XX (XX.X%) 
        Alive and Not in CR/sCR 
XX (XX.X%) 
XX (XX.X%) 
        Dead  
XX (XX.X%) 
XX (XX.X%) 
        Not Evaluable 
XX 
XX 
 
 
 


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EXHIBIT 1401-4: Disease Response 
Disease response to treatment on surviving participants will be tabulated at each 
assessment time point post-transplant at 6 months, 1 year and 2 years. 
Disease Response at Each Assessment Time Point Post Transplant 
Assessment Time 
Point 
Disease Response1  
Vaccine 
(N=) 
N (%) 
Lenalidomide/GM-
CSF 
(N=) 
N (%) 
Lenalidomide 
Alone 
(N=) 
N (%) 
Total 
(N=) 
N (%) 
6 months Post 
Transplant 
 
 
Stringent Complete Response 
(sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response 
(VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
1 Year Post 
Transplant 
 
 
Stringent Complete Response 
(sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response 
(VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
2 Years Post 
Transplant 
 
Stringent Complete Response 
(sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response 
(VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death  
 
 
 
 
Loss to Follow Up 
 
 
 
 
 
 
Proportion of Surviving Participants with sCR/CR/VGPR 
Assessment Time Point 
Post Transplant 
Vaccine 
(N=) 
N (%) 
Combined Non-
vaccine 
(N=) 
N (%) 
P-value2 
6 Months 
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
1 Year 
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
2 Years 
XX (XX.X%) 
XX (XX.X%) 
X.XXX 
Note:  
1 Participants that died or loss to follow up prior to the assessment time will be categorized as failures for this analysis. 
2 P-value from Chi-square test.  
 


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Disease response to treatment on surviving participants will be tabulated at each 
assessment time point during the maintenance therapy. 
Assessment 
Time Point 
Disease Response  
Vaccine 
(N=) 
N (%) 
Lenalidomide/GM-
CSF 
(N=) 
N (%) 
Lenalidomide 
Alone 
(N=) 
N (%) 
Total 
(N=) 
N (%) 
Cycle 3 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
Cycle 6 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
Cycle 9 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
Cycle 12 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
Cycle 15 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death  
 
 
 
 
Loss to Follow Up 
 
 
 
 
Cycle 18 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death  
 
 
 
 
Loss to Follow Up 
 
 
 
 
Cycle 21 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
Cycle 24 
Stringent Complete Response (sCR) 
 
 
 
 
Complete Response (CR) 
 
 
 
 


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June 7, 2019 
 
Very Good Partial Response (VGPR) 
 
 
 
 
Partial Response (PR) 
 
 
 
 
Stable Disease (SD) 
 
 
 
 
Progression (PD) 
 
 
 
 
Death 
 
 
 
 
Loss to Follow Up 
 
 
 
 
 
 
 
 
A secondary pairwise analysis for sCR/CR/VGPR rate will be conducted between 
vaccine and each non-vaccine group. 
 
Assessment Time 
Point Post 
Transplant 
Vaccine 
(N=) 
N (%) 
Lenalidomide/GM-
CSF  
(N=) 
N (%) 
Lenalidomide 
Alone 
(N=)              
N (%) 
6 Months 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
1 Year 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
2 Years 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
Treatment Group Comparison 
p-value1 
Vaccine vs Lenalidomide/GM-CSF 
0.XX 
Vaccine vs Lenalidomide Alone 
0.XX 
Lenalidomide/GM-CSF vs Lenalidomide Alone 
0.XX 
Note: 1 P-value from Chi-square test. The two-sided significance level is 0.05 for each pairwise comparison. 
 
The proportions of participants achieving CR among the subset of participants who are 
not in CR at the time of randomization will be compared between groups.  
 
CR/sCR Rate 
Among Non-CR at 
Randomization 
Vaccine 
(N=) 
N (%) 
Lenalidomide/GM-
CSF  
(N=) 
N (%) 
Lenalidomide 
Alone 
(N=)              
N (%) 
6 Months 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
1 Year 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
2 Years 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 


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EXHIBIT 1401-5:  Cumulative Incidence of Relapse/Progression 
The cumulative incidence of myeloma progression/disease progression will be plotted. 
Disease Progression by Treatment Arm 
 
Cumulative Incidence Estimates and 95% Confidence Intervals for Disease Progression: 
Disease Progression  
Vaccine 
(N=) 
Combined Non-
Vaccine 
(N=) 
P-value from Gray’s 
Test 
At 1 Year (95% CI) 
 
 
 
At 2 Years (95% CI) 
 
 
 
 
 
 
 
 
 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Incidence for Progression
Non-vaccine
Vaccine
66
64
62
60
57
56
55
55
66
64
62
60
57
56
55
55
Non-vaccine
Vaccine
t Risk


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For the secondary pairwise analysis, the cumulative incidence of myeloma 
progression/disease progression will be plotted by each treatment group. 
 
 
Cumulative Incidence Estimates and 95% Confidence Intervals for Disease Progression: 
Disease Progression  
Vaccine 
(N=) 
Lenalidomide/GM-CSF  
(N=) 
Lenalidomide Alone  
(N=) 
At 1 Year (95% CI) 
 
 
 
At 2 Years (95% CI) 
 
 
 
 
 
Gray’s Test for Pairwise Comparisons Post Randomization 
Treatment Group Comparison 
p-value1 
Vaccine vs Lenalidomide/GM-CSF 
0.XX 
Vaccine vs Lenalidomide Alone 
0.XX 
Lenalidomide/GM-CSF vs Lenalidomide Alone 
0.XX 
Note: 1The two-sided significance level is 0.05 for each pairwise comparison. 
 
 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Incidence of Progression
Len
Len/GM-CSF
Vaccine
66
64
62
60
57
56
55
55
33
32
32
31
31
30
29
29
33
31
30
30
29
28
27
27
Len
Len/GM-CSF
Vaccine
t Risk


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EXHIBIT 1401-6:  Cumulative Incidence of Treatment-related Mortality (TRM) 
The cumulative incidence of treatment-related mortality will be plotted. 
Treatment-related Mortality by Treatment Arm 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Incidence for TRM
Non-vaccine
Vaccine
66
64
62
60
57
56
55
55
66
64
62
60
57
56
55
55
Non-vaccine
Vaccine
t Risk
Cumulative Incidence Estimates and 95% Confidence Intervals for TRM: 
TRM  
Vaccine 
(N=) 
Combined Non-Vaccine 
(N=) 
P-value from Gray’s 
Test 
At 1 Year (95% CI) 
 
 
 
At 2 Years (95% CI) 
 
 
 
 
 
 
 
 
 
 
 
 
 


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For the secondary pairwise analysis, the cumulative incidence of treatment-related 
mortality will be plotted by three treatment groups. 
 
 
Cumulative Incidence Estimates and 95% Confidence Intervals for TRM: 
TRM  
Vaccine 
(N=) 
Lenalidomide/GM-CSF  
(N=) 
Lenalidomide Alone  
(N=) 
At 1 Year (95% CI) 
 
 
 
At 2 Years (95% CI) 
 
 
 
 
 
Gray’s Test for Pairwise Comparisons 
Treatment Group Comparison 
p-value1 
Vaccine vs Lenalidomide/GM-CSF 
0.XX 
Vaccine vs Lenalidomide Alone 
0.XX 
Lenalidomide/GM-CSF vs Lenalidomide Alone 
0.XX 
Note: 1The two sided-significance level is 0.05 for each pairwise comparison. 
 
 
 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Incidence of TRM
Len
Len/GM-CSF
Vaccine
66
64
62
60
57
56
55
55
33
32
32
31
31
30
29
29
33
31
30
30
29
28
27
27
Len
Len/GM-CSF
Vaccine
t Risk


Version 1.0 
29 
June 7, 2019 
 
EXHIBIT 1401-7: Progression-Free Survival (PFS)  
The progression-free survival post randomization will be plotted and summarized 
 
*Note: P-value from log-rank test can be added to the plot 
 
Kaplan Meier Estimates and 95% Confidence Intervals for PFS  
Progression-free Survival 
Vaccine 
(N=) 
Non-Vaccine 
(N=) 
P-value from 
Log-rank test 
At 1 Year (95% CI) 
 
 
 
At 2 Years (95% CI) 
 
 
       
Cox Proportional Hazards Regression Model for PFS 
 
Covariates 
Level 
N 
HR 
95% CI 
P-value 
Treatment 
Group 
 Non-vaccine 
XX 
1.00 
 
 
 
Vaccine  
XX 
X.XX 
X.XX – X.XX 
X.XX 
 
 
 
 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Progression-free Survival Probability
Non-vaccine
Vaccine
66
64
62
60
57
56
55
55
66
62
61
56
56
56
54
53
Non-vaccine
Vaccine
t Risk


Version 1.0 
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June 7, 2019 
 
For the secondary pairwise analysis, the progression-free survival will be plotted by 
three treatment groups. 
 
Kaplan Meier Estimates and 95% Confidence Intervals for PFS: 
Progression-free Survival 
Vaccine 
(N=) 
Lenalidomide/GM-CSF  
(N=) 
Lenalidomide Alone  
(N=) 
At 1 Year (95% CI) 
 
 
 
At 2 Years (95% CI) 
 
 
 
 
Log Rank Test for Pairwise Comparisons 
Treatment Group Comparison 
p-value1 
Vaccine vs Lenalidomide/GM-CSF 
0.XX 
Vaccine vs Lenalidomide Alone 
0.XX 
Lenalidomide/GM-CSF vs Lenalidomide Alone 
0.XX 
Note: 1The two-sided significance level is 0.05 for each pairwise comparison. 
 
 
 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Progression-free Survival Probability
Len
Len/GM-CSF
Vaccine
66
64
62
60
57
56
55
55
33
32
32
31
31
30
29
29
33
31
30
30
29
28
27
27
Len
Len/GM-CSF
Vaccine
t Risk


Version 1.0 
31 
June 7, 2019 
 
EXHIBIT 1401-8: Overall Survival (OS) 
The overall survival post randomization will be plotted and summarized.  
The summary table and figures will follow exactly the same format as for PFS in Exhibit 
1401-7. 
 
 


Version 1.0 
32 
June 7, 2019 
 
EXHIBIT 1401-9:  Incidence of Toxicities Grade ≥ 3 per CTCAE Version 4.0 
Toxicities will be summarized in system organ class (SOC). If investigators have interest 
in specific toxicities with high incidence, we can tabulate frequencies for these toxicities 
per request. Toxicity frequencies by SOC and breakdown down by grade 3, grade 4, 
grade 5 can be summarized at each assessment time point.  
Category (SOC) 
Involved Toxicity/Organ 
Auditory Disorders 
hearing loss 
Blood and Lymphatic Disorders 
anemia, lymphopenia, neutropenia, thrombocytopenia, thrombotic thrombocytopenic purpura, 
disseminated intravascular coagulation, febrile neutropenia 
Cardiovascular Disorders 
left ventricular systolic dysfunction, cardiac arrhythmia, myocardial infarction, pericardial effusion, 
new or worsening heart failure, pericarditis 
Endocrine Disorders 
hyperthyroidism, hypothyroidism 
GI Disorders 
abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia, nausea, oral mucositis, 
vomiting 
General Disorders 
non-cardiac chest pain, chills, generalized edema, fatigue, fever 
Hemorrhagic Disorders 
hemorrhage 
Hepatobiliary/Pancreas Disorders 
hepatitis, liver failure, pancreatitis, bilirubin, ALT, AST, alkaline phosphatase 
Immune System Disorders 
allergic reaction, anaphylaxis 
Investigations 
increased creatinine, weight loss, prolongation of QTc interval 
Metabolism and Nutrition Disorders 
dehydration, hypercalcemia, hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, tumor 
lysis syndrome  
Musculoskeletal and Connective Tissue 
Disorders 
arthralgia, myalgia, muscle weakness, musculoskeletal pain 
Nervous System Disorders 
anxiety, ataxia, confusion, depression, dizziness, headache, insomnia, somnolence, seizure, 
stroke, tremor, cranial palsy, depressed level of consciousness, edema cerebral, encephalopathy, 
neuralgia, neuropathy, PRES, spinal cord compression (non-malignant), syncope 
Ocular/Visual Disorders 
conjunctivitis, blurred vision 
Renal Disorders 
cystitis noninfective, acute kidney injury, chronic kidney disease  
Respiratory, Thoracic and Mediastinal 
Disorders 
cough, dyspnea, hypoxia, sinusitis, sore throat, adult respiratory distress syndrome, pleural 
effusion (non-malignant), pneumonitis, pulmonary hypertension 
Skin and Subcutaneous Tissue Disorders 
dry skin, pruritus, rash, erythema multiforme, pyoderma gangrenosum, Sweet’s syndrome (acute 
neutrophilic dermatosis) 
Vascular Disorders 
lymphedema, hypertension, hypotension, capillary leak syndrome, thromboembolic event, 
vasculitis 
Abnormal Liver Symptoms 
jaundice, hepatomegaly, right upper quadrant pain, weight gain (>5%) from baseline 
 
 
 
 
 


Version 1.0 
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June 7, 2019 
 
Toxicity Summary by System Organ Class 
 
Grade 3-5 Toxicities  
 
Vaccine 
(N=) 
Lenalidomide/GM-CSF 
(N=) 
Lenalidomide Alone 
(N=) 
System Organ Class 
# Event 
# Participants1 
# Event 
# Participants1 
# Event 
# Participants1 
Auditory Disorders 
 
 
 
 
 
 
Blood and Lymphatic System Disorders  
 
 
 
 
 
Cardiac disorders 
 
 
 
 
 
 
Endocrine Disorders 
 
 
 
 
 
 
Gastrointestinal Disorders 
 
 
 
 
 
 
General Disorders 
 
 
 
 
 
 
Hemorrhagic Disorders 
 
 
 
 
 
 
Hepatobiliary/Pancreas Disorders 
 
 
 
 
 
 
Immune System Disorders 
 
 
 
 
 
 
Investigations 
 
 
 
 
 
 
Metabolism and Nutrition Disorders 
 
 
 
 
 
 
Musculoskeletal and Connective Tissue 
Disorders 
 
 
 
 
 
 
Nervous System Disorders 
 
 
 
 
 
 
Ocular/Visual Disorders 
 
 
 
 
 
 
Renal and Urinary Disorders 
 
 
 
 
 
 
Respiratory,Thoracic,and Mediastinal 
Disorders 
 
 
 
 
 
 
Skin and Subcutaneous Tissue 
Disorders 
 
 
 
 
 
 
Vascular Disorders 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
Toxicity Summary by Time Period 
 
Assessment Time 
Period  
Vaccine 
Lenalidomide/GM-CSF 
Lenalidomide Alone 
# 
Pts1 
# Pts with 
an event 
reported 
# 
Events 
% Pts 
with 
events 
# 
Pts1 
# Pts with 
an event 
reported 
# 
Events 
% Pts 
with 
events 
# 
Pts1 
# Pts with 
an event 
reported 
# 
Events 
% Pts 
with 
events 
Within Day 100 
 
 
 
 
 
 
 
 
 
 
 
 
100 Days to 1 Year 
 
 
 
 
 
 
 
 
 
 
 
 
1 Year to 2 Years 
 
 
 
 
 
 
 
 
 
 
 
 
Overall  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 1.0 
34 
June 7, 2019 
 
EXHIBIT 1401-10: Incidence of Infections 
Infection events will be tabulated for two periods. 
Period 1: From transplant to Randomization: 
 
 
Total 
N    % 
# Participants transplanted 
 
# Participants with Infections 
 
# Participants with Infection Reports 
 
           =1 
 
           =2 
 
           =3 
 
           =4 
 
           =5 
 
           >=6 
 
Total Infection Events 
 
Infection Period 
 
           Within First month of Transplant 
 
           Post first month of Transplant 
 
Maximum Severity by Participant 
 
           None 
 
           Grade 2 
 
           Grade 3 
 
Infection by Type (# of Participants) 
 
           Bacterial 
 
           Viral 
 
           Fungal 
 
           Protozoal 
 
           Other 
 
 
 
Period 2: Post randomization by treatment arm 
 
 
Treatment Arm 
 
Vaccine   
Lenalidomide/G
M-CSF 
Lenalidomide 
Alone 
Total 
N    % 
N    % 
N    % 
N    % 
# Participants Randomized 
 
 
 
 
# Participants with Infections 
 
 
 
 
# Participants with Infection Reports 
 
 
 
 
           =1 
 
 
 
 
           =2 
 
 
 
 
           =3 
 
 
 
 
           =4 
 
 
 
 


Version 1.0 
35 
June 7, 2019 
 
 
Treatment Arm 
 
Vaccine   
Lenalidomide/G
M-CSF 
Lenalidomide 
Alone 
Total 
N    % 
N    % 
N    % 
N    % 
           =5 
 
 
 
 
           >=6 
 
 
 
 
Total Infection Events 
 
 
 
 
Infection Period 
 
 
 
 
           First 100 Days 
 
 
 
 
           100 Days to 1 Year 
 
 
 
 
           1 Year to 2 Years 
 
 
 
 
Maximum Severity by Participant 
 
 
 
 
           None 
 
 
 
 
           Grade 2 
 
 
 
 
           Grade 3 
 
 
 
 
Infection by Type (# of Participants) 
 
 
 
 
           Bacterial 
 
 
 
 
           Viral 
 
 
 
 
           Fungal 
 
 
 
 
           Protozoal 
 
 
 
 
           Other 
 
 
 
 
 
The cumulative incidence of Grade 3 infections will be compared between the vaccine 
and the combined non-vaccine groups.  
 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Incidence for Infection
Non-vaccine
Vaccine
66
64
62
60
57
56
55
55
66
64
62
60
57
56
55
55
Non-vaccine
Vaccine
t Risk


Version 1.0 
36 
June 7, 2019 
 
For the secondary pairwise analysis, the cumulative incidence will be plotted by three 
treatment groups. 
 
 
Cumulative Incidence Estimates and 95% Confidence Intervals for Grade 3 Infections  
Incidence of Grade 3 Infections 
Vaccine 
(N=) 
Lenalidomide/GM-CSF  
(N=) 
Lenalidomide Alone  
(N=) 
At 1 Year (95% CI) 
 
 
 
At 2 Years (95% CI) 
 
 
 
 
 
Log Rank Test for Pairwise Comparisons 
Treatment Group Comparison 
P-value1 
Vaccine vs Lenalidomide/GM-CSF 
0.XX 
Vaccine vs Lenalidomide Alone 
0.XX 
Lenalidomide/GM-CSF vs Lenalidomide Alone 
0.XX 
Note: 1The two-sided significance level is 0.05 for each pairwise comparison. 
 
 
 
 
 
 
 
 
 
3
6
9
12
15
18
21
24
Months Post Randomization
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Incidence of Infection
Len
Len/GM-CSF
Vaccine
66
64
62
60
57
56
55
55
33
32
32
31
31
30
29
29
33
31
30
30
29
28
27
27
Len
Len/GM-CSF
Vaccine
t Risk


Version 1.0 
37 
June 7, 2019 
 
EXHIBIT 1401-11: Minimal Residual Disease Assessment 
The proportions of patients with MRD present (MRD+) will be described using 
frequencies at pre-randomization and 9th cycle post randomization and compared 
between the vaccine arm with the no-vaccine arms combined using the chi-square test.   
 
MRD by Treatment Group 
% MRD + 
Vaccine 
(N=) 
Non-vaccine 
(N=) 
P-value 
Pre-randomization 
 
 
— 
Post-randomization at Cycle 9 
 
 
 
 
 
 
A secondary pairwise analysis of MRD comparing the vaccine arm, lenalidomide/GM-
CSF arm and the lenalidomide alone arm will also be conducted. 
 
% MRD + 
Vaccine 
(N=) 
Lenalidomide/GM-
CSF 
(N=) 
Lenalidomide 
Alone  
(N=) 
P-value 
Pre-randomization 
 
 
 
— 
Post-randomization at Cycle 9 
 
 
 
 
 
 
Pairwise Comparisons 
 
Treatment Group Comparison 
P-value 
Post-randomization at 
Cycle 9 
Vaccine vs Lenalidomide/GM-CSF 
0.XX 
Vaccine vs Lenalidomide Alone 
0.XX 
Lenalidomide/GM-CSF vs Lenalidomide Alone 
0.XX 
Note: 1The two-sided significance level is 0.05 for each pairwise comparison. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 1.0 
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June 7, 2019 
 
EXHIBIT 1401-12: Primary Immunologic Endpoint: Myeloma Reactive T Cells 
Myeloma-reactive T cells, as defined by the percentage of circulating CD4+ and CD8+ T 
cells that express IFN following ex vivo exposure to autologous tumor lysate will be 
assess in both treatment arms and summarized in below table. Log transformations will 
be used to induce normality in quantitative measurements, and if still non-normal, then 
nonparametric tests will be used.  The primary endpoint of log 10 peak change in tumor 
reactive T cells from baseline will be compared across the 3 groups using analysis of 
variance (ANOVA), and if significant then two-sample t-tests will be conducted for each 
pairwise comparison to determine which groups are different from one another.  If 
normal, two-sample t-test will be used for pairwise comparison. If not, the non-
parametric Kruskal-Wallis and Wilcoxon tests will be used. The two-sided significance 
level 0.05 will be used for each comparison.  
 
ANOVA for Log 10 Peak Change in Tumor Reactive T cells from Baseline 
Analysis of Variance on primary immunologic endpoint 
P-value 
Log 10 Peak Change From Baseline 
 
Pairwise Comparison if above is significant 
 
        Vaccine vs Lenalidomide/GM-CSF 
 
        Vaccine vs Lenalidomide Alone 
 
        Lenalidomide/GM-CSF vs Lenalidomide Alone 
 
 
Summary Statistics Table for Myeloma Reactive T Cells by Assessment Time Points 
Endpoint 
Assessment Time Point 
Vaccine 
Lenalidomide/GM-
CSF  
Lenalidomide 
Alone  
% CD8+ and CD4+ 
that express IFNγ 
Baseline 
 
 
 
Cycle 1 
 
 
 
Cycle 2 
 
 
 
Cycle 3 
 
 
 
Cycle 4 
 
 
 
Cycle 9 
 
 
 
 
Change from Baseline to Cycle 1 
 
 
 
 
Change from Baseline to Cycle 2 
 
 
 
 
Change from Baseline to Cycle 3 
 
 
 
 
Change from Baseline to Cycle 4 
 
 
 
 
Change from Baseline to Cycle 9 
 
 
 
 
Peak change from Baseline 
 
 
 
% Participants with >2.4-fold increase in IFNγ expression 
 
 
 
% Participants with >10-fold increase in IFNγ expression 
 
 
 
 
Note: Descriptive Statistics including N, Mean (Std), Median (Range), percentage will be calculated for each treatment 
group 


Version 1.0 
39 
June 7, 2019 
 
Secondary analyses of myeloma reactive T cell will be conducted and summarized.  
 
Linear Mixed Model for Repeated Measurements 
 
Treatment Group 
Least Squares 
Means 
Std Err 
P-value 
Vaccine 
 
 
Lenalidomide/GM-CSF 
 
 
Lenalidomide Alone 
 
 
 
Difference (Vaccine – Lenalidomide/GM-CSF) 
 
 
Difference (Vaccine – Lenalidomide Alone) 
 
 
Difference (Lenalidomide/GM-CSF – Lenalidomide Alone) 
 
 
 
Myeloma Reactive T Cells by Clinical Response (best clinical response) 
Myeloma reactive T cells  
Participants in 
CR/sCR 
Participants not 
in CR/sCR 
P-value 
Baseline 
 
 
 
Change from Baseline to Cycle 1 
 
 
 
Change from Baseline to Cycle 2 
 
 
 
Change from Baseline to Cycle 3 
 
 
 
Change from Baseline to Cycle 4 
 
 
 
Change from Baseline to Cycle 9 
 
 
 
Peak Change from baseline Over Time 
 
 
 
 
Multivariate Cox Proportional Hazards Regression Model for PFS 
 
Covariates 
N 
HR 
Parameter 
Estimate 
95% CI 
P-value 
Treatment group 
 
 
 
 
        Non-vaccine 
XX 
1.000 
- 
- 
 
- 
 
        Vaccine 
XX 
X.XXX 
 
(X.XXX, X.XXX) 
X.XXX 
Peak % CD8+ and CD4+ that express 
IFNγ (as time-dependent covariate, 
treated as continuous variable) 
 
 
 
 
 
Treatment group 
 
 
 
 
        Non-vaccine 
XX 
1.000 
- 
- 
- 
        Vaccine 
XX 
X.XXX 
 
(X.XXX, X.XXX) 
X.XXX 
Most Recent % CD8+ and CD4+ that 
express IFNγ (as time-dependent 
covariate, treated as continuous 
variable) 
 
 
 
 
 
 
 
 
 


Version 1.0 
40 
June 7, 2019 
 
EXHIBIT 1401-13:  Secondary Immunologic Endpoints 
Additional exploratory analyses will be conducted in a similar fashion to examine a 
number of secondary immunologic endpoints, including: 1) antigen specific reactivity by 
tetramer analysis, 2) quantification of T-cell subsets and PD-1 expressing lymphocytes 
by flow cytometry 3) quantification of NK cell populations with inhibitor and activating 
markers, 4) NK-cell cytotoxic function as measured by IFNγ and CD107a degranulation 
in response to ex vivo exposure to autologous MM cells, and 5) humoral response 
against autologous MM cells and myeloma associated antigens such as MUC1, and 
vaccine-induced myeloma-specific plasmablast responses. 
Profiles of these secondary immunologic endpoints will be described at each time point 
for each group using summary statistics and compared between the groups using mixed 
models for repeated measures data, using the same format as described in Exhibit 
1401-12.  Exploratory analysis on the association of secondary immunologic endpoints 
and the primary clinical outcome ((1-year disease response) will be conducted for each 
secondary immunologic endpoint with treatment groups pooled. 
 
Summary Statistics Table for Secondary Immunologic Endpoints by Treatment Group 
Endpoint 
Assessment 
Time Point 
Vaccine 
Lenalidomide/GM-
CSF  
Lenalidomide 
Alone  
Myeloma Antigen-specific T 
Cells: CD8+ binding tetramer 
Baseline 
 
 
 
Cycle 1 
 
 
 
Cycle 2 
 
 
 
Cycle 3 
 
 
 
Cycle 4 
 
 
 
Cycle 9 
 
 
 
Functionla Characteristics of 
Tetramer + Population 
IFNγ, granzyme B, IL-4, IL-
10 
Baseline 
 
 
 
Cycle 1 
 
 
 
Cycle 2 
 
 
 
Cycle 3 
 
 
 
Cycle 4 
 
 
 
Cycle 9 
 
 
 
Subset of T Cells: CR45RA, 
CR45RO, CD27, CD62L, 
CD4/CD25/FOP3, CD11b, 
HLA-dr, CD14, CD15, CD33 
Baseline 
 
 
 
Cycle 1 
 
 
 
Cycle 2 
 
 
 
Cycle 3 
 
 
 
Cycle 4 
 
 
 
Cycle 9 
 
 
 
NK Cells 
Prior to Cycle 
1 
 
 
 
Cycle 2+7 
days 
 
 
 


Version 1.0 
41 
June 7, 2019 
 
Cycle 3 
 
 
 
Cycle 4+7days 
 
 
 
Cycle 9 
 
 
 
Vaccine-induced 
myeloma-specific 
Plasmabast Response 
Baseline 
 
 
 
Cycle 2 
 
 
 
Cycle 2+7 
days 
 
 
 
Cycle 4 
 
 
 
Note: Descriptive Statistics including N, Mean (Std), Median (Range) will be calculated for each treatment group 
 
 
e.g. for the CD8+ endpoint, 
Linear Mixed Model for Repeated Measurements 
 
CD8+ by Treatment Group 
Least Squares 
Means 
Std Err 
P-value 
Vaccine 
 
 
Lenalidomide/GM-CSF 
 
 
Lenalidomide Alone 
 
 
 
Secondary Immunologic Endpoint CD8+ by Primary Clinical Endpoint  
Myeloma Antigen-specific T Cells: 
CD8+ binding tetramer 
Participants in 
CR/sCR @ 1 year 
Participants not in 
CR/sCR @ 1 year 
P-value 
Baseline 
 
 
 
Change from Baseline to Cycle 1 
 
 
 
Change from Baseline to Cycle 2 
 
 
 
Change from Baseline to Cycle 3 
 
 
 
Change from Baseline to Cycle 4 
 
 
 
Change from Baseline to Cycle 9 
 
 
 
Peak Change from baseline Over Time 
 
 
 
 
If normal, two-sample t-test will be used for the comparison. If not, non-parametric test 
will be used. 
 
 
 


Version 1.0 
42 
June 7, 2019 
 
Supplemental Exhibit 1401-1:  Enrollment  
A table will be provided showing actual monthly accrual for each participating center 
from study initiation to accrual closure. The number of randomized participants will be 
provided in a separate table.  
A figure will be provided showing projected and actual accrual from study initiation to 
accrual closure.  
 
 
Accrual to Protocol 1401 
Number of Participants 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Months Post Study Initiation 
 
Supplemental Exhibit 1401-2:  Significant Protocol Deviations 
A listing of significant protocol deviations will be provided to describe each deviation.   
Supplemental Exhibit 1401-3:  Primary Cause of Death 
A table summarizing the primary cause of death by treatment group will be provided.   
Supplemental Exhibit 1401-4:  Adverse Events 
A table summarizing the MedDRA-coded System Organ Class (SOC) of the adverse 
events reported will be provided by treatment group.   
Supplemental Exhibit 1401-5:  Serious or Grades 3-5 Adverse Events 
A table summarizing the SOC of the serious or Grades 3-5 adverse events will be 
provided by treatment group. 


Version 1.0 
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June 7, 2019 
 
 
Grade 3-5 AEs Post-Randomization 
 
Vaccine 
(N=) 
Lenalidomide/GM-
CSF 
(N=) 
Lenalidomide Alone 
(N=) 
Total 
System Organ Class 
# 
Event 
# 
Participants 
# 
Event 
# 
Participants # Event 
# 
Participants 
# 
Event 
# 
Participants 
Auditory Disorders 
 
 
 
 
 
 
Blood and Lymphatic System Disorders 
 
 
 
 
 
 
Cardiac disorders 
 
 
 
 
 
 
Endocrine Disorders 
 
 
 
 
 
 
Gastrointestinal Disorders 
 
 
 
 
 
 
General Disorders 
 
 
 
 
 
 
Hemorrhagic Disorders 
 
 
 
 
 
 
Hepatobiliary/Pancreas Disorders 
 
 
 
 
 
 
Immune System Disorders 
 
 
 
 
 
 
Investigations 
 
 
 
 
 
 
Metabolism and Nutrition Disorders 
 
 
 
 
 
 
Musculoskeletal and Connective Tissue 
Disorders 
 
 
 
 
 
 
Nervous System Disorders 
 
 
 
 
 
 
Ocular/Visual Disorders 
 
 
 
 
 
 
Renal and Urinary Disorders 
 
 
 
 
 
 
Respiratory,Thoracic,and Mediastinal 
Disorders 
 
 
 
 
 
 
Skin and Subcutaneous Tissue Disorders  
 
 
 
 
 
Vascular Disorders 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 1.0 
44 
June 7, 2019 
 
Supplemental Exhibit 1401-6:  Safety Monitoring (Safety Endpoints) 
Figure of SPRT to illustrate safety monitoring stopping guidelines. 
 
 
 
 

Prot_000.pdf: 
 
 
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple 
Myeloma with or without Vaccination with Dendritic Cell /Myeloma 
Fusions  
(Posted on clinincaltrials.gov as NCT02728102) 
 
BMT CTN PROTOCOL 1401 
Version 4.0 
 
Study Co-Chairs 
David Avigan, MD1, Nina Shah, MD2, David Chung, MD3 
 
Protocol Team 
Devine, Steven4 
Fay, Joseph5 
Geller, Nancy6 
Holstein, Sarah7 
Lazarus, Hillard8 
 
Logan, Brent9 
Mendizabal, Adam10 
Nelson, Courtney10 
O’Brien, Kelly10 
Pasquini, Marcelo9 
 
Poland, Nancy11 
Rosenblatt, Jacalyn1 
Rapoport, Aaron12 
Soiffer, Robert13 
Waller, Edmund14
Manufacturing Team: 
Choi, Chris7 
Copland, Ian14 
Hematti, Peiman15 
O'Donnell, Lynn4 
Reese, Jane8 
Keever-Taylor, Carolyn16 
Young, James3   
Zurawski, Gerard5 
Uhl, Lynne1 
Stroopinsky, Dina1 
Herman, Michele1
 
Sponsored by the National Institutes of Health 
National Heart, Lung, and Blood Institute and National Cancer Institute 
FDA IND # 16655 
 
1 Beth Israel Deaconess Medical 
Center  
2 University of California-  San 
Francisco 
3 Memorial Sloan-Kettering 
Cancer Center 
4 The Ohio State University  
5 Baylor Institute for 
Immunology Research, Baylor 
Research Institute  
6 National Heart, Lung, and 
Blood Institute 
7 Roswell Park Cancer Institute  
8 University Hospitals Case 
Medical Center, Case Western 
Reserve University 
9 Center for International Blood 
and Marrow Transplant 
Research, Medical College of 
Wisconsin 
10 The EMMES Corporation 
11 National Marrow Donor 
Program 
12University of Maryland 
13 Dana Farber Cancer Institute  
14 Emory University 
15 University of Wisconsin  
16 Medical College of Wisconsin   
 
 
________________________________________                     ________________________________________ 
Approval Signature (Protocol Chair/Officer) 
 
Approval Signature (Protocol Chair/Officer) 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine - 1401  
Version 4.0 dated July 24, 2018  
 
i 
 
Core Study Participants: 
Affiliate Study Participants: 
University Hospitals Case Medical Center,  
Case Western Reserve University 
Emory University  
Fred Hutchinson Cancer Research Center  
Memorial Sloan Kettering Cancer Center 
Mount Sinai Medical Center  
Ohio State University  
Roswell Park Cancer Institute  
University of Minnesota 
University of Nebraska  
University of California-San Francisco  
Medical College of Wisconsin  
Beth Israel Deaconess Medical Center  
University of Maryland 
University of Wisconsin 
University of Texas, MD Anderson Cancer
Center 
Thomas Jefferson University  
 
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine - 1401  
Version 4.0 dated July 24, 2018  
 
ii 
PROTOCOL SYNOPSIS – BMT CTN 1401 PROTOCOL 
 
 
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed 
by Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination with 
Dendritic Cell (DC)/Myeloma Fusions  
 
Co- Principal Investigators: 
David Avigan, MD, Nina Shah, MD, David Chung, MD 
 
Study Design: 
The study is designed as a Phase II, multicenter trial of 
vaccination with DC/myeloma fusions with granulocyte 
macrophage colony-stimulating factor (GM-CSF) adjuvant plus 
lenalidomide maintenance therapy versus maintenance therapy 
alone or with GM-CSF following autologous transplant as part of 
upfront treatment of multiple myeloma (MM).   
 
Primary Objective: 
The primary objective of this randomized trial is to compare the 
proportion of patients alive and in complete response (defined as 
CR or sCR) at one year post transplant (or approximately 10 
months post randomization) between patients receiving 
DC/myeloma vaccine/GM-CSF with lenalidomide maintenance 
therapy to those receiving lenalidomide maintenance therapy 
with or without GM-CSF.   
 
Clinical Secondary Objectives:  
 
 
To compare DC/myeloma vaccine/GM-CSF with lenalidomide 
maintenance therapy to lenalidomide maintenance therapy  with 
or without GM-CSF with respect to: myeloma response (sCR, 
CR, VGPR, PR, and SD), conversion of partial to complete 
response, disease progression, treatment-related mortality, 
progression-free survival, overall survival, toxicities according to 
the Common Terminology Criteria for Adverse Events (CTCAE) 
v4.0, incidence of infections, and  measures of minimal residual 
disease at one year post transplant (or approximately 10 months 
from randomization). Secondary exploratory analyses will also 
be conducted to compare in a pairwise fashion the vaccine arm, 
lenalidomide/GM-CSF arm, and lenalidomide alone arm, to 
describe the proportion of patients with collection of tumor cells 
who reach randomization, compliance with vaccine, and to 
describe the reproducibility of the vaccine manufacturing based 
on the release criteria. 
 
Immunologic Objectives: 
The primary immunologic endpoint is to compare the effect of 
DC/myeloma vaccine/GM-CSF with lenalidomide maintenance 
therapy to lenalidomide maintenance therapy alone or with GM-
CSF on treatment-induced expansion of myeloma-specific  


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T cells, defined as a 2.4-fold increase from pre-therapy to peak 
post-treatment levels. 
 
Secondary immunologic endpoints will compare each of the 
treatment arms for: a) the percent of patients achieving at least a 
10-fold expansion of myeloma-specific T cells; b) expansion of 
myeloma antigen-specific T cells by tetramer analysis; c) 
quantification of T cell subsets and PD-1 expressing 
lymphocytes; d) quantification of NK cells and identification of 
activation and inhibitory ligands; e) assessment of NK-mediated 
killing of myeloma targets; f) assessment of humoral response 
against whole myeloma cells and myeloma-associated antigens 
by SEREX and by characterizing myeloma-specific plasmablast 
responses. 
 
Eligibility: 
Patients must be considered transplant eligible by treating 
physician at the time of study. Patients will be enrolled prior to 
tumor cell collection for vaccine manufacturing. Eligible patients 
are ≥18.00 and < 71.00 years of age with symptomatic multiple 
myeloma requiring treatment, without history of prior disease 
progression or prior HCT, Karnofsky performance score ≥70%, 
evidence of at least 20% plasma cells in a bone marrow 
differential within 60 days of enrollment, and have received <1 
cycle of systemic anti-myeloma therapy. If patient receives anti-
myeloma therapy treatment after bone marrow aspirate to assess 
eligibility and before bone marrow aspirate for tumor cell 
collection, a repeat bone marrow evaluation will be required to 
confirm > 20% plasma cells in the bone marrow aspirate 
differential prior to enrollment and tumor cell collection.  Patients 
with prior auto or allo transplant are not eligible. Patients with 
active autoimmune diseases will be excluded.  
 
Treatment Plan: 
After meeting the initial eligibility criteria, patients will undergo 
harvesting of myeloma cells for assessment of immune response 
and for vaccine generation.   Patients will have 30 mL of marrow 
harvested 
and 
cryopreserved 
after 
undergoing 
immunophenotypic analysis per the BMT CTN 1401 
Manufacturing SOPs.  Patients will then complete initial systemic 
anti-myeloma therapy and autologous hematopoietic stem cell 
mobilization and collection according to institutional practices.  
 
 
Approximately 2 months post-transplant, patients will undergo 
disease response assessment and will be randomized 2:1:1 to 
vaccine/GM-CSF plus lenalidomide maintenance, lenalidomide 
alone, or lenalidomide/GM-CSF. Patients randomized to the 
vaccine plus lenalidomide arm will undergo leukapheresis for 


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dendritic cell generation for vaccine manufacturing. All patients 
will start lenalidomide maintenance Day 90-100 post transplant. 
Patients randomized to the vaccine arm will receive vaccine the 
first day of cycles 2, 3, and 4 of maintenance. Vaccine will be 
administered by subcutaneous injection with 100 ug GM-CSF 
given subcutaneously at the vaccine site on day of vaccination 
and daily for a total of 4 days. Patients randomized to 
lenalidomide/GM-CSF will receive 100 ug GM-CSF given 
subcutaneously daily for a total of 4 days starting the first day of 
cycles 2, 3 and 4 of maintenance.  Lenalidomide maintenance 
will continue for 2 years for patients who continue free of 
progression. 
 
  
Vaccine Production and Characterization: 
Vaccine Production will consist of the following steps per the 
BMT CTN 1401 Manufacturing SOPs: 
1) Bone marrow aspiration of 30 mL, isolation of mononuclear 
cells by ficoll centrifugation, quantification of CD138+ or 
CD38+ 
cells 
by 
immunocytochemistry, 
and 
cryopreservation. 
2) Leukapheresis 
collection 
post 
transplant 
and 
after 
randomization.   
3) Mononuclear cells isolated by ficoll density centrifugation.  
Adherent cells segregated following 1 hour culture and then 
cultured for 5-7 days with GM-CSF and IL-4.  Cultures are 
re-fed with cytokines after 3 days.  Maturation with TNFα for 
48-72 hours.  DCs are harvested and undergo characterization 
by immunocytochemistry for expression of DR, CD86, and 
CD83.   
4) Tumor cells are thawed and re-characterized. 
5) DC and tumor cells are pelleted and co-cultured in the 
presence of PEG at a ratio of 3:1. 
6) Fusion cells are quantified by determining the percentage of 
dual expressing cells by immunocytochemistry. 
 
Vaccine Release criteria: 
1) At least 20% of tumor cell prep must express CD38 or CD138 
by staining 
2) Tumor cell prep must yield >10 million plasma cells1 
3) 50% of DC prep express CD86 
4) Viability of DC prep > 50% 
5) Fusion efficiency > 15% 
6) Fusion viability > 50% 
                                                 
1 Plasma cell count is determined by multiplying the total mononuclear cell yield by the percent of CD38 and CD138 
staining reported on the Immunohistochemistry Report 


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7) Sterility, mycoplasma, and endotoxin assays are negative 
 
Accrual Objective: 
Target accrual is 132 patients randomized to vaccine/GM-CSF/ 
lenalidomide (n=66), lenalidomide alone (n=33), lenalidomide 
/GM-CSF (n=33), with an estimated total enrollment of 188, 
assuming about 30% of patients are unable to proceed with  
post-transplant immunotherapy. 
  
Accrual Period: 
36 months 
 
Study Duration: 
Patients will be followed for approximately 3 years after 
maintenance initiation  
 
Interim Analysis: 
There will be no interim analysis for efficacy or futility.  
 
 
 


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STUDY SCHEMA 
 
 
 
Initial Inclusion Criteria  
1. 
Transplant Eligible  
2. 
Meet criteria for symptomatic multiple myeloma (Appendix A)  
3. 
Age >18.00 – < 71.00  
4. 
Karnofsky Performance of > 70% 
5. 
20% plasma cells in the bone marrow < 60 days prior to 
enrollment1 
6. 
Received < 1 cycles of systemic anti-myeloma therapy2 
7. 
Creatinine clearance > 40 mL/min (estimated or calculated) 
 
1 
If patient receives anti-myeloma therapy treatment after bone 
marrow aspirate to assess eligibility and before bone marrow 
aspirate for tumor cell collection, a repeat bone marrow 
evaluation will be required to confirm > 20% plasma cells in the 
bone marrow aspirate differential prior to enrollment and tumor 
cell collection.   
2 
Anti-myeloma therapy is defined as systemic treatment intended 
to treat the underlying myeloma disease. Treatments intended to 
alleviate pain and other symptoms of disease and/or 
administration of ≤160mg of dexamethasone or equivalent 
alternative steroid dose within a 30 day period are not considered 
anti-myeloma therapy. 
Initial Exclusion Criteria  
1. 
Prior Autologous or Allogeneic HCT   
2. 
Non secretory multiple myeloma (defined as normal serum and 
urine immunofixation and normal serum free light chain assay). 
3. 
Patients with a history of Plasma Cell Leukemia at any time 
prior to enrollment  
4. 
Patients with prior disease progression at any time prior to 
enrollment 
5. 
Patients seropositive for the human immunodeficiency virus 
(HIV). 
6. 
Patients receiving treatment with Daratumumab or other CD38 
Monoclonal Antibodies.  
7. 
Patient receiving other investigational or  
anti-myeloma drugs within 14 days of enrollment. 
8. 
Patients with active clinically significant autoimmune disease 
9. 
Patients who have received mid-intensity melphalan (>50 mg 
IV) as part of prior therapy. 
10. Additional exclusion criteria outlined in section 2.3.2 
 
Inclusion Criteria for Randomization   
1. 
No disease progression since initiation of systemic anti-
myeloma therapy  
2. 
Received autologous transplant with melphalan 200mg/m2 
with a minimum cell dose of 2x106 CD34+ cells/kg <12 
months from enrollment onto BMT CTN 1401Tumor cell 
preparation must (1) Express > 20% CD38 or CD138 by 
staining (2) yield > 10 million plasma cells (Plasma cell 
count is determined by multiplying the total mononuclear cell 
yield by the percent of CD38 and CD138 staining reported 
on the Immunohistochemistry Report) (3) Have a negative 
microbiology assessment  
3. 
No evidence of uncontrolled infection requiring systemic 
therapy  
4. 
Platelet count ≥75,000/mm3 (without transfusion in previous 
7 days). 
5. 
Absolute neutrophil count (ANC) ≥ 1,500/mm3   without 
filgrastim administration within 7 days, or pegfilgrastim 
within 14 days of measurement. 
6. 
Bilirubin < 2x the upper limit of normal 
7. 
ALT and AST < 2.5x the upper limit of normal 
8. 
Creatinine clearance of ≥ 40 mL/min.  Patients with 
creatinine clearance >30 but < 40 will be considered with 
review/approval from the protocol chairs or officer if the 
cause of renal insufficiency is associated with multiple 
myeloma  
9. 
Patients must be willing to receive DVT prophylaxis 
10. Patient must be willing to follow birth control and pregnancy 
testing practices outlined in the protocol 
Primary Clinical Endpoint: 
Complete response (CR or sCR) at one year between patients 
receiving DC/myeloma vaccine/GM-CSF with lenalidomide 
maintenance therapy to those receiving lenalidomide maintenance 
therapy with or without GM-CSF. 
Primary Immunologic Endpoint:  
Treatment-induced expansion of myeloma-specific T cells as defined 
by the 2.4-fold increase from pre-therapy to peak post-treatment levels 
comparing the vaccine arm with patients receiving lenalidomide 
maintenance therapy with and without GM-CSF. 
 
Secondary Endpoints:  
Clinical: Myeloma Response; Rate of conversion to CR; Disease 
Progression; Treatment-Related Mortality; Progression-Free Survival; 
Overall Survival; Toxicity and rates of infection; Minimal Residual 
Disease; CR and sCR rates will be compared between the vaccine arm 
and each of the no-vaccine arms; proportion of patients with tumor cell 
collection who reach randomization; compliance with vaccine; and 
reproducibility of the vaccine. 
Immunologic:Secondary immunologic endpoint :a)  the percent of 
patients achieving at least a 10 fold expansion of myeloma specific T-
cells cells; b) expansion of myeloma antigen-specific T cells by tetramer 
analysis; c) quantification of T-cells subsets and PD-1 expressing 
lymphocytes; d) quantification of NK cells and identification of 
activation and inhibitory ligands; e) assessment of NK mediated killing 
of myeloma targets; f) assessment of humoral response against whole 
myeloma cells and myeloma associated antigens by SEREX and by 
characterizing myeloma-specific plasmablast responses. 


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OUTLINE OF TREATMENT PLAN 
  
 
 
Note: Len = Maintenance lenalidomide 
 
• Accrual targets 188 patients to be enrolled with a target of 132 patients to be randomized, 
assuming about 30% of patients are unable to proceed with post-transplant immunotherapy. 
o Arm A: Maintenance lenalidomide + vaccine + GM-CSF (n=66) 
o Arm B: Maintenance lenalidomide + GM-CSF (n=33) 
o Arm C: Maintenance lenalidomide alone (n=33) 
• Patients will be stratified according to disease status at time of randomization between CR/ 
sCR and VGPR/PR/stable disease.  
 
 


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TABLE OF CONTENTS 
1. 
OVERVIEW ................................................................................................................... 1-1 
1.1. 
Background .................................................................................................................... 1-1 
1.1.1. 
Vaccination with DC/Myeloma fusion cells following autologous transplant ........... 1-1 
1.1.2. 
Post-transplant lenalidomide maintenance .................................................................. 1-2 
1.2. 
Study Specific Information ........................................................................................... 1-3 
1.3. 
Rationale for Study ........................................................................................................ 1-3 
2. 
STUDY DESIGN ............................................................................................................ 2-1 
2.1. 
Study Overview .............................................................................................................. 2-1 
2.2. 
Hypotheses and Specific Objectives ............................................................................. 2-1 
2.2.1. 
Hypothesis ................................................................................................................... 2-1 
2.2.2. 
Study Objectives ......................................................................................................... 2-1 
2.2.3. 
Clinical Secondary Objectives .................................................................................... 2-1 
2.2.4. 
Immunologic Secondary Objectives ........................................................................... 2-2 
2.3. 
Patient Eligibility ........................................................................................................... 2-2 
2.3.1. 
Initial Inclusion Criteria .............................................................................................. 2-2 
2.3.2. 
Initial Exclusion Criteria ............................................................................................. 2-3 
2.3.3. 
Patient Eligibility Criteria for Randomization ............................................................ 2-4 
2.4. 
Treatment Plan............................................................................................................... 2-6 
2.4.1. 
Treatment Prior to Enrollment .................................................................................... 2-6 
2.4.2. 
Tumor Cell Collection................................................................................................. 2-6 
2.4.3. 
Systemic Anti-myeloma Therapy ............................................................................... 2-6 
2.4.4. 
Stem Cell Mobilization ............................................................................................... 2-6 
2.4.5. 
Autologous Stem Cell Transplantation ....................................................................... 2-7 
2.4.6. 
Maintenance Therapy .................................................................................................. 2-7 
2.4.7. 
Vaccine Manufacturing and Administration ............................................................... 2-9 
2.4.8. 
GM-CSF Administration ........................................................................................... 2-11 
2.5. 
Supportive Care ........................................................................................................... 2-12 
2.5.1. 
Post Autologous Transplantation(s) .......................................................................... 2-12 
2.5.2. 
Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) Prophylaxis .......... 2-12 
2.6. 
Risks and Toxicities ..................................................................................................... 2-12 
2.6.1. 
Therapy Toxicities .................................................................................................... 2-12 
2.6.2. 
Lenalidomide............................................................................................................. 2-12 
2.6.3. 
DC/Fusion Vaccine - Manufacturing and Administration ........................................ 2-13 
2.6.4. 
GM-CSF .................................................................................................................... 2-14 
2.7. 
Study Drug Supply ....................................................................................................... 2-14 
2.7.1. 
Lenalidomide............................................................................................................. 2-14 
2.8. 
Patient Withdrawal from Study and Off Study Criteria ......................................... 2-18 
3. 
STUDY ENDPOINTS AND DEFINITIONS............................................................... 3-1 
3.1. 
Definition of Disease Status ........................................................................................... 3-1 
3.1.1. 
Response Categories ................................................................................................... 3-1 


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3.1.2. 
Progressive Disease (PD) ............................................................................................ 3-2 
3.2. 
Primary Endpoint .......................................................................................................... 3-3 
3.3. 
Clinical Secondary Endpoints ....................................................................................... 3-3 
3.3.1. 
Response to treatment ................................................................................................. 3-3 
3.3.2. 
Myeloma Progression ................................................................................................. 3-4 
3.3.3. 
Minimal Residual Disease Assessment ....................................................................... 3-4 
3.3.4. 
Treatment-related Mortality ........................................................................................ 3-4 
3.3.5. 
Incidence of Toxicities Grade ≥3 per CTCAE vesion 4.0 .......................................... 3-4 
3.3.6. 
Incidence of Infections per BMT CTN Technical MOP ............................................. 3-4 
3.3.7. 
Progression-free survival ............................................................................................ 3-4 
3.3.8. 
Overall Survival .......................................................................................................... 3-5 
3.4. 
Primary Immunologic Endpoints ................................................................................. 3-5 
3.4.1. 
Myeloma-Reactive T-cells .......................................................................................... 3-5 
3.5. 
Secondary Immunologic Endpoints: ............................................................................ 3-5 
3.5.1. 
Myeloma-Reactive T-cells .......................................................................................... 3-5 
3.5.2. 
Assessment of antigen specific reactivity: .................................................................. 3-5 
3.5.3. 
Quantification of T-cell subsets: ................................................................................. 3-5 
3.5.4. 
Assessment of effect on NK cell populations: ............................................................ 3-6 
3.5.5. 
Assessment of humoral immune response: ................................................................. 3-6 
4. 
PATIENT REGISTRATION, ENROLLMENT, AND EVALUATION .................. 4-1 
4.1. 
Enrollment Procedures .................................................................................................. 4-1 
4.2. 
Study Monitoring ........................................................................................................... 4-1 
4.2.1. 
Follow - Up Schedule ................................................................................................. 4-1 
4.3. 
Patient Evaluations ........................................................................................................ 4-3 
4.3.1. 
Pre- Enrollment Segment A Evaluations and Requirements ...................................... 4-3 
4.3.2. 
Tumor Cell Collection Evaluations and Requirements at Enrollment ........................ 4-4 
4.3.3. 
Pre- Randomization Evaluations and Requirements ................................................... 4-4 
4.3.4. 
Pre- Maintenance Evaluations and Requirements....................................................... 4-5 
4.3.5. 
Evaluations during Maintenance ................................................................................. 4-6 
4.4. 
Data Reporting ............................................................................................................. 4-11 
4.4.1. 
Criteria for Forms Submission .................................................................................. 4-11 
4.4.2. 
Reporting Patient Deaths........................................................................................... 4-11 
4.4.3. 
Center for International Blood and Marrow Transplant Research (CIBMTR) Data 
Reporting ................................................................................................................... 4-11 
4.4.4. 
Adverse Event Reporting .......................................................................................... 4-11 
4.4.5. 
Pregnancy Reporting ................................................................................................. 4-13 
4.4.6. 
Celgene Drug Safety Contact Information:............................................................... 4-14 
4.4.7. 
Reporting of other Special Events of Interest ........................................................... 4-14 
4.5. 
Ancillary Correlative Laboratory Studies Procedures ............................................ 4-14 
4.5.1. 
Obtaining Informed Consent ..................................................................................... 4-14 
4.5.2. 
Data Entry Requirements .......................................................................................... 4-15 
5. 
STATISTICAL CONSIDERATIONS ......................................................................... 5-1 


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5.1. 
Study Design ................................................................................................................... 5-1 
5.1.1. 
Accrual ........................................................................................................................ 5-1 
5.1.2. 
Randomization ............................................................................................................ 5-1 
5.1.3. 
Primary Endpoint ........................................................................................................ 5-1 
5.1.4. 
Primary Hypothesis ..................................................................................................... 5-1 
5.1.5. 
Duration of follow-up ................................................................................................. 5-2 
5.2. 
Sample Size and Power Considerations ....................................................................... 5-2 
5.2.1. 
Primary Endpoint (Clinical) ........................................................................................ 5-2 
5.2.2. 
Power Considerations for Primary Immunologic Endpoint ........................................ 5-2 
5.3. 
Interim Analysis and Stopping Guidelines .................................................................. 5-2 
5.3.1. 
Interim Analysis for Efficacy ...................................................................................... 5-2 
5.3.2. 
Interim Analysis for Futility........................................................................................ 5-2 
5.3.3. 
Guidelines for Safety Monitoring ............................................................................... 5-3 
5.4. 
Demographic and Baseline Characteristics ................................................................. 5-4 
5.5. 
Analysis of Primary Clinical Endpoint ........................................................................ 5-4 
5.6. 
Analysis of Secondary Clinical Endpoints ................................................................... 5-4 
5.6.1. 
Response to treatment ................................................................................................. 5-4 
5.6.2. 
Myeloma Progression ................................................................................................. 5-4 
5.6.3. 
Treatment-related Mortality ........................................................................................ 5-4 
5.6.4. 
Progression-free survival ............................................................................................ 5-5 
5.6.5. 
Overall survival ........................................................................................................... 5-5 
5.6.6. 
Incidence of toxicities grade ≥ 3 per CTCAE version 4.0 .......................................... 5-5 
5.6.7. 
Incidence of infections ................................................................................................ 5-5 
5.6.8. 
Minimal Residual Disease assessment ........................................................................ 5-5 
5.7. 
Analysis of Immunological Endpoints ......................................................................... 5-5 
5.7.1. 
Primary immunologic endpoint: Myeloma reactive T-cells ....................................... 5-5 
5.7.2. 
Secondary immunologic endpoints: ............................................................................ 5-6 
5.8. 
Endpoint Review Committee ........................................................................................ 5-6 
 
 
LIST OF APPENDICES 
APPENDIX A 
CRITERIA FOR SYMPTOMATIC MULTIPLE MYELOMA 
APPENDIX B1 
INFORMED CONSENT FORM FOR BMT CTN 1401 
APPENDIX B2 
INFORMED CONSENT DOCUMENTS FOR BMT CTN 1401 
OPTIONAL CORRELATIVE LABORATORY STUDY 
PARTICIPANTION 
APPENDIX C  
LABORATORY PROCEDURES 
APPENDIX D 
LENALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY 
TESTING GUIDELINES AND ACCEPTABLE BIRTH CONTROL 
METHODS 
APPENDIX E  
Revlimid REMS® PROGRAM 
APPENDIX F  
HUMAN SUBJECTS 
APPENDIX G 
KARNOFSKY PERFORMANCE STATUS SCALE 
APPENDIX H 
NEW YORK HEART ASSOCIATION (NYHA) CLASSIFICATION OF 
CARDIAC DISEASE 


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APPENDIX I  
ADVERSE EVENTS  
APPENDIX J  
VCAN ANCILLARY STUDY 
APPENDIX K 
T CELL/MYELOMA GENOMIC SIGNATURE ANCILLARY STUDY 
APPENDIX L  
REFERENCES 


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1-1 
CHAPTER 1 
 
1. 
OVERVIEW 
 
1.1.Background 
Immune therapy has emerged as a leading area of cancer therapeutics due to its potential to recruit 
multiple effectors that broadly target malignant cells and overcome mechanisms of resistance. 
Multiple myeloma (MM) is characterized by the loss of critical mediators of immune surveillance, 
resulting in the suppression of antigen-presenting and effector cell function and the development 
of an immunologic milieu that fosters disease progression1- 6. We have developed a tumor vaccine 
in which patient-derived myeloma cells are fused with autologous dendritic cells (DCs), such that 
a broad array of myeloma antigens are presented in the context of DC-mediated costimulation7- 10. 
In diverse tumor models that include MM, vaccination of animals with DC/tumor fusions results 
in protection from an otherwise lethal challenge of malignant cells and, more significantly, 
eradication of disease in the setting of advanced metastatic involvement11,12.  In a phase I study, 
17 patients with advanced myeloma (median of 4 prior regimens) underwent vaccination with 
DC/MM fusions in conjunction with 4 days of GM-CSF administered at the vaccine site.  As 
previously described, MM cells were isolated from bone marrow aspirates and fused with 
autologous DCs generated from adherent mononuclear cells cultured with GM-CSF, IL-4, and 
TNFα13.  Vaccine production was successful in all patients and was well-tolerated without 
evidence of clinically significant autoimmunity.  Vaccination resulted in a mean 10-fold expansion 
of CD4 and CD8 myeloma-specific T cells, as determined by the percentage of cells expressing 
IFNγ in response to ex vivo exposure to autologous tumor lysate. Similarly, vaccination resulted 
in the development of myeloma-specific antibody responses as documented by SERAX analysis13.    
 
1.1.1. Vaccination with DC/Myeloma fusion cells following autologous transplant 
Vaccination with DC/Myeloma fusion cells following autologous transplant is associated with 
potent immune response and conversion from PR to CR in a subset of patients14.  We completed 
a clinical trial in which MM patients were vaccinated with DC/MM fusion cells in conjunction 
with autologous transplantation (ASCT). In the first cohort of the study, twenty-four patients 
received serial vaccinations following post-transplant hematopoietic recovery. A second cohort of 
12 patients received a pre-transplant vaccine followed by post-transplant vaccinations. Vaccine 
preparation was successful in all patients.  Mean yield of the DC and MM cells was 1.74 x 108 and 
6.5 x 107 cells, respectively. Mean fusion efficiency, as determined by the percentage of cells that 
co-expressed unique DC (CD80, CD86, and/or CD83) and MM (CD38 and/or CD138) antigens, 
was 38%. The mean dose administered was 3.6 x 106 fusion cells. Mean viability of the DC, 
myeloma, and fusion preparations was 87%, 87%, 79%, respectively. The DC/MM fusion 
preparations exhibited potent antigen presenting capacity, as evidenced by their stimulation of 
allogeneic T cell proliferation, with a mean stimulation index of 36.6, similar to that observed with 
the DC preparation prior to fusion (mean stimulation index of 52.3). In contrast, the unfused 
myeloma cells demonstrated minimal capacity for T cell stimulation (mean stimulation index of 
13.7). All vaccine-associated toxicities were of grade I-II intensity. The most common toxicity 
was erythema and induration at the vaccine injection site associated with T cell infiltration on 
biopsy. The other common side effects were transient pruritus, rash, fatigue, fever, and myalgias. 
One patient had a transiently elevated ANA level without clinical evidence of autoimmunity. One 
patient developed transient grade 2 leukopenia, but no evidence of graft compromise was observed 
following vaccination. Consistent with prior reports, the post-transplant period was associated with 


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the relative suppression of general measures of cellular immunity as manifested by decreased T 
cell proliferative responses to mitogen or recall antigens. In contrast, the period of post-transplant 
lymphopoietic reconstitution was associated with the expansion of myeloma-specific T cells that 
was further boosted following vaccination, as determined by percentage of CD4+ and CD8+ T 
cells expressing IFNγ in response to ex vivo exposure to autologous tumor lysate.  In the first 
cohort that received only post-transplant vaccination, the mean log10 fold increase in myeloma-
specific CD4+ T cells from pre-mobilization to post-transplant and from pre-mobilization to peak 
post-vaccination was 3.55 (95% CI 0.81;15.49) and 10.72 (95% CI 3.89;29.51), respectively. 
Similarly, the mean log10 fold increase in myeloma specific CD8+ T cells from pre-mobilization 
to post-transplant and from pre-mobilization to peak post-vaccination was 6.76 (95% CI 
3.02;15.49) and 11.48 (95% CI 4.17;32.36), respectively.  A smaller subset of patients underwent 
a single pre-transplant vaccination followed by post-transplant boosting.  Of note, no difference in 
peak levels of CD4+ or CD8+ circulating myeloma-specific T cells was observed between the 
cohort receiving a pre-transplant vaccine and that undergoing post-transplant vaccination alone 
(p=0.185 and p=0.689, respectively).  For the entire study population, the mean log10 fold increase 
in myeloma-specific CD4+ T cells from pre-mobilization to post-transplant and from pre-
mobilization to peak post-vaccination was 3.55 (95% CI 1.58;8.13) and 9.55 (95% CI 5.37;16.98), 
respectively. The mean log10 fold increase in myeloma-specific CD8+ T cells from pre-
mobilization to post-transplant and from pre-mobilization to peak post-vaccination was 4.37 (95% 
CI 2.40;7.76) and 8.32 (95% CI 4.68;15.14), respectively.  Notably, vaccination was associated 
with the expansion of T cells targeting the myeloma-specific antigen, MUC1, as determined by 
tetramer analysis. In a cohort of patients who were HLA-A2, the median percentage of MUC1-
specific T cells was 0.12 pre-transplant and increased to 1.84 at 3 months after completion of 
vaccination (p<0.05), representing a median fold increase of 17.5. The expansion of T cells 
targeting MUC1 in response to vaccination is of particular interest, as we have identified a 
population of CD34+/MUC1+ cells in the bone marrow of patients with myeloma that demonstrate 
myeloma-initiating capacity.  
Seventy-eight percent of patients achieved a CR or VGPR (47% CR/nCR; 31% VGPR). Thirty-
one percent achieved a CR/nCR in the early post-transplant period, whereas an additional 17% (6 
patients: 4 from VGPR, 2 from PR) achieved CR/nCR as best response only after day 100 post-
transplant and after undergoing vaccination. The presence of late responses several months after 
ASCT is consistent with an impact of vaccine therapy on post-transplant residual disease.  
1.1.2. Post-transplant lenalidomide maintenance   
Post-transplant lenalidomide maintenance prolongs disease-free and overall survival15.  This is 
thought to be potentially due to its immunomodulatory characteristics.  In pre-clinical studies, we 
demonstrated that lenalidomide potently enhances immune response to vaccination16. T cells were 
stimulated in vitro with DC/MM fusions in the absence or presence of lenalidomide. After 5–7 
days of stimulation by the vaccine, the percentage of CD8+ T cells expressing IFNγ increased 
significantly in the presence of lenalidomide (from 6.37 to 9.9 %; n = 7, p = 0.03). A concomitant 
statistically significant decrease in the proportion of regulatory T cells was also observed (4.4 % 
in the lenalidomide group as opposed to 9.6 % in the control group; n = 3, p = 0.02). As determined 
by a flourochrome assay measuring granzyme B release in target cells, CTL-mediated lysis of 
autologous MM tumor targets was increased by 50% when T cells were stimulated by DC/MM 
fusions in the presence of lenalidomide, as compared to those cultured with fusions alone (mean 
29.2% vs. 19.7%; n=3, p=0.004).   


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1.2.Study Specific Information 
Based on these encouraging data, the DC/MM fusion vaccine was chosen to be the first cellular 
immunotherapy to be evaluated in a multicenter cooperative group study involving several 
nationally prominent cancer centers (BMT CTN protocol 1401).  We will conduct a multicenter 
phase II randomized study comparing post-transplant vaccination with DC/MM fusions/GM-CSF 
and lenalidomide maintenance to lenalidomide maintenance with and without GM-CSF, with 
vaccine manufacturing performed locally at each participating center.  The primary objective is to 
assess the impact of post-transplant immunotherapy on the percentage of patients in CR at 1 year 
between the vaccine arm and both no-vaccine arms combined.  Secondary endpoints include 
determining the effect of therapy on progression-free survival, myeloma response, minimal 
residual disease, toxicities, transplant-related mortality, and overall survival. Additionally, this 
study includes several immunologic endpoints to understand the effect of the vaccine on the anti-
myeloma immunity, the immune effects of lenalidomide, and general immune reconstitution after 
transplant. The primary immunologic endpoint is to compare the expansion of myeloma-specific 
T cells across all three arms.  
 
1.3.Rationale for Study  
MM is associated with immune suppression, including defects in antigen presentation and effector 
cell function that are thought to play a role in disease progression. Although the outcomes for 
myeloma patients have improved greatly over the past decade, the majority of patients relapse even 
after autologous stem cell transplant and post-transplant maintenance therapy with lenalidomide. 
Early phase clinical data demonstrate that post-transplant vaccination with a DC-MM fusion 
product with GM-CSF adjuvant increases the number of MM-specific T cells. Furthermore, it 
appears that lenalidomide can specifically augment vaccine-stimulated induction of MM-specific 
T cells. We are therefore interested in combining standard immunomodulatory therapy 
(lenalidomide) with a potential immune stimulant (DC-MM vaccination) to increase post-
transplant clinical response. Finally, pre-clinical data has suggested that immunomodulatory 
agents augment NK cell activity17 and that NK cells interact with and can be activated by DCs18. 
Thus, we are interested in further defining the NK immmunophenotype in the setting of post-
transplant maintenance lenalidomide and the changes to this phenotype in the setting of DC-MM 
fusion vaccination. We postulate that post-transplant lenalidomide maintenance will augment post-
transplant anti-myeloma immunity, thus providing an ideal platform for DC/MM fusion 
vaccination. Additionally, to understand the effect of vaccine versus the adjuvant in the post-
transplant setting, we split the non-vaccine arms into lenalidomide alone and lenalidomide plus 
GM-CSF, with GM-CSF administered in the exact same schedule and dosing as in the vaccine 
arm. Although there is no evidence that GM-CSF has an anti-myeloma effect, this additional 
control arm is important to understand whether any effect of the vaccine is due to its adjuvant and 
whether GM-CSF influences any of the immunologic outcomes.  We further hypothesize that 
vaccination in this setting will effectively target post-transplant residual disease, increase the 
percentage of patients achieving CR, and create durable responses. 
 
 


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The results of this trial will provide information on whether this patient-specific vaccine 
administered after transplant is promising for further comparison with current standard of care 
treatment. Furthermore, this trial will address several important aspects of anti-myeloma 
immunity, including how lenalidomide maintenance influences post-transplant recovery and 
myeloma control.  Lastly, isolating the effect of the GM-CSF adjuvant will address whether any 
effect observed is related solely to the vaccine.  
 


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CHAPTER 2 
 
2. 
STUDY DESIGN  
 
2.1.Study Overview  
The study is a three-arm, phase II randomized, open-labeled clinical trial to evaluate vaccination 
with DC/myeloma fusions/GM-CSF plus lenalidomide maintenance therapy compared to 
lenalidomide maintenance therapy with or without GM-CSF following autologous transplant as 
part of upfront treatment for patients diagnosed with multiple myeloma.  Patients meeting initial 
eligibility will be enrolled, and tumor cells will be harvested.  Patients will proceed or continue 
with systemic anti-myeloma therapy and stem cell mobilization according to institutional 
practices. Patients with available cryopreserved tumor cells who are eligible to proceed to 
transplantation will be randomized in the study around Day 56 post-transplant.  
 
Approximately 2 months post-transplant, patients will undergo their first disease response 
assessment and will be randomized 2:1:1 to the vaccine/GM-CSF plus lenalidomide arm, 
lenalidomide/GM-CSF arm, or lenalidomide alone arm.  Patients assigned to vaccine plus 
lenalidomide maintenance will subsequently undergo leukapheresis for collection of dendritic cell 
precursors and vaccine production (DC/myeloma vaccine). For all patients, lenalidomide 
maintenance will start at Day 90-100 post-transplant and continue for two years or until disease 
progression, whichever comes first. Vaccines will be administered on the first day of cycles 2, 3, 
and 4 of lenalidomide maintenance, followed by four daily doses of GM-CSF for patients 
randomized to the vaccine arm. Patients randomized to lenalidomide/GM-CSF will receive GM-
CSF in the same schedule and dose as patients in the vaccine arm. Primary endpoint assessment 
will occur at 1 year post-transplant. 
 
2.2.Hypotheses and Specific Objectives 
 
2.2.1. Hypothesis  
Vaccination with DC/myeloma fusions plus lenalidomide maintenance therapy will result in 
improved responses in patients with multiple myeloma after autologous HCT.  
 
2.2.2. Study Objectives 
Compare the proportion of patients alive and in complete response (CR or sCR) at one year post-
transplant, corresponding to 1 year post transplant (approximately 10 months after randomization) 
between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance 
therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. 
 
2.2.3. Clinical Secondary Objectives  
Compare myeloma response, rate of conversion to CR, myeloma progression, treatment-related 
mortality, progression-free survival, overall survival, incidence of grade > 3 toxicity according to 
the Common Terminology Criteria for Adverse Events (CTCAE) v4.0, incidence of infections, 
measures of minimal residual disease, between the vaccine and the combined no-vaccine treatment 
arms. A secondary pairwise analysis of the proportion of patients alive and in CR at one year post-
transplant will also be conducted between the vaccine arm, lenalidomide/GM-CSF arm, and the 


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lenalidomide alone arm.  Additionally, the study will describe the proportion of patients with 
collection of tumor cells who reach randomization, compliance with vaccine, and the 
reproducibility of the vaccine manufacturing based on the release criteria.  
 
2.2.4. Immunologic Secondary Objectives  
Primary immunologic endpoints:  
- 
Compare the expansion of treatment-induced myeloma-specific T cells, defined as a 2.4-
fold increase from pre-therapy to peak post-treatment levels between the vaccine arm and 
each of the no-vaccine arms separately. 
 
Secondary immunologic endpoints:  
- 
Determine the percentage of patients achieving at least a 10-fold expansion of myeloma-
specific T cells in each treatment arm.  
- 
Quantify myeloma antigen-specific T cells by tetramer analysis. 
- 
Quantify T cell subsets and PD-1 expressing lymphocytes.  
- 
Quantify NK cells and identify activation and inhibitory ligands.  
- 
Assess NK cell-mediated killing of myeloma targets.  
- 
Assess humoral response against whole myeloma cells and myeloma-associated antigens 
by SEREX and by characterizing myeloma-specific plasmablast responses. 
 
2.3.Patient Eligibility  
Patients must meet specified eligibility criteria outlined in section 2.3.1 and 2.3.2 to be registered 
on the study. Additional criteria must also be met to continue to successive stages of the 
protocol. All questions regarding eligibility criteria should be directed to the protocol coordinator 
at 301-251-1161.  
 
2.3.1. Initial Inclusion Criteria  
1. Patients must be considered transplant eligible by the treating physician at time of 
study entry. 
2. Patients must meet the criteria for symptomatic multiple myeloma (Appendix A) prior 
to initiating systemic anti-myeloma treatment. 
3. Age >18.00 years and < 71.00 years at the time of enrollment 
4. Karnofsky Performance status of ≥ 70% 
5. Patients must have > 20% plasma cells in the bone marrow aspirate differential <60 
days prior to enrollment.  If patient receives anti-myeloma therapy1 treatment after 
bone marrow aspirate to assess eligibility and before bone marrow aspirate for tumor 
cell collection, a repeat bone marrow evaluation will be required to confirm > 20% 
                                                 
1 Anti-myeloma therapy is defined as systemic treatment intended to treat the underlying myeloma disease. Treatments 
intended to alleviate pain and other symptoms of disease and/or administration of ≤160mg of dexamethasone or 
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plasma cells in the bone marrow aspirate differential prior to enrollment and tumor 
cell collection.  
6. Patients must have received < 1 cycle of systemic anti-myeloma therapy1.  
7. Renal:  Creatinine clearance of ≥ 40 mL/min, estimated or calculated. 
2.3.2. Initial Exclusion Criteria  
1. Patients with a prior autologous or allogeneic HCT  
2. Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) 
in serum as measured by electrophoresis and immunofixation and the absence of Bence 
Jones protein in the urine defined by use of conventional electrophoresis and 
immunofixation techniques and the absence of involved serum free light chain >100 
mg/L].  Patients with light chain MM detected in the serum by free light chain assay 
are eligible. 
3. Patients with a history of Plasma Cell Leukemia at any time prior to enrollment.  
4. Patients with disease progression at any time prior to enrollment (see Section 3.1.3 for 
disease progression definition). 
5. Patients seropositive for the human immunodeficiency virus (HIV). 
6. Myocardial infarction within 6 months prior to enrollment or New York Heart 
Association (NYHA) Class III or IV heart failure (see Appendix H), uncontrolled 
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence 
of acute ischemia or active conduction system abnormalities.  Prior to study entry, any 
ECG abnormality at screening will be documented by the investigator as not medically 
relevant. 
7. Patients with active clinically significant autoimmune disease, defined as a history of 
requiring systemic immunosuppressive therapy and at ongoing risk for potential 
disease exacerbation.  Patients with a history of autoimmune thyroid disease, asthma, 
or limited skin manifestations are potentially eligible.  
8. Patients receiving other investigational immunotherapy or anti-myeloma drugs within 
14 days before enrollment. 
9. Patients receiving prior treatment with daratumumab, elotuzumab, and/or any other 
monoclonal antibody-based therapy at any time prior to enrollment.  
                                                 
1 Anti-myeloma therapy is defined as systemic treatment intended to treat the underlying myeloma disease. Treatments 
intended to alleviate pain and other symptoms of disease and/or administration of ≤160mg of dexamethasone or 
equivalent alternative steroid dose within a 30-day period are not considered anti-myeloma therapy. 


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10. Patients with prior malignancies except resected basal cell carcinoma or treated cervical 
carcinoma in situ.  Cancer treated with curative intent < 5 years prior to enrollment will 
not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.  
Cancer treated with curative intent > 5 years prior to enrollment is allowed. 
11. Female patients who are pregnant (positive β-HCG) or breastfeeding. 
12. Females of childbearing potential (FCBP)1 or men who have sexual contact with FCBP 
unwilling to use contraceptive techniques (Appendix D) during the length of 
lenalidomide maintenance therapy. 
13. Patients who have received mid-intensity melphalan (>50 mg IV) as part of prior 
therapy. 
14. Prior organ transplant requiring immunosuppressive therapy. 
15. Patients who previously received lenalidomide and have experienced toxicities 
resulting in treatment discontinuation. 
16. Patients who experienced thromboembolic events while on full anticoagulation during 
prior therapy with lenalidomide or thalidomide. 
17. Patients unwilling to take DVT prophylaxis. 
18. Patients unable or unwilling to provide informed consent. 
19. Patients unable or unwilling to return to the transplant center for their assigned 
treatments. 
 
2.3.3. Patient Eligibility Criteria for Randomization  
1. No disease progression since initiation of systemic anti-myeloma therapy as 
determined ≤ 10 days prior to randomization/enrollment.  
2. Received an autologous cell transplant with melphalan 200mg/m2 with a minimum cell 
dose of 2x106 CD34+ cells/kg (actual body weight) < 12 months of enrollment onto 
BMT CTN 1401.  
3. Tumor cell preparation must: 
a. Express > 20% CD38 or CD138 by staining 
b. Yield > 10 million plasma cells2 
c. Have a negative microbiology assessment  
                                                 
1 A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral 
oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had 
menses at any time in the preceding 24 consecutive months). 
2 Plasma cell count is determined by multiplying the total mononuclear cell yield by the percent of CD38 and CD138 
staining reported on the Immunohistochemistry Report 


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4. Mucositis and gastrointestinal symptoms resolved, off hyperalimentation and 
intravenous hydration.  
5. No evidence of uncontrolled infection requiring systemic therapy. Patients who 
completed treatment for an infection but are continuing antibiotics, anti-viral, or anti-
fungal therapy for prophylaxis are eligible to continue on protocol. 
6. Platelet count ≥75,000/mm3 (without transfusion in previous 7 days). 
7. Absolute neutrophil count (ANC) ≥ 1,500/mm3 without filgrastim administration 
within 7 days, or pegfilgrastim within 14 days of measurement. 
8. Hepatic: bilirubin < 2x the upper limit of normal and ALT and AST < 2.5x the upper 
limit of normal. (Patients who have been diagnosed with Gilbert’s Disease are allowed 
to exceed the defined bilirubin value of 2x the upper limit of normal.) 
9. Renal:  Creatinine clearance of ≥ 40 mL/min, estimated or calculated. Patients with 
creatinine clearance ≥30 but <40 will be considered with review/approval from the 
protocol chairs or officer if the cause of renal insufficiency is associated with multiple 
myeloma.  
10. All study participants must be registered into the mandatory Revlimid REMs program, 
and be willing and able to comply with the requirements. 
11. Females of childbearing potential (FCBP) as defined in section 2.7.1.1 must have a 
negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10 – 14 
days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must 
be filled within 7 days)  
12. FCBP must either commit to abstain continuously from sexual intercourse or use TWO 
acceptable methods of birth control, one highly effective method and one additional 
effective method AT THE SAME TIME, at least 4 weeks before she starts taking 
lenalidomide, during therapy, during dose interruptions, and continuing for 4 weeks 
following discontinuation of lenalidomide.   
13. FCBP must agree to ongoing pregnancy testing as required by the RevlimidREMs 
program.  
14. Men must agree to use a latex condom during sexual contact with females of child 
bearing potential even if they have had a successful vasectomy while taking 
lenalidomide, during dose interruptions and for 28 days after discontinuing 
lenalidomide.   
15. Patients must be willing to receive DVT prophylaxis. 
 


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2.4.Treatment Plan 
 
2.4.1. Treatment Prior to Enrollment  
Patients must have < 1 cycle of anti-myeloma therapy prior to enrolling on the study. It is 
recommended whenever clinically feasible to minimize the treatment administered prior to 
enrollment to ensure adequate tumor cell collection and preparation for vaccine production. 
Patients receiving treatment with daratumumab or other CD38 monoclonal antibodies prior to 
enrollment should not be considered for this study.  
2.4.2. Tumor Cell Collection 
An initial eligibility assessment will be performed at time of study entry prior to tumor collection 
for immune monitoring and subsequent vaccine production. Eligible patients will undergo 
aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated 
(Appendix 
C 
and 
BMT 
CTN 
1401 
Manufacturing, 
Clinical 
and  
Reference SOPs). Bone marrow will be aspirated into sterile heparinized syringes with 
approximately 5-8 mL aspirated per syringe to avoid significant hemodilution of bone marrow 
mononuclear cells.  Bone marrow aspirate samples will be transferred in sterile syringes to the cell 
manipulation facility, and mononuclear cells will be isolated by ficoll density gradient 
centrifugation. Autologous plasma will be obtained by harvesting supernatant following 
centrifugation of 50 mL of peripheral blood. An aliquot of the tumor cells will be sent to BIDMC 
for centralized immunohistochemical staining as detailed in Appendix C.  Tumor lysate will be 
prepared by freeze/thawing or sonication of an aliquot of tumor cells for immunological analysis. 
The remaining myeloma cells will be frozen in 10% DMSO/90% autologous plasma stored in 
liquid nitrogen for potential subsequent vaccine generation. 
 
2.4.2.1.Second Tumor Cell Collection 
If the initial bone marrow harvest does not yield a sufficient cell count as required by the BMT 
CTN 1401 Vaccine Product Release criteria, a second collection may be considered if the 
following items are completed prior to the second collection:  
- 
Submission and review of an occurrence report in AdvantageEDC 
- 
Written approval from the BMT CTN 1401 Protocol Chairs/Officer and Medical Monitor 
is received 
- 
All corrective actions are completed and appropriate documentation is submitted to the 
BMT CTN DCC  
- 
Final written approval from the BMT CTN DCC is received by the site  
 
2.4.3. Systemic Anti-myeloma Therapy 
Pre-transplant systemic anti-myeloma therapy will be administered per investigator discretion 
following enrollment and tumor cell collection.  
 
2.4.4. Stem Cell Mobilization 
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2.4.5. Autologous Stem Cell Transplantation  
Autologous hematopoietic cell transplant will be done with high-dose melphalan (200mg/m2) at 
the schedule and timing according to institutional practices and must be within 12 months of 
enrollment on to the study 
 
2.4.5.1.Peripheral blood stem cell infusion  
All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg 
patient actual body weight per autologous transplantation.  The graft may not be CD34+ selected 
or otherwise manipulated to remove tumor or other cells.  Cryopreservation and thawing of product 
will comply with FACT standards and local institutional practice.   
 
2.4.6. Maintenance Therapy  
All patients who meet the eligibility criteria to proceed to randomization and who have completed 
the post-transplant disease response assessment will be randomized between day 53 and day 80 
post-transplant and within 10 days of a disease response assessment.  
 
Patients will begin maintenance therapy with lenalidomide between 90 and 100 days after stem 
cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously.  
Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two 
years from initiation of therapy or until one of the criteria in section 2.8 applies. For patients 
receiving GM-CSF and/or Vaccine, lenalidomide is recommended to be taken in the evening at 
least 4 hours after vaccination to avoid confusion with immediate vaccine and/or GM-CSF site 
reactions.  
 
Patients who stop maintenance therapy for any reason prior to two years from initiation of 
maintenance will continue to be followed per protocol for 3 years post maintenance initiation. 
Upon completion of protocol specified maintenance therapy, patients will be treated at the 
investigator’s discretion. However, it is recommended that patients continue receiving 
lenalidomide as per standard of care.    
 
2.4.6.1.Lenalidomide maintenance dose modifications 
Lenalidomide dose will be adjusted for toxicity.  Table 2.4.5B describes the dose reduction steps 
to be utilized during maintenance therapy. In the presence of lenalidomide-related toxicities (Table 
2.4.5A), the study drug will be held until the toxicity resolves then restarted at a reduced dose as 
described in Table 2.4.5B. If lenalidomide is held for >8 weeks for any reason, study chair approval 
must be obtained prior to re-starting lenalidomide.  Patients will be given DVT prophylaxis.  DVT 
prophylaxis for patients will be given per institutional guidelines.  See section 2.5.2 for suggested 
dose and more information. 
 


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Table 2.4.6A – Required Treatment Modification Guidelines for Lenalidomide Maintenance Therapy 
for Non-Hematologic Toxicities 
Grade by  NCI CTCAE# 1 
Action 
Grade 3 neutropenia  
associated with fever 
 (temperature > 38. 5º C)  
or Grade 4 neutropenia  
 Hold lenalidomide. Follow CBC weekly.  
If the toxicity resolves to <grade 2 restart lenalidomide at next lower dose level.  
If neutropenia is the only toxicity for which a dose reduction is required, granulocyte growth factors could be considered 
at the discretion of the treating physician and the lenalidomide dose maintained. .  
Thrombocytopenia 
 (platelet count < 30,000/mm³) 
Hold lenalidomide. Follow CBC weekly.  
If the toxicity resolves to <grade 2 restart lenalidomide at next lower dose level.  
 
Non-blistering rash 
Grade  3 
(Generalized rash ≥  25% BSA) 
Hold lenalidomide:  Follow weekly. Treatment with antihistamine may be initiated at the discretion of the investigator.  
If the toxicity resolves to ≤ grade 1 restart lenalidomide at next lower dose level.   
Non-blistering rash 
Grade 4 
Discontinue lenalidomide permanently. Continue to follow the patient per-protocol 
Desquamating (blistering) rash 
any Grade 
Discontinue lenalidomide permanently. Continue to follow the patient per-protocol 
Venous thrombosis/embolism 
≥  Grade 3 
(DVT or cardiac thrombosis; intervention 
indicated) 
Hold lenalidomide and start anticoagulation per institutional guidelines. Restart therapy and maintain dose level. 
Other non-hematologic toxicity 
assessed as Lenalidomide-related 
≥  Grade 3 
Hold lenalidomide.   
If the toxicity resolves to ≤ grade 2 restart lenalidomide at next lower dose level.  
Hyperthyroidism or 
Hypothyroidism 
Hold lenalidomide.  
Evaluate etiology, and initiate appropriate therapy. 
Restart lenalidomide at next lower dose level . 
Pregnancy3 
Discontinue lenalidomide study drug.  
1Please consult NCI CTCAE version 4  http://ctep.cancer.gov/reporting/ for complete Grade descriptions.  The “≥  Grade 3”  descriptions listed 
above are minimums 
3If a subject, or the partner of a male study subject, misses her period or if her pregnancy test or her menstrual bleeding is abnormal, pregnancy 
testing and counseling must be performed (Section 4.4.5).  
 
Table 2.4.6B – Lenalidomide Dose Reduction Steps During Lenalidomide  
Maintenance Therapy 
Lenalidomide Dose Reduction Steps for Non-Hematologic Toxicity 
Dose at Time of Toxicity 
Dose reduction 
10 mg daily  
5 mg daily  
5 mg daily  
5 mg daily for 21 days every 28 days 
5 mg daily for 21 days every 28 days 
 2.5 mg daily for 21 days every 28 days 
2.5 mg daily for 21 days every 28 days Discontinue lenalidomide 
 
2.4.6.2. Lenalidomide maintenance dose re-escalation 
If a dose reduction has occurred and ANC ≥ 1000/µL and platelet count is ≥ 75,000/µL, the study 
drug dose may be re-escalated as shown on Table 2.4.5c, one step per cycle to a maximum of 10 
mg daily.  
 


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Table 2.4.6C – Lenalidomide Dose Re-Escalation Steps During Lenalidomide  
Maintenance Therapy 
Current Patient Dose  
Dose Re-Escalation  
2.5 mg daily for 21 days every 28 days 5 mg daily for 21 days every 28 days 
5 mg daily for 21 days every 28 days 
5 mg daily 
5 mg daily 
10 mg daily 
10 mg daily 
No more dose escalations permitted  
2.4.7. Vaccine Manufacturing and Administration  
Vaccine preparation is outlined in detail in the BMT CTN 1401 SOPs and will be performed locally 
at each participating institution. Patients randomized to receive the DC/MM fusion vaccine will 
undergo leukapharesis for DC and vaccine generation per the BMT CTN 1401 manufacturing, 
clinical, and reference SOPs. Leukapheresis should occur by day 85 post-transplant to ensure 
sufficient time for vaccine production and sterility testing. The leukapheresis product will be 
transferred in a sterile container to the cell manipulation facility, and PBMC will be isolated from 
the leukapheresis product and cultured in the presence of autologous plasma for 1 hour and then 
cultured for 5-7 days with GM-CSF and IL-4.  Cultures will be re-fed with cytokines, GM-CSF, 
and IL-4 after 5-7 days.  Twenty-five ng/mL of TNFαwill be added for 48-72 hours to induce DC 
maturation after 5-7 days. An aliquot of the DC preparation will be sent to BIDMC for 
immunocytochemical staining for immunophenotypic analysis. Tumor cells and DC preparations 
will be co-cultured at ratio of 1:3 and washed in serum-free medium. After low-speed 
centrifugation, the cell pellet will be re-suspended in 50% solution of polyethylene glycol (PEG) 
and will be progressively diluted by the slow addition of serum-free medium. An aliquot of the 
DC, tumor, and fusion cell preparations will be sent to BIDMC for immunocytochemical analysis 
for vaccine characterization at the timepoints indicated in the BMT CTN 1401 manufacturing 
SOPs. The vaccine doses will be prepared per the Vaccine Dose Guidelines in section 2.4.7.1. The 
fusion cells will then be irradiated at 30 Gy, and frozen in 10% DMSO/90% autologous plasma in 
liquid nitrogen. An aliquot of the vaccine product will be sent for microbiological assessment 
consisting of endotoxin, mycoplasma and sterility testing as per the BMT CTN 1401 
manufacturing SOPs. Release criteria for vaccine administration are: 
 
1) At least 20% of tumor cell prep must express CD38 or CD138 by staining 
2) Tumor cell prep must yield >10 million plasma cells1 
3) > 50% of DC prep express CD86 
4) Viability of DC prep > 50% 
5) Fusion efficiency > 15% 
6) Fusion viability > 50% 
7) Sterility, mycoplasma, and endotoxin assays are negative 
                                                 
1 Plasma cell count is determined by multiplying the total mononuclear cell yield by the percent of CD38 and CD138 
staining reported on the Immunohistochemistry Report 


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At time of administration, fusion cells will be thawed. Patients randomized to the vaccine arm will 
receive the DC/myeloma fusion vaccine/GM-CSF (vaccine) on day 1 of cycles 2, 3, and 4 of 
lenalidomide maintenance.  Vaccine will be administered by subcutaneous injection with 100 ug 
GM-CSF given subcutaneously at the vaccine site on day of vaccination and daily for a total of 4 
days of each cycle. Patients who are randomized to the vaccine arm and are unable to receive 
vaccine for any reason, will receive lenalidomide alone for the duration of the study per section 
2.4.6.    
All vaccine related procedures are detailed in the BMT CTN 1401 manufacturing, clinical, and 
reference SOPs which must be adhered to by all sites for each patient enrolled on the study. Patients 
who are unable to receive vaccine for any reason (i.e. toxicity, failure to meet release criteria, etc) 
should receive lenalidomide only for the duration of the study.  
2.4.7.1.Vaccine Dose Guidelines  
The target dose is 3 x 106 fusion cells per vaccine. A minimum of 3 x 106 fusion cells will be 
required to proceed with vaccine administration. Patients who have < 3 x 106 fusion cells will not 
proceed with vaccination.  
Table 2.4.7A – Vaccine Dose Guidelines 
Total Fusion Cell Yield 
Dose Guidance 
> 9 x 106 fusion cells 
- 
3 doses of 3 x 106 fusion cells are cryopreserved 
for patient administration 
- 
Excess product should be cryopreserved in 
aliquots of 3x106  fusion cells when possible. 
> 3x106 fusion cells and < 9x106 fusion cells 
- Divide product in to 3 equal doses for 
cryopreservation and patient administration 
< 3x106 fusion cells 
- Patient will not receive vaccine.  
2.4.7.2.Vaccine Production Occurrences  
Deviations from the manufacturing process outlined in the BMT CTN 1401 manufacturing, 
clinical, and reference SOPs will be documented on the Occurrence Report form in 
AdvantageEDC as per the Occurrence Report SOP (BMT 1401-RF 04). Following submission of 
an occurrence report, sites will be required to complete the following items prior to enrolling 
additional patients and proceeding with vaccine production:  
- 
All queries and corrective actions associated with the report must be completed 
- 
The BMT CTN 1401 protocol chairs/officer and BMT CTN DCC will provide approval 
for continuing enrollment on the study.  
2.4.7.2.1. Failure to Meet Release Criteria  
Sites experiencing difficulties with production as evidenced by failure to meet release criteria for 
3 products will have vaccine production temporarily halted while undergoing onsite review of 
procedures by a member from the protocol team and central site. Additional training or guidance 
will be provided if needed.  
 


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Table 2.4.7B –Vaccine Administration Guidelines for Vaccine, GM-CSF and/or Lenalidomide 
Toxicities 
Toxicity 
Action 
Hold/delay in 
lenalidomide therapy 
Hold/delay vaccine. 
When lenalidomide is restarted, adjust date of vaccine administration to coincide 
with Day 1 of cycles 2, 3 and 4 of lenalidomide maintenance.   
Discontinuation in 
lenalidomide therapy 
Administer vaccine at monthly intervals for a total of 3 doses 
 
Grade 4 toxicity 
judged to be related to 
vaccine alone 
No additional vaccines. 
Grade 3 toxicity 
judged to be related to 
vaccine alone 
 Hold Vaccine Dose.   
If the toxicity resolves to ≤ grade 2 by time of subsequent vaccine administration, 
vaccine may continue. 
Grade 3-4 toxicity 
judged to be related to 
GM-CSF alone 
Omit GM-CSF administration for subsequent vaccine injections or subsequent 
scheduled administrations in the non-vaccine arm. Re-challenging GM-CSF 
administrated when toxicity resolves to ≤ grade 2 can be considered at the discretion 
of the treating investigator. Vaccine administration may continue.  
Grade 3-4 toxicity 
possibly related to 
combination of 
lenalidomide and 
vaccine 
Follow lenalidomide dose adjustments. Vaccine administration may continue.  
2.4.8. GM-CSF Administration  
For patients randomized to the vaccine and GM-CSF plus lenalidomide maintenance and 
lenalidomide maintenance plus GM-CSF arms, GM-CSF will be administered at cycles 2, 3, and 
4 of maintenance therapy. 100 ug GM-CSF will be given subcutaneously (at the vaccine site for 
patients receiving vaccine) on days 1-4 of cycles 2, 3, and 4 per the BMT CTN 1401 manufacturing 
SOPs.  
On the first day of GM-CSF administration, the clinical research nurse will administer 100 ug of 
GM-CSF subcutaneously. The patient will be trained to inject the remaining three GM-CSF 
injections (100ug dose once a day at the vaccination site) for self-administration subcutaneously 
at home. Alternatively, if patients are unwilling or unable to self-administer the GM-CSF, they 
can return to the transplant center for subsequent injections. For patients receiving vaccine, tumor 
vaccine will be administered before the GM-CSF injection. GM-CSF is given on Day 1 at time of 
vaccination and around the same time of day (+/- an hour whenever feasible) for subsequent doses. 
If a patient experiences a grade 2 or higher (graded according to CTCAE v4.0) injection site 
reaction during the days when GM-SCF is administered, subsequent doses of GM-CSF may be 
held until the injection site reaction improves to grade 1 or less at the discretion of the treating 
investigator. For subsequent administrations, patients will receive pre-medication with 
diphenhydramine (Benadryl) 25-50 mg and/or acetaminophen (Tylenol) 650-1000 mg to minimize 
potential allergic-related symptoms. 


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2.5.Supportive Care 
 
2.5.1. Post Autologous Transplantation(s) 
All supportive care will be given at the investigators discretion. 
 
2.5.2. Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) Prophylaxis 
Prophylaxis for DVT/PE will be done according to institutional guidelines. Upon initiation of 
lenalidomide maintenance it is recommended that patients without a history of thromboembolic 
events should be on aspirin daily (81mg, 165mg or 350 mg); low molecular weight heparin or warfarin 
is usually administered in patients with a history of thromboembolic events or those that cannot 
tolerate aspirin. 
 
2.6.Risks and Toxicities  
 
Recipients of autologous transplantation incur risks from pre-transplant conditioning and post-
transplant therapy, which must be weighed against the risk of the disease for which the transplant 
is prescribed. Major risks following transplantation include: 1) Infection, which can be bacterial, 
viral, parasitic, or fungal. Often, these infections are life-threatening, particularly when caused by 
viral or fungal agents, and are associated with high mortality in the transplant population; 2) Graft 
Failure can occur and is associated with a high-risk of mortality; 3) End Organ Damage of one or 
more major organs may occur as a result of reactions to drugs (e.g., melphalan, antibiotics, anti-
fungal medications, etc.), and as a result of destructive processes (e.g., infection, etc.) and may 
have a fatal outcome; 4) Progression of MM may occur; 5) Unknown Toxicities may occur in any 
individual patient due to multiple events and cumulative effects which may involve any and all 
organs, including the brain.  Brain damage can result in severe loss of cognitive or neurologic 
function; and, 6) Death.  These risks may or may not be increased by the post-transplant therapies 
to be evaluated in this protocol. 
 
2.6.1. Therapy Toxicities 
All toxicities will be graded using the Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.0 with BMT CTN 1401 specific definitions when appropriate. 
 
2.6.2. Lenalidomide 
Common toxicities described for lenalidomide include: 
• Neurologic: Somnolence, dizziness, headache, tremor, asthenia, paresthesia, and numbness 
• Hematologic: anemia, neutropenia, leucopenia, lymphopenia and thrombocytopenia; 
thromboembolic events (deep vein thrombosis and pulmonary embolism).   
• Gastrointestinal: Constipation, dehydration, dry mouth, diarrhea, dyspepsia, nausea, 
vomiting and stomatitis. 
• Constitutional: Weakness, insomnia, rigors, chills, sweating, weight loss and fever. 
• Reproductive: teratogenicity and miscarriage. 
• Musculoskeletal: arthralgia, back/neck pain, joint pain, muscle cramp and weakness. 


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• Cardiac: hypotension. 
• Dermatologic: rash, dry skin, itching. 
• Endocrine: hypothyroidism. 
• Infection. 
• Pulmonary: cough, dyspnea. 
• Metabolic: hypokalemia, liver damage. 
• Renal: increased creatinine, renal failure. 
• Second Primary Malignancies 
 
Pregnancy reporting: 
See Section 4.2.3, Adverse Event Reporting. 
 
Other instructions related to lenalidomide: 
During maintenance, only one cycle (maximum 28-day supply) of therapy may be dispensed to 
the patient each month.  If a dose of lenalidomide is missed, it should be taken as soon as possible 
on the same day.  If it is missed for the entire day, it should not be made up.  Patients taking more 
than the prescribed dose of lenalidomide should be instructed to seek emergency medical care if 
needed and contact study staff immediately.  See Section 2.7.1.1, Chapter 4, Appendices D (Risks 
of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods) and E 
(Revlimid REMS program). 
 
2.6.3. DC/Fusion Vaccine - Manufacturing and Administration  
 
2.6.3.1. Tumor Collection 
All eligible patients will undergo a bone marrow biopsy and collection of 30 mL of bone marrow 
aspirate. The risks of this procedure are not different than bone marrow aspirates performed for 
diagnosis or disease status assessments. The risks include: bleeding, pain in the site of marrow 
collection, claudication and bruising. 
 
2.6.3.2.Dendritic Cell Precursor Collection 
Collection of dendritic cell precursors will occur in patients randomized to receive vaccine post-
transplant. Collection will be done through leukapheresis in a single session. Risks of this 
collection are related to placement of an intravenous leukapheresis catheter that can be associated 
with bleeding and pain. The leukapheresis procedure has a risk of hypocalcemia, 
thrombocytopenia, anemia, leukopenia and bleeding diathesis.  
 
2.6.3.3.Vaccine Administration 
Vaccines will be administered at three time points approximately one month a part. GM-CSF will 
also be administered at the site of vaccine for 4 consecutive days. Toxicities related to the vaccine 
are: 
 


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• Hematologic: Leucopenia, Neutropenia 
• Neurologic: Headache, light headedness 
• Gastrointestinal: Diarrhea,  
• Constitutional: Weakness, chills and fever. Pain at tumor site, fatigue, night sweats 
• Musculoskeletal: arthralgia and myalgia. 
• Dermatologic: rash, itching, edema and local reaction in the site of infusion (swelling, pain, 
bruising, erythema, and pruritus). 
• Endocrine: elevated TSH. 
• Other: ANA positivity, candida infection 
 
In prior studies, one participant with myeloma and a history of deep vein thrombosis developed a 
pulmonary embolus, which was determined to be serious and possibly related to the vaccine and 
GM-CSF. 
 
2.6.4. GM-CSF 
Potential side effects of GM-CSF treatment include fever, chills, nausea, vomiting, diarrhea, 
fatigue, weakness, headache, decreased appetite, facial flushing, bone and muscle pain, local 
reaction at the site of injections, rashes, low blood pressure, shortness of breath and low blood 
counts. Rarely patients may develop blood clots, rapid or irregular heartbeats, feeling of faintness, 
and allergic reactions or fluid retention, including potential fluid retention in lungs or around the 
heart. 
2.7.Study Drug Supply 
 
2.7.1. Lenalidomide  
Lenalidomide will be provided by Celgene and distributed by Biologics, Incorporated. Patients 
must be registered in the Revlimid REMS program in order to receive lenalidomide through the 
program (please see Appendix E). 
 
2.7.1.1.Lenalidomide (NSC 703813) 
 
NOTE: 
Before lenalidomide is dispensed, patients must 1) have a negative pregnancy test (if 
applicable) and 2) study patients must be be counseled through the Revlimid REMS 
program.  A maximum 28-day supply may be dispensed to a patient at one time. For more 
information please refer to www.revlimidrems.com. Only use the study specific drug 
request form per patient for ordering through Biologics.   
 
Chemical Name:  3-(4’-amino-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-2,6-piperidinedione 
 
Other Names:  CC-5013, Revlimid™, CDC-501 


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Classification:  Immunomodulatory Agent  
 
CAS Registry Number:  191732-72-6 
Molecular Formula:   C13H13N303  
 
M.W.:   259.25 
 
Mechanism of Action: 
Lenalidomide, a thalidomide analog, is an immunomodulatory agent with a spectrum of activity 
that is still under investigation.  Some of its effects include inhibition of inflammation, inhibition 
of angiogenesis, inhibition of hematopoietic tumor cell proliferation, modulation of stem cell 
differentiation and up regulating responses of T cells and NK cells.  
 
Drug Supply and Storage: 
Celgene supplies and Biologics, Inc. distributes lenalidomide 5 mg (size 2) and 2.5 mg hard gelatin 
capsules in tamper-evident, child-resistant, opaque, high density polyethylene (HDPE) bottles with 
HDPE caps.  Bottles will contain a sufficient number of capsules per container for one cycle of dosing.  
 
The capsules also contain anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, and 
magnesium stearate.  
 
Lenalidomide (Revlimid®) will be provided to research subjects for the duration of their 
participation in this trial at no charge to them or their insurance providers.  Lenalidomide will be 
provided in accordance with the Revlimid REMSTM program of Celgene Corporation.  Per standard 
Revlimid REMSTM requirements all physicians who prescribe lenalidomide for research subjects 
enrolled into this trial, and all research subjects enrolled into this trial, must be registered in and 
must comply with all requirements of the Revlimid REMSTM.  Prescriptions must be filled within 
7 days for FCBP and 14 days for all other risk categories.  
 
All study participants must be registered into the mandatory Revlimid REMSTM program, and be 
willing and able to comply with the requirements of the Revlimid REMSTM program. 
 
Any unused lenalidomide supplies distributed through the Revlimid REMSTM program must be 
returned to the clinical site and destroyed per institutional guidelines. 
 
Administration: 
Take lenalidomide by mouth with or without food.  Do not crush, chew or open capsules. 
 
Dispensing:  
Only enough lenalidomide for one cycle may be dispensed at one time.   
 


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Patient Care Implications and Counseling: 
Risks Associated with Pregnancy 
Lenalidomide is structurally related to thalidomide.  Thalidomide is a known human teratogenic 
active substance that causes severe life-threatening birth defects.  An embryofetal development 
study in animals indicates that lenalidomide produced malformations in the offspring of female 
monkeys who received the drug during pregnancy.  The teratogenic effect of lenalidomide in 
humans cannot be ruled out.  Therefore, a risk minimization plan to prevent pregnancy must be 
observed. 
 
Definition of female of childbearing potential (FCBP) 
This protocol defines a female of childbearing potential as a sexually mature female who: 1) has 
not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 
for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive 
months). 
 
Before starting study drug:   
 
Female Subjects:   
• FCBP must have two negative pregnancy tests (minimum sensitivity of 50 mIU/mL) prior 
to prescribing study drug.  The first pregnancy test must be performed within 10-14 days 
prior to prescribing study drug and the second pregnancy test must be performed within 24 
hours prior to prescribing study drug (prescriptions must be filled within 7 days as required 
by Revlimid REMSTM).  The subject may not receive study drug until the Investigator has 
verified that the results of these pregnancy tests are negative. 
• FCBP must commit either to abstain continuously from heterosexual intercourse or to use 
TWO methods of reliable birth control AT THE SAME TIME—one highly effective form 
of contraceptions and one additional effective contraceptive method as defined below. 
Contraception must begin 4 weeks prior to initiating treatment with lenalidomide, during 
therapy, during dose interruptions, and continuing for 4 weeks following discontinuation 
of lenalidomide.   
o HIGHLY EFFECTIVE:  
 Tubal Litigations  
 IUD  
 Hormonal contraceptives (birth control pills, injections, hormonal patches, 
vaginal rings or implants) 
 Partners Vasectomy  
o EFFECTIVE: 
 Male latex or synthetic condom 
 Diaphragm 
 Cervical cap  
 
 


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Male Subjects:   
• Must agree to use a latex or synthetic condom during sexual contact with females of 
childbearing potential while participating in the study, during dose interruptions and for at 
least 28 days following discontinuation from the study even if he has undergone a 
successful vasectomy.  
 
All Subjects: 
• Only enough lenalidomide for one cycle of therapy may be dispensed with each cycle of 
therapy.  
• If pregnancy or a positive pregnancy test does occur in a study subject or the partner of a 
male study subject during study participation, lenalidomide must be immediately 
discontinued. 
 
Potential Drug Interactions: 
Periodic monitoring of digoxin levels is recommended during co-administration with lenalidomide.   
 
Monitor patients receiving concomitant warfarin per standard practice guidelines. 
 
Lenalidomide is not a substrate of human CYP enzymes, nor is it an inhibitor or inducer. 
 
Drug Ordering and Accountability: 
The REMs program provides education and counseling on the risks of fetal exposure, blood clots 
and reduced blood counts.  Counseling will be provided by Biologics, Inc. prior to drug 
distribution.  Please refer to Appendix E (Lenalidomide REMs program).  The patient will be 
required to receive counseling every 28 days during treatment with lenalidomide, follow the 
pregnancy testing and birth control requirements of the program that are appropriate in order to 
take the telephone surveys regarding compliance with the program.  All physicians must be 
registered prescribers of Revlimid® in the REMs program.  Physician registration allows access 
to the REMs software to enroll patients in the REMs program.  The prescriber should submit the 
Registration Form via fax number 919-256-0794 or REMsOnline (RAO)for Revlimid®) to 
Celgene Customer Care.  Please reference Appendix E (REMsprogram) and follow the directions 
for submitting the registration.  Biologics, the distributor of the lenalidomide, will not dispense or 
ship Revlimid® prior to Celgene’s receipt of registration.  Prescription information MUST BE 
entered using the REMs study specific electronic prescription form referenced in Appendix E 
(REMs program).  An authorization number must be on the prescription form at the time of faxing.  
Prescriptions for Revlimid® must be sent to Biologics Clinical Trial Division at the following 
FAX number: 919-256-0794.  A maximum of a 28-day supply of Revlimid® may be dispensed 
per cycle sent to the actual address noted on the REMs electronic prescription form.  Biologics 
will verify the authorization number and complete the patient counseling.  Patients will be provided 
with instructions from Biologics with each new dispense on the procedures for return of any un-
used Revlimid® capsules.  Refer to Appendix E (REMsprogram).  
 


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2.8.Patient Withdrawal from Study and Off Study Criteria  
Patients on the BMT CTN 1401 study have voluntarily agreed to the study and may withdraw at 
anytime. Additionally, the treating physician may discontinue therapy with reasonable 
justification. The following criteria would result in discontinuation of study therapy:  
• Disease progression 
• Unacceptable adverse event(s)  
• Participant decides to withdraw from the study 
• General or specific changes in the participant's condition render the participant 
unacceptable for further treatment in the opinion of the treating investigator. 
 
After randomization, patients who stop therapy for any reason prior to two years from initiation 
will continue to be followed per protocol for 3 years post maintenance initiation unless the patient 
withdraws consent for study follow up. In the event of patient withdrawal, written documentation 
of the withdrawal must be provided to the BMT CTN. 
 


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CHAPTER 3 
 
3. 
STUDY ENDPOINTS AND DEFINITIONS  
 
3.1.Definition of Disease Status  
Patients’ disease status at each data collection period will be evaluated based on the International 
Uniform Response Criteria19. Until disease progression, all disease classifications are relative to 
the patient’s disease status prior to autologous transplant. At time of disease progression, disease 
classifications are relative to the patient’s best response since time of study entry.  
 
3.1.1. Response Categories  
 
Stringent Complete Response (sCR): 
sCR requires, in addition to CR (defined below), all of the following: 
• Normal free light chain ratio (FLC). 
• Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. 
 
Complete Response (CR): 
CR requires all of the following: 
• Absence of the original monoclonal paraprotein in serum and urine by routine 
electrophoresis and by immunofixation.  The presence of new monoclonal bands consistent 
with oligoclonal immune reconstitution does not exclude CR. 
• Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if 
biopsy is performed.   
• No increase in size or number of lytic bone lesions on radiological investigations 
(development of a compression fracture does not exclude CR)*. 
• Disappearance of soft tissue plasmacytomas. 
*If not clinically indicated, radiographs are not required to document CR. 
 
Patients in whom some, but not all, the criteria for CR are fulfilled are classified as partial 
responses (see below), providing the remaining criteria satisfy the requirements for partial 
response.  This includes patients in whom routine electrophoresis is negative but in whom 
immunofixation has not been performed. 
 
Very Good Partial Remission (VGPR) 
VGPR requires, in addition to PR (defined below), all of the following: 
• Serum or urine paraprotein detectable by immunofixation but not on electrophoresis.  
OR 
• Greater than or equal to 90% reduction in serum paraprotein plus urine paraprotein  
<100 mg/24hrs.  


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• For free light chain only disease, VGPR requires a 90% reduction of involved light chain 
 
Partial Response (PR) 
PR requires one of the following: 
• Greater than or equal to 50% reduction in the level of the serum monoclonal paraprotein and 
reduction in 24 hour urinary monoclonal paraprotein either by greater than or equal to 90% 
or to <200 mg/24 hours in light chain disease. 
• If the only measurable non-bone marrow parameter is FLC, greater than or equal to 50% 
reduction in the difference between involved and uninvolved FLC levels or a 50% decrease 
in level of involved FLC with 50% decrease in ratio,  
• If the bone marrow is the only measurable parameter, greater than or equal to 50% reduction 
in bone marrow plasma cells given that the baseline count was greater or equal to 30%, 
• Greater than or equal to 50% reduction in the size of soft tissue plasmacytomas if present at 
baseline (by radiography or clinical examination). 
 
Stable Disease (SD) 
• Patients who do not meet criteria for sCR, CR, VGPR, partial response or progressive 
disease (section 3.1.1.2) are considered to have stable disease (SD). 
 
3.1.2. Progressive Disease (PD) 
 
Disease Progression (PD) 
Progression from CR or sCR requires one or more of the following:  
• A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL.  
• 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours. 
• Abnormal FLC levels of >10 mg/dl, only in patients without measurable paraprotein in the 
serum and urine.  
• At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy.  
• Definite increase in the size of existing bone lesions or soft tissue plasmacytomas.  
• Development of new bone lesions or soft tissue plasmacytomas.  
• Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not 
attributable to any other cause.  
 


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Progressive Disease (PD)  
For patients not in CR or sCR, progressive disease requires one or more of the following measured 
from the time of randomization: 
• >25% increase in the level of the serum monoclonal paraprotein, which must also be an 
absolute increase of at least 0.5 g/dL. 
• >25% increase in 24-hour urine protein electrophoresis, which must also be an absolute 
increase of at least 200 mg/24 hours. 
• Absolute increase in the difference between involved and uninvolved FLC levels (absolute 
increase must be >10 mg/dl), only in patients without measurable paraprotein in the serum 
and urine.  
• >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must 
also be an absolute increase of at least 10%. 
• Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. 
• Development of new bone lesions or soft tissue plasmacytomas.  
• Development of a compression fracture does not exclude continued response and may not 
indicate progression. 
• Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not 
attributable to any other cause. 
 
3.2.Primary Endpoint  
 
The primary objective of this randomized trial is to compare the proportion of patients alive and 
in complete response (CR or sCR) at one year post transplant between patients receiving 
DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving 
lenalidomide maintenance therapy with or without GM-CSF. 
 
3.3.Clinical Secondary Endpoints  
 
3.3.1. Response to treatment 
The trial will assess the rates of VGPR or better (VGPR, nCR, CR and sCR) responses) according 
to the International Uniform Response Criteria (Section 3.2) at specific time points in both arms 
from the time of randomization.  Assessment of disease response will be done immediately prior 
to randomization, prior to cycles 3, 6, and then every 3 months until approximately 22 months 
from randomization or evidence of disease progression. Additionally, assessments of disease 
response will be conducted at 6, 12, and 24 months post-transplant. Rates of VGPR or better 
responses will be compared between the two arms.  For patients not in CR at randomization, the 
rate of CR conversion (CR and sCR) will be compared between the vaccine and no-vaccine arms 
combined. A secondary pairwise analysis will compare the CR rates at 1 year between the vaccine 
arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.   
 


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3.3.2. Myeloma Progression 
Myeloma progression defined according to Section 3.2 or initiation of off protocol anti-myeloma 
therapy is the event for this endpoint. Death without documentation of disease progression is the 
competing event.  Patients alive without disease progression at last contact are considered censored 
for this event.  The cumulative incidence of myeloma progression will be compared between 
vaccine and no-vaccine arms combined.  A secondary pairwise analysis will compare the 
cumulative incidence of myeloma progression between the vaccine arm, lenalidomide/GM-CSF 
arm and lenalidomide alone arm.     
 
3.3.3. Minimal Residual Disease Assessment  
Minimal residual disease (MRD) is defined as the presence of malignant plasma cells detected by 
multicolor flow cytometry among patients who are in complete remission. Multichannel flow 
cytometry will be used to establish MRD based on the presence of malignant plasma cells that are 
CD45 (-/dim), CD38+, CD138+, CD19-, CD56+ kappa or lambda restricted. The result will 
determine whether that patients has MRD (MRD +) or not (MRD -). The proportion of patients 
who are MRD negative at one year will be compared between vaccine and no-vaccine arms 
combined.  A secondary pairwise analysis will be conducted comparing the proportion of patients 
who are MRD negative at one year between the vaccine arm, lenalidomide/GM-CSF arm and 
lenalidomide alone arm.   
 
3.3.4. Treatment-related Mortality 
TRM is defined as death occurring in a patient from causes other than disease relapse or 
progression. Disease progression is the competing event for TRM.  Patients alive without disease 
progression at last contact are considered censored for this event. TRM from time of randomization 
will be compared between vaccine and no-vaccine arms combined starting at time of 
randomization. A secondary pairwise analysis will compare TRM between the vaccine arm, 
lenalidomide/GM-CSF arm and lenalidomide alone arm.   
 
3.3.5. Incidence of Toxicities Grade ≥3 per CTCAE vesion 4.0 
All Grade ≥ 3 toxicities will be tabulated for treatment arms. The proportion of patients developing 
Grade ≥ 3 toxicity will be compared between the vaccine and no-vaccine arms combined until 
disease progression or end of follow up. A secondary pairwise analysis will compare the incidence 
of toxicities between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.   
 
3.3.6. Incidence of Infections per BMT CTN Technical MOP 
The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for 
each patient.  The proportion of patients in each treatment arm with these infections will be 
compared from randomization until disease progression or end of follow up.  
 
3.3.7. Progression-free survival 
Patients are considered a failure of this endpoint if they die or suffer from disease progression.  
The time to this event is the time from randomization to progression, death, initiation of non-
protocol anti myeloma therapy, loss to follow up or end of study whichever comes first and it will 
be compared between the vaccine and no-vaccine arms combined from time of randomization.  


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A secondary pairwise analysis will compare progression-free survival between the vaccine arm, 
lenalidomide/GM-CSF arm and lenalidomide alone arm.   
 
3.3.8. Overall Survival 
The event is death from any cause.  The time to this event is the time from randomization to death, 
loss to follow-up or the end of the study, whichever comes first.  Patients alive at the time of last 
observation are considered censored.  Overall survival will be compared between the vaccine and 
no-vaccine arms combined from time of randomization.  A secondary pairwise analysis will 
compare overall survival between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide 
alone arm.   
   
3.4.Primary Immunologic Endpoints  
 
3.4.1. Myeloma-Reactive T-cells 
The effect of DC/Myeloma Fusion Vaccine/GM-CSF with lenalidomide maintenance; 
lenalidomide maintenance; and lenalidomide maintenance with GM-CSF on levels of circulating 
myeloma reactive T cells will be quantified.  Myeloma-reactive T cells, as defined by the 
percentage of circulating CD4+ and CD8+ T cells that express IFNγ following ex vivo exposure 
to autologous tumor lysate will be assess in both treatment arms. The percent of patients achieving 
at least a 2.4-fold increase in tumor reactive T cells will be compared between the vaccine and 
each of the no-vaccine arms separately. 
 
3.5.Secondary Immunologic Endpoints: 
 
3.5.1. Myeloma-Reactive T-cells 
The percent of patients achieving at least a 10-fold increase in tumor-reactive T cells will be 
compared between the vaccine and no-vaccine arms separately as described above. 
 
3.5.2. Assessment of antigen specific reactivity:   
The effect of DC/Myeloma Fusion Vaccine/GM-CSF + lenalidomide maintenance; lenalidomide 
maintenance; and lenalidomide maintenance + GM-CSF on immunologic responses directed 
against previously identified myeloma antigens will be assessed.  In HLA-A2.1 patients, 
circulating CD8+ T cells binding tetramer constructed from MUC1, SOX2, NY-ESO, and XBP-1 
will be quantified.  At serial time points PBMC and BMMC will undergo dual staining for CD8 
and the appropriate tetramer, and analyzed by multichannel flow cytometry.  When cell yields 
allow, functional characteristics of the tetramer positive population will be determined by 
measuring IFNγ, granzyme B, IL-4, and IL-10 expression in the tetramer positive cells by 
intracellular staining.  
 
3.5.3. Quantification of T-cell subsets:  
Quantification of regulatory T cells and activated memory effector cells will be performed at the 
serial time points (Appendix C).  T cell subsets will be quantified with respect to the relative 
proportion of CD4 and CD8+ T cells and the presence of naïve, effector memory, and central 
memory cells will be determined by staining for CD45RA, and CD45RO, CD27, and CD62L by 
multichannel flow cytometry.  Regulatory T cells will be quantified as CD4/CD25/FOXP3 cells.  


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T cells expressing PD-1 will be quantified at the time points indicated above.  Quantification of 
granulocytic and monocytic myeloid derived suppressor cells will be performed from peripheral 
blood and bone marrow samples undergoing multichannel flow cytometry for CD11b, HLA-DR, 
CD14, CD15 and CD33.    
 
3.5.4. Assessment of effect on NK cell populations: 
The effect of lenalidomide alone and in combination with DC/MM vaccination on the phenotype 
and function of circulating NK cell populations will be assessed as detailed in Appendix C.  The 
expression of a panel of NK receptors including activating receptors (NKp30, NKp44, NKp46, 
NKG2D, NKG2C, DNAM1), inhibitory receptors (NKG2A and KIRs) and markers of NK 
function (CD16, CD25, CD132) will be assessed. The effector function of NK cells against MHC 
class I-deficient leukemia targets and primary MM cells (where available) from the recipient will 
be assessed by intracellular cytokine assay for interferon-gamma (IFN-γ) production, and 
cytotoxicity, including CD107a degranulation and 51chromium release assay. The expression of 
receptors important in the regulation of human NK cell trafficking and homing in vivo, including 
CD62L, CXCR4, CXCR3, CCR6 and CCR7 will be measured. The effect of treatment on NK 
function will be assessed by examining expression of the canonical transcription factors 
eomesodermin (Eomes) and T-bet prior to and serially following initiation of therapy. Surface 
expression of CD57 and KLRG1, both markers of mature NK cells, will be evaluated.  
 
3.5.5. Assessment of humoral immune response:  
Serological Analysis of Recombinant cDNA Expression Library (SEREX) will be performed on 
serum samples to assess humoral response targeting myeloma antigens in patients treated with 
lenalidomide maintenance alone or in conjunction with DC/MM fusion vaccination as detailed in 
Appendix C.   Peripheral blood will be transported for a cell based assay to assess the kinetics, 
magnitude and specificity of vaccine-induced myeloma specific plasmablast responses, as detailed 
in Appendix C.  


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CHAPTER 4 
 
4. 
PATIENT REGISTRATION, ENROLLMENT, AND EVALUATION  
 
4.1.Enrollment Procedures  
Patients are enrolled in to the Segment A prior to initial systemic therapy (<1 cycle) and first 
autologous transplant. At the time of enrollment, an authorized user at the clinical center completes 
the demographics and primary eligibility form which includes questions confirming that the patient 
signed the consent and meets the eligibility criteria for study entry. Patients must be successfully 
enrolled in Segment A prior the collection of tumor cells.  
 
Once the patient is enrolled in the study (Eligibility Form, Segment A competed):  
1. A visit schedule based on enrollment date will be available for printing  
2. Following enrollment and tumor cell collection the patient should proceed with initial 
systemic therapy and autologous transplant. Patients should be transplanted within one 
year of enrollment into Segment A.  
3. Patient will be seen 14 days or less prior to randomization for eligibility assessments 
prior to randomization/enrollment in Segment B. The pre-randomization disease 
response assessment must be performed < 10 days prior to randomization. 
Randomization should occur between day 53 and day 80 after the autologous HCT. An 
authorized user at the clinical center completes a checklist confirming that the patient 
is eligible to proceed to the next stage of treatment on the study.  
4. If the patient is eligible, they will be enrolled in Segment B and randomized to their 
treatment assignment and the treatment plan is continued. 
5. A visit schedule based on the date of randomization will be available for printing.   
 
4.2.Study Monitoring  
 
4.2.1. Follow - Up Schedule  
The follow up schedule for study visits after Segment A enrollment and subsequently after 
randomization are outlined below in tables 4.2.1A and 4.2.1B, respectively. The follow up 
schedule is the intended schedule; however, the date of the follow up evaluations may vary due to 
delays in treatment or treatment interruption related to Adverse Events and toxicities. The visit 
window for the scheduled evaluations is included in each table. Patients will be followed for three 
years post maintenance initiation.  
 
 


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4.2.1A: FOLLOW UP SCHEDULE  
AFTER ENROLLMENT (SEGMENT A) 
 
Study Visit 
Target Day  
Pre- Enrollment Screening 
< 8 weeks prior to enrollment  
Tumor cell collection 
7 days post enrollment±7 days1 
Pre- Randomization 
Screening 
< 14 days prior to randomization 
Randomization 
Day 53- Day 80 post transplant2 
Dendritic Cell Collection3 
< 14 days after randomization and prior to 
Day 85 post transplant  
Pre- Maintenance Screening 
< 14 days prior to maintenance initiation 
Maintenance Start  
90-100 days post transplant 
1  Tumor cell collection by bone marrow aspirate can occur the same day of enrollment and up to 14 days 
after enrollment.   
2 Randomization must also occur within 10 days of a disease response assessment.  
3 Leukapheresis for dendritic cell collection is only required for patients randomized to the vaccine/GM-
CSF/Lenalidomide arm.  
 
 
4.2.1B: FOLLOW UP SCHEDULE  
POST RANDOMIZATION TO MAINTENANCE 
 
Study Visit 
Target Day Post Maintenance 
(+ 7 days)1 
Baseline  
< 14 days prior to randomization 
Prior to initiation of 
maintenance 
< 14 days prior to maintenance 
Start of Maintenance2 
Cycle 1 
Day 1 
Cycle 2 
29 days 
Cycle 2 + 7 days 
35 days 
Cycle 3 
57 days 
Cycle 4 
85 days 
Cycle 4 + 7 days 
91 days 
Cycle 6 
141 days 
Cycle 9 (Start) 
225 days 
Cycle 9 (End) 
253 days 
 Cycle 12 
309 days 
Cycle 15 
393 days 
Cycle 18 
477 days 
Cycle 21 
561 days 
Cycle 24 
645 days  
1After 9 cycles of maintenance therapy, patients can be seen + 14 days from the target date.  


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4.2.1C: FOLLOW UP SCHEDULE 
ENDPOINT ASSESSMENTS1  
 
Endpoints  
Days From Transplant 
6 months post 
transplant (6T) 
Day 180 ± 14 days 
12 months post 
transplant (12T)2 
Day 365 + 14 days  
24 months post 
transplant (24T)3  
Day 730 + 14 days  
1Endpoint assessments will occur at 6 months posttransplant and yearly post-transplant for 2 years 
or until disease progression. These assessments may be conducted at the required visits outlined in 
table 4.2.1B if they fall within 14 days of the target date for the post randomization visit.  
2 The 6 month posttransplant visit should correspond to the start of the 4th cycle of maintenance 
unless the patient has been delayed for any reason.  
The 12 month posttransplant visit should correspond to the start of the 11th cycle of maintenance 
unless the patient has been delayed for any reason.  
3The 24 month post transplant visit should correspond to the start of the 24th cycle of maintenance 
unless the patient has been delayed for any reason.  
 
4.3.Patient Evaluations  
 
4.3.1. Pre- Enrollment Segment A Evaluations and Requirements  
 
The following evaluations must be determined < 8 weeks prior enrollment on BMT CTN 1401. 
See table 4.3.1A.  
1. History, physical examination, height and weight  
2. Karnofsky Performance Score 
3. CBC with differential, platelet count 
4. Liver Functions and blood chemistries: Serum creatinine, total bilirubin, alkaline 
phosphatase, AST, ALT  
5. Evaluation of creatinine clearance 
6. Laboratory Disease Evaluation:  
a. Quantitative serum immunoglobulin levels. 
b. Serum protein electrophoresis (SPEP). 
c. 24 hour urine collection to determine protein excretion,urine electrophoresis 
(UPEP). 
d. Immunofixation of urine and serum protein regardless of SPEP and UPEP results. 
e. Serum free light chain ratios (FLC) 


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7. Bone Marrow Evaluation: unilateral bone marrow biopsy and aspirate are required to 
assess plasma cell involvement in the marrow as per eligibility criteria outlined in section 
2.3.1  
8. Skeletal bone survey to include cranium, axial skeleton and proximal long bones or other 
imaging study to evaluate for bone involvement.  
 
4.3.2. Tumor Cell Collection Evaluations and Requirements at Enrollment 
1. Tumor Cell Collection1  
a. Bone marrow aspiration (30mL) is required for vaccine production and eligibility 
validation.  
b. Peripheral Blood (50mL) collection  
2. Protocol-required Samples for Correlative Studies (Table 4.3B)2 
a. Bone marrow aspirate (4mL) for immunologic endpoints (see Appendix C for 
details)  
b. Peripheral Blood (40mL) collection for immunologic endpoints (see Appendix C 
for details)  
3. Optional Samples for Future Research2 
a. Bone marrow aspirate (3mL) (see Appendix C for details)  
b. Peripheral Blood (6mL) collection (see Appendix C for details)  
4.3.3. Pre- Randomization Evaluations and Requirements  
The following evaluations to determine eligibility for randomization must be performed < 14 days 
prior to randomization unless otherwise noted below.  
1. History and physical examination  
2. Assessment for toxicities  
3. Laboratory Disease Evaluation (<10 days from randomization):  
a. Quantitative serum immunoglobulin levels. 
b. Serum protein electrophoresis (SPEP). 
c. 24 hour urine collection to determine protein excretion, urine electrophoresis 
(UPEP). 
d. Immunofixation of urine and serum protein regardless of SPEP and UPEP 
results. 
e. Serum free light chain ratios (FLC) 
4. Bone Marrow Evaluation: unilateral bone marrow biopsy and aspirate are required only 
to confirm CR in patients unless required for BMT CTN 1401 correlative studies.  
                                                 
1 Must be collected < 14 days after enrollment  
2 Must be collected < 14 days after enrollment 


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5. Protocol-required Samples for Correlative Studies (Table 4.3B)3 
a. Bone marrow aspirate (10mL) for immunologic endpoints (see Appendix C for 
details)  
b. Peripheral Blood collection (30mL) for immunologic endpoints (see Appendix 
C for details)  
 
6. Optional Samples for Future Research 
a. Bone marrow aspirate (3mL) (see Appendix C for details)  
b. Peripheral Blood (6mL) collection (see Appendix C for details)  
7. Optional Samples for Ancillary Research: To be collected only on patients providing 
consent for ancillary research per Appendix J and/or K (see Appendix C for details) 
a. Bone marrow aspirate (4mL) - additional sample volume collected at the time 
of required sample for immunologic endpoints 
b. Four (4) Paraffin Embedded Slides from Core Bone Marrow Biopsy required 
to confirm CR in some study patients prior to randomization  
8. Skeletal bone survey to include cranium, axial skeleton and proximal long bones or 
other imaging study to evaluate for bone involvement.   
9. CBC with differential, platelet count 
10. Liver Functions and blood chemistries: Serum creatinine, total bilirubin, alkaline 
phosphatase, AST, ALT  
11. Evaluation of creatinine clearance 
12. Pregnancy test, serum HCG (sensitivity of at least 50 mIU/mL) for FCBP.   
 
4.3.4. Pre- Maintenance Evaluations and Requirements 
The following evaluations to determine eligibility for maintenance initiation must be performed < 
14 days prior to the initiation of lenalidomide maintenance therapy unless otherwise noted below.  
1. History and Physical Exam  
2. Assessment for toxicities  
3. CBC with differential, platelet count 
4. Liver Functions and blood chemistries: Serum creatinine, total bilirubin, alkaline 
phosphatase, AST, ALT  
5. Required evaluation prior Lenalidomide: Pregnancy test, serum HCG (sensitivity 
of at least 50 mIU/mL) for FCBP.  Women are required to have 2 pregnancy tests 
prior to the initiation of lenalidomide as follows (Appendix D) 
                                                 
3 Should be collected + 14 days from date of randomization however, randomization samples are preferred to be 
collected after the patient is randomized. If samples(s) need to be collected prior to randomization, contact the protocol 
coordinator.  


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a. The first is required within 10 to 14 days prior to prescribing lenalidomide,  
b. The second is required within 24 hours of prescribing lenalidomide.  
 
4.3.5. Evaluations during Maintenance 
 
1. The following evaluations will be done monthly for the first 4 cycles and then at cycles 6, 
9, 12, 15, 18, 21, 24:  
a. History and physical exam  
b. CBC with differential, platelet count4  
c. Liver Functions and blood chemistries: Serum creatinine, total bilirubin, alkaline 
phosphatase, AST, ALT  
2. Assessment for Toxicities monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 
and 245.   
3. Required evaluation for Lenalidomide: Pregnancy test, serum HCG (sensitivity of at least 
50 mIU/mL) for female of childbearing potential (FCBP): 
a. FCBP with regular or no menstruation must have a pregnancy test weekly for the 
first 28 days and then every 28 days while on therapy (including breaks in therapy); 
at discontinuation of lenalidomide and at Day 28 post the last dose of lenalidomide.  
Females with irregular menstruation must have a pregnancy test weekly for the 
first 28 days and then every 14 days while on therapy (including breaks in therapy), 
at discontinuation of lenalidomide and at Day 14 and Day 28 post the last dose of 
lenalidomide (Appendix D). 
b. The subject must follow the requirements of the Revlimid REMS® program of the 
Celgene Corporation.  This program provides education and counseling on the 
risks of fetal exposure, blood clots and reduced blood counts.  The patient will be 
required to receive counseling every 28 days during treatment with lenalidomide, 
follow the pregnancy testing and birth control requirements of the program that 
are appropriate in order to take the telephone surveys regarding compliance with 
the program. 
4. Laboratory Disease Evaluation at prior to cycles 3, and 6, and every 3 cycles thereafter. 
Disease evaluations will also be collected at 6 months, 1 and 2 years post-transplant:  
a. Quantitative serum immunoglobulin levels. 
b. Serum protein electrophoresis (SPEP). 
c. 24 hour urine collection to determine protein excretion, urine electrophoresis 
(UPEP). 
d. Immunofixation of urine and serum protein regardless of SPEP and UPEP results. 
e. Serum free light chain ratios (FLC) 
                                                 
4 Patients receiving lenalidomide should receive monthly CBCs per the requirements of the RevlimidREMs program.  
5 Patients experiencing adverse events outside of the toxicity assessment timelines are still required to adhere to the 
adverse event reporting requirements in section 4.4.4 and Appendix I.  


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5. Bone Marrow Evaluation: unilateral bone marrow biopsy and aspirate are required only 
to confirm CR in patients  
6. Skeletal bone survey to include cranium, axial skeleton and proximal long bones or other 
imaging study to evaluate for bone involvement at 1 and 2 years post transplant.  
7. Samples for Correlative Studies (Table 4.3B) 
a. Bone marrow aspirate (10mL) just prior to the start of cycle 9 of maintenance for 
immunologic endpoints (see Appendix C for details).  
b. Peripheral Blood collection prior to cycles 1, 2, 3, 4, and 9 and at day 7 of cycles 
2 and 4 for immunologic endpoints (see Appendix C for details).  
  
8.  Optional Samples for Future Research 
a. Bone marrow aspirate (3mL) collection just prior to the start of cycle 9 of 
maintenance (see Appendix C for details) 
b. Peripheral Blood (6mL) collection just prior to the start of cycle 9 of maintenance 
(see Appendix C for details) 
9. Optional Samples for Ancillary Research: To be collected only on patients providing 
consent for ancillary research per Appendix K (see Appendix C for details)  
a. Bone marrow aspirate (4mL) (see Appendix C for details) – additional volume 
collected just prior to the start of cycle 9 of maintenance along with required 
research sample being collected for the primary trial, and a (5mL) marrow aspirate 
sample collected at time of disease progression determination. 
b. Peripheral Blood Collection: additional volume of blood collected prior to cycles 
1, 2, and 4 (10mL) along with the required research samples being collected for 
the primary trial, and (40mL) blood collected at the time of disease progression 
determination.


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TABLE 4.3A: PATIENT CLINICAL ASSESSMENTS 
 
Study Assessments 
Pre- 
Enrollment 
Pre- 
Randomization 
Pre 
maintenance 
Cycles of maintenance 
Post-transplant 
visits 
1 
2 
3 
4 
6 
9 
12 
15 
18 
21 
24 
6T 
12T 
24T 
History, physical exam, weight and height1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Karnofsky performance score 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC, differential, platelet count, and blood 
chemistries2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Evaluation of Creatinine Clearance 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test3 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Quantitative serum immunoglobulins 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SPEP and immunofixation 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
24 Hour Urine for UPEP, protein excretion 
and immunofixation 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum free light chain ratio 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Skeletal Survey or other imaging study 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Bone marrow aspirate and biopsy 
X4 
X5 
 
 
X
5 
 
X5 
X5 
X5 
X5 
X5 
X5 
X5 
X5 
X5 
X5 
Toxicity assessment6 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
 
 
1Height and Weight are only required at pre-enrollment and pre-randomization visits.  
2Blood chemistries include: serum creatinine, bilirubin, alkaline phosphatase, AST and ALT as required per protocol. 
3 For female of childbearing potential: A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; 
or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). 
 4Bone Marrow aspirate and biopsy required within 60 days of enrollment; must be repeated if patient receives additional therapy between initial pre-treatment BM and enrollment 
5Bone Marrow aspirate and biopsy required only to confirm CR in patients 
6The toxicity assessment will include a review of all toxicities and appropriate lab evaluations experienced during the entire assessment period and the highest grade for each 
toxicity during the assessment period will be recorded on the Toxicity form in AdvantageEDC using CTCAE version 4. 
 
 


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TABLE 4.3B: SAMPLE COLLECTION TIME POINTS 
 
Sample Collection 
Tumor Cell 
Collection 
(At 
Enrollment)4 
Pre- 
Randomization6 
Cycles of maintenance 
17 
27 
2 
+7d8 
37 
47 
4 
+ 7d8 
 
97 
(prior) 
Progression10 
Bone Marrow Aspirate 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow aspirate for tumor collection (30mL) 
X1 
 
 
 
 
 
 
 
 
 
 
MRD Assessment (6 mL)2 
 
X 
 
 
 
 
 
 
 
X 
 
Myeloma Reactive T Cells (4 mL)  
X1 
X 
 
 
 
 
 
 
 
X 
 
T Cell/Genomic Signature Study (4mL unless 
otherwise noted) 
 
X 
 
 
 
 
 
 
 
X 
X (5mL) 
VCAN Assessment9 
 
X 
 
 
 
 
 
 
 
 
 
Optional Repository Sample for Future Research 
(3mL) 
X1 
X 
 
 
 
 
 
 
 
X 
 
Total Maximum Marrow Volume (mL)5 
37 
17 
 
 
 
 
 
 
 
17 
5 
Peripheral Blood 
 
 
 
 
 
 
 
 
 
 
 
Plasma for Vaccine Production (50mL)  
X5 
 
 
 
 
 
 
 
 
 
 
Plasmablast Responses (30mL) 
 
X 
 
X3 
X3 
 
X3 
X 
 
 
 
Myeloma Reactive T Cells (40mL)  
X5 
 
X 
X 
 
X 
X 
 
 
X 
 
NK cell reconstitution (30mL) 
 
 
X 
 
X 
X 
 
X 
 
X 
 
T Cell/Genomic Signature Study (10mL unless 
otherwise noted) 
 
 
X 
X 
 
 
X 
 
 
 
X (40mL) 
Optional Repository Sample for Future Research 
(6mL) 
X5 
X 
 
 
 
 
 
 
 
X 
 
Total Maximum Blood Volume (mL) 
965 
36 
80 
803 
603 
70 
803 
60 
 
76 
40 
1 Bone marrow aspirate for collection of tumor cells should be done with 1-2 pull(s) per site until the total volume is achieved. The first 30mL will be dedicated 
for vaccine production, which will be cryopreserved at the transplant center. The remainder volume (7mL) will be aliquoted into two samples, which will be shipped 
to the BMT CTN repository and to BIDMC.  
2 Minimal residual disease (MRD) assessment will be done at the center and centrally at RPCI, the MRD sample will be aliquot in two 3 mL samples, one will be 
sent to RPCI and the other for analysis at the transplant center. Patients with overt evidence of disease progression are not required to submit sample for MRD 
assessment.  
3 Assessment for plasmablast only applies to patients who were randomized to the vaccine arm. 
4 The Tumor Cell Collection Visit should occur < 14 days post enrollment in Segment A.  
5 Blood collection at study entry can be collected over a 10 day period to avoid collection of excessive volumes in a single day. 


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6The Pre-Randomization collection should be collected + 14 days from date of randomization however, randomization samples are preferred to be collected after 
a patient is randomized. If samples(s) need to be collected prior to randomization, contact the protocol coordinator. 
7Samples should be collected < 3 days from target date (If target date is a Friday, Saturday or Sunday, collect the previous Thursday)  
8Samples should be collected -2 days to +1 day from target (If target date is a Friday or, Saturday, collect the previous Thursday. If Sunday, collect Monday.) 
9No additional sample is required. Four (4) Paraffin embedded slides prepared at the clinical site from the core biopsy required for clinical assessment prior to 
randomization. 10Collected at the time of  confirmation of disease progression per Chapter 3. 


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4.4.Data Reporting  
 
4.4.1. Criteria for Forms Submission 
Forms that are not entered into AdvantageEDCSM within the specified time will be considered 
delinquent.  A missing form will continue to be requested either until the form is entered into the 
AdvantageEDCSM and integrated into the Data and Coordinating Center’s (DCC) master database, 
or until an exception is granted and entered into the Missing Form Exception File. 
 
4.4.2. Reporting Patient Deaths  
Recipient death information must be entered into AdvantageEDCSM within 24 hours of knowledge 
of the patient’s death.  If the cause of death is unknown at that time, it need not be recorded at that 
time.  However, once the cause of death is determined, the form must be updated in 
AdvantageEDCSM. 
 
4.4.3. Center for International Blood and Marrow Transplant Research (CIBMTR) Data 
Reporting  
Centers participating in BMT CTN trials must register pre- and post-transplant outcomes on all 
consecutive hematopoietic stem cell transplants done at their institution during their time of 
participation to the Center for International Blood and Marrow Transplant Research (CIBMTR).  
Registration is done using procedures and forms of the Stem Cell Transplant Outcomes Database 
(SCTOD).  (Note: Federal legislation requires submission of these forms for all US allotransplant 
recipients.)  Enrollment in BMT CTN 1401 must be indicated on the SCTOD pre-transplant 
registration form.  Additionally, CIBMTR pre- and post- transplant Comprehensive Report Forms 
must also be submitted for all patients enrolled on this trial. CIBMTR forms will be submitted 
directly to the CIBMTR at the times specified on the Form Submission Schedule. 
 
4.4.4. Adverse Event Reporting  
Reporting of adverse events on the BMT CTN 1401 protocol has unique requirements due to the 
addition of lenalidomide as part of the protocol. Adverse event reporting requirements are 
summarized below and further described in Appendix I.  
4.4.4.1.Definitions  
 
Adverse Event: An adverse event (AE) is any undesirable sign, symptom or medical condition or 
experience that develops or worsens in severity after starting the first dose of study treatment or 
any procedure specified in the protocol, even if the event is not considered to be related to the 
study.   
 
Expectedness: An adverse event can be Expected or Unexpected  
• Expected adverse events are those that have been previously identified as resulting from 
administration of the agent. For the purposes of this study, an adverse event is considered 
expected when it appears in the current adverse event list, the Investigator’s Brochure, the 
package insert or is included in the informed consent document as a potential risk. 
• Unexpected adverse events are those that vary in nature, intensity or frequency from 
information in the current adverse event list, the Investigator’s Brochure, the package 
insert, or when it is not included in the informed consent document as a potential risk. 


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4.4.4.2. BMT CTN Adverse Event Reporting Guidelines  
It is BMT CTN policy that AEs must be reported even if the investigator is unsure whether a 
relationship exists between the adverse event and the use of the study treatment. Reporting of AEs 
for BMT CTN 1401 will be consistent with the BMT CTN Administrative Manual of Procedures.  
Additional requirements specific to this protocol are outlined below and in Appendix I. 
 
In BMT CTN studies, expected adverse events are reported via the web-based electronic data 
capture system, AdvantageEDC. Events are captured on calendar-driven case report forms (e.g., 
Toxicity) or event-driven case report forms (e.g., Progression, and Death).  
 
From the time of enrollment until randomization, only deaths, secondary primary malignancies 
and progressions are required to be reported. From time of randomization until 3 years post 
maintenance initiation, unexpected, grades 3-5 AEs, irrespective of the attribution of the event to 
the study drug /procedure/treatment, will be reported through the expedited AE reporting system 
via AdvantageEDC, and will be graded according to the NCI Common Terminology Criteria for 
Adverse Events (CTCAE), Version 4.0. The BMT CTN 1401 protocol has two distinct 
interventions: transplant and maintenance therapy. Determination of expectedness for events 
occurring post-transplant and/or post-maintenance therapy will be at the discretion of the 
investigator as described in Appendix I. Unexpected, grades 4-5 AEs must be reported within 
24 hours of knowledge of the event. Unexpected, grade 3 AEs must be reported within three 
business days of knowledge of the event. The NHLBI Data and Safety Monitoring Board will 
receive summary reports of all adverse experiences at least twice yearly. 
 
Since this study is under an FDA Investigational New Drug, all suspected and unexpected fatal or 
life-threatening adverse events are reported to the FDA within seven calendar days after receipt of the 
information, following FDA guidelines. All suspected and unexpected Grade 3 serious adverse events 
are reported to the FDA via a written report within fifteen days of receipt of the information (21 CFR 
312.32). If the Medical Monitor assesses the event to be unrelated to the study, then the event will 
not require expedited reporting but will be included in a summary report issued annually.  All 
expected adverse events (i.e., those listed in the informed consent, product inserts, or study 
materials) not covered under the above requirements need not be reported via the AE Form.  They 
will be captured on other CRFs.  Although death and graft failures are not considered unexpected 
post-transplant events, they are reported to the FDA via annual reports. Safety reporting to the FDA 
will be done by the BMT CTN based upon date of initial entry on the Adverse Event Forms and requires 
no additional action from the participating site. 
 
All second primary malignancies (SPM), excluding non-melanoma skin cancers, experienced by 
patients enrolled on the study will be reported using the expedited AE reporting system in 
AdvantageEDC and must be reported within three business days of knowledge of the event.  The 
Event Description entered in AdvantageEDC should include histologic type. 
 
4.4.4.3. Additional Adverse Event Reporting 
 
Celgene Corporation (Celgene) is supplying lenalidomide for this study and a description of 
additional reporting requirement for this study is detailed in Appendix I. The additional adverse 


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event reporting period for lenalidomide begins with the first dose and continues until 28 days after 
permanent discontinuation of lenalidomide.  
4.4.4.4.Adverse Event Reporting Following Progression  
If a patient meets the protocol defined definition of progression (Chapter 3), Unexpected Grade 3-
5 Adverse Events and events listed in Appendix I are no longer required to be reported on the 
Adverse Event Form once the patient is more than 28 days from their last dose of lenalidomide. 
However, SPMs should continue to be reported within three business days of the knowledge of the 
event through 3 years post-maintenance initiation.  
 
4.4.4.5.Adverse Event Reporting Following an SPM  
 
Adverse Event reporting following an SPM is dependent on the treatment received for the reported 
SPM.  
- 
If a patient experiences an SPM resulting in permanent discontinuation of lenalidomide 
and initiation of non-protocol systemic therapy, Unexpected Grade 3-5 Adverse Events 
and events listed in Appendix I are no longer required to be reported on the Adverse 
Event Form once the patient is more than 28 days from their last dose of lenalidomide.  
- 
If a patient experiences an SPM that does not result in permanent discontinuation of 
lenalidomide, Adverse Events will continue to be reported as per section 4.2.3 and 
appendix I of the protocol.  
- 
Requests to discontinue Adverse Event Reporting for events that do not meet the 
criteria above will be considered on a case by case basis.  
 
4.4.5. Pregnancy Reporting  
Pregnancies, suspected exposure of a pregnant woman (including female partner of a male patient 
and exposure to lenalidomide while dispensing) and suspected pregnancies (including a positive 
pregnancy test regardless of age or disease state) of a female subject occurring while the subject is 
on lenalidomide, or within 28 days of the subject’s last dose of lenalidomide, are considered 
immediately reportable events. Lenalidomide is to be discontinued immediately. The pregnancy, 
suspected pregnancy, or positive pregnancy test must be reported through the expedited AE 
reporting system in AdvantageEDC. The female subject should be referred to an obstetrician-
gynecologist, preferably one experienced in reproductive toxicity for further evaluation and 
counseling. 
 
The Investigator will follow the female subject until completion of the pregnancy, and must notify 
Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or abnormal 
outcome) using the expedited AE reporting system in AdvantageEDC.  If the outcome of the 
pregnancy was abnormal (e.g., spontaneous or therapeutic abortion), the Investigator should report 
the abnormal outcome as an AE.  
 
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality through the expedited AE reporting system in AdvantageEDC. In addition, any infant 
death after 28 days that the Investigator suspects is related to the inutero exposure to lenalidomide 


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should also be reported through the expedited AE reporting system within 24 hours of the 
Investigator’s knowledge of the event 
 
Male Subjects 
If a female partner of a male subject taking investigational product becomes pregnant, the male 
subject taking lenalidomide should notify the Investigator, and the pregnant female partner should 
be advised to call her healthcare provider immediately. 
 
4.4.6. Celgene Drug Safety Contact Information: 
 
Celgene Corporation  
Global Drug Safety and Risk Management    
Connell Corporate Park      
300 Connell Dr.  Suite 6000     
Berkeley Heights, NJ  07922        
Fax: 
 
(908) 673-9115 
E-mail:  
drugsafety@celgene.com 
 
4.4.7. Reporting of other Special Events of Interest 
There are other special events of interest to Celgene that require reporting through the AE 
expedited reporting system in AdvantageEDC. If any of the following events occur, they are 
required to be reported within 3 business days of the site’s knowledge of the event: 
 
• 
overdose, abuse and misuse that meets one of the criteria of a serious adverse 
event 
• 
medication errors that meets one of the criteria of a serious adverse event 
• 
occupational exposure of any kind 
• 
public health emergency 
• 
Celgene product technical complaint that leads to an adverse event 
 
4.5. Ancillary Correlative Laboratory Studies Procedures  
Selected study patients will be presented with the opportunity to participate in the ancillary studies 
outlined in Appendix J and K. This section describes procedures associated with the ancillary 
studies including data entry and obtaining informed consent. Additional details including 
eligibility requirements for each ancillary study can be found in the protocol appendices.  
 
4.5.1. Obtaining Informed Consent  
The Optional Research Sample Consent form should be presented to eligible patients ≤ 30 days 
prior to randomization on BMT CTN 1401.  
The following 3 documents are provided for documentation of informed consent to participate on 
the ancillary studies in appendix J and K:  


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• 
Informed Consent Form to Participate in Optional Ancillary Correlative Laboratory 
Research: The purpose of this document is to obtain consent to participate in the Optional 
Ancillary Research for BMT CTN 1401. This consent provides an overview of the required 
components required to obtain informed consent. However, it must be presented in 
conjunction with at least one of the two supplementary consent documents.  
• 
Supplementary Consent Document for the VCAN Study: The purpose of this document is 
to be presented alongside the Informed Consent Form to Participate in Optional Ancillary 
Research. This consent document should be presented to patients eligible for the VCAN 
study per appendix J. Patients must sign this Supplementary Consent Document along with 
the Informed Consent Form to Participate in Optional Ancillary Research in order to move 
forward with providing the required sample for the VCAN Study.  
• 
Supplementary Consent Document for T Cell/Genomic Signature Study: The purpose of 
this document is to be presented alongside the Informed Consent Form to Participate in 
Optional Ancillary Research. This consent document should be presented to patients 
eligible for the T Cell/Genomic Signature Study per appendix K Patients must sign this 
Supplementary Consent Document along with the Informed Consent Form to Participate 
in Optional Ancillary Research in order to move forward with providing the required 
samples for the T Cell/Genomic Signature Study. 
 
4.5.2. Data Entry Requirements  
Consent and Eligibility for ancillary research participation will be documented on the BMT CTN 
1401 Segment B Enrollment Form.  
Sample collection and shipment will be documented in GlobalTrace and on the Specimen 
Acquisition Form in AdvantageEDC. Further information regarding sample collection, shipment, 
and documentation can be found in the Research Sample Information Guide and the BMT CTN 
1401 Forms Guide.  
Additional information on the data entry and laboratory procedures are outlined in appendix J and 
K.  


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CHAPTER 5 
 
5. 
STATISTICAL CONSIDERATIONS  
 
5.1.Study Design 
The study is designed as a Phase II randomized, open label, multicenter trial to evaluate the use of 
vaccination with DC/myeloma fusions/GM-CSF plus lenalidomide maintenance therapy 
compared to lenalidomide maintenance therapy with and without GM-CSF following autologous 
transplant as part of upfront treatment for patients diagnosed with multiple myeloma.  Patients 
meeting initial eligibility will be enrolled for the purpose of harvesting tumor cells.  Randomization 
will then occur approximately 2 months after autologous transplant and within 10 days of disease 
assessment.  The target enrollment is 132 patients randomized; assuming that 30% will drop out 
between tumor collection and randomization, the study will target 188 patients for initial 
enrollment.  As the impact of GM-CSF without vaccine on clinical outcomes is expected to be 
minimal, analysis of clinical outcomes will focus on comparing the vaccine arm vs. the combined 
no-vaccine arms.   This will help maintain power for these primary analyses. Further 
randomization of the no-vaccine arms into maintenance vs. maintenance +GM-CSF is done to 
isolate the effect of the GM-CSF adjuvant on immunological outcomes and address whether any 
observed effect of vaccine is truly related to the vaccine.   
 
5.1.1.  Accrual 
It is estimated that 36 months of accrual will be necessary to enroll the targeted sample size.  
Accrual will be reported by race, ethnicity, gender, and age. 
 
5.1.2. Randomization 
Randomization will occur approximately 2 months after autologous transplant and within 10 days 
of disease assessment.  Randomization will be performed in a 2:1:1 ratio using random block sizes 
for the vaccine/GM-CSF (n=66), lenalidomide/GM-CSF (n=33) and lenalidomide alone (n=33) 
treatment arms, respectively.  Randomization will be stratified according to disease response at 
time of randomization between sCR/CR and VGPR/PR/Stable disease.  
 
5.1.3. Primary Endpoint 
The primary endpoint is the proportion of patients alive and in CR or sCR at one year post 
transplant, corresponding to approximately 10 months post randomization.  The primary analysis 
will be performed using the intent-to-treat principle so that all randomized patients will be included 
in the analysis.   
 
5.1.4. Primary Hypothesis 
The primary objective of the study is to determine whether vaccination with DC/myeloma 
fusions/GM-CSF in combination with lenalidomide maintenance therapy increases the proportion 
of patients alive and in CR or sCR at one year compared to the combined maintenance groups 
without vaccine.  Letting P denote the proportion of patients alive and in CR and sCR at one year, 
the hypotheses of interest are: 
H0: PVACCINE/GMCSF +MAINT = PMAINT±GMCSF vs. Ha: PVACCINE/GMCSF +MAINT > PMAINT±GMCSF. 


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5.1.5. Duration of follow-up 
All patients will be followed for approximately 3 years post-maintenance initiation for primary 
and secondary endpoints.   
 
5.2.Sample Size and Power Considerations  
 
5.2.1. Primary Endpoint (Clinical) 
Based on the prior cooperative group studies, we anticipate approximately 40% of patients will 
achieve CR and sCR at 1 year.  In the prior phase II study of patients undergoing post-transplant 
vaccination in the absence of lenalidomide maintenance, CR was achieved in 29% and 54% of 
patients at 100 days and 1 year post-transplant respectively.  Given that we anticipate that 
lenalidomide maintenance will enhance vaccine efficacy, we will consider the experimental arm 
of vaccine/GM-CSF + maintenance promising if the CR rate at 1 year is improved from 40% to 
60%.  A sample size of 66 patients (132 total) randomized to the vaccine arm and the combined 
no-vaccine arms will have 85% power to detect this improvement in the CR rate at 1 year from 
40% to 60%, using a two-sample comparison of proportions with a one-sided type I error of 10%.  
Because randomization occurs post collection of tumor sample and post-transplant, we anticipate 
needing to enroll 188 at the time of initial tumor collection pre-transplant assuming that 30% will 
drop out between tumor collection and randomization. 
 
Secondary comparisons of CR rate at 1 year post HCT between the vaccine/GM-CSF arm vs. either 
lenalidomide/GM-CSF or lenalidomide alone separately will have 80% power to detect a 23% 
increase in the CR rate, using the same one-sided alpha level of 10%.  Comparison between the 
two no-vaccine arms will have 80% power to detect a 26% improvement in the CR rate.   
 
5.2.2. Power Considerations for Primary Immunologic Endpoint  
The primary immunologic endpoint will be to quantify the expansion of myeloma reactive T cells 
as determined by the pretreatment and peak post-treatment levels.  The anticipated standard 
deviation of the log 10 peak change in tumor reactive T cells from baseline is 0.61, based on prior 
studies.  Assuming 15% of patients will not be evaluable for immune reconstitution studies, the 
expected evaluable sample sizes will be 56 for the vaccine group and 28 for each of the no-vaccine 
groups.  Comparisons between the vaccine group and either of the no-vaccine groups will have 
80% power to detect a log 10 fold change of 0.4, corresponding to a 2.5 fold expansion of myeloma 
specific T cells, using a two-sample t-test with a 5% two-sided significance level.  Comparisons 
between the two no-vaccine groups will have 80% power to detect a log 10 fold change of 0.46, 
corresponding to a 2.9 fold expansion of myeloma specific T cells.  Note that a stricter alpha level 
is used for immunologic endpoints to reduce the risk of type I errors while still being adequately 
powered to detect larger quantitative differences likely to translate into clinical improvements. 
 
5.3.Interim Analysis and Stopping Guidelines 
 
5.3.1. Interim Analysis for Efficacy 
There will be no interim analyses for efficacy. 
 
5.3.2. Interim Analysis for Futility 
There will be no interim analyses for futility.   


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5.3.3. Guidelines for Safety Monitoring 
Monitoring of a key safety endpoint will be conducted monthly, and if rates significantly exceed 
pre-set thresholds, the NHLBI will be notified in order that the DSMB can be advised.  Policies 
and composition of the DSMB are described in the BMT CTN's Manual of Procedures.  The 
stopping guideline serves as trigger for consultation with the DSMB for additional review. 
 
The key safety endpoint for this study is treatment limiting toxicity (TLT) within the first month 
of combined therapy, defined as any grade V event regardless of attribution to combined therapy, 
grade IV hematologic (lasting greater than 7 days) and grade III-IV non-hematologic toxicity 
judged to be related to combined therapy.  At least three events must be observed in order to trigger 
review.  The rate of TLT within the first month is expected to be no higher than 25%.  Each month, 
the null hypothesis that the 1 month TLT rate is 25% will be tested. This outcome will be monitored 
using a truncated Sequential Probability Ratio Test (SPRT) for binary data as described below.  
The SPRT conserves type I error at 5% across all of the monthly examinations.   
 
The SPRT can be represented graphically.  At each interim analysis, the total number of patients 
enrolled and started combined therapy is plotted against the total number of patients who have 
experienced treatment limiting toxicities.  The continuation region of the SPRT is defined by two 
decision boundaries.  Only the upper boundary will be used for monitoring the study to protect 
against high incidences of TLT.  If the graph falls above the upper boundary, the SPRT rejects the 
null hypothesis, and concludes that the TLT incidence is higher than predicted by the observed 
number of patients enrolled on study.  Otherwise, the SPRT continues until enrollment reaches the 
target goal.  The SPRT for TLT was developed from the following SPRT: 
A SPRT contrasting 25% versus 40% 1 month incidence, with nominal type I and II errors of 12% 
and 15%, respectively, which results in decision boundaries with a common slope of 0.322 and an 
upper intercept of 2.824. 
 
The actual operating characteristics of this truncated test, shown in Table 5.3.3, were determined 
in a simulation study that assumed uniform accrual of 66 individuals over a three-year time period.   
 
TABLE 5.3.3:  OPERATING CHARACTERISTICS OF SEQUENTIAL TESTING 
PROCEDURE FOR 1 MONTH TLT FROM A SIMULATION STUDY WITH 10,000 
REPLICATIONS 
 
True 1 month Incidence 
25% 
35% 
40% 
45% 
Probability Reject Null  
0.100 
0.595 
0.836 
0.957 
Mean Month Stopped 
34.8 
25.0 
18.3 
13.5 
Mean # Endpoints in 1 month 
15.5 
15.4 
13.1 
10.6 
Mean # Patients Enrolled 
62.1 
43.8 
32.7 
23.7 
 
For example, the testing procedure rejects the null hypothesis in favor of the alternative 10% of 
the time when the true 1 month TLT rate is 25%, and 84% of the time when the rate is 40%.  This 
corresponds to a type I error rate of α = 0.1 and a type II error rate of β = 0.16.  When the true  


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1 month TLT rate is 40%, on average, the DSMB will be consulted 18 months after opening, when 
13 events have been observed in 33 patients. 
 
5.4.Demographic and Baseline Characteristics 
Demographics and baseline characteristics will be summarized for all patients.  Characteristics to 
be examined are: age, gender, race/ethnicity, performance status, pre-randomization disease 
response.  Between group comparisons will be performed for continuous variables via a Kruskal-
Wallis test and for categorical variables, via the chi-square test.      
 
5.5.Analysis of Primary Clinical Endpoint 
The intent-to-treat principle will be followed, so that all patients who are randomized will be 
included in the analysis.  The proportion of patients alive and in CR/sCR at 1 year post transplant 
will be described in the vaccine and no vaccine groups with 80% confidence intervals and 
compared between groups using a two-sample Z test comparing binomial proportions.  A one-
sided significance level of 0.1will be used for this comparison to indicate whether the vaccine plus 
maintenance treatment is promising compared to the combined no-vaccine groups in this phase II 
trial.  An 80% two-sided confidence interval (consistent with one-sided significance level of 0.1) 
will be constructed for the difference in proportions.  A secondary analysis stratified on disease 
response prior to randomization will be conducted using a Cochran-Mantel-Haenszel test, and a 
stratified odds ratio along with 80% confidence intervals will be estimated.  A secondary pairwise 
analysis of CR rates comparing the vaccine arm, lenalidomide/GM-CSF arm and the lenalidomide 
alone arm will also be conducted. 
 
5.6.Analysis of Secondary Clinical Endpoints 
 
5.6.1. Response to treatment 
The distribution of disease response will be tabulated at each time point.  The proportion of patients 
alive and with a response of VGPR or better will be compared between the vaccine arm with the 
no-vaccine arms combined at 6 months, 1 year, and 2 years post-transplant using a chi-square test. 
A secondary pairwise analysis of response to treatment comparing the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm will also be conducted.  Rates of 
conversion to CR will also be compared using a chi-square test among the subset of patients who 
are not in CR at the time of randomization.   
 
5.6.2. Myeloma Progression 
Incidence of myeloma progression will be estimated using cumulative incidence function, treating 
death as a competing risk.  Incidence of myeloma progression will be compared between the 
vaccine arm with the no-vaccine arms combined using Gray’s test.  A secondary pairwise analysis 
of myeloma progression comparing the vaccine arm, lenalidomide/GM-CSF arm and the 
lenalidomide alone arm will also be conducted. 
 
5.6.3. Treatment-related Mortality 
Incidence of TRM will be estimated using the cumulative incidence function, treating myeloma 
progression as a competing risk.  Incidence of TRM will be compared between the vaccine arm 
with the no-vaccine arms combined using Gray’s test.  A secondary pairwise analysis of TRM 


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comparing the vaccine arm, lenalidomide/GM-CSF arm and the lenalidomide alone arm will also 
be conducted. 
 
5.6.4. Progression-free survival 
Progression-free survival curves will be estimated using the Kaplan-Meier estimator, and 
compared between the vaccine arm with the no-vaccine arms combined using the log-rank test.  
Hazard ratios, along with confidence intervals, will be estimated from a Cox model with treatment 
group as a covariate. A secondary pairwise analysis of PFS comparing the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm will also be conducted. 
 
5.6.5.  Overall survival 
Overall survival curves will be estimated using the Kaplan-Meier estimator, and compared 
between the vaccine arm with the no-vaccine arms combined using the log-rank test.  Hazard 
ratios, along with confidence intervals, will be estimated from a Cox model with treatment group 
as a covariate. A secondary pairwise analysis of overall survival comparing the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm will also be conducted. 
 
5.6.6. Incidence of toxicities grade ≥ 3 per CTCAE version 4.0 
All Grade ≥ 3 toxicities will be tabulated by grade for each treatment arm, by type of toxicity as 
well as the peak grade overall.  Toxicity frequencies will be described for each time interval as 
well as cumulative over time.   
 
5.6.7. Incidence of infections 
The number of infections and the number of patients experiencing infections will be tabulated by 
type of infection, severity, and time period after transplant.  The cumulative incidence of 
infections, treating death as a competing event, will be compared between the vaccine arm with 
the no-vaccine arms combined using Gray’s test.  A secondary pairwise analysis of the incidence 
of infections comparing the vaccine arm, lenalidomide/GM-CSF arm and the lenalidomide alone 
arm will also be conducted. 
 
5.6.8. Minimal Residual Disease assessment 
The proportions of patients with MRD present (MRD+) will be described using frequencies at each 
timepoint and compared between the vaccine arm with the no-vaccine arms combined using the 
chi-square test.  A secondary pairwise analysis of MRD comparing the vaccine arm, 
lenalidomide/GM-CSF arm and the lenalidomide alone arm will also be conducted. 
 
5.7.Analysis of Immunological Endpoints  
 
5.7.1. Primary immunologic endpoint: Myeloma reactive T-cells 
Log transformations will be used to induce normality in quantitative measurements, and if still 
non-normal, then nonparametric tests will be used.  The primary endpoint of log 10 peak change 
in tumor reactive T cells from baseline will be compared across the 3 groups using analysis of 
variance, and if significant then two-sample t-tests will be conducted for each pairwise comparison 
to determine which groups are different from one another.  A secondary analysis of peak change 
in tumor reactive T cells will be done by comparing the proportions of patients who experience 
>10-fold increase in IFNγ expression, using a chi-squared test.  Myeloma reactive T-cell response 


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profiles over time will be compared between the treatment groups using linear mixed models for 
repeated measures data.  Peak immune response as well as most recent immune response will be 
compared between those in CR and those not in CR at each assessment, using a two-sample t-test, 
to assess the relationship between immune response and clinical response.  Peak and most recent 
immune response will also be considered as time-dependent covariates in a Cox proportional 
hazards model to assess their impact on progression-free survival.   
 
5.7.2. Secondary immunologic endpoints: 
Additional exploratory analyses will be conducted in a similar fashion to examine a number of 
secondary immunologic endpoints, including: 1) antigen specific reactivity by tetramer analysis, 
2) quantification of T-cell subsets and PD-1 expressing lymphocytes by flow cytometry 3) 
quantification of NK cell populations with inhibitor and activating markers, 4) NK-cell cytotoxic 
function as measured by IFNγ and CD107a degranulation in response to ex vivo exposure to 
autologous MM cells, and 5) humoral response against autologous MM cells and myeloma 
associated antigens such as MUC1, and vaccine-induced myeloma-specific plasmablast responses.  
In each case, log transformations will be considered to induce normality, and if still non-normal 
then nonparametric tests will be used. Profiles of these secondary immunologic endpoints will be 
described at each time point for each group using summary statistics and compared between the 
groups using mixed models for repeated measures data.    The correlation between the immune 
environment measures and the myeloma specific T-cell response will be assessed and reported 
using Spearman rank correlation at each time point.   
 
5.8.Endpoint Review Committee   
An Endpoint Review Committee of appointed physicians will convene to adjudicate the primary 
endpoint of complete response as defined by a protocol endpoint review charter.  The charter outlines 
the primary and secondary endpoints to be evaluated and details the endpoints to be adjudicated, 
process for adjudication, procedures for discrepancy resolution, and recording of results. This 
review will be done in a blinded manner.  


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APPENDIX A 
 
CRITERIA FOR SYMPTOMATIC MULTIPLE MYELOMA 
 


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APPENDIX A 
 
CRITERIA FOR SYMPTOMATIC MULTIPLE MYELOMA 
 
 
All three required: 
1. Monoclonal plasma cells in the bone marrow ≥ 10% and/or presence of a  
biopsy-proven plasmacytoma 
2. Monoclonal protein present in the serum and/or urinea 
3. Myeloma defining events (1 or more)  
a. Myeloma- related organ dysfunctionb: 
i. Calcium elevation in the blood (serum calcium > 10.5 mg/l or upper limit 
of normal) 
ii. Renal insufficiency (serum creatinine > 2mg/dl) 
iii. Anemia (hemoglobin <10 g/dL) 
iv. Lytic bone lesions or osteoporosisc 
b. Any one or more of the following biomarkers of malignancy:  
i. Clonal bone marrow plasma cell percentage > 60% 
ii. Involved: uninvolved serum free light chain ratio >100 
iii. >1 focal lesion of MRI  
 
*Note: These criteria identify Stage IB and Stages II and III A/B myeloma by Durie/Salmon stage.  
Stage IA becomes smoldering or indolent myeloma.  
 
a If no monoclonal protein is detected (nonsecretory disease), then ≥30% monoclonal bone 
marrow plasma cells and/or a biopsy-proven plasmacytoma required. 
b A variety of other types of end organ dysfunctions can occasionally occur and lead to a need 
for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to 
be myeloma related. 
c If a solitary (biopsy-proven) plasmacytoma or osteoporosis alone (without fractures) are the 
sole defining criteria, then ≥ 30% plasma cells are required in the bone marrow. 
 
*Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma 
Foundation.   The Hematology Journal (2003) 4, 379–398 
 
 
 


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APPENDIX B 
 
INFORMED CONSENT DOCUMENTS 
 
 


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APPENDIX B-1 
 
INFORMED CONSENT FORM FOR BMT CTN 1401  
 
 


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Informed Consent to Participate in Research 
 
BMT CTN 1401 v4.0 
 
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant 
Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
 
 
 
 
Your Name:   
__________________________ 
 
 
Study Title:  
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma 
with or without Vaccination with Dendritic Cell /Myeloma Fusions  
 
Protocol:  
BMT CTN 1401 v4.0 
 
Principal  
Investigator:  
Insert local PI information  
 
Sponsor:  
The National Institutes of Health (NIH) is sponsoring this study by 
providing financial support for the coordination of this study through the 
Blood and Marrow Transplant Clinical Trials Network (BMT CTN).  
 
 
 
 


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1. 
Introduction  
We invite you to join this clinical trial, also known as a research study. You are being asked to 
join because: 
• You’re >18 and <71 years old 
• You have multiple myeloma (MM)  
• Your doctor thinks an autologous transplant is a possible treatment option for you. 
The standard of care for patients with MM is an autologous transplant and maintenance 
treatment. Maintenance treatment is chemotherapy after transplant. There’s no cure for MM, so 
patients get maintenance treatment to slow the return of MM after a transplant.   
We’re doing this study to learn if maintenance treatment works better alone or with a vaccine 
made from your own blood cells.   
This study will take at least 3 years and will include 203 participants. Your participation will 
last for a maximum of 4 years from when you are enrolled.  
 
This consent form will tell you about the purpose of the study, the possible risks and benefits, 
other options available to you, and your rights as a participant in the study.  
Everyone who takes part in research at [insert facility name] should know that: 
• Being in any research study is voluntary. 
• You may or may not benefit from being in the study. Knowledge we gain from this study 
may benefit others. 
• If you join the study, you can quit the study at any time.  
• If you decide to quit the study, it will not affect your care at [insert name of facility or 
institution]. 
• Please ask the study staff questions about anything that you do not understand, or if you 
would like to have more information. 
• You can ask questions now or any time during the study. 


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• Please take the time you need to talk about the study with your doctor, study staff, and 
your family and friends. It is your decision to be in the study. If you decide to join, please 
sign and date the end of the Consent Form.  
You and your doctor will discuss other treatment choices if you do not want to participate in this 
study. 
2. 
Study Background 
The National Institutes of Health (NIH), through the Blood and Marrow Transplant Clinical 
Trials Network (BMT CTN), are providing staff support and money for this research study. The 
BMT CTN and the NIH will make decisions about how to manage the study.  
For this study, you will receive an autologous transplant (transplant). An autologous transplant 
uses blood-forming cells that are collected from your blood stream. After they are collected and 
frozen, you will get a high dose of chemotherapy. Chemotherapy before a transplant is called the 
“conditioning regimen”.  
The goal of chemotherapy is to kill as many cancer cells in your body as possible. It also 
destroys most of the normal cells in your bone marrow. To restore your marrow, your frozen 
blood-forming cells are thawed and transplanted back into your blood stream. The cells find their 
way into the bone marrow where they start making healthy blood-forming cells. 
The standard of care for patients with MM is an autologous transplant and maintenance 
treatment. Maintenance treatment is chemotherapy after transplant. There’s no cure for MM, so 
patients get maintenance treatment to slow the return of MM after a transplant.  
Some patients may receive a vaccine, and/or GM-CSF (also known as Leukine) with their 
maintenance therapy. GM-CSF helps your body make new white blood cells after transplant. 
The vaccine is made from dendritic cells and MM tumor cells in a laboratory. We will collect a 
sample of your cells through your central line (or catheter). This process is called leukapheresis. 
If the vaccine is made successfully, it will be frozen and stored to give to you later. 
We’re doing this study to learn if maintenance treatment works better alone, or with a vaccine 
made from your own blood cells.  
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-6 
3. 
Study Purpose 
We are inviting you to take part in this study because you have multiple myeloma (MM) and an 
autologous transplant is a treatment option for you. We are doing this study to learn more about 
ways to prevent or slow the return of MM after transplant.  
We will use 3 treatments to see which one works best to prevent or slow the return of MM. See 
Table 1 for information on each treatment group.  
Table 1. Study Treatment Groups 
Treatment Group A 
(maintenance treatment with 
GM-CSF and vaccines) 
Treatment Group B 
(maintenance treatment with 
GM-CSF)  
Treatment Group C (only 
maintenance treatment) 
• 
Melphalan (chemotherapy 
drug) 
• 
Autologous transplant 
• 
Lenalidomide (maintenance 
treatment) 
• 
GM-CSF  
• 
Vaccine 
• 
Melphalan 
(chemotherapy drug) 
• 
Autologous transplant 
• 
Lenalidomide 
(maintenance treatment) 
• 
GM-CSF 
 
• Melphalan (chemotherapy 
drug) 
• Autologous transplant  
• Lenalidomide (maintenance 
treatment)  
•  
 
This study will help doctors make the best choice about treatment after transplant for patients 
with MM. See section 5: Study Tests and Treatments for information on how your treatment 
group will be determined and for information about the drugs listed in Table 1. 
4. 
Rights to Ask Questions and/or Withdraw  
You have the right to ask questions about the study at any time. If you have questions about your 
rights as a participant or you want to leave the study, please contact:  
[insert contact info] 


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Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-7 
Being in this study is voluntary. You can choose not to be in this study or leave this study at any 
time. If you choose not to take part or leave this study, it will not affect your regular medical care 
in any way.  
Your study doctor and study staff will be available to answer any questions that you may have 
about taking part in or leaving this study.  
5. 
Study Treatment and Tests  
We will check your health before you start treatment, during your treatment, and for 3 years after 
you begin your maintenance treatment.  
Before You Start Your Treatment  
You will need to have several check-ups and tests to see if you can be in the study. These check-
ups and tests are part of your regular cancer care and would be done even if you were not part of 
this study. These tests include: 
• Medical history and physical exam 
• Blood tests for cell counts 
• Liver and kidney function tests 
• Tests to measure your disease 
• Bone marrow tests  
• Skeletal survey 
• A pregnancy test (if you are a woman able to have children)  
During Your Treatment 
Tumor Cell Collection 
After you join the study, we will collect about 30mL (approximately 2 tablespoons) of bone 
marrow and 50mL (approximately 3 tablespoons) of blood. The bone marrow and blood samples 
will be frozen until it is determined if you will receive the vaccine as part of your treatment. This 
tumor cell collection is not part of your standard of care treatment 
If you are assigned to Treatment Group A after your transplant, your bone marrow will be 
thawed and used to make your vaccine. If you are assigned to Treatment Group B or C, your 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-8 
bone marrow sample will not be used in this study. Your doctor may talk to you about other uses 
for your stored bone marrow samples not related to this study.   
We will also talk with you about giving extra blood and marrow samples for future research (see 
section 17: Blood and Marrow Samples for Future Research). The extra blood and marrow 
samples are also completely optional.  
Initial Treatment for Multiple Myeloma (MM) 
The first step (initial) is standard chemotherapy treatment (chemo). Chemo lowers the number of 
MM cells in your body. Different chemotherapy drugs can be used to treat MM. Your doctor will 
decide which drug or combination of drugs is best for you.  
You will be asked to sign a separate consent form that will explain the side effects of whichever 
drug your doctor chooses. This step may last several months.  
Blood-Forming Cell Collection 
Next, we’ll collect blood-forming cells from your blood stream. This is known as apheresis. 
These cells will be frozen and stored until your transplant day. 
Conditioning Regimen Before Transplant 
The third step is the conditioning regimen, or the chemotherapy, you will get before your 
transplant. The conditioning regimen helps the blood-forming cells start to grow and make new 
cells in your bone marrow (engraft). The regimen includes a chemo drug called melphalan, 
given by intravenous infusion (IV) in your arm.  
Your doctor will decide when you are ready to get melphalan. You will start this treatment step 
no more than 12 months after you start on this study. Melphalan works better for some patients 
than it does for others. If the drug does not work well for you, you may not be able to have a 
transplant. Your doctor will talk to you about other treatment options.  
Infusion of Blood Forming Cells (Transplant) 
On your transplant day (Day 0), your cells will be given to you through your catheter. The cells 
will travel to your bone marrow where they will start to make healthy, new blood cells (engraft).  
Your Treatment Group 
Approximately 2 months after transplant, we will check to see if you’re healthy enough to start 
maintenance treatment. If you are found healthy enough, we will randomize you to 1 of the 3 
treatment groups. “Randomize” means that you will be put in one or another group by chance, 
just like flipping a coin. We will use a computer program to assign you by chance to Treatment 


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Version 4.0 dated July 24, 2018  
 
B-9 
Group A, B, or C. You won’t be able to choose your group. Once you are assigned to a group, 
you can’t change to another group. The study doctor can’t change your group either.  
Half of the patients on this study (about 66), will be assigned to Treatment Group A. One-fourth 
of the patients (about 33) will be assigned to Treatment Group B; and one-fourth of patients 
(about 33) will be assigned to Treatment Group C. See the section below, Your Maintenance 
Treatment After Transplant, for a description of the treatments. 
Once all these tests are done, you will be randomized to Treatment Group A, B or C. See Table 
2 for a schedule of these tests.   
If you’re not healthy enough after transplant, you won’t be randomized. If this happens, your 
Follow up on this study is complete 
Your Maintenance Treatment After Transplant 
You will start maintenance treatment about 3 months after your transplant.  
 Treatment Group A: Lenalidomide, Vaccine, and GM-CSF injections 
If you are assigned to Treatment Group A, you will get: lenalidomide, vaccines, and GM-CSF 
injections. 
We will collect extra blood samples to make the vaccine. We will insert a catheter into a large 
vein in your neck or chest. The catheter will collect some blood cells and the rest are returned to 
your body. This process is called leukapheresis. We will use the blood cells and the marrow that 
was collected and frozen to create your vaccine. The vaccine will be made in a laboratory and 
frozen until you’re ready for maintenance treatment. 
You will take lenalidomide as a pill every day for 2 years or until your disease returns. You will 
receive enough pills for 1 cycle (28 days in each cycle) at a time. It’s important to take the pill at 
the same time every day. Be sure to talk with your doctor to figure out a good time to take the 
pill every day.  
You will also receive 3 doses of the vaccine. This will be given to you on the first day of your 2nd, 
3rd, and 4th cycle of lenalidomide. The vaccine is the part of the treatment we are testing in this 
study. This is also called the research treatment.  
With each vaccine, you will also get an injection of GM-CSF in your upper thigh. GM-CSF helps 
to boost the effect of the vaccine. You will receive the GM-CSF injection on the day you get the 
vaccine and every day for 3 days after the vaccine.  This will either be given to you in the clinic 
or you will be taught to give the injections to yourself at home.  
See Table 2 for a timeline of the drugs for Treatment Group A. 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-10 
Table 2: Treatment Group A 
 
 
Treatment 
Group A 
drugs: 
Amount: 
Timeline for Maintenance Treatment Drugs 
Cycle: 
(28 days 
in each 
cycle)  
1  
2 
3  
4 
6 
9  
12 
15 
18 
21 
 
24 
Lenalidomide 
1 dose every day for 
2 years 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vaccine 
3 doses total 
 
X 
X 
X 
 
 
 
 
 
 
 
GM-CSF 
12 doses total 
 
X (+3 
days) 
X   
(+3 
days) 
X   
(+3 
days) 
 
 
 
 
 
 
 
 
 Treatment Group B: Lenalidomide and GM-CSF 
If you are assigned to Treatment Group B, you will get: lenalidomide and GM-CSF injections.  
You will take lenalidomide every day for 2 years or until your disease returns. You will receive 
the enough pills for 1 cycle (28 days in each cycle) at a time. It’s important to take the pill at the 
same time every day. Be sure to talk with your doctor to figure out a good time to take the pill 
every day.  
You will also get an injection of GM-CSF in upper thigh. You will get the GM-CSF injection 
every day for 4 days starting the first day of cycles 2, 3 and 4. This will either be given to you in 
the clinic or you will be taught to give the injections to yourself at home.  
See Table 3 for a timeline of the drugs for Treatment Group B.  


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-11 
Table 3: Treatment Group B 
Treatment 
Group B 
drugs: 
Amount: 
Timeline for Maintenance Treatment Drugs 
 
Cycle: 
(28 days in 
each cycle) 
1  
2 
3  
4 
6 
9  
12 
15 
18 
21 
24 
Lenalidomide 
1 dose every day for 2 
years 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GM-CSF 
12 doses total  
 
X  
(+ 3 
days) 
X  
(+ 3 
days)   
X  
(+ 3 
days)    
 
 
 
 
 
 
 
 
 Treatment Group C: Lenalidomide  
If you are assigned to Treatment Group C, you will take lenalidomide every day for 2 years or 
until your disease returns. You will receive enough pills for 1 cycle (28 days in each cycle) at a 
time. It’s important to take the pill at the same time every day. Be sure to talk with your doctor to 
figure out a good time to take the pill every day.  
 
Maintenance treatment dose (All treatment groups)  
 
How We Will Give You Lenalidomide 
Lenalidomide is available only from a certified pharmacy through the Revlimid REMS® program.  
During maintenance therapy, only a 28-day supply (1 cycle) will be given to you at a time. 
If this is the first time you’ve taken lenalidomide, you’ll have to sign-up, or register, for the 
program. This will include a separate consent process, which calls out the reproductive risks of 
taking this medicine. You’ll have to give your name, address, phone number, birth date, and social 
security number to sign-up for the program. This information will be provided to Celgene 
Corporation and Biologics Incorporated to show you’re taking part in this study.   
After you’re registered, you’ll be counseled at the site or through the program: 
• When you’re first given the drug 
• At least every 28 days while you’re taking it, and 


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Version 4.0 dated July 24, 2018  
 
B-12 
• When you stop taking it  
You will be counseled about: 
• Side effects 
• Not sharing lenalidomide (or other study drugs) 
• Risks of exposing a fetus (unborn baby) 
• Donating blood 
• How to take the pills  
We’ll give you the, “Lenalidomide Information Sheet for Patients Enrolled in Clinical Research 
Studies” with each new supply of lenalidomide to remind you of these safety issues. 
How to Take the Lenalidomide Pills 
• Swallow the whole lenalidomide pill with water at the same time each day.  Do not break, 
chew or open the capsules.   
• If you miss a dose, take it as soon as you remember on the same day. If you miss taking 
your dose for the entire day, take your regular dose the next scheduled day (do not take a 
double dose to make up for the missed dose).   
• If you take more than the prescribed dose you should seek emergency medical care if 
needed and contact study staff right away. 
• Women who can become pregnant that care for you should wear gloves whenever they need 
to touch the lenalidomide pills or bottles. 
Checking Your Health 
We will watch your health closely during your maintenance treatment, including how well your 
organs work. We will lower your dose if your organs don’t handle the treatment well.  
We won’t start a new cycle until your organs work well again. If we lower your dose and then 
your organs start working normally, we may raise your dose again.      
We will stop the maintenance treatment if you:  
• 
Have a serious side effect  


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Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-13 
• Have low blood cell counts  
• Are a woman and become pregnant, or there is a chance that you are pregnant 
• Go more than 56 days before starting a new maintenance treatment cycle  
• Don’t follow the study directions, or 
• Choose to leave the study. 
You will need to visit your clinic for several check-ups and tests during your maintenance 
treatment. These tests are shown in Table 4. These assessments are standard of care for 
patients receiving lenalidomide maintenance therapy.   
Table 4. Timeline of Tests Before and During Your Maintenance Treatment 
Tests 
Before 
you‘re 
Random
ized 
Timeline for Maintenance Treatment Tests (CYCLES) 
Timeline for 
Post-Transplant 
Tests (Months) 
1 
2 
3 
4 
6 
9 
12 
15 
18 
21 
24 
6T 
12T 
24T 
Physical 
exam, 
height, and 
weight 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tests for 
toxicities, 
and 
infections 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
 
 
Blood tests 
for cell 
counts, liver 
and kidney 
function 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Tests to see 
how much 
cancer you 
still have 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy 
test (women 
able to have 
children) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-14 
Blood and Bone Marrow Samples 
Throughout the study, we will collect blood and marrow samples to check if the treatments are 
working. These samples are being done as a part of the standard of care disease assessment.  In 
addition, blood and marrow samples are also collected as part of this research study to check 
your immune response to the vaccine and are not part of your standard of care. The maximum 
amount of blood we will collect for this study in one day is 70mL (approximately 4.5 
tablespoons). If more blood is required at a particular time, we will collect blood on 2 or more 
days spread out over 1-2 weeks.  
The maximum amount of bone marrow sample we will collect is 37mL (approximately 2.5 
tablespoons). Table 5 shows the timeline and amount of samples we may collect from you 
during the study. 
Table 5: Timeline and Sample Amount Collected during Study (in approximate tablespoons 
(Tbsp) or teaspoons (tsp)) 
 
6. 
Risks and Discomforts  
You may have side effects while on the study. Side effects can range from mild to serious. The 
risks and discomforts of autologous transplant are the same if you join this study, or if you don’t 
join this study.  
Sample 
When 
you join 
the 
study 
Before 
you’re  
randomized 
Maintenance Cycles 
1 
2 
2 
(day 7) 
3 
4 
4 
(day 7) 
9 
Bone marrow  
2.5 Tbsp 
1 tsp 
 
 
 
 
 
 
2 tsp 
Optional bone 
marrow 
samples for 
future research  
<1 tsp 
<1 tsp 
 
 
 
 
 
 
<1 tsp 
Blood-forming 
cells  
6.5 Tbsp 
*over 10 
days 
2 Tbsp 
4.5  
Tbsp 
4.5  
Tbsp 
4   
Tbsp 
4.5  
Tbsp 
4.5  
Tbsp 
4 Tbsp 
4.5  
Tbsp 
Optional blood 
samples for 
future research  
1.5 tsp 
1.5 tsp 
 
 
 
 
 
 
1.5 tsp 


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B-15 
You might do better or worse than you would with a standard transplant. Your healthcare team 
may give you medicines to help with side effects like nausea (feeling sick to your stomach). In 
some cases, side effects can last a long time or may never go away.  
Risks of Making the Vaccine  
We will collect bone marrow samples on all patients. 
We will take the bone marrow samples from your hip bone with a large needle. This is called a 
bone marrow aspirate. After, you may feel pain and bleed at the site where the needle went in 
your hip. A small number of patients will have pain that runs down their legs, pain that lasts 
more than a few days, and/or get an infection.  
If you are assigned to Treatment Group A, we will collect blood and bone marrow samples to 
make the vaccine (see Table 5. Timeline and Sample Amount Collected during Study).  
We will also collect extra samples of blood through a catheter in your neck or chest 
(leukaphereis). The risks of leukapheresis include:   
• 
Bleeding 
• 
Punctured lung (hole in lung) 
• 
Infection  
• 
Low blood cell counts. 
Risks of Medications  
The risks of the chemotherapy and maintenance drugs you will get as part of the treatment are 
listed below.  
 


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Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-16 
Melphalan - Conditioning Regimen Drug (Before Transplant) 
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less than 20% of 
patients) 
Rare, but Serious  
(May happen in less than 2% of 
patients) 
• Loss of appetite 
• Constipation 
• Diarrhea 
• Nausea (feeling sick 
to your stomach) 
• Vomiting (throwing 
up) 
• Temporary hair loss 
• Sensitive skin 
• Infection 
• Low number of white 
blood cells 
 Low number of 
platelets in the blood 
with increased risk of 
bleeding  
• Anemia (low number 
of red blood cells) 
• Mouth sores 
• Sore throat (red with 
swelling) 
• Skin breakdown (if 
drug leaks from vein)   
• Changes in heart beat 
• Dizzy 
• Feeling faint  
• Shortness of breath 
• Hepatitis (swelling of the 
liver) 
• Kidney failure 
• Weight loss 
• Feeling weak 
• Allergic reaction 
• Lung infection 
• Scarring of lung tissue  
• Seizure 
• Vasculitis (inflammation of 
blood vessels)   
• Low blood pressure 
• Sweating too much 
• Sterility (unable to have 
children) 
• Liver damage 
• Heart stops beating 
• New cancer of bone marrow 
cells  
 
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-17 
Vaccine  
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less 
than 20% of patients) 
Rare, but Serious  
(May happen in less than 2% of patients) 
• Twitching (at 
injection site) 
• Itching (general or 
at injection site) 
• Discomfort (at 
injection site) 
• Swelling (at 
injection site) 
• Bruising at the 
injection site 
 
 
• Fluid retention 
(too much water 
in your body) 
• Fatigue  
• Muscle aches 
• Itching 
• Fever 
• Abnormal 
Antinuclear 
Antibody (ANA) 
blood test   
• Decreased white 
blood cell count 
(including 
neutrophils)  
• Headache 
• Diarrhea 
• Feeling light 
headed 
• Flu-like 
symptoms  
• Night sweats 
• Allergic reaction leading to rashes, 
joint pain, kidney, heart or lung 
damage, drop in blood counts  
• Tumor growth or the spread of your 
cancer  
• Infection at the vaccine site 
• Change in thyroid function (fatigue, 
weight gain, sensitivity to cold and 
lack of interest or emotion) 
• Pulmonary embolus (blood clot in 
the lungs)  


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-18 
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less 
than 20% of patients) 
Rare, but Serious  
(May happen in less than 2% of patients) 
• Elevated TSH 
(TSH is a thyroid 
hormone) 
• Candida 
infection  
 
 


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Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-19 
GM-CSF (Leukine) 
Likely  
(May happen in more than 
20% of patients) 
Less Likely  
(May happen in less than 20% 
of patients) 
Rare, but Serious  
(May happen in less than 
2% of patients) 
• Fever  
• Chills  
• Nausea 
• Vomiting  
• Diarrhea  
• Fatigue  
• Feeling weak  
• Headache 
• Loss of appetite 
• Flushed face (red or pink 
cheeks)  
• Bone and muscle pain in 
arms, legs and feet  
• Red skin, swelling, or 
itching at needle injection 
site 
• Low blood pressure  
• Shortness of Breath 
• Rapid, irregular heartbeats 
• Feeling lightheaded or 
dizzy 
• Allergic reaction 
• Fluid in lungs or around 
your heart  
• Changes in vision 
• Low blood cell counts 
• Infection at needle 
injection site 
 
• Blood clots  
 
 
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-20 
Lenalidomide- Maintenance Treatment Drug 
Likely  
(May happen in more 
than 10% of patients) 
Less Likely  
(May happen in less than 10% of 
patients) 
Rare, but Serious  
(May happen in less than 2% of 
patients) 
• Low number of 
white blood cells 
(with or without 
fever) 
• Anemia; Decrease 
in cells that help 
your blood clot  
• Vision Blurred 
• Diarrhea 
• Pain, Constipation 
• Indigestion 
•  Nausea 
•  Vomiting 
•  Feeling weak and 
unwell 
•  Tired  
• Swelling 
•  Fever 
• Chills  
• Pneumonia or 
other infections 
• Sore throat 
• Stuffy nose  
• Weight loss  
• Decreased appetite 
• High blood sugar  
• Abnormally low number of 
blood cells 
• Destruction of red blood cells 
•  Heart attack 
• Abnormal heart beats 
• Heart stops working 
• Low oxygen to heart tissue 
•  Dry mouth 
• Decreased action of intestine 
•  Bile flow from liver slowed 
or blocked 
• Gout 
• Fall 
• Bruise 
• Lowered level of 
consciousness with 
drowsiness, listlessness, and 
apathy 
• Abnormal liver lab tests 
•  Increase in liver protein that 
indicates inflammation in 
body 
• Loss of fluid 
• Diabetes 
• High uric acid in blood 
• Iron build up in body 
• Swelling of lungs 
 
• Over and underactive thyroid 
 
• 
Severe allergic conditions 
including: Swelling under 
skin; Severe skin reactions 
involving lining of the nose, 
mouth, stomach and intestines 
or rash leading to the 
separation of the top layer of 
skin  
 
• Tumor Lysis Syndrome 
(TLS) is caused by the 
sudden, rapid death of cancer 
cells in response to treatment. 
When cancer cells die they 
may spill their inner 
(intracellular) contents, which 
accumulate faster than they 
can be eliminated. This debris 
from the cancer cells can 
change the balance of the 
chemistry of the body, which 
can be dangerous. 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
B-21 
You shouldn’t donate blood while you’re in the study and for 28 days after you stop taking 
lenalidomide. 
• Chemical 
imbalance in blood 
• Pain including 
muscles, joints, 
and non-cardiac 
chest pain 
•  Dizziness 
•  Altered sense of 
taste  
• Headache  
• Eye lens cloudy  
• Abnormal sense of 
touch 
• Pain and decreased 
sensation in nerves  
• Shaking 
• Cough  
• Shortness of 
breath 
•  Nosebleed  
• Blood clot in 
lower extremities, 
lungs, heart, brain, 
and other organs  
• Dry skin  
• Itching  
• Allergic reaction 
• Feeling sad  
• Not sleeping well 
 
• Muscle weakness 
• Cancer 
• Stroke 
• Tingling of skin 
•  Fainting 
• Moody 
• Kidney failure 
• Breathing disorder  
• Excessive sweating 
• Night sweats 
• Skin redness 
• Swelling of skin filled with 
blood 
• Swelling of blood vessels 
•  High or low blood pressure 
•  Blood not getting to 
extremities 
• Clot in vein 
• Sudden increase in tumor size 
• Rapid death of cancer cells 
where the accumulating 
contents of dying cancer cells 
cause an imbalance in the 
chemistry of the body which 
can lead to kidney damage 
•  Blood cancer that causes 
decreased number of red 
blood cells, white blood cells, 
and platelets because they do 
not develop normally. 
 


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B-22 
Risk to the Unborn 
Lenalidomide can cause severe birth defects or death of a baby if the mother or the father is taking 
this medicine at the time of conception or during pregnancy. Because of this, it is extremely 
important that you don’t get pregnant while you’re taking lenalidomide. 
If you’re pregnant or nursing, you’re not eligible to take part in this study. Women who can become 
pregnant must use at least 2 forms of effective birth control while in the study or abstain from all 
reproductive sexual intercourse. Effective birth control is defined as the following:  
1. Refraining from all acts of vaginal sex (abstinence)  
2. Consistent use of birth control pills 
3. Injectable birth control methods (Depo-Provera, Norplant) 
4. Tubal sterilization or male partner who has undergone a vasectomy 
5. Placement of an IUD (intrauterine device) 
6. Use of a cervical cap or a diaphragm with contraceptive jelly and/or condoms with 
contraceptive foam every time you have sex. 
Females taking lenalidomide have blood clots more often. Because of this, you should talk to 
your doctor about birth control pills and hormone replacement therapy, and the risks and 
benefits. 
You do not need to use effective birth control only if you are a woman and cannot have children 
because you: 
 Had a hysterectomy (your ovaries and uterus were removed), OR 
 Had a bilateral oophorectomy (your ovaries were removed), OR 
 Went through menopause (post-menopausal). 
Reproductive Risks  
The drugs used in this research study may damage your reproductive organs, affect your ability to 
have children, or cause birth defects if you take them while you are pregnant or nursing.  
Both women who can become pregnant and their male partners should use birth control while on 
this study and for 28 days after maintenance treatment is stopped. If you or your partner 
becomes pregnant during this study, you must tell the study doctor immediately.  


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Your doctor will discuss the risks to your unborn child and options with you.  
It is important that females who aren’t pregnant or nursing don’t become pregnant while part of 
the study. If you are a woman and become pregnant while on this study, we will stop the 
maintenance treatment drug right away.  
Your study doctor will watch your health closely while you are pregnant and for 30 days after 
the pregnancy ends. 
 
Females who join the study 
If you are female and can become pregnant, you will need to take a pregnancy test before you 
start the study. You should discuss ways to prevent pregnancy while you’re in the study. Women 
who have gone through puberty might experience irregular menstrual cycles or their cycle might 
stop forever. This doesn’t mean that you can’t become pregnant. You must still use 2 effective 
forms of birth control during the study and continue with it for 28 days after you finish 
maintenance treatment.  
Be sure to talk with your doctor about options for fertility planning, like storing your eggs, 
before starting chemotherapy treatment. 
 
Males who join the study 
If you are male, your body may not be able to produce sperm (become sterile). Be sure to talk 
with your doctor about options for fertility planning, like banking your sperm, before starting 
chemotherapy treatment. 
Damage to the vital organs in your body 
Your vital organs include your heart, lungs, liver, intestines, kidneys, bladder and brain. The 
chemotherapy drugs may hurt these organs. You may develop lung problems from chemotherapy 
or an infection.  
Some patients can have veno-occlusive disease (VOD) of the liver. Patients with VOD become 
jaundiced (yellow skin), have problems with their liver, retain too much water (feel swollen and 
uncomfortable), and have stomach swelling and pain.  
If there is serious damage to your vital organs, you may have to stay in the hospital longer or 
return to the hospital after your transplant. Many patients get better, but these complications can 
cause permanent damage to your organs or death. 
Relapse (return) of disease or a new blood cancer 
Your disease may come back even if the transplant was successful at first.  


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We don’t know if new blood cancers are caused by lenalidomide or other drugs. Other research 
looked at the number of patients who got new blood cancers after taking lenalidomide for: 
 Diseases other than multiple myeloma, AND 
 Relapsed multiple myeloma. 
In these studies, no difference was shown in the number of patients who got new blood cancers. 
Researchers for other studies of lenalidomide are still watching patients to see if they get new 
blood cancers. We will give you any new information that we learn about new blood cancers.  
 
 
 


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All Patients Taking Lenalidomide 
 
In order to participate in this study you must register into and follow the requirements of 
the REVLIMID REMS™ program of Celgene Corporation.  This program provides 
education and counseling on the risks of fetal exposure, blood clots and reduced blood counts.  
You will be required to receive counseling every 28 days during treatment with lenalidomide, 
follow the pregnancy testing and birth control requirements of the program that are 
appropriate for you and take telephone surveys regarding your compliance with the 
program.    
 
You have been informed of the risk of birth defects.  If you are female, you agree not to become 
pregnant while taking lenalidomide. For this reason, lenalidomide is provided to patients under a 
special distribution program called REVLIMID REMS TM. 
 
. 
Other Information: 
 
There may be some unknown or unanticipated discomforts or risks associated with this treatment 
in addition to those specified above, but every precaution will be taken to assure your personal 
safety and to minimize discomforts. 
 
Throughout the study, the researchers will tell you of new information that might affect your 
decision to remain in the study. 
 
If you wish to discuss the information above or any other discomforts you may experience, you 
may ask questions now or call your doctor _______________________, the Principal Investigator 
or contact person listed on the front page of this form. 
 
Other Risks  
Serious infections 
It may take many months for your immune system to recover from the chemotherapy and 
maintenance therapy drugs. There is an increased risk of infection during this time when your 
body is healing. We will give you drugs to reduce the chance of infection, but they may not 
work. If you have an infection, you may have to stay in the hospital longer or return to the 
hospital after transplant. Many patients get better, but some infections can cause death. 
Unforeseen Risks  
Chemo drugs can damage your blood cells, which may cause a new blood cancer to grow. We 
know from other MM research studies, that more patients had a second cancer after chemo 
and/or autologous transplant with maintenance lenalidomide than those who didn’t get 
lenalidomide. We don’t know if taking lenalidomide for a long time raises the risk of having a 
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Other new risks might appear at any time during the study. These risks might be different from 
what is listed in this Consent Form. There may be some unknown or unanticipated discomforts 
or risks associated with this treatment in addition to those specified above, but every precaution 
will be taken to assure your personal safety and to minimize discomforts. 
Other Treatments or Medicines 
Some medicines react with each other, and it is important that you tell the study doctor or staff 
about any other drugs, treatments, or medicines you are taking. This includes non-prescription or 
over-the-counter medicines, vitamins, and herbal treatments.  
It is also important that you tell the study staff about any changes to your medicines while you’re 
in the study. 
For more information about risks and side effects, ask your study doctor. 
7. 
Other Treatments 
Participation in this study is optional. If you choose not to take part, you may still receive non-
transplant treatments or an autologous or an allogeneic transplant to treat your disease. The 
treatment and evaluations you would receive could be very similar to what would receive if you 
join this study.  
Your study doctor will talk with you about your options. If you decide not to participate in this 
study, your medical care will not be affected in any way. 
Your other options may include: 
• Treatment with other drugs, radiation, or a combination of drugs and radiation 
without a transplant. 
• An allogeneic (donor) blood or marrow transplant that is not part of the study, or 
another type of transplant 
• Participation in another clinical trial, if available (check with your doctor) 
• No treatment for your blood cancer at this time 
• Comfort care 
Every treatment option has benefits and risks. Talk with your doctor about your treatment 
choices before you decide if you will take part in this study. 


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8. 
Possible Benefits 
Taking part in this study may or may not make your health better. The information from this 
study will help doctors learn more about drugs used to treat MM.  
This information could help people with multiple myeloma who may need a transplant in the 
future. 
9. 
New Information Available During the Study 
During this research study, the study doctors may learn about new information about the study 
drugs or the risks and benefits of the study. If this happens, they will tell you about the new 
information. The new information may mean that you can no longer participate in the study, or that 
you may not want to continue in the study.  
If this happens, the study doctor will stop your participation in the study and will offer you all 
available care to suit your needs and medical conditions. 
10. 
Privacy, Confidentiality and Use of Information  
Your privacy is very important to us.  The study doctors will make every effort to protect it.  The 
study doctors have a privacy permit to help protect your records if there is a court case.  However, 
some of your medical information may be given out if required by law.  If this should happen, the 
study doctors will do their best to make sure that any information that goes out to others will not 
identify who you are.  
 
Data regarding your clinical situation, including follow-up after 2 years, may be obtained from 
the CIBMTR, which captures information on all US transplants. 
All your medical and demographic information (such as race and ethnicity, gender and 
household income) will be kept private and confidential. (Name of Transplant Center) and the 
organizations listed below will not disclose your participation by any means of communication 
to any person or organization, except by your written request, or permission, or unless required 
by federal, state or local laws, or regulatory agencies.  
The individuals below will have access to your research and medical information. They may use 
this information for inspections or audits to study the outcomes of your treatment. By agreeing to 
participate, you consent to such inspections and to the copying of parts of your records, if 
required by these organizations. 


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We may give out your personal information if required by law. If information from this study is 
published or presented at scientific meetings, your name and other personal information will not 
be used.  
Information about your transplant from your original medical records may be seen or sent to 
national and international transplant registries, including:  
1. /Institution/ 
2. The Center for International Blood and Marrow Transplant Research (CIBMTR) 
3. The National Marrow Donor Program (NMDP) 
4. The Food and Drug Administration (FDA) 
5. The National Institutes of Health (NIH), which include the National Heart, Lung, and Blood 
Institute (NHLBI) and the National Cancer Institute (NCI) 
6. Data and Coordinating Center of the Blood and Marrow Transplant Clinical Trials Network 
(BMT CTN)  
7. Data and Safety Monitoring Board (DSMB), not part of /Institution/ 
8. Study investigators.   
9. Celgene, the manufacturer of lenalidomide 
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. For 
questions about access to your medical records, please contact /name/ at /number. 
11. 
Ending Your Participation 
The study doctor or the study sponsor may stop the study at any time, and we may ask you to 
leave the study. We may ask you to leave the study if you do not follow directions or if you 
suffer from side effects of the treatment. If we ask you to leave the study, the reasons will be 
discussed with you. Possible reasons to end your participation in this study include: 
1. You do not meet the study requirements.  
2. You need a medical treatment not allowed in this study. 
3. The study doctor decides that it would be harmful to you to stay in the study. 


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4. You are having serious side effects. 
5. You become pregnant. 
6. You cannot keep appointments or take study drugs as directed. 
7. The study is stopped for any reason. 
You could have serious health risks if you stop treatment during the conditioning process before 
you receive your transplant. If you stop taking the immune suppressing drugs (see Section 6: 
Risks and Discomforts) too soon after transplant, your body could reject the stem cells or you 
could develop serious complications and possibly die.  
We ask that you talk with the research doctor and your regular doctor before you leave the study. 
Your doctors will tell you how to stop safely and talk with you about other treatment choices.  
If you decide to leave this study after getting the study treatment, or are asked to leave by your 
doctor for medical reasons, you will need to come back to the doctor’s office for tests for your 
safety. Even if you leave the study, the information collected from your participation will be 
included in the study evaluation, unless you specifically ask that it not be included. 
12. 
Physical Injury as a Result of Participation  
It is important that you tell your doctor, __________________ [investigator's name(s)] or study 
staff if you feel that you have been injured because of taking part in this study.  You can tell the 
doctor in person or call him/her at __________________ [telephone number]. 
You will get all available medical treatment if you are injured from taking part in this study. You 
and/or your health plan will be charged for this treatment. There is no provision for free medical 
care or monetary compensation from the study sponsor, The National Institutes of Health or the 
study contributor, Celgene Corporation.  
In case you are injured in this study, you do not lose any of your legal rights to ask for or receive 
payment by signing this form. 
13. 
Compensation or Payment 
You will not be paid for your participation in this research study. You will not get compensation or 
reimbursement for any extra expenses (travel, meals, etc.) you may have through your participation 
on this trial.  
Taking part in this study might help researchers make products to sell. Celgene or others may 
profit from these products. You will not have any rights to the patents or discoveries that could 
happen from this research, and you will not receive any payments from it. 


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14. 
 Costs and Reimbursements 
Most of the visits for this research study are standard medical care for your autologous transplant 
and will be billed to your insurance company. You and/or your health plan/insurance company 
will need to pay for some or all of the costs of standard treatment in this study.    
 
You or your insurance will not be charged for blood and marrow samples for research on this study. 
You will not pay for any extra tests that are being done for the study. Lenalidomide will be provided 
to you for free for two years. After that your doctor will discuss what treatment is best for you.   
Some health plans will not pay these costs for people taking part in studies. Check with your 
health plan or insurance company to find out if they will pay. 
For questions about your costs, financial responsibilities, and/or medical insurance coverage for 
your transplant and this study, please contact /Center/ Financial Counselor at /Number/. 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage. You can 
print a copy of the “Clinical Trials and Insurance Coverage” information from this Web site. 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy. 
15. 
For More Information 
If you need more information about this study, or if you have problems while taking part in this 
study, you can contact the study doctor or his/her staff.  
They can be reached at the telephone numbers listed here: 
[Insert name and contact details] 
16. 
Contact Someone about Your Rights 
If you wish to speak to someone not directly involved in the study, or if you have any complaints 
about any aspect of the project, the way it is being conducted or any questions about your rights as a 
research participant, then you may contact:  
[Insert appropriate contact details] 
The ethical aspects of this study have been reviewed and approved by [name of IRB]. 


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17. 
Blood and Bone Marrow Samples for Future Research (Optional)  
This section of the informed consent form is about future research studies that will use blood and 
bone marrow samples from people who are taking part in the main study. You may choose to 
give samples for these future research studies if you want to. You can still be a part of the main 
study even if you say 'no' to give samples for future research studies. 
Researchers are trying to learn more about how the human body processes the drugs used for 
transplant and how the body recovers after transplant. This research is meant to gain knowledge 
that may help people in the future and make transplants even more successful.  
If you agree to provide blood and bone marrow samples, here is what will happen: 
• We will collect 3 extra blood samples at the same time you have routine blood tests done 
(Table 3):  
o Around the time of your enrollment 
o About 2 months after your transplant  
o Before the start of your 9th cycle of maintenance therapy  
• The amount of blood collected from you is about 1 teaspoon (6 ml) each time.  
• We will collect 3 bone marrow samples at the same time you have routine bone biopsies 
done. The amount of tissue collected from you is about a half of a teaspoon (3 mL) each 
time. We will collect samples at 3 different dates in the study (see Table 3): 
o Around the time of your enrollment 
o About 2 months after your transplant  
o Before the start of your 9th cycle of maintenance therapy.  
• The blood and bone marrow samples will be sent to the BMT CTN Repository for processing 
and storage. A repository is a place that protects, stores and sends out samples for approved 
research studies. All research samples will be given a bar code that cannot be linked to you 
by future researchers testing your samples. 
• Materials stored in the Repository will be used mainly by clinicians and researchers in the 
BMT CTN network. In the future, the unused research samples and clinical data will be made 
available outside of this network.  


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• Researchers can apply to study the materials stored in the Repository. The BMT CTN 
Steering Committee and/or the BMT CTN Executive Committee must approve each request 
before they will share samples or information with researchers. This is to make sure that the 
investigators requesting the samples are qualified, and that the research is of high quality. 
• DNA from your stored blood samples might be used in genome-wide association (GWA) 
studies for a future project either done or supported by the National Institutes of Health 
(NIH). Genome-wide association studies are a way for scientists to find genes that have a 
role in human disease or treatment. Each study can look at hundreds of thousands of genetic 
changes at the same time. 
If your coded samples are used in such a study, the researcher is required to add your test 
results and sample information into a shared, public research database. This public 
database is called the NIH Genotype and Phenotype Database and it is managed by the 
National Center for Biotechnology Information (NCBI). The NCBI will never have any 
information that would identify you, or link you to your information or research samples.  
Some general things you should know about letting us store your blood samples for research are: 
1. We will only store samples from people who give us permission. 
2. Research is meant to gain knowledge that my help people in the future. You will not get any 
direct benefit from taking part. Additionally, you or your doctor will not be given results and 
they will not be added to your medical record. 
3. A possible risk is the loss of confidentiality about your medical information. We will use 
safety measures with both your samples and clinical information to make sure that your 
personal information will be kept private. The chance that this information will be given to 
someone else is extremely small.  
4. Your blood will be used only for research and will not be sold. The research done with your 
blood may help to develop new products in the future. You will not get paid for any samples 
or for any products that may be developed from current or future research. 
You can change your mind at any time about allowing us to use your samples and health 
information for research.  
We ask that you contact [Principal Investigator] in writing and let him/her know you do not 
want us to use your research samples or health information for research. His/her mailing address 
is on the first page of this form. However, samples and information that have already been shared 
with other researchers cannot be taken back or destroyed.  


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Making Your Choice  
Please read each sentence below and think about your choice. After reading each sentence, 
please indicate your choice below. If you have any questions, please talk to your doctor or nurse, 
or call our research review board at _[contact information].  
No matter what you decide to do, it will not affect your care. 
 
 


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Statement of Consent for Research Samples 
The purpose of storing blood and tissue samples, the procedures involved, and the risks and 
benefits have been explained to me. I have asked all the questions I have at this time and I have 
been told whom to contact if I have more questions. I have been told that I will be given a signed 
copy of this consent form to keep. 
I understand that I do not have to allow the use of my blood and tissue for research. If I decide to 
not let you store research samples now or in the future, it will not affect my medical care in any 
way. 
I voluntarily agree that my blood, tissue, and information can be stored indefinitely by the BMT 
CTN and/or NHLBI Repositories for research to learn about, prevent, or treat health problems. I 
also understand that my DNA and health information may or may not be used in genome-wide 
association studies. 
Blood 
 I agree to allow my blood samples to be stored for research. 
 I do not agree to allow my blood samples to be stored for research. 
Bone marrow 
 I agree to allow my bone marrow samples to be stored for research. 
 I do not agree to allow my bone marrow samples to be stored for research. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
 
 


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Health Insurance Portability and Accountability Act 1 (HIPAA12) Authorization to use 
and disclose individual health information for research purpose 
 
• Purpose: 
As a research participant, I authorize the Principal Investigators and the researcher’s staff to use 
and disclose my individual health information for the purpose of conducting the research study:  
Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed 
by Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination with 
Dendritic Cell /Myeloma Fusions 
 
• Individual Health Information to be Used or Disclosed:  
My individual health information that may be used or disclosed to do this research includes:  
1. Demographic information (for example, date of birth, sex, weight).  
2. Medical history (for example, diagnosis, complications with prior treatment). 
3. Findings from physical exams. 
4. Laboratory test results obtained at the time of work up and after transplant (for example, 
blood tests, biopsy results).  
• Parties Who May Disclose My Individual Health Information:  
The researcher and the researcher’s staff may collect my individual health information from: 
[List hospitals, clinics or providers from which health care information can be requested]. 
• Parties Who May Receive or Use My Individual Health Information:  
The individual health information disclosed by parties listed in item c and information disclosed 
by me during the course of the research may be received and used by the following parties: 
1. Dr. David Avigan, Co-Principal Investigator  
2. Dr. Nina Shah, Co-Principal Investigator  
3. Dr. David Chung, Co-Principal Investigator 
                                                 
12 HIPAA is the Health Insurance Portability and Accountability Act of 1996, a federal law related to privacy of health 
information 


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4. Celgene, its collaborators or designees 
5. National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute 
(NCI), both of the National Institutes of Health (NIH),  
6. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Data and 
Coordinating Center 
7. U.S. government agencies that are responsible for overseeing research such as the Food 
and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) 
8. U.S. government agencies that are responsible for overseeing public health concerns 
such as the Centers for Disease Control (CDC) and federal, state and local health 
departments. 
• Right to Refuse to Sign this Authorization:  
I do not have to sign this Authorization.  If I decide not to sign the Authorization, I will not be 
allowed to participate in this study or receive any treatment related to research that is provided 
through the study.   
My decision not to sign this authorization will not affect any other treatment, payment, or 
enrollment in health plans or eligibility for benefits.   
• Right to Revoke:   
I can change my mind and withdraw this authorization at any time by sending a written notice to 
the Principal Investigator to inform the researcher of my decision.  
If I withdraw this authorization, the researcher may only use and disclose the protected health 
information already collected for this research study.  No further health information about me 
will be collected by or disclosed to the researcher for this study. 
• Potential for Re-disclosure:  
My individual health information disclosed under this authorization may be subject to re-
disclosure outside the research study and no longer protected. 
Examples include potential disclosures for law enforcement purposes, mandated reporting or 
abuse or neglect, judicial proceedings, health oversight activities and public health measures. 
• Genetic Information Nondiscrimination Act (GINA)  
A new federal law (2009), called the Genetic Information Nondiscrimination Act (GINA) 
generally makes it illegal for health insurance companies, group health plans, and employers of 15 
or more persons to discriminate against you based on your genetic information.  


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Health insurance companies and group health plans may not request your genetic information that 
we get from this research. This means that they must not use your genetic information when 
making decisions regarding insurability. Be aware that this new federal law will not protect you 
against genetic discrimination by companies that sell life insurance, disability insurance, or long-
term care insurance. 
• This authorization does not have an expiration date. 
 
 


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TITLE: Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant 
Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
PROTOCOL NUMBER: BMT CTN #1401 
PRINCIPAL INVESTIGATOR:  
Name: 
Address: 
Email:  
Phone:  
 
 
 
 
 
 
 
 
 
 
 
Fax:  
I have read and understood this Consent Form. The nature and purpose of the research study has 
been explained to me. 
• I have had the chance to ask questions, and understand the answers I have been given. I 
understand that I may ask questions at any time during the study. 
• I freely agree to be a participant in the study. 
• I understand that I may not directly benefit from taking part in the study. 
• I understand that, while information gained during the study may be published, I will not be 
identified and my personal results will stay confidential. 
• I have had the chance to discuss my participation in this research study with a family member 
or friend. 
• I understand that I can leave this study at any time, and doing so will not affect my current 
care or prevent me from receiving future treatment. 
• I understand that I will be given a copy of this signed consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant Name 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
I certify that I have provided a verbal explanation of the details of the research study, including 
the procedures and risks. I believe the participant has understood the information provided. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Counseling Physician 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Counseling Physician 
 
    
 
 
 
Date 


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APPENDIX B-2 
 
INFORMED CONSENT DOCUMENTS FOR BMT CTN 1401 OPTIONAL 
CORRELATIVE LABORATORY STUDY PARTICIPATION 
 
 


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Informed Consent to Participate in Research 
 
Optional Correlative Laboratory Study Participation for patients enrolled on BMT CTN 1401 
entitled “Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant 
Followed by Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination 
with Dendritic Cell /Myeloma Fusions” 
 
 
 
Your Name:   
__________________________ 
 
Study Title: 
Optional Correlative Laboratory Study Participation for patients enrolled on 
BMT CTN 1401 “Phase II Multicenter Trial of Single Autologous 
Hematopoietic Cell Transplant Followed by Lenalidomide Maintenance for 
Multiple Myeloma with or without Vaccination with Dendritic Cell 
/Myeloma Fusions” 
 
 
Parent Study Title:  Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma 
with or without Vaccination with Dendritic Cell /Myeloma Fusions  
 
Protocol:  
BMT CTN 1401 v4.0 
 
Principal  
Investigator:  
Insert local PI information  
 
Sponsor:  
The National Institutes of Health (NIH) is sponsoring this study by 
providing financial support for the coordination of this study through the 
Blood and Marrow Transplant Clinical Trials Network (BMT CTN).  
 
 
 
 


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1. 
Introduction  
We invite you to participate in one or both of the optional correlative laboratory studies associated 
with the BMT CTN 1401 trial.  You’re being asked to join these optional studies because you were 
enrolled on BMT CTN 1401 and are being evaluated for randomization. Participation in these 
studies will involve you agreeing to allow investigators to either use previously collected research 
samples required by the primary trial and/or provide additional blood and marrow samples during 
your participation on the primary BMT CTN 1401 trial.   
It is your choice to participate in these optional studies and to provide additional blood or bone 
marrow samples for this optional research. Even if you decide not to participate in these optional 
research studies, you can still participate on the primary BMT CTN 1401 study.  
This Consent Form will tell you about the purpose of the optional research studies, the clinical 
samples needed for this research, the possible risks and benefits, other options available to you, 
and your rights as a research participant. 
Everyone who takes part in research at [insert facility name] should know that: 
 Being in any research study is voluntary. 
 You will not directly benefit from being in the study. Knowledge we gain from this study may 
benefit others. 
 If you give blood and bone marrow samples for research, you can change your mind at any 
time. The blood and marrow samples that you already provided will be used for research but 
no further research will be done after you change your mind.  
 If you decide to quit the study, it will not affect your at [insert name of facility or institution]. 
 Please ask the study staff questions about anything that you do not understand, or if you would 
like to have more information. 
 You can ask questions now or any time during the study. 
 Please take the time you need to talk about the study with your doctor, study staff, and your 
family and friends. It is your decision to provide samples for research. If you decide to join, 
please sign and date the end of the Consent Form. 
 
2. 
Study Background 
The National Institutes of Health (NIH), through the Blood and Marrow Transplant Clinical Trials 
Network (BMT CTN), are providing staff support and money for this research study. The BMT 
CTN and the NIH will make decisions about how to manage the study.  


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For participation in one or both of these optional research studies, you will be asked to provide 
blood or bone marrow samples that will be shipped to a lab for further testing. Your doctor will 
discuss the research studies that are available to you as a part of this study.  
 
3. 
Study Purpose 
We are conducting these additional laboratory studies to further our understanding and knowledge 
about how the treatments you receive as part of the parent study (BMT CTN 1401) work.  
4. 
Rights to Ask Questions and/or Withdraw  
You have the right to ask questions about the study at any time. If you have questions about your 
rights as a participant or you want to leave the study, please contact:  
[insert contact info] 
Participating in either of these optional research studies is voluntary. You can choose not to be in 
these studies or leave either study at any time. However, some of the blood and bone marrow 
already donated may have already been used for research. If you choose not to take part or leave 
one of these studies, it will not affect your regular medical care in any way.  
Your study doctor and study staff will be available to answer any questions that you may have 
about taking part in or leaving these optional research studies.  
5. 
Study Treatment and Tests  
There are two different research studies associated with the primary parent trial (BMT CTN 1401) 
that you are participating in.  You doctor will explain which studies you are being asked to 
participate on at the end of this consent form and you will be presented with one or two more 
informed consent forms. These consent forms will go over the study tests in detail. The schedule 
of blood or bone marrow collections will depend on which studies you agree to participate in.  If 
you would like to participate in this optional research, you will be asked to sign this informed 
consent form along with the other consent form(s) associated with the optional research your 
doctor is asking you to be a part of.   
If you agree to participate on either of these research studies, your blood and or bone marrow will 
be shipped to laboratories at either Beth Israel Deaconess Medical Center and/or the University of 
Wisconsin. All research samples will be given a bar coded ID that cannot be linked to you by the 
researchers testing your samples. Samples will not be used for purposes other than those specified 
in this consent form.  


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6. 
Risks and Discomforts  
Information about your demographics, disease, and response to the treatments you receive as part 
of the main clinical study may be provided to the investigators listed in the privacy portion of this 
consent form. This information is used to help the investigators understand how the research 
samples correlate to your disease. There are no major risks to having your blood or bone marrow 
drawn. It can be uncomfortable to have your blood and bone marrow taken and it can sometimes 
leave a bruise. You might faint, but this is unlikely to happen. Only trained people will take your 
blood and bone marrow.  
A possible risk is the loss of confidentiality about your medical information. We will use safety 
measures with both your samples and clinical information to make sure that your personal 
information will be kept private. The chance that this information will be given to someone else is 
extremely small.  
For more information about risks and side effects, ask your study doctor. 
7. 
Other Treatments 
Participation in this study is optional. The alternative to participating on this research sample study, 
is not agreeing to provide blood or bone marrow samples. If you choose not to take part, your 
treatment on BMT CTN 1401 will not be affected 
This information could help people with multiple myeloma who may need a transplant in the future 
8. 
Possible Benefits 
Taking part in this study will not make your health better. You will not get any direct benefit from 
taking part in this study. The information from this study will help doctors and researchers learn 
more about how well unrelated transplant works as treatment for people with a blood disease. 
9. 
Privacy, Confidentiality and Use of Information  
Your privacy is very important to us.  The study doctors will make every effort to protect it.  The 
study doctors have a privacy permit to help protect your records if there is a court case.  However, 
some of your medical information may be given out if required by law.  If this should happen, the 
study doctors will do their best to make sure that any information that goes out to others will not 
identify who you are.  
 
Data regarding your clinical situation, including follow-up after 2 years, may be obtained from the 
CIBMTR, which captures information on all US transplants. 
All your medical and demographic information (such as race and ethnicity, gender and household 
income) will be kept private and confidential. (Name of Transplant Center) and the organizations 
listed below will not disclose your participation by any means of communication to any person or 


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organization, except by your written request, or permission, or unless required by federal, state or 
local laws, or regulatory agencies.  
The individuals below will have access to your research and medical information. They may use 
this information for inspections or audits to study the outcomes of your treatment. By agreeing to 
participate, you consent to such inspections and to the copying of parts of your records, if required 
by these organizations. 
We may give out your personal information if required by law. If information from this study is 
published or presented at scientific meetings, your name and other personal information will not 
be used.  
Information about your transplant, research samples, and treatment on BMT CTN 1401 from your 
original medical records may be seen or sent to national and international transplant registries, 
including:  
1. /Institution/ 
2. The Center for International Blood and Marrow Transplant Research (CIBMTR) 
3. The National Marrow Donor Program (NMDP) 
4. The Food and Drug Administration (FDA) 
5. The National Institutes of Health (NIH), which include the National Heart, Lung, and Blood 
Institute (NHLBI) and the National Cancer Institute (NCI) 
6. Data and Coordinating Center of the Blood and Marrow Transplant Clinical Trials Network 
(BMT CTN)  
7. Data and Safety Monitoring Board (DSMB), not part of /Institution/ 
8. Study investigators.   
9. Dr. David Avigan and laboratory staff at Beth Israel Deaconess Medical Center/Dana Farber 
Cancer Institute   
10. Dr. Fotis Asimakopoulos and laboratory staff at University of Wisconsin and at Medical 
College of Wisconsin.   
11. Celgene, the manufacturer of lenalidomide 
DNA from your blood samples might be used in genome-wide association (GWA) studies for a 
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association studies are a way for scientists to find genes that have a role in human disease or 
treatment. Each study can look at hundreds of thousands of genetic changes at the same time. 
If your coded samples are used in such a study, the researcher is required to add your test 
results and sample information into a shared, public research database. This public database is 
called the NIH Genotype and Phenotype Database and it is managed by the National Center 
for Biotechnology Information (NCBI). The NCBI will never have any information that would 
identify you, or link you to your information or research samples.  
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.  
For questions about access to your medical records, please contact /name/ at /number. 
10. 
Ending Your Participation 
The study doctor or the study sponsor may stop the study at any time, and we may ask you to leave 
the study. We may ask you to leave the study if you do not follow directions or if you suffer from 
side effects of the treatment. If we ask you to leave the study, the reasons will be discussed with 
you. Possible reasons to end your participation in this study include: 
1. You do not meet the study requirements.  
2. The study doctor decides that it would be harmful to you to stay in the study. 
3. You become unable to donate blood or bone marrow for any reason  
4. The study is stopped for any reason. 
Even if you leave the study, the information collected from your participation will be included in 
the study evaluation, unless you specifically ask that it not be included. 
11. 
Physical Injury as a Result of Participation  
It is important that you tell your doctor, __________________ [investigator's name(s)] or study 
staff if you feel that you have been injured because of taking part in this study.  You can tell the 
doctor in person or call him/her at __________________ [telephone number]. 
You will get all available medical treatment if you are injured from taking part in this study. You 
and/or your health plan will be charged for this treatment. There is no provision for free medical 
care or monetary compensation from the study sponsor, The National Institutes of Health or the 
study contributor, Celgene Corporation.  
 


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In case you are injured in this study, you do not lose any of your legal rights to ask for or receive 
payment by signing this form. 
12. 
Payment and Study Costs  
You will not be paid for donating your blood and/or bone marrow.. You will not be paid  or 
reimbursed for any extra expenses (travel, meals, etc.) you may have to donate blood and bone 
marrow. 
Your blood and marrow will be used only for research and will not be sold. The research done 
with your blood may help to develop new products in the future. You will not get paid for any 
samples or for any products that may be developed from current or future research. 
The visits for this research study are standard medical care for your autologous transplant and will 
be billed to your insurance company. You and/or your health plan/insurance company will need to 
pay for some or all of the costs of standard treatment in this study.  
 
For questions about your costs, financial responsibilities, and/or medical insurance coverage for 
your transplant and this study, please contact /Center/ Financial Counselor at /Number/. 
 
13. 
For More Information 
If you need more information about these studies, or if you have problems while taking part in either 
of these studies, you can contact the study doctor or his/her staff.  
They can be reached at the telephone numbers listed here: 
[Insert name and contact details] 
14. 
Contact Someone about Your Rights 
If you wish to speak to someone not directly involved in the study, or if you have any complaints 
about any aspect of the project, the way it is being conducted or any questions about your rights as a 
research participant, then you may contact:  
[Insert appropriate contact details] 
The ethical aspects of this study have been reviewed and approved by [name of IRB]. 
Health Insurance Portability and Accountability Act 1 (HIPAA13) Authorization to use and 
disclose individual health information for research purpose 
 
                                                 
13 HIPAA is the Health Insurance Portability and Accountability Act of 1996, a federal law related to privacy of health 
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• Purpose: 
As a research participant, I authorize the Principal Investigators and the researcher’s staff to use 
and disclose my individual health information for the purpose of conducting either of the research 
studies described in this consent:  
Optional Correlative Laboratory Study Participation for patients enrolled on “Phase II 
Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed by 
Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination with Dendritic 
Cell /Myeloma Fusions” 
 
• Individual Health Information to be Used or Disclosed:  
My individual health information that may be used or disclosed to do this research includes:  
1. Demographic information (for example, date of birth, sex, weight).  
2. Medical history (for example, diagnosis, complications with prior treatment). 
3. Findings from physical exams. 
4. Laboratory test results obtained at the time of work up and after transplant (for example, blood 
tests, biopsy results).  
• Parties Who May Disclose My Individual Health Information:  
The researcher and the researcher’s staff may collect my individual health information from: 
[List hospitals, clinics or providers from which health care information can be requested]. 
• Parties Who May Receive or Use My Individual Health Information:  
The individual health information disclosed by parties listed in item c and information disclosed 
by me during the course of the research may be received and used by the following parties: 
1. Dr. David Avigan, Co-Principal Investigator  
2. Dr. Nina Shah, Co-Principal Investigator  
3. Dr. David Chung, Co-Principal Investigator 
4. Laboratory staff at Beth Israel Deaconess Medical Center/Dana Farber Cancer Institute   
5. Dr. Fotis Asimakopoulos and laboratory staff at University of Wisconsin and at Medical 
College of Wisconsin.   


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6. Celgene, its collaborators or designees 
7. National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute 
(NCI), both of the National Institutes of Health (NIH),  
8. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Data and 
Coordinating Center 
9. U.S. government agencies that are responsible for overseeing research such as the Food 
and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) 
10. U.S. government agencies that are responsible for overseeing public health concerns such 
as the Centers for Disease Control (CDC) and federal, state and local health departments. 
• Right to Refuse to Sign this Authorization:  
I do not have to sign this Authorization.  If I decide not to sign the Authorization, I will not be 
allowed to participate in this study. 
My decision not to sign this authorization will not affect any other treatment, payment, or 
enrollment in health plans or eligibility for benefits.   
• Right to Revoke:   
I can change my mind and withdraw this authorization at any time by sending a written notice to 
the Principal Investigator to inform the researcher of my decision.  
If I withdraw this authorization, the researcher may only use and disclose the protected health 
information already collected for this research study.  No further health information about me will 
be collected by or disclosed to the researcher for this study. 
• Potential for Re-disclosure:  
My individual health information disclosed under this authorization may be subject to re-
disclosure outside the research study and no longer protected. 
Examples include potential disclosures for law enforcement purposes, mandated reporting or abuse 
or neglect, judicial proceedings, health oversight activities and public health measures. 
• Genetic Information Nondiscrimination Act (GINA)  
A federal law (2009), called the Genetic Information Nondiscrimination Act (GINA) generally 
makes it illegal for health insurance companies, group health plans, and employers of 15 or more 
persons to discriminate against you based on your genetic information.  


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Health insurance companies and group health plans may not request your genetic information that 
we get from this research. This means that they must not use your genetic information when 
making decisions regarding insurability. Be aware that this federal law will not protect you against 
genetic discrimination by companies that sell life insurance, disability insurance, or long-term care 
insurance. 
• This authorization does not have an expiration date. 
 
 


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TITLE: Optional Correlative Laboratory Study Participation for Patients Enrolled on BMT 
CTN 1401 entitled, “Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions” 
PROTOCOL NUMBER: BMT CTN #1401 
PRINCIPAL INVESTIGATOR:  
Name: 
Address: 
Email:  
Phone:  
 
 
 
 
 
 
 
 
 
 
 
Fax:  
I have read and understood this Consent Form. The nature and purpose of the research study has 
been explained to me. 
• I have had the chance to ask questions, and understand the answers I have been given. I 
understand that I may ask questions at any time during the study. 
• I freely agree to be a participant in the study. 
• I understand that I may not directly benefit from taking part in the study. 
• I understand that, while information gained during the study may be published, I will not be 
identified and my personal results will stay confidential. 
• I have had the chance to discuss my participation in this research study with a family member 
or friend. 
• I understand that I can leave this study at any time, and doing so will not affect my current care 
or prevent me from receiving future treatment. 
• I understand that I will be given a copy of this signed consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant Name 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
 


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I certify that I have provided a verbal explanation of the details of the research study, including 
the procedures and risks. I believe the participant has understood the information provided. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Counseling Physician 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Counseling Physician 
 
    
 
 
 
Date 
 
 


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Supplemental Informed Consent Form to Participate in Research  
 
Study Title: Characterization of the T cell immune response and myeloma genomic signature as 
predictors of immunologic and clinical response 
 
Parent Study Title: Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
 
 
A. What is this Document?  
The purpose of this document is to give you more information on the specific research sample 
study your physician is asking for your consent to join. This document will explain further 
details of what samples are collected, why they are being collected, and where they are being 
sent. Details about risks, study participation, and your rights are explained in the primary 
informed consent form that your doctor already presented to you.  
B. Why am I here? 
You are being asked to participate in this study because you are participating on BMT CTN 
1401 and are approaching the randomization portion of the parent study.  
If you give us your permission, we would like to collect extra samples of your blood and 
marrow at several time points during your participation on the parent trial. 
C. Why are you doing this study? 
We are collecting samples to learn more about how your body responds to the treatment on the 
parent trial. We will collect samples on 60 patients across all treatment arms. Your 
participation on this study is expected to last up to 3 years.  
D. What will happen to me if I join the study? 
If you say you want to be in the study, we will ask you for the following samples:  
• Bone Marrow Aspirate Samples: About 1 teaspoon of bone marrow will be collected at the 
following timepoints:  
o Just before you are randomized on the parent trial (about 50-80 days after your bone 
marrow transplant). This is one teaspoon more of bone marrow being collected at 
the  time of a required bone marrow aspirate being performed as part of the primary 
trial.  
o Just before you start your 9th Cycle of Maintenance (about 1 year after your bone 
marrow transplant). This is one teaspoon more of bone  marrow being collected at 


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the time of a required bone marrow aspirate being performed as part of the primary 
trial.   
o If your disease comes back, an additional bone marrow aspirate sample will be 
collected at that time. This is an additional aspirate not required as part of the 
primary trial. 
• Blood Samples:  
o About 2 teaspoons of blood will be collected just before you start Cycles 1, 2, and 
4 of Maintenance Therapy. This is extra  blood being collected at the time of  a 
required blood sample collection being performed as part of the primary trial. 
o If your disease comes back, about 10 teaspoons of blood will be collected at that 
time. This is an additional collection not required as part of the primary trial.  
• We will also use a portion of the bone marrow aspirate sample that you already provided 
at the time of agreeing to participate on the BMT CTN 1401 study as part of this research 
sample  study.  
 
E. Where will my samples be sent? 
Your samples will be sent to a laboratory at Beth Israel Deaconess Medical Center.  
All research samples will be tied to a number. This number will not be linked to your name or 
other identifying information.  
 
 


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Statement of Consent for Research Samples  
The purpose of providing blood and bone marrow samples, the procedures involved, and the risks 
and benefits have been explained to me. I have asked all the questions I have at this time and I 
have been told whom to contact if I have more questions. I have been told that I will be given a 
signed copy of this consent form to keep. 
I understand that I do not have to allow the use of my blood and bone marrow for this research. If 
I decide to not let collect research samples now or in the future, it will not affect my medical care 
in any way. 
I voluntarily agree that my blood, bone marrow, and information can be used for the study entitled 
“Characterization of the T cell immune response and myeloma genomic signature as predictors 
of immunologic and clinical response”. I also understand that my DNA and health information 
may or may not be used in genome-wide association studies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
 
 


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Supplemental Informed Consent Form to Participate in Research  
 
Study Title: VCAN Proteolysis: Investigation of a Potential Novel Immune Biomarker in 
Myeloma 
 
Parent Study Title: Phase II Multicenter Trial of Single Autologous Hematopoietic Cell 
Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or without 
Vaccination with Dendritic Cell /Myeloma Fusions 
 
 
A. What is this Document?  
The purpose of this document is to give you more information on the bone marrow sample 
study your physician is asking for your consent to join. This document will explain further 
details of what samples are collected, why they are being collected, and where they are being 
sent. Details about risks, study participation, and your rights are explained in the primary 
informed consent form that your doctor already presented to you. If you want to participate in 
this research you will be asked to sign the primary informed consent form as well as this 
document.  
B. Why am I here? 
You are being asked to participate in this study because you are participating on BMT CTN 
1401 and are approaching the randomization portion of the parent study.  
If you give us your permission, we would like to send a portion of a clinical bone marrow  
sample to study investigators at the time of randomization. The sample we are asking for is 
part of a clinical sample collection procedure you will have already undergone as part of the 
parent trial. We will not collect any additional samples as part of this study. We are asking for 
your consent to ship a portion of this clinical bone marrow  sample to a different lab and study 
it for research purposes.  
C. Why are you doing this study? 
We are collecting bone marrow samples to learn more about how your body responds to the 
treatment on the parent trial. We will collect samples on 20 patients across all treatment arms. 
Your participation on this study is expected to last 1 month. We may use data collected on the 
parent trial for this study for up to 3 years after you are randomized on the parent trial.  
D. What will happen to me if I join the study? 
The bone marrow sample we are asking for is part of a procedure you will already undergo as 
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asking for your consent to ship a portion of this bone marrow sample to a different lab and 
study it for research purposes.  
If you say you want to be in the study, we will not collect any additional samples. The clinical 
pathology lab at /Institution/ will cut a small piece of your bone marrow biopsy that you 
provided for the BMT CTN 1401 parent trial and ship it to investigators at University of 
Wisconsin. If the lab is not able to obtain enough sample from the bone marrow biopsy you 
provided for the parent trial (BMT CTN 1401), you will not be asked to provide additional 
samples and you will be removed from the study.  
E. Where will my samples be sent? 
Your samples will be sent to a laboratory at University of Wisconsin.  
All research samples will be tied to a number. This number will not be linked to your name or 
other identifying information.  


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Statement of Consent for Research Samples  
The purpose of providing bone marrow biopsy samples, the procedures involved, and the risks and 
benefits have been explained to me. I have asked all the questions I have at this time and I have 
been told whom to contact if I have more questions. I have been told that I will be given a signed 
copy of this consent form to keep. 
I understand that I do not have to allow the use of my bone marrow biopsy samples for this 
research. If I decide to not let collect research samples now or in the future, it will not affect my 
medical care in any way. It will also not affect my participation in the Parent Trial.  
I voluntarily agree that my bone marrow biopsy samples and information can be used for the study 
entitled “VCAN Proteolysis: Investigation of a Potential Novel Immune Biomarker in Myeloma”. 
I also understand that my DNA and health information may or may not be used in genome-wide 
association studies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 


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APPENDIX C 
 
LABORATORY PROCEDURES 
 


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APPENDIX C 
 
LABORATORY PROCEDURES 
 
 
Collection of MANDATORY Samples for TC-DC/Myeloma Fusion Vaccine Production 
and Immunologic Endpoints  
 
Bone marrow aspirate and peripheral blood will be collected for patients who consent to the BMT 
CTN 1401 study. Sample collection will be performed periodically throughout the study and will 
provide clinical samples required for: (1) DC/Myeloma fusion cell vaccine production and (2) 
correlative laboratory testing associated with critical immunologic study endpoints. 
 
 TC-DC/Myeloma Fusion Vaccine Production: Upon enrollment on the BMT CTN 1401 
study, all patients will have both peripheral blood and marrow aspirate samples collected, and 
delivered to the clinical center’s cell processing facility for the isolation and storage of 
myeloma tumor cells as summarized in the table below. A sample of the processed myeloma 
tumor cells will be shipped to the BIDMC Central Laboratory for phenotypic characterization. 
 
For patients randomized to the cellular vaccine arm of the study, a therapeutic apheresis 
product will be collected and delivered to the clinical center’s cell processing facility for the 
isolation of therapeutic cell dendritic cells (TC-DC) and the manufacturing of the TC-
DC/Myeloma fusion cell vaccine as summarized in the table below.  A sample of the processed 
TC-DC cells and manufactured TC-DC/Myeloma fusion cell vaccine will be shipped to the 
BIDMC Central Laboratory for phenotypic characterization. And finally, additional samples 
of the manufactured TC-DC/Myeloma fusion cell vaccine will be shipped to Labs, Inc. 
Reference Laboratory for final product release sterility testing, endotoxin testing and 
mycoplasma screening. 
 
 Research Samples for Laboratory Correlatives Associated with Immunologic Endpoints: 
Required research samples for study-specific immunologic correlatives include the collection 
of blood and marrow aspirate samples as summarized in the table below (and in table 4.3B). 
The correlative studies include MRD Assessment, measurement of Plasmablast Response, NK 
Cell Reconstitution and the evaluation of Myeloma Reactive T-Cells.  Once the samples are 
collected at specified time points they will be shipped on the day of collection directly to 
specified ancillary study laboratory for processing and testing. These samples will be tracked 
through GlobalTrace.  Detailed procedures regarding specimen collection schedules, 
procedures and shipping instructions will be found in the BMT CTN 1401 Research Sample 
Information Guide.  
   
Collection of Research Samples Associated with OPTIONAL Ancillary Correlative 
Laboratory Studies  
 
Additional marrow and/or peripheral blood samples, often linked to mandatory research sample 
collections for laboratory correlatives associated with protocol-defined immunologic endpoints, 
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laboratory studies described in Appendices J and K of this protocol. Sample collection will be 
done at the transplant center and will require minimum processing. Once the samples are collected 
at specified time points they will be shipped on the day of collection directly to specified ancillary 
study laboratory for processing and testing. The collection, processing and shipping of these 
biospecimens are summarized in the table below (and in table 4.3B). These samples will be tracked 
through GlobalTrace. Detailed procedures regarding specimen collection schedules, procedures 
and shipping instructions will be found in the BMT CTN 1401 Research Sample Information 
Guide. 
 
 
• Bone Marrow Aspirate or Marrow Biopsy Samples  
o Patients participating in the VCAN Proteolysis Assessment Study: Once correlative 
study consent has been signed and patient has been randomized to one of the 
maintenance therapy arms of the trial, the clinical site will request 4 slides of 
decalcified marrow biopsy material to be made by the center’s Clinical Pathology 
laboratory using stored paraffin blocks containing the processed clinical marrow 
tissue. 
o Patients participating in the T Cell/Genomic Signature Study: Once correlative 
study consent has been signed and patient has been randomized to one of the 
maintenance therapy arms of the trial, the clinical site will collect: 
 
 Additional 4 mL of marrow aspirate at two of the mandatory sample 
collection time points on the primary trial (1) at time of randomization, and 
(2) just prior to the initiation of cycle 9 of maintenance therapy. 
 
Event Driven Sample Collection: At disease progression collect 5 mL of 
marrow aspirate when possible. 
 
• Peripheral Blood Samples 
o Patients participating in the T Cell/Genomic Signature Study: Once correlative 
study consent has been signed and patient has been randomized to one of the 
maintenance therapy arms of the trial, the clinical site will collect: 
 
 Additional 10 mL of peripheral blood at three of the mandatory sample 
collection time points on the primary trial: just prior to the initiation of cycles 
1, 2 and 4 of maintenance therapy. 
 
Event Driven Sample Collection: At disease progression collect 40 mL of 
peripheral blood. 
 
Collection of OPTIONAL Samples for Future Research 
 
Bone marrow aspirate and peripheral blood will be collected from patients who signed consent to 
provide additional samples for future research.  Sample collection will be done at the transplant 
center and will require minimum processing.  Once the samples are collected at specified time 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
 
C-4 
points they will be shipped on the day of collection to the BMT CTN Central Processing 
Laboratory for final processing and storage at the BMT CTN Research Repository.  The collection, 
processing and shipping of these biospecimens are summarized in the table below (and in table 
4.3B). These samples will be tracked through GlobalTrace. Detailed procedures regarding 
specimen collection schedules, procedures and shipping instructions will be found in the BMT 
CTN 1401 Research Sample Information Guide. 
 
 
• Bone Marrow Aspirate Samples  
Patients who consented for marrow sample collection for future research studies will 
have 3 mL of bone marrow aspirate collected at three time points (1) time of enrollment, 
(2) time of randomization, and (3) just prior to the initiation of cycle 9 of maintenance 
(~1 year post transplant)  
• Peripheral Blood Samples 
Patients who consented for peripheral blood sample collection for future research studies 
will have 6 mL blood samples collected at three time points (1) time of enrollment, (2) 
following randomization onto the study, and (3) just prior to the initiation of cycle 9 of 
maintenance (~1 year post transplant)  
 
 


BMT CLINICAL TRIALS NETWORK 
 
 Myeloma Vaccine 1401 
Version 4.0 dated July 24, 2018  
 
 
C-5 
 
 
Mandatory Research Samples & Testing Associated with TC-DC/Myeloma Fusion Vaccine Production 
Purpose 
 Sample 
Type 
Sample Collection Summary 
Dates Samples Obtained 
Cell Processing 
Laboratory 
Shipping 
Location 
Myeloma Tumor 
Cell Collection 
30 mL 
Bone Marrow 
Aspirate 
Bone marrow aspirates will be 
collected using sodium-heparin 
anticoagulant, following standard 
institutional procedures and 
promptly delivered to the center’s 
cell processing facility for the 
isolation and storage of myeloma 
tumor cells.  
At time of enrollment for all study 
patients 
Bone marrow aspirate sample 
will be processed and myeloma 
tumor cells stored for possible 
future use for DC/Myeloma 
cell fusion vaccine production.  
Processing will be performed 
according to protocol-specific 
standardized procedures used 
by all BMT CTN 1401 center 
cell processing laboratories. 
Transplant 
Center 
Autologous 
Plasma for 
Vaccine 
Production 
50 mL 
Peripheral 
Blood 
Collect blood sample in five 10 
mL fill green top plastic BD 
Vacutainer® tubes, containing 
Sodium-Heparin anticoagulant, 
and promptly deliver to the 
center’s cell processing facility. 
At time of enrollment for all study 
patients 
Peripheral blood samples will 
be processed and plasma 
recovered for use in tumor cell 
processing/storage as well as 
subsequent DC/Myeloma 
fusion cell vaccine 
manufacturing steps. 
Transplant 
Center 
Myeloma Tumor 
Cell Phenotype 
Characterization 
3 mL 
Processed 
Myeloma 
Tumor Cells 
No additional sample collection 
needed from patient 
N/A 
5-7 million processed myeloma 
tumor cells in 3 mL tumor 
media will be shipped at 2-8o C 
by priority overnight FED EX 
delivery to BIDMC Laboratory 
for tumor lysate and 
immunohistochemical staining. 
BIDMC 
Central 
Project 
Laboratory 
Isolation of 
Therapeutic 
Dendritic Cells 
Peripheral 
Blood 
Therapeutic 
Cells, 
Apheresis 
Product 
A therapeutic peripheral blood 
apheresis product will be 
collected following standard 
institutional procedures and 
promptly delivered to the center’s 
cell processing facility for the 
isolation of dendritic cells to be 
used in cellular vaccine 
preparation. 
At time of randomization to only the 
DC/Myeloma Vaccine arm of the 
study 
Apheresis products will be 
processed and TC-Dendritic 
cells recovered for 
manufacturing the 
DC/Myeloma fusion cell 
vaccine.  Processing will be 
performed according to 
protocol-specific standardized 
procedures. 
Transplant 
Center 


BMT CLINICAL TRIALS NETWORK 
 
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Version 4.0 dated July 24, 2018  
 
 
C-6 
Mandatory Research Samples & Testing Associated with TC-DC/Myeloma Fusion Vaccine Production (continued) 
Purpose 
 Sample 
Type 
Sample Collection Summary 
Dates Samples Obtained 
Cell Processing 
Laboratory 
Shipping 
Location 
TC– DC Cell 
Phenotype 
Characterization 
Processed TC-
Dendritic cells 
No additional sample collection 
needed from patient 
N/A 
2-5 x 106 processed dendritic 
cells in media will be shipped 
at 2-8o C by priority overnight 
FED EX delivery to BIDMC 
Laboratory for 
immunohistochemical staining. 
BIDMC 
Central 
Project 
Laboratory 
TC-DC/Myeloma 
Fusion Cell  
 
Phenotype 
Characterization 
Processed TC-
DC/Myeloma 
Fusion cells 
No additional sample collection 
needed from patient 
N/A 
1-2 x 106 processed TC-
DC/Myeloma Fusion cells in 
media will be shipped at 2-8o C 
by priority overnight FED EX 
delivery to BIDMC Laboratory 
for immunohistochemical 
staining. 
BIDMC 
Central 
Project 
Laboratory 
TC-DC/Myeloma 
Fusion Cell 
Vaccine 
 
Final Release 
Microbiological 
Assessment 
Processed TC-
DC/Myeloma 
Fusion cells 
No additional sample collection 
needed from patient 
N/A 
2.0-5.0 x106 cells (fusion cell 
vaccine) in 3 mL of media will 
be shipped at ambient 
temperature by priority 
overnight FED EX delivery to 
Labs, Inc., for product release 
sterility testing. 
Labs, Inc. 
Reference 
Laboratory 
1 mL of fusion cell product 
media will be shipped at 2-
8o C by priority overnight 
FED EX delivery to Labs, 
Inc. for endotoxin testing. 
Two sample aliquots, each 
containing 0.5-1.0x106 cells 
(fusion cell vaccine) in 0.5 mL 
media will be shipped at 2-8o C 
by priority overnight FED EX 
delivery to Labs, Inc. for 
Mycoplasma screening. 
 
 


BMT CLINICAL TRIALS NETWORK 
 
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Version 4.0 dated July 24, 2018  
 
 
C-7 
Mandatory Research Samples Associated with Immunologic Study Endpoints  
Purpose 
 Sample 
Type 
Sample Collection Summary 
Dates Samples Obtained 
Shipping Specifications 
Shipping 
Location 
MRD 
Assessment 
6 mL 
Bone Marrow 
Aspirate 
Collect bone marrow aspirated 
sample and place 3 mL into each 
of two green top plastic BD 
Vacutainer® tube, containing 
Sodium-Heparin anticoagulant. 
Gently mix sample by inversion 
8-10 times to mix sample well 
with heparin anticoagulant. 
Following randomization onto the 
study; and following the completion 
of cycle 9 of maintenance (~ 1 year 
post transplant) 
One 3 mL bone marrow 
aspirate sample will be shipped 
at ambient temperature on the 
day of collection to RPCI by 
priority overnight FED EX 
delivery for MRD assessment.  
RPCI 
Laboratory 
The remaining 3 mL bone 
marrow sample will be sent to 
the local pathology department 
for MRD assessment. 
Transplant 
Center 
Myeloma 
Reactive T Cells 
4 mL 
Bone Marrow 
Aspirate 
Collect bone marrow aspirated 
sample and place into a green top 
plastic BD Vacutainer® tube, 
containing Sodium-Heparin 
anticoagulant.  
At time of enrollment, following 
randomization onto the study; and 
just prior to the initiation of cycle 9 
of lenalidomide maintenance 
Bone marrow aspirate sample 
will be shipped at at 2-8o C on 
the day of collection to BIDMC 
by priority overnight FED EX 
delivery. 
BIDMC 
Laboratory 
Plasmablast 
Response 
30 mL 
Peripheral 
Blood 
Collect blood sample and place 
into three 10 mL fill green top 
plastic BD Vacutainer® tubes, 
containing Sodium-Heparin 
anticoagulant. Gently mix sample 
by inversion 8-10 times to mix 
sample well with heparin 
anticoagulant. 
For all patients: at time of 
randomization; and 7 days after the 
initiation of the 4th cycle (cycle 4+7) 
of maintenance therapy. 
 
Additional collections for patients in 
the vaccine arm: immediately prior 
the first dose of the vaccine (cycle 
2) and 7 days later (cycle 2+7); and 
immediately prior to the third dose 
of vaccine (cycle 4). 
Blood sample tubes will be 
shipped on the day of 
collection at ambient 
temperature, to the Wrammert 
Laboratory at Emory 
University by priority 
overnight FED EX delivery.  
Emory 
University 
Laboratory 
Myeloma 
Reactive T Cells 
40 mL 
Peripheral 
Blood 
Collect blood sample and place 
into four 10 mL fill green top 
plastic BD Vacutainer® tubes, 
containing Sodium-Heparin 
anticoagulant. Gently mix sample 
by inversion 8-10 times to mix 
sample well with heparin 
anticoagulant. 
At time of enrollment, and just prior 
to initiation of cycles 1, 2, 3, 4, and 
9 of maintenance. 
Blood sample tubes will be 
shipped at at 2-8o C on the day 
of collection to BIDMC by 
priority overnight FED EX 
delivery. 
BIDMC 
Laboratory 
 
 


BMT CLINICAL TRIALS NETWORK 
 
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C-8 
Mandatory Research Samples Associated with Immunologic Study Endpoints (continued) 
Purpose 
 Sample 
Type 
Sample Collection Summary 
Dates Samples Obtained 
Shipping Specifications 
Shipping 
Location 
NK Cell 
Reconstitution 
30 mL 
Peripheral 
Blood 
Collect blood sample and place 
into three 10 mL fill green top 
plastic BD Vacutainer® tube, 
containing Sodium-Heparin 
anticoagulant. Gently mix sample 
by inversion 8-10 times to mix 
sample well with heparin 
anticoagulant. 
Immediately prior to initiation of 
cycle 1 of maintenance; 7 days after 
initiation of cycle 2 (cycle 2+7); 
immediately prior to initiation of 
cycle 3; 7 days after initiation of 
cycle 4 (cycle 4+7); and just prior to 
the initiation of cycle 9. 
Blood sample tubes will be 
shipped at ambient temperature 
on the day of collection, to 
MDACC by priority overnight 
FED EX delivery  
MDACC 
Laboratory 
 
 
 
 
 
 
OPTIONAL Undefined Future Research Sample Collections 
Purpose 
 Sample 
Type 
Sample Collection Summary 
Dates Samples Obtained 
Shipping Specifications 
Shipping 
/Storage 
Location 
OPTIONAL 
Future Research 
3 mL 
bone marrow 
aspirate 
Collect bone marrow aspirated 
sample and place into a green top 
plastic BD Vacutainer® tube, 
containing Sodium-Heparin 
anticoagulant. Gently mix sample 
by inversion 8-10 times to mix 
sample well with heparin 
anticoagulant. 
At time of enrollment, following 
randomization onto the study, and 
just prior to the initiation of cycle 9 
of maintenance 
Bone marrow aspirate tube will 
be shipped at ambient 
temperature on the day of 
collection, to the BMT CTN 
Research Repository by 
priority overnight FED EX 
delivery for processing and 
final frozen storage of marrow 
aliquots.  
BMT CTN 
Research 
Repository 
OPTIONAL 
Future Research 
6 mL 
peripheral 
blood 
Collect blood sample in a 
Red/Gray Top BD SST™ Tube 
with Silica Clot Activator & 
Polymer Gel. Let sample sit 
upright in rack for 30-60 minutes. 
Centrifuge for 10 minutes.  Gel 
barrier will form separating the 
serum specimen from clot. 
At time of enrollment, following 
randomization onto the study, and 
just prior to the initiation of cycle 9 
of maintenance 
Serum blood tube will be 
shipped at ambient temperature 
on the day of collection, to the 
BMT CTN Research 
Repository by priority 
overnight FED EX delivery for 
processing and final frozen 
storage of serum aliquots.  
BMT CTN 
Research 
Repository 
 
 


BMT CLINICAL TRIALS NETWORK 
 
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Version 4.0 dated July 24, 2018  
 
 
C-9 
Research Samples Associated with Optional Correlative Laboratory Studies  
VCAN Proteolysis: Investigation of a Potential Novel Immune Biomarker in Myeloma (Appendix J) 
Purpose 
 Sample 
Type 
Sample Collection Summary 
Dates Samples Obtained 
Shipping Specifications 
Shipping 
Location 
VCAN 
Proteolysis 
Assessment 
4 slides 
paraffin-
embedded, 
decalcified 
bone marrow 
biopsy 
Slides of decalcified clinical 
marrow biopsy material will be 
made by the center’s Clinical 
Pathology laboratory using stored 
paraffin blocks containing the 
processed marrow tissue. 
Core bone marrow biopsy required 
to be collected to confirm CR in a 
subset of study patients prior to 
randomization. 
 
Slides will be requested once patient 
is consented for this correlative 
study and has been randomized to 
an appropriate maintenance arm of 
the 1401 trial. 
The 4 marrow biopsy slides 
will be packaged and shipped 
at ambient temperature to the 
Asimakopoulos Laboratory by 
priority overnight FED EX 
delivery.  
University of 
Wisconsin-
Madison 
Laboratory 
Characterization of the T cell Immune Response and Myeloma Genomic Signature as Predictors of Immunologic and Clinical Response (Appendix K) 
T Cell/Genomic 
Signature Study 
4-5 mL 
Bone Marrow 
Aspirate 
Collect 4-5 mL bone marrow 
aspirated sample (based on visit 
requirements) and place into a 
green top plastic BD Vacutainer® 
tube, containing Sodium-Heparin 
anticoagulant. Gently mix sample 
by inversion 8-10 times to mix 
sample well with heparin 
anticoagulant. 
4 mL marrow collected at time of 
randomization; and just prior to the 
initiation of cycle 9 of maintenance 
therapy. 
 
EVENT DRIVEN SAMPLE: 
At disease progression collect 5 mL 
of marrow when possible. 
Bone marrow aspirate sample 
will be shipped at 2-8o C on 
the day of collection to the 
BIDMC laboratory by priority 
overnight FED EX delivery. 
BIDMC 
Laboratory 
10-40 mL 
Peripheral 
Blood 
Collect blood sample and place 
into 1-4 10 mL fill green top 
plastic BD Vacutainer® tubes, 
(based on visit requirements), 
containing Sodium-Heparin 
anticoagulant. Gently mix sample 
by inversion 8-10 times to mix 
sample well with heparin 
anticoagulant. 
Collect 10 mL blood just prior to 
initiation of cycles 1, 2, and 4 of 
maintenance therapy. 
 
EVENT DRIVEN SAMPLE: 
At time of disease progression, 
collect 40 mL of blood. 
Blood sample tubes will be 
shipped at 2-8o C on the day of 
collection to BIDMC 
laboratory by priority 
overnight FED EX delivery. 
BIDMC 
Laboratory 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
D-1 
APPENDIX D 
 
LENALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY 
TESTING GUIDELINES AND ACCEPTABLE  
BIRTH CONTROL METHODS 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
D-2 
APPENDIX D 
 
LENALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY TESTING 
GUIDELINES AND ACCEPTABLE BIRTH CONTROL METHODS 
 
 
Risks Associated with Pregnancy 
Lenalidomide is structurally related to thalidomide.  Thalidomide is a known human teratogenic 
active substance that causes severe life-threatening birth defects.  An embryofetal development 
study in animals indicates that lenalidomide produced malformations in the offspring of female 
monkeys who received the drug during pregnancy.  The teratogenic effect of lenalidomide in 
humans cannot be ruled out.  Therefore, a risk minimization plan to prevent pregnancy must be 
observed. 
 
The use of lenalidomide in pregnant females and nursing mothers has not been studied nor has the 
effect of the lenalidomide on human eggs and sperm.  The risks to a fetus are not known.  However, 
because lenalidomide is related to thalidomide, and thalidomide is known to cause severe birth 
defects, the following requirements must be observed. 
 
Females of childbearing potential (FCBP)† must agree to use two reliable forms of contraception 
simultaneously or to practice complete abstinence from heterosexual intercourse during the 
following time periods related to this study: 1) for at least 28 days before starting study drug; 2) 
while participating in the study; and, 3) for at least 28 days after discontinuation from the study.  
The two methods of reliable contraception must include one highly effective method (i.e. 
intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, 
partner’s vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, 
cervical cap).  FCBP must be referred to a qualified provider of contraceptive methods if needed.   
 
Criteria for females of childbearing potential (FCBP) 
This protocol defines a female of childbearing potential as a sexually mature female who: 1) has 
not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 
for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive 
months). 
 
                                                 
† A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral 
oophorectomy; or, 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses 
at any time in the preceding 24 consecutive months). 


BMT CLINICAL TRIALS NETWORK 
 
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Version 4.0 dated July 24, 2018  
 
D-3 
Counseling 
All counseling will be conducted through the Revlimid REMS  program. 
 
For a female of childbearing potential, lenalidomide is contraindicated unless all of the following 
are met (i.e., all females of childbearing potential must be counseled concerning the following 
risks and requirements prior to the start of lenalidomide):  
• She understands the potential teratogenic risk to the unborn child 
• She understands the need for effective contraception, without interruption, 28 days before 
starting study treatment, throughout the entire duration of study treatment, dose 
interruption and 28 days after the end of study treatment 
• She should be capable of complying with effective contraceptive measures 
• She is informed and understands the potential consequences of pregnancy and the need to 
notify her study doctor immediately if there is a risk of pregnancy 
• She understands the need to commence the study treatment as soon as study drug is 
dispensed following a negative pregnancy test 
• She understands the need and accepts to undergo pregnancy testing based on the frequency 
outlined in this protocol 
• She acknowledges that she understands the hazards and necessary precautions associated 
with the use of lenalidomide 
The investigator must ensure that for females of childbearing potential: 
• Complies with the conditions for pregnancy risk minimization, including confirmation that 
she has an adequate level of understanding 
• Acknowledge the aforementioned requirements 
For a female NOT of childbearing potential, lenalidomide is contraindicated unless all of the 
following are met (i.e., all females NOT of childbearing potential must be counseled concerning 
the following risks and requirements prior to the start of lenalidomide):  
• She acknowledges that she understands the hazards and necessary precautions associated 
with the use of lenalidomide 
Traces of lenalidomide have been found in semen.  Male patients taking lenalidomide must meet 
the following conditions (i.e., all males must be counseled concerning the following risks and 
requirements prior to the start of lenalidomide): 
• Understand the potential teratogenic risk if engaged in sexual activity with a pregnant 
female or a female of childbearing potential 
• Understand the need for the use of a condom even if he has had a vasectomy, if engaged in 
sexual activity with a pregnant female or a female of childbearing potential.   
 
Contraception 
Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable 
forms of contraception simultaneously or to practice complete abstinence from heterosexual 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
D-4 
contact during the following time periods related to this study: 1) for at least 28 days before starting 
study drug; 2) while participating in the study; 3) during dose interruptions; and, 4) for at least 28 
days after study treatment discontinuation.  
The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method.  FCBP must be referred to a qualified provider of 
contraceptive methods if needed. The following are examples of highly effective and additional 
effective methods of contraception:   
Highly effective methods: 
− Intrauterine device (IUD) 
− Hormonal (birth control pills, injections, implants) 
− Tubal ligation 
− Partner’s vasectomy 
Additional effective methods: 
− Male condom 
− Diaphragm 
− Cervical Cap 
 
Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking 
lenalidomide and dexamethasone, combined oral contraceptive pills are not recommended.  If a 
patient is currently using combined oral contraception the patient should switch to one of the 
effective method listed above.  The risk of venous thromboembolism continues for 4 to 6 weeks 
after discontinuing combined oral contraception.  The efficacy of contraceptive steroids may be 
reduced during co-treatment with dexamethasone. 
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of 
infection at the time of insertion and irregular vaginal bleeding.  Prophylactic antibiotics should 
be considered particularly in patients with neutropenia.  
 
Pregnancy testing 
Medically supervised pregnancy tests with a minimum sensitivity of 50 mIU/mL must be 
performed for females of childbearing potential, including females of childbearing potential who 
commit to complete abstinence, as outlined below. 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
D-5 
Before starting study drug 
Female Patients:  
FCBP must have two negative pregnancy tests (minimum sensitivity of 50mIU/mL) prior to 
starting study drug.  The first pregnancy test must be performed within 10 to 14 days prior to the 
start of study drug and the second pregnancy test must be performed within 24 hours prior to the 
start of study drug (prescriptions must be filled within 7 days as required by the Revlimid REMS®  
program).  The patient may not receive study drug until the study doctor has verified that the results 
of these pregnancy tests are negative. 
Male Patients: 
Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant 
female or a female of childbearing potential while participating in the study, during dose 
interruptions and for at least 28 days following study drug discontinuation, even if he has 
undergone a successful vasectomy.   
 
During study participation and for 28 days following study drug discontinuation  
Female Patients: 
• FCBP with regular or no menstrual cycles must agree to have pregnancy tests weekly for 
the first 28 days of study participation and then every 28 days while on study, at study 
discontinuation, and at day 28 following study drug discontinuation.  If menstrual cycles 
are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 
14 days while on study, at study discontinuation, and at days 14 and 28 following study 
drug discontinuation.   
• At each visit, the Investigator must confirm with the FCBP that she is continuing to use 
two reliable methods of birth control.   
• Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted at a minimum of every 28 days.  
• If pregnancy or a positive pregnancy test does occur in a study patient, study drug must be 
immediately discontinued. 
• Pregnancy testing and counseling must be performed if a patient misses her period or if her 
pregnancy test or her menstrual bleeding is abnormal.  Study treatment must be 
discontinued during this evaluation. 
• Females must agree to abstain from breastfeeding during study participation and for at least 
28 days after study drug discontinuation. 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
D-6 
Male Patients: 
• Counseling about the requirement for complete abstinence or condom use during sexual 
contact with a pregnant female or a female of childbearing potential and the potential risks 
of fetal exposure to lenalidomide must be conducted at a minimum of every 28 days.   
• If pregnancy or a positive pregnancy test does occur in the partner of a male study patient 
during study participation, the investigator must be notified immediately. 
Additional precautions 
• Patients should be instructed never to give this medicinal product to another person and to 
return any unused capsules to the study doctor at the end of treatment. 
• Female patients should not donate blood during treatment and for at least 28 days following 
discontinuation of lenalidomide. 
• Male patients should not donate blood, semen or sperm during treatment or for at least 28 
days following discontinuation of lenalidomide. 
• Only enough study drug for 28 days or one cycle of therapy (whichever is shorter) may be 
dispensed with each cycle of therapy.  
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
E-1 
APPENDIX E 
 
Revlimid REMS ® PROGRAM  
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
E-2 
APPENDIX E 
 
 
 
Revlimid Overview 
Revlimid REMS® for Study Participants 
 
Revlimid REMS® description:  
A program that allows patients enrolled in authorized clinical trials access to free Revlimid® through 
the Revlimid REMS® program.  
Access to the Revlimid REMS Program:  
1. All physicians must be registered prescribers of Revlimid® in the Revlimid REMS® 
Program All clinical sites must have access to the Revlimid REMS® software to enroll 
patients in the Revlimid REMS® program  
1) Prescriber submits Registration Form via fax or RevAssist® Online (RAO for Revlimid) to 
Celgene Customer Care.  
2) Prescriber is registered within 15 minutes.  
3) Registration confirmation fax is sent to prescriber’s office via fax. (For RAO, the confirmation 
notification is displayed on the screen immediately)  
4) Starter Kit is sent to prescriber’s office (overnight).  The starter kit will contain the following:  
• 
Instructions For Prescribers  
• 
Patient Resource Packs  
• 
Guide to English and Non-English Materials  
• 
Computer software used to generate Patient-Physician Agreement Forms (PPAF)  
 
2. All studies must have an FDA letter of IND exemption or an active IND, active IRB approval 
and Celgene required regulatory documents.  
3. Patients must sign the research specific IRB-approved informed consent and be enrolled 
in a Celgene-approved Medical Affairs clinical trial using Revlimid®  
4. Celgene Customer Care Center must be contacted to confirm if a patient needs to be registered 
by calling 1-888-423-5436 
5. Patients must also sign the appropriate PPAF form and follow all the procedures of the 
Revlimid REMS® Program   
1) Patient and Prescriber complete the PPAF together. 
2) The form is faxed to Celgene Customer Care or submitted electronically through RAO. 
3) Patient is registered within 15 minutes.  
4) Confirmation fax is sent to prescribing office notifying them that the patient is now 
registered. For RAO, the confirmation notification is displayed on the screen 
immediately.  
6.  Patients and prescribers must take the phone surveys as required by the Revlimid REMS® 
Program (The PPAF generated for the patient determines which phone survey questions 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
E-3 
will be asked.)  An authorization number is provided at the completion of the phone 
survey, the authorization number should be noted on the prescription form.  
Patient Survey requirements: 
• 
For men: Do not need to call Celgene the first month but must call monthly starting the 
second month. 
• 
For females of non - child bearing potential: Must call for the first month and then call 
every 6 months after. 
• 
For females of child bearing potential: Must call for the first month and then every month 
after. 
 
Prescribing Revlimid® in the Revlimid REMS® program  
• 
Celgene Medical Affairs Operations will activate the study with Biologics upon receipt of all 
required regulatory documents.   
• 
Biologics will not dispense or ship Revlimid® prior to Celgene’s notification of activation.  
• 
Prescription information MUST BE entered using the BMT CTN 1401 Revlimid REMS® 
study specific electronic prescription form.  This form can be found on the BMT CTN 
SharePoint website (https://bmtctnsp.net) 
• 
An authorization number must be on the prescription form at the time of faxing.  
• 
Prescriptions for Revlimid® must be sent to Biologics Clinical Trial Division at the following 
FAX number: 919-256-0794  
• 
Only a 28-day supply of Revlimid® may be provided per cycle sent to the actual address noted 
on the Revlimid REMS® electronic study specific prescription form.  
• 
Biologics will verify the authorization number and complete the patient counseling.  
 
Protocol compliance and drug return  
• 
Patients will be required to return unused drug to the study site for destruction per institutional 
guidelines.  
• 
Sites may request that patients maintain a diary and/or to bring their bottles in for a pill count 
at each visit in order to review “patient compliance.”  
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
E-4 
IMPORTANT INFORMATION ABOUT Revlimid REMS®  
 
 
 
 
 
 
 
How to Fill a REVLIMID® (lenalidomide) Prescription  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
To avoid fetal exposure REVLIMID®(lenalidomide) is only available under a special restricted distribution program 
called Revlimid REMS® 
• 
Only prescribers registered with Revlimid REMS®  can prescribe REVLIMID®(lenalidomide) 
• 
Only Revlimid REMS® contract pharmacies can dispense REVLIMID®(lenalidomide) 
• 
In order to receive REVLIMID® (lenalidomide), patients must enroll in Revlimid REMS® and agree to comply with 
the requirements of the Revlimid REMS®  program 
• 
Information about REVLIMID®(lenalidomide) and the Revlimid REMS® program can be obtained by calling the 
Celgene Customer Care Center toll-free at 1-888-423-5436, or at www. REVLIMID.com 
1. 
Healthcare provider (HCP) instructs patient to complete patient survey  
2. 
HCP completes survey  
3. 
HCP completes patient prescription form  
4. 
HCP obtains Revlimid REMS® authorization number  
5. 
HCP provides authorization number on patient prescription form  
6. 
HCP faxes form, including prescription  
7. 
HCP advises patient that a representative from a Revlimid REMS® contract pharmacy will contact them  
8. 
Revlimid REMS® contract pharmacy conducts patient education  
9. 
Revlimid REMS®contract pharmacy calls for confirmation number  
10. 
 Revlimid REMS®contract pharmacy ships REVLIMID® with the FDA-approved MEDICATION GUIDE  
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
F-1 
APPENDIX F 
 
HUMAN SUBJECTS 
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
F-2 
APPENDIX F  
 
HUMAN SUBJECTS 
 
1. Subject Consent 
 
A conference will be held with the patient, donor and family to discuss this study and alternative 
treatments available for the treatment of multiple myeloma.  The conference will be conducted by 
the Principal Investigator or other designated physician.  Potential risks associated with the study 
interventions should be discussed as objectively as possible.  Consent will be obtained using an 
IRB-approved consent. 
 
The BMT CTN will provide a template of the consent form to each center.  Each center will 
customize the template according to their local requirements and submit it for review by the local 
Internal Review Board (IRB).  The DCC will verify the adequacy of the consent forms prior to 
submission to the IRB.  Each center must provide evidence of IRB approval. 
. 
 
2. Confidentiality 
 
Confidentiality will be maintained by individual names being masked and assigned a patient 
identifier code.  The code relaying the patient’s identity with the ID code will be kept separately 
at the center.  The ID code will be transmitted to the network. 
 
 
3. Participation of Women and Minorities and Other Populations 
 
Women and ethnic minorities and other populations will be included in this study.  Accrual of 
women and minorities at each center will be monitored to determine whether their rates of 
enrollment are reflective of the distribution of potentially eligible women and minorities expected 
from data reported to the CIBMTR and from published data on incidence of MM in these groups.  
Centers will be notified if their rates differ significantly from those expected and asked to develop 
appropriate recruitment strategies. 
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
G-1 
 
APPENDIX G 
 
KARNOFSKY PERFORMANCE STATUS SCALE 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
G-2 
APPENDIX G 
 
KARNOFSKY PERFORMANCE STATUS SCALE 
 
 
Index 
Specific Criteria 
General 
100 
Normal, no complaints, no 
evidence of disease. 
 
Able to carry on normal activity; no special 
care needed. 
90 
Able to carry on normal activity, 
minor signs or symptoms of 
disease. 
80 
Normal activity with effort, some 
signs or symptoms of disease. 
70 
Care for self, unable to carry on 
normal activity or to do work. 
Unable to work, able to live at home and care 
for most personal needs, varying amount of 
assistance needed. 
60 
Requires occasional assistance 
from others but able to care for 
most needs. 
50 
Requires considerable assistance 
from others and frequent medical 
care 
40 
Disabled, requires special care 
and assistance. 
Unable to care for self, requires institutional 
or hospital care or equivalent, disease may be 
rapidly progressing. 
 
30 
Severely disabled, hospitalization 
indicated, but death not 
imminent. 
20 
Very sick, hospitalization 
necessary, active supportive 
treatment necessary. 
10 
Moribund 
0 
Dead 
 
 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
H-1 
APPENDIX H 
 
NEW YORK HEART ASSOCIATION (NYHA) 
CLASSIFICATION OF CARDIAC DISEASE 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
H-2 
APPENDIX H 
 
NEW YORK HEART ASSOCIATION (NYHA) 
CLASSIFICATION OF CARDIAC DISEASE 
 
The following table presents the NYHA classification of cardiac disease.  
 
Class 
Functional Capacity 
Objective Assessment 
I 
Patients with cardiac disease but without resulting limitations of 
physical activity.  Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea, or anginal pain. 
No objective evidence 
of cardiovascular 
disease. 
II 
Patients with cardiac disease resulting in slight limitation of physical 
activity.  They are comfortable at rest.  Ordinary physical activity 
results in fatigue, palpitation, dyspnea, or anginal pain. 
Objective evidence of 
minimal 
cardiovascular disease. 
III 
Patients with cardiac disease resulting in marked limitation of 
physical activity.  They are comfortable at rest.  Less than ordinary 
activity causes fatigue, palpitation, dyspnea, or anginal pain. 
Objective evidence of 
moderately severe 
cardiovascular disease. 
IV 
Patients with cardiac disease resulting in inability to carry on any 
physical activity without discomfort.  Symptoms of heart failure or 
the anginal syndrome may be present even at rest.  If any physical 
activity is undertaken, discomfort is increased. 
Objective evidence of 
severe cardiovascular 
disease. 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
I-1 
APPENDIX I 
 
ADVERSE EVENTS 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
I-2 
APPENDIX I 
 
ADVERSE EVENTS 
 
 
I.1. Adverse Event Reporting  
Adverse events (AEs) will be collected on calendar-driven forms and event-driven forms in 
AdvantageEDC..   
 
The calendar-driven forms are those that appear in the AdvantageEDC Forms grid for each 
enrolled patient at designated timepoints (e.g. Day 28 post transplant) throughout the course of the 
study. Completion of calendar-driven forms is expected by the target date for the given assessment 
period.  
 
Calendar Driven forms for the BMT CTN 1401 study are as follows:  
• Toxicity Form: this form documents all expected toxicities for the BMT CTN 1401 study; 
each toxicity is also assigned a grade, based on the NCI CTCAE Version 4.0. 
• Follow Up Status Form: this form documents the status of each patient at various intervals 
on the study. 
 
 
Event-driven forms must be completed when a certain event triggers the appearance of the form 
in the AdvantageEDC Forms Grid. Most often the event-driven form is triggered by information 
entered on the Follow-up Status Form. Event-driven forms for the BMT CTN 1401 study are as 
follows: 
• 
Re-Admission/Hospitalization Form: this form documents all hospital admissions, including the 
admission for transplant for this study.  
• 
Infection Form: this form documents infections from Day 0 (date of transplant) through the 1-year 
post-transplant follow-up period.  
• 
Progression/Relapse Form: the form captures detailed information associated with progression or 
relapse of the primary disease. DO NOT report progression or relapse as an Unexpected, Grade 3-
5 Adverse Event. 
• 
Death Form: this form documents the death of a patient from the time of study enrollment and 
randomization through the 1-year post-transplant follow-up period.  
• 
Adverse Event Forms: this series of forms captures details on adverse events that are both 
unexpected and grades 3-5, based on the NCI CTCAE Version 4.0, regardless of attribution to 
any of the study interventions. These forms are also used to collect information on any SAE event 
required by the additional adverse event reporting requirements. These events require expedited 
reporting and will be reviewed by the Medical Monitor associated with the BMT CTN Data and 
Coordinating Center (DCC) within 2 business days of receiving the summary of the adverse event 
from the transplant center. If the Medical Monitor requires additional information to make his/her 
assessment, the transplant center will have 4 business days to respond to the request for additional 
information. 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
I-3 
I.2 Reporting Expected Toxicities  
Expected toxicities for all patients enrolled on BMT CTN 1401 will be collected on the BMT CTN 
1401 Calendar-Driven Toxicity Form and some of the event-driven forms (Infection, 
Readmission/Hospitalization, Progression/Relapse, Graft Failure and Death forms). Any grade 4 
expected event not collected on the calendar-driven toxicity or specified event- driven form must 
be reported through the expedited AE reporting system in AdvantageEDC.  
 
I.3  Reporting Unexpected, Grade 3-5 Adverse Events  
All Unexpected, Grade 3-5 Adverse Events should be reported for every patient enrolled on 
the study from the time of randomization until 3 years post maintenance initiation.  
 
I.4 Reporting Secondary Malignancies 
 
All secondary primary malignancies (SPMs), excluding non-melanoma skin cancers, 
experienced by participants from the time of enrollment until 3 years post maintenance 
initiation will be reported using the Adverse Event forms (AE1-AE6) in AdvantageEDC and 
must be reported within three business days of knowledge of the event.  The Event 
Description of the Adverse Event forms should include histologic type. 
I.5 Reporting Adverse Events from enrollment until randomization  
No adverse event reporting is required from the time of enrollment until randomization. All patient 
deaths, SPMs,  and progressions must still be reported during this time.  
I.6 Reporting Adverse Events after the start of Lenalidomide  
Additional Adverse Event reporting applies to patients who receive lenalidomide. Refer to Chapter 
4 for additional instructions for reporting of Second Primary Malignancies and other special events 
of interest. Determination of the expectedness of adverse events should be differentiated between 
the initial transplant, maintenance, or vaccine therapy at the discretion of the investigator. For 
example, oral mucositis would be an expected risk associated with transplantation, but the 
investigator should assess the expectedness for oral mucositis during maintenance with or without 
vaccine therapy.   
 
 
TABLE I-1: ADVERSE EVENTS FOR BMT CTN 1401 FROM FIRST DOSE OF 
LENALIDOMIDE THROUGH 28 DAYS AFTER LAST DOSE1 BY ORGAN SYSTEM 
 
Adverse Event 
Collection Type 
Collection Form2 
AUDITORY DISORDERS 
Hearing loss 
Calendar-Driven 
Toxicity 
BLOOD AND LYMPHATIC DISORDERS 
Anemia 
Calendar-Driven 
Toxicity  


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
I-4 
Adverse Event 
Collection Type 
Collection Form2 
Disseminated intravascular 
coagulation3 
Event-Driven 
Adverse Event Form 
Febrile neutropenia5 
Event-Driven 
Adverse Event Form 
Lymphopenia 
Calendar-Drive 
Toxicity 
Neutropenia 
Calendar-Driven 
Toxicity  
Thrombocytopenia 
Calendar-Driven 
Toxicity 
Thrombotic thrombocytopenic 
purpura/ Thrombotic 
microangiopathy 
Calendar-Driven 
Toxicity 
CARDIAC DISORDERS 
Asystole3 
Event-Driven 
Adverse Event Form 
Atrial fibrillation3 
Event-Driven 
Adverse Event Form 
Atrial flutter3 
Event-Driven 
Adverse Event Form 
Atrioventricular block3 
Event-Driven 
Adverse Event Form 
Left ventricular systolic dysfunction 
Calendar-Driven 
Toxicity 
Myocardial infarction3 
Event-Driven 
Adverse Event Form 
New or worsening heart failure3 
Event-Driven 
Adverse Event Form 
Pericardial effusion3 
Event-Driven 
Adverse Event Form 
Pericarditis3 
Event-Driven 
Adverse Event Form 
Sinus bradycardia3 
Event-Driven 
Adverse Event Form 
Ventricular arrhythmia 
Calendar-Driven 
Toxicity 
Ventricular tachycardia3 
Event-Driven 
Adverse Event Form 
ENDOCRINE DISORDERS 
Hyperthyroidism3 
Event-Driven 
Adverse Event Form 
Hypothyroidism 
Calendar-Driven 
Toxicity 
GASTROINTESTINAL DISORDERS 
Abdominal pain 
Calendar-Driven 
Toxicity 
Anorexia 
Calendar-Driven 
Toxicity 
Constipation 
Calendar-Driven 
Toxicity 
Diarrhea 
Calendar-Driven 
Toxicity 
Diverticulitis3 
Event-Driven 
Adverse Event Form 
Dry mouth 
Calendar-Driven 
Toxicity 
Dysgeusia (taste alteration) 
Calendar-Driven 
Toxicity 
Dyspepsia (heartburn) 
Calendar-Driven 
Toxicity 
GI perforation3 
Event-Driven 
Adverse Event Form 
Intestinal obstruction3 
Event-Driven 
Adverse Event Form 
Ischemic bowel3 
Event-Driven 
Adverse Event Form 
Nausea 
Calendar-Driven 
Toxicity 
Oral mucositis 
Calendar-Driven 
Toxicity 
Vomiting 
Calendar-Driven 
Toxicity 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
I-5 
Adverse Event 
Collection Type 
Collection Form2 
GENERAL DISORDERS 
Chest pain- non-cardiac 
Calendar-Driven 
Toxicity 
Chills 
Calendar-Driven 
Toxicity 
Edema- generalized 
Calendar-Driven 
Toxicity 
Fatigue 
Calendar-Driven 
Toxicity 
Fever 
Calendar-Driven 
Toxicity 
Sudden death3 
Event-Driven 
Adverse Event Form 
HEPATOBILIARY/PANCREAS DISORDERS 
Abnormal liver function tests 
Calendar-Driven 
Toxicity 
Hepatitis3 
Event-Driven 
Adverse Event Form 
Liver failure3 
Event-Driven 
Adverse Event Form 
Pancreatitis3 
Event-Driven 
Adverse Event Form 
HEMORRHAGIC DISORDERS 
Intracranial3 
Event-Driven 
Adverse Event Form 
Gastrointestinal3 
Event-Driven 
Adverse Event Form 
Genitourinary 
Calendar-Driven 
Toxicity 
Pulmonary/Upper respiratory3 
Event-Driven 
Adverse Event Form 
IMMUNE SYSTEM DISORDERS 
Allergic reaction3 
Event-Driven 
Adverse Event Form 
Anaphylaxis (swelling of the skin 
and/or swelling of the face or 
throat)3 
Event-Driven 
Adverse Event Form 
INFECTIONS 
Infections/ Sepsis 
Event-Driven 
Infection 
INVESTIGATIONS 
Increased ALT > 3.0 x ULN4 
Event-Driven 
Adverse Event Form 
Increased AST > 3.0 x ULN4 
Event-Driven 
Adverse Event Form 
Increased bilirubin > 3.0 x ULN4 
Event-Driven 
Adverse Event Form 
Increased creatinine 
Calendar-Driven 
Toxicity 
Prolongation of QTc interval4 
Event-Driven 
Adverse Event Form 
Weight loss 
Calendar-Driven 
Toxicity 
METABOLISM AND NUTRITION DISORDERS 
Dehydration 
Calendar-Driven 
Toxicity  
Hypercalcemia 
Calendar-Driven 
Toxicity  
Hyperglycemia 
Calendar-Driven 
Toxicity  
Hypoglycemia 
Calendar-Driven 
Toxicity  
Hypokalemia 
Calendar-Driven 
Toxicity  
Hyponatremia 
Calendar-Driven 
Toxicity 
Tumor lysis syndrome3 
Event-Driven 
Adverse Event Form 
MUSCULOSKELETAL AND TISSUE DISORDERS 
Arthralgia 
Calendar-Driven 
Toxicity 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
I-6 
Adverse Event 
Collection Type 
Collection Form2 
Myalgia 
Calendar-Driven 
Toxicity 
Muscle weakness (generalized or 
specific area) 
Calendar-Driven 
Toxicity 
Musculoskeletal pain 
Calendar-Drive 
Toxicity 
NERVOUS SYSTEM DISORDERS 
Anxiety 
Calendar-Driven 
Toxicity 
Ataxia  
Calendar-Driver 
Toxicity 
Confusion 
Calendar-Driven 
Toxicity 
Cranial palsy3 
Event-Driven 
Adverse Event Form 
Depression 
Calendar-Driven 
Toxicity 
Depressed level of consciousness3 
Event-Driven 
Adverse Event Form 
Dizziness 
Calendar-Driven 
Toxicity 
Edema cerebral3 
Event-Driven 
Adverse Event Form 
Encephalopathy3 
Event-Driven 
Adverse Event Form 
Headache 
Calendar-Driven 
Toxicity 
Insomnia 
Calendar-Driven 
Toxicity 
Neuralgia3 
Event-Driven 
Adverse Event Form 
Neuropathy3 
Event-Driven 
Adverse Event Form 
Reversible posterior 
leukoencephalopathy syndrome 
(PRES)3 
Event-Driven 
Adverse Event Form 
Seizure3 
Event-Driven 
Adverse Event Form 
Severe muscle weakness/paralysis3 
Event-Driven 
Adverse Event Form 
Somnolence 
Calendar-Driven 
Toxicity 
Spinal cord compression (non-
malignant)3 
Event-Driven 
Adverse Event Form 
Stroke 
Calendar-Driver 
Toxicity 
Syncope (fainting)3 
Event-Driven 
Adverse Event Form 
Tremor 
Calendar-Drive 
Toxicity 
OCULAR/VISUAL DISORDERS 
Blurred vision3 
Event-Driven 
Adverse Event Form 
Conjunctivitis 
Calendar-Driven 
Toxicity 
Sudden loss of vision3 
Event-Driven 
Adverse Event Form 
RENAL DISORDERS 
Cystitis Non-infective 
Calendar-Driven 
Toxicity 
Acute kidney injury3 
Event-Driven 
Adverse Event Form 
Chronic kidney disease3 
Event-Driven 
Adverse Event Form 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
Adult respiratory distress syndrome3 
Event-Driven 
Adverse Event Form 
Bronchitis 
Calendar-Driven 
Infection 
Bronchopulmonary hemorrhage3 
Event-Driven 
Adverse Event Form 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
I-7 
Adverse Event 
Collection Type 
Collection Form2 
Cough 
Calendar-Driven 
Toxicity 
Dyspnea 
Calendar-Driven 
Toxicity 
Hypoxia 
Calendar-Driven 
Toxicity 
Pleural effusion (non-malignant)3 
Event-Driven 
Adverse Event Form 
Pneumonia 
Calendar-Driven 
Infection 
Pneumonitis3 
Event-Driven 
Adverse Event Form 
Pulmonary Hypertension3 
Event-Driven 
Adverse Event Form 
Sinusitis 
Calendar-Driven 
Toxicity 
Sore throat 
Calendar-Driven 
Toxicity 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
Dry skin 
Calendar-Driven 
Toxicity 
Erythema multiforme3 
Event-Driven 
Adverse Event Form 
Pruritis 
Calendar-Driven 
Toxicity 
Pyoderma gangrenosum3 
Event-Driven 
Adverse Event Form 
Rash 
Calendar-Driven 
Toxicity 
Sweet’s syndrome (acute 
neutrophilic dermatosis)3 
Event-Driven 
Adverse Event Form 
VASCULAR DISORDERS 
Capillary leak syndrome3 
Event-Driven 
Adverse Event Form 
Edema 
Calendar-Driven 
Toxicity 
Hypertension 
Calendar-Drive 
Toxicity 
Hypotension 
Calendar-Driven 
Toxicity 
Thromboembolic event (DVT, 
pulmonary emboli)3 
Event-Driven 
Adverse Event Form 
Vasculitis3 
Event-Driven 
Adverse Event Form 
OTHER 
Pregnancy3 
Event-Driven 
Adverse Event Form 
Secondary malignancies6 
Event-Driven 
Adverse Event Form 
Other unexpected grade 3-5 AE 
Event-Driven 
Adverse Event Form  
1Last dose of lenalidomide refers to the last dose prior to permanent discontinuation of study lenalidomide. 
2The form listed for collection may not be the only form that the toxicity should be reported on, but the lists the 
highest/most expeditious level of reporting.  
3Any AEs that meets one of the criteria of a serious adverse event (SAE) as defined by the 21 CFR (312.32) and occurs 
from the first dose through 28 days after the last dose of lenalidomide, the Adverse Event Forms are required to be 
submitted. 
4Any elevation in AST, ALT or bilirubin > 3.0 times the upper limit of normal (ULN) and occurs from the first dose 
through 28 days after the last dose of lenalidomide, requires completion of the Adverse Event forms regardless of 
whether the event meets one of the seriousness criteria as defined by 21 CFR (312.32). 
5Febrile neutropenia will be collected on the event-driven Infection Form. If febrile neutropenia meets one of the 
criteria of a serious adverse event (SAE) as defined by the 21 CFR (312.32) and occurs from the first dose through 28 
days after the last dose of lenalidomide, the Adverse Event Forms are required to be submitted.  
6 Secondary malignancies will be collected on the adverse event forms at any time from study enrollment through 3 
years post-maintenance. 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
J-1 
APPENDIX J 
 
VCAN ANCILLARY STUDY 


 
J-2 
 
 
 
 
 
 
 
 
VCAN Proteolysis: Investigation of a Potential Novel 
Immune Biomarker in Myeloma 
Version 1.0 
 
Principal Investigator 
Fotis Asimakopoulos, MD, PhD 
 
Co-Principal Investigator 
Binod Dhakal, MD, MS 
 
BMT CTN 1401 Study Co-Chairs and Protocol Officer 
David Avigan, MD, Nina Shah, MD, David Chung, MD, Marcelo Pasquini, MD, MS 
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
J-3 
 
CHAPTER 1 
1 BACKGROUND AND RATIONALE 
1.1 
Background 
Myeloma tumor cells are critically dependent on their interactions with their cellular and non-
cellular microenvironment (the extracellular matrix) in both bone-marrow and extramedullary 
niches (1-5). We have recently focused on the unique interplay between extracellular matrix, 
myeloid and stromal cells in fine-tuning the inflammatory and immune microenvironment of the 
myeloma niche (6). Myeloma progression is characterized by accumulation of the large matrix 
proteoglycan, versican (VCAN) (7). VCAN contributes to myeloma homeostasis through the 
activation of tumor-infiltrating myeloid cells [and resultant production of trophic cytokines, such 
as IL-1β  and IL-6) but also by generating immune privilege (through interference with the 
functionality of antigen-presenting dendritic cells (DC)] (8). By contrast, the regulated proteolysis 
of VCAN by ADAMTS proteases generates fragments (VCAN-matrikines, including versikine) 
with opposing, immunostimulatory activities (9). Thus VCAN proteolysis intensity (and the 
resultant balance between parent, tolerogenic VCAN and its immunogenic fragments) may help 
determine the immunogenicity of the tumor microenvironment. Because efficacy of 
immunotherapies depends on prior cancer-immunity “set points” (10), the VCAN proteolysis 
status may provide a novel predictive immune biomarker. 
With regard to the relevance of the VCAN pathway to BMT CTN 1401’s scientific premise, we 
hypothesize that the more immunogenic marrow microenvironment generated through VCAN 
proteolysis will potentiate the primary effector response generated through CTN1401 vaccination. 
Specifically, we have shown that versikine enhances Batf3-DC differentiation and maturation (IL-
12 production)(6, 9, 11). Batf3-DC are a key DC subset that is essential for tumor antigen cross-
presentation (12) and for efficacy of immunotherapies such as checkpoint inhibition (13). 
Intratumoral Batf3-DC are also critical for the efferent arm of the immune response: Gajewski has 
shown that Batf3-DC in the tumor microenvironment are responsible for T-cell effector 
recruitment through chemokine networks involving CXCL9 and CXCL10 (14). Thus, active 
VCAN proteolysis will be predicted to potentiate effector responses post-ASCT (15). Improved 
infiltration of primary effector cells and enhanced abundance and activation of (versikine-
promoted) Batf3-DC at the tumor site (or, residual disease site) will result in secondary, in situ 
vaccination effects that will amplify the primary effector response. Therefore, patients with active 
VCAN proteolysis in the bone marrow are predicted to be more likely to activate a beneficial 
cancer immunity cycle (16), to generate more robust effector responses and experience better 
clinical outcomes.  
Consistent with this hypothesis, at ASH 2017 we presented data that corroborated a correlation 
between bone marrow VCAN proteolysis and increased CD8+ infiltration and activation post-
ASCT for myeloma (Pagenkopf et al., ASH abstract #1756, ASH Annual Meeting 2017). Our 
findings on the immunoregulatory role of VCAN in myeloma were independently corroborated by 
Bruno Paiva’s group: they demonstrated that VCAN-producing macrophages expand post-
autologous SCT and may be associated with MRD persistence through tolerogenic actions of intact 
VCAN (17).  
 


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
J-4 
CHAPTER 2 
 
2 STUDY DESIGN AND PROCEDURES 
2.1 
Study Overview  
This study is a laboratory ancillary study that will investigate the versican proteolysis status on 
randomized patients for BMT CTN 1401. The study will examine samples provided from 10 
patients on the Lenalidomide/Vaccine/GM-CSF arm and 10 patients on either the Lenalidomide 
alone or the Lenalidomide/GM-CSF arms 
2.2 
Specific Study Aims  
To investigate VCAN proteolysis as a predictive biomarker for dendritic cell (DC) vaccine-based 
immunotherapy post- ASCT for myeloma.  
The study will correlate versican proteolysis status with study-mandated immunological endpoints 
(myeloma-specific T cells). It is hypothesized that versican proteolysis-predominant status will 
predict those patients that meet or exceed the primary immunologic endpoint criteria (expansion 
of myeloma-specific T cells).  
Additionally, the study will correlate versican proteolysis status with the primary and relevant 
secondary clinical endpoints. It is hypothesized that versican proteolysis-predominant status will 
correlate with improved clinical outcomes.  
2.3 
Patient Eligibility  
Patients must meet specified eligibility criteria outlined in section 2.3.1 and 2.3.2 to be registered 
on the study. All questions regarding eligibility criteria should be directed to the protocol 
coordinator at 301-251-1161. 
 
2.3.1 Patient Inclusion Criteria 
1. Patients successfully enrolled in Segment A of BMT CTN 1401  
 
2. Patients eligible for randomization per Patient Eligibility Criteria for Randomization in 
Chapter 2 of BMT CTN 1401  
 
3. Patients with an available core biopsy at time of randomization 
  
2.3.2 Patient Exclusion Criteria  
1. Patients unable or unwilling to provide informed consent for participation on the ancillary 
study  


BMT CLINICAL TRIALS NETWORK 
 
Myeloma Vaccine- 1401  
Version 4.0 dated July 24, 2018  
 
J-5 
2.4 
Study Procedures  
Patients will be consented at the time of randomization.  
Patients who agree to participate in the ancillary study will provide permission for the BMT CTN 
DCC to obtain a portion of the pre-randomization clinical bone marrow biopsy that was collected 
for the BMT CTN 1401 parent trial. Following randomization, 4 slides of paraffin-embedded, 
decalcified bone marrow tissue will be prepared from the core biopsy sample at the clinical site 
and shipped to University of Wisconsin for analysis.  
No additional samples are required for this study.  
2.5 
Patients for whom adequate sample cannot be provided for the planned research study 
analysis will be removed from the study.Data Reporting  
Shipment of the samples will be tracked in GlobalTrace and on the Specimen Acquisition Form in 
AdvantageEDC for all required samples. Detailed procedures regarding specimen collection 
schedules and data entry will be found in the BMT CTN 1401 Research Sample Information Guide 
and the BMT CTN 1401 Forms Guide. 
2.6 
Participant Risks  
Risks of the BMT CTN 1401 procedures are described in the parent clinical trial protocol. There 
are no additional risks associated with this ancillary study.  
2.7 
Study Analysis  
This is a pilot study of a small initial group and all analyses are exploratory. Results from this pilot 
study will inform plans for expansion into larger cohorts. 
 
 


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ANCILLARY STUDY REFERENCES 
 
1. Kawano Y, Moschetta M, Manier S, Glavey S, Gorgun GT, Roccaro AM, Anderson KC, Ghobrial IM. 
Targeting the bone marrow microenvironment in multiple myeloma. Immunol Rev. 2015;263(1):160-72. 
Epub 2014/12/17. doi: 10.1111/imr.12233. PubMed PMID: 25510276. 
2. Lemaire M, Deleu S, De Bruyne E, Van Valckenborgh E, Menu E, Vanderkerken K. The 
microenvironment and molecular biology of the multiple myeloma tumor. Adv Cancer Res. 2011;110:19-
42. Epub 2011/06/28. doi: B978-0-12-386469-7.00002-5 [pii]10.1016/B978-0-12-386469-7.00002-5. 
PubMed PMID: 21704227. 
3. Mitsiades CS, McMillin DW, Klippel S, Hideshima T, Chauhan D, Richardson PG, Munshi NC, Anderson 
KC. The role of the bone marrow microenvironment in the pathophysiology of myeloma and its 
significance in the development of more effective therapies. Hematol Oncol Clin North Am. 
2007;21(6):1007-34, vii-viii. Epub 2007/11/13. doi: S0889-8588(07)00115-3 [pii] 
10.1016/j.hoc.2007.08.007. PubMed PMID: 17996586. 
4. Podar K, Chauhan D, Anderson KC. Bone marrow microenvironment and the identification of new targets 
for myeloma therapy. Leukemia. 2009;23(1):10-24. Epub 2008/10/10. doi: leu2008259 [pii] 
10.1038/leu.2008.259. PubMed PMID: 18843284; PMCID: 3418600. 
5. Ribatti D, Nico B, Vacca A. Importance of the bone marrow microenvironment in inducing the angiogenic 
response in multiple myeloma. Oncogene. 2006;25(31):4257-66. Epub 2006/03/07. doi: 1209456 
[pii]10.1038/sj.onc.1209456. PubMed PMID: 16518413. 
6. Asimakopoulos F, Hope C, Johnson MG, Pagenkopf A, Gromek K, Nagel B. Extracellular matrix and the 
myeloid-in-myeloma compartment: balancing tolerogenic and immunogenic inflammation in the myeloma 
niche. J Leukoc Biol. 2017. doi: 10.1189/jlb.3MR1116-468R. PubMed PMID: 28254840. 
7. Hebron E, Hope C, Kim J, Jensen JL, Flanagan C, Bhatia N, Maroulakou I, Mitsiades C, Miyamoto S, 
Callander N, Hematti P, Asimakopoulos F. MAP3K8 kinase regulates myeloma growth by cell-
autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages. Br 
J Haematol. 2013;160(6):779-84. Epub 2012/12/21. doi: 10.1111/bjh.12175. PubMed PMID: 23252623; 
PMCID: 3594344. 
8. Tang M, Diao J, Gu H, Khatri I, Zhao J, Cattral MS. Toll-like Receptor 2 Activation Promotes Tumor 
Dendritic Cell Dysfunction by Regulating IL-6 and IL-10 Receptor Signaling. Cell Rep. 2015;13(12):2851-
64. doi: 10.1016/j.celrep.2015.11.053. PubMed PMID: 26711349. 
9. Hope C, Foulcer S, Jagodinsky J, Chen SX, Jensen JL, Patel S, Leith C, Maroulakou I, Callander N, 
Miyamoto S, Hematti P, Apte SS, Asimakopoulos F. Immunoregulatory roles of versican proteolysis in the 
myeloma microenvironment. Blood. 2016;128(5):680-5. doi: 10.1182/blood-2016-03-705780. PubMed 
PMID: 27259980. 
10. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 
2017;541(7637):321-30. doi: 10.1038/nature21349. PubMed PMID: 28102259. 
11. Hope C, Emmerich PB, Papadas A, Pagenkopf A, Matkowskyj KA, Van De Hey DR, Payne SN, Clipson 
L, Callander NS, Hematti P, Miyamoto S, Johnson MG, Deming DA, Asimakopoulos F. Versican-Derived 
Matrikines Regulate Batf3-Dendritic Cell Differentiation and Promote T Cell Infiltration in Colorectal 
Cancer. J Immunol. 2017;199(5):1933-41. doi: 10.4049/jimmunol.1700529. PubMed PMID: 28754680; 
PMCID: PMC5568487. 
12. Vanpouille-Box C, Galluzzi L. CD103(+) cells at the forefront of anticancer immunity. Oncoimmunology. 
2017;6(11):e1356154. doi: 10.1080/2162402X.2017.1356154. PubMed PMID: 29147613; PMCID: 
PMC5674943. 
13. Sanchez-Paulete AR, Cueto FJ, Martinez-Lopez M, Labiano S, Morales-Kastresana A, Rodriguez-Ruiz 
ME, Jure-Kunkel M, Azpilikueta A, Aznar MA, Quetglas JI, Sancho D, Melero I. Cancer Immunotherapy 
with Immunomodulatory Anti-CD137 and Anti-PD-1 Monoclonal Antibodies Requires BATF3-Dependent 
Dendritic Cells. Cancer Discov. 2016;6(1):71-9. doi: 10.1158/2159-8290.CD-15-0510. PubMed PMID: 
26493961; PMCID: PMC5036540. 
14. Spranger S, Dai D, Horton B, Gajewski TF. Tumor-Residing Batf3 Dendritic Cells Are Required for 
Effector T Cell Trafficking and Adoptive T Cell Therapy. Cancer Cell. 2017;31(5):711-23 e4. doi: 
10.1016/j.ccell.2017.04.003. PubMed PMID: 28486109. 
15. Chung DJ, Pronschinske KB, Shyer JA, Sharma S, Leung S, Curran SA, Lesokhin AM, Devlin SM, Giralt 
SA, Young JW. T-cell Exhaustion in Multiple Myeloma Relapse after Autotransplant: Optimal Timing of 


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Immunotherapy. Cancer Immunol Res. 2016;4(1):61-71. doi: 10.1158/2326-6066.CIR-15-0055. PubMed 
PMID: 26464015; PMCID: PMC4703436. 
16. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1-
10. doi: 10.1016/j.immuni.2013.07.012. PubMed PMID: 23890059. 
17. Arana P, Zabaleta A, Lasa M, Maiso P, Alignani D, Jelinek T, Segura V, van den Bossche W, Teodosio C, 
Damasceno D, Rodriguez-Otero P, Prosper F, Mateos M-V, Lahuerta JJ, Bladé J, van Dongen JJM, San 
Miguel J, Orfao A, Paiva B. High-Throughput Characterization and New Insight into the Role of Tumor 
Associated Macrophages (TAMs) in Multiple Myeloma (MM). Blood. 2016;128(22):482-. 
18. Hope C, Emmerich PB, Papadas A, Pagenkopf A, Matkowskyj KA, Van De Hey DR, Payne SN, Clipson 
L, Callander NS, Hematti P, Miyamoto S, Johnson MG, Deming DA, Asimakopoulos F. Versican-Derived 
Matrikines Regulate Batf3-Dendritic Cell Differentiation and Promote T Cell Infiltration in Colorectal 
Cancer. J Immunol. 2017. doi: 10.4049/jimmunol.1700529. PubMed PMID: 28754680. 
 


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APPENDIX K 
 
T CELL/MYELOMA GENOMIC SIGNATURE ANCILLARY STUDY  
 


 
K-2 
 
 
 
 
 
 
 
 
 
 
 
 
Characterization of the T cell immune response and 
myeloma genomic signature as predictors of immunologic 
and clinical response 
Version 1.0 
 
Principal Investigator 
David Avigan, MD 
 
Co-Principal Investigator 
Jacalyn Rosenblatt, MD 
 
BMT CTN 1401 Study Co-Chairs and Protocol Officer 
David Avigan, MD, Nina Shah, MD, David Chung, MD, Marcelo Pasquini, MD, MS  
 


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PROTOCOL SYNOPSIS 
 
Characterization of the T cell immune response and myeloma genomic signature as predictors of 
immunologic and clinical response 
 
Study Design: 
This is a laboratory ancillary study to the BMT CTN 1401 parent 
clinical trial. The study will further characterize the T cell 
response to vaccination with respect to targeting of neoantigens, 
assessment of T cell clonality, and characterization of the 
immune landscape via CYTOF analysis.  In addition, genomic 
characterization of immunoregulatory pathways in the myeloma 
cells at baseline and presence of immunoregulatory noncoding 
RNAs will be correlated with immunologic response.  Samples 
will consist of additional bone marrow and peripheral blood 
sampling at the time of collection for other indications outlined 
in the parent protocol.  
 
Primary Objective: 
Determine the impact of therapy on the expansion of T cells 
recognizing tumor associated neo-antigens and compare 
response between patients randomized to the Vaccine/GM-
CSF/Lenalidomide arm and patients randomized to the 
Lenalidomide/GM-CSF or Lenalidomide Alone arms. 
 
Secondary Objective: 
Correlate of neoantigen T cell response with expansion of 
myeloma specific T cell and achievement and maintenance of 
complete remission at 1 year post-transplant, characterize T cell 
clonality and TCR identity following therapy, assess measures of 
the immune landscape and correlated with expansion of myeloma 
specific T cell and achievement and maintenance of complete 
remission at 1 year post-transplant, characterize myeloma cell 
expression of immunoregulatory pathways by genomic analysis 
and correlate with expansion of myeloma specific T cell and 
achievement and maintenance of complete remission at 1 year 
post-transplant, 
to 
characterize 
the 
presence 
of 
immunoregulatory noncoding RNAs and correlate with 
expansion of myeloma specific T cell and achievement and 
maintenance of complete remission at 1 year post-transplant 
 
Eligibility Criteria: 
Eligible patients are patients enrolled on BMT CTN 1401 that are 
eligible to proceed to randomization within the BMT CTN 1401 
protocol specified window. Patients must also have consented to 
provide optional future research samples and have provided a 
bone marrow aspirate for future research at time of enrollment on 


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BMT CTN 1401. Patients must sign the additional research 
sample consent prior to enrollment on this study.  
 
Treatment Description: 
Patients will be consented at time of randomization on the BMT 
CTN 1401 parent trial. Eligible patients will undergo sample 
collections at the following time points:  
 
 
• Randomization: Additional 4mL Bone Marrow Aspirate 
sample, collected at the time of this required bone marrow 
aspirate being performed as part of the primary 1401 trial.   
 
• Prior to Cycles 1, 2, and 4 of Maintenance: Additional 
10mL Peripheral Blood sample, collected at the time of these 
required research blood collections are being performed as 
part of the primary 1401 trial.     
• Prior to Cycle 9 of Maintenance: Additional 4mL Bone 
Marrow Aspirate sample, collated at the time of this required 
bone marrow aspirate being performed as part of the primary 
1401 trial.   
• At time of Disease Progression: 5mL Bone Marrow 
Aspirate collection and 40mL Peripheral Blood collection  
 
Additionally, a portion of the research bone marrow aspirate sample provided to the protocol-
defined lab and/or BMT CTN Biorepository at time of initial 
enrollment on to BMT CTN 1401 will be used for this correlative 
laboratory study.   
Accrual Objective: 
60 patients randomized on BMT CTN 1401 (30 randomized to 
Vaccine/Lenalidomide/GM-CSF and 30 randomized to either 
Lenalidomide/GM-CSF 
or 
Lenalidomide). The 
estimated 
accrual period is 2 years 
 
Accrual Period: 
The estimated accrual period is 2 years.  
 
Study Duration: 
The estimated study duration is 5 years.  
 
 
 


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CHAPTER 1 
 
1. 
BACKGROUND AND RATIONALE  
1.1. Background 
Despite the advances in biologic therapy for Multiple Myeloma (MM), curative outcomes remain 
elusive and patients ultimately experience life threatening disease progression. Tumor 
heterogeneity results in significant plasticity in response to therapy and the emergence of resistant 
clones[1,2]. In a paradigm shift for cancer therapeutics, cellular immunotherapy has emerged as a 
highly promising strategy with the potential to eradicate diverse tumor clones and provide ongoing 
surveillance against disease relapse. Two critical areas of investigation in cellular immunotherapy 
are the development of chimeric antigen receptor (CAR) T cells and cancer vaccines.  
One vital area of investigation is the development of tumor vaccines to elicit the expansion of 
tumor specific effector cells, maintain regulatory mechanism of host immunity to minimize off 
target effects, and develop long term memory response to protect against relapse. Vaccines 
targeting individual antigens have been developed, but clinical efficacy may be limited by the 
inability to target the diversity of tumor clones and the development of antigen negative variants 
as a means of resistance[22, 23].  The group of Avigan and Rosenblatt has developed a promising 
cancer vaccine in which patient derived tumor cells are fused with autologous dendritic cells 
(DCs), presenting a broad array of antigens that capture the heterogeneity of the tumor clonal 
populations. In diverse animal models, vaccination with DC/tumor fusions results in eradication 
of established metastatic disease[24-26]. In phase I clinical studies of patients with hematological 
malignancies and solid tumors, vaccination with DC/tumor fusions was well tolerated, induced the 
expansion of tumor specific T cells, and resulted in disease regression or stabilization in patients 
with advanced disease[27-30].  In a recently reported trial, vaccination of patients with acute 
leukemia with DC/AML fusions following chemotherapy induced durable expansion in the 
peripheral blood and marrow of tumor reactive lymphocytes as defined by recognition of whole 
tumor cells and shared tumor antigens.  The role of neoantigens in driving this response is also 
being explored.  Remarkably, 71% of vaccinated patients demonstrating ongoing remission at 
nearly 5 years of follow up despite a median age of 63.  These results are in stark contrast to 
previously reported outcomes where 4-year survival of patients over the age of 55 approximates 
10%.   
 
The DC/tumor vaccine platform has been studied as a strategy to induce tumor specific immunity 
and disease response in patients with myeloma.  In a phase I trial of patients with advanced MM 
(median of 4 prior lines of therapy) vaccination with DC/MM fusions was feasible, was not 
associated with clinical evidence of autoimmunity or cytokine release syndrome, induced the 10 
fold expansion of CD4 and CD8 myeloma specific T cells, and resulted in prolonged disease 
stabilization in nearly 70% of patients.  In a subsequent study, vaccination of patients with MM 
following autologous transplantation induced the persistent expansion of myeloma specific T cells 
and was associated with the near doubling of patients achieving complete remission between day 
100 and 1 year post-transplant in the absence of other maintenance therapy. Of note, based on its 
immunologic potency and efficacy in targeting post-transplant residual disease in a post-transplant 


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phase II study in MM, the fusion vaccine was chosen for a multicenter randomized trial  (CTN 
1401).  Patients undergoing autologous transplantation are randomized in the post-transplant 
period in a 2:1:1 pattern to one of three arms A) vaccination with DC/MM fusions and GM-CSF 
in conjunction with lenalidomide maintenance; B) lenalidomice maintenance and GM-CSF; c) 
lenalidomide maintenance alone.  Patients undergo tumor cell collection at time of initial 
presenation, standard induction, stem cell mobilization and collection, and high dose melphalan 
with stem cell rescue.  Patients undergo randomization day 56-80 post-transplant.  Patients 
assigned to the vaccine arm undergo leukapheresis, DC generation, and vaccine production.  
Patients begin maintenance therapy day 90-100 post-transplant.   The primary aim of the study is 
to compare the vaccine and nonvaccine arms with respect to patients in CR ata 1 year.  Secondary 
aims of the study include assessment of PFS at 2 years, and post-transplant conversion from PR to 
CR.  Immunologic endpoints include an assessment of the impact of therapy on presence of 
myeloma specific T cells in the peripheral blood and bone marrow.  Serial samples of peripheral 
blood and bone marrow are conducted to provide material or this analysis.  17 leading cancer 
centers who have been trained and validated for vaccine production as a part of an FDA approved 
protocol. This study provides an important precedent demonstrating feasibility and the potential 
for expanding the fusion vaccine platform to a multicenter setting to definitively demonstrate 
vaccine efficacy.  
 
A vital aspect of the design of immunotherapy clinical trials is the development of effective 
platforms to further characterize the nature of the immunologic response, establish assays that 
reflect the effect of therapy on the immunologic milieu, and most, importantly, determine those 
measures that most closely correlate with clinical efficacy.  In addition, the identification of 
biomarkers predictive of immune responsiveness is critical to apply these therapies to the 
appropriate patient subsets.  Personalized cellular therapy offers a unique platform to assess the 
relative contribution of immunologic response to shared as compared to neo-antigens as 
determinative of clinical outcome. While mutational burden has been defined as predictive of 
response to checkpoint inhibition in solid tumor settings, the relevance of neo-antigen burden and 
associated immunologic response has not been well defined for myeloma or in patients following 
vaccine therapy.   
 
In the present accessory study, we will examine the impact of therapy on the functional and 
phenotypic assessment on the T cell repertoire including clonal nature of the T cell response, the 
relative role of shared vs. neoantigens, the functional competence of tumor-specific T cells, and 
the durability of T cell expansion. In addition, we will characterize landscape of the tumor 
microenvironment to identify tumor- and immune-related cell subsets (effector, antigen 
presenting, and accessory cell populations, MM subpopulations) associating with response or 
resistance to the different immunotherapies. We will utilize whole genome sequencing (WGS) and 
RNA seq analysis to further interrogate the impact of tumor immunobiology, patterns of T cell 
clonality, identification of T cell receptors, and characterization of the immune repertoire on 
response.  In this context, utilizing a platform of 60 microRNAs that impact immune presentation 
and regulation, including miR200c and miR34a, we will determine if levels are predictive of 
immune responsiveness.  
 


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CHAPTER 2 
 
2. STUDY DESIGN 
2.1. Study Overview 
The study is a laboratory ancillary study that will further characterize the nature of the T cell 
response to vaccination and provide for genomic characterization of immunoregulatory aspects of 
the tumor and microenvironment. These assessments will occur with tumor cells acquired at time 
of study entry, immune cells obtained from bone marrow prior to maintenance therapy and cycle 
9; T cells obtained from peripheral blood prior to cycles 1, 2, 4 and at time of disease progression 
(if applicable); and characterization of the immune landscape from peripheral blood obtained prior 
to cycle 5 of maintenance.  Each of the blood and bone marrow samples are being obtained at an 
already designated time of bone marrow aspiration or peripheral blood draw in the parent 1401 
protocol. 
2.2.  Hypothesis and Specific Objectives 
2.2.1. Hypothesis 
Evidence of tumor specific immunity as manifested by response to neo-antigens, oligoclonal 
expansion and emergence of tumor directed TCR will be more common with the vaccinated cohort 
and will correlate with expansion of myeloma specific T cells in the blood and achievement and 
maintenance of complete response at 1 year post-transplant. Similarly, genomic analysis of 
myeloma cells and tumor microenvironment will demonstrate a correlation between presence of 
immune activation pathways and microRNA and better response to vaccination.  
2.2.2. Primary Objective  
Determine the impact of therapy on the expansion of T cells recognizing tumor associated neo-
antigens and compare response between the Vaccine/GM-CSF/Lenalidomide arm and patients 
randomized to the Lenalidomide/GM-CSF or Lenalidomide Alone arms.  
2.2.3. Secondary Objectives  
Correlate of neoantigen T cell response with expansion of myeloma specific T cell and 
achievement and maintenance of complete remission at 1 year post-transplant 
Characterize T cell clonality and TCR identity following therapy 
Assess measures of the immune landscape and correlated with expansion of myeloma specific T 
cell and achievement and maintenance of complete remission at 1 year post-transplant 
Characterize myeloma cell expression of immunoregulatory pathways by genomic analysis and 
correlate with expansion of myeloma specific T cell and achievement and maintenance of complete 
remission at 1 year post-transplant 
Characterize the presence of immunoregulatory noncoding RNAs and correlate with expansion of 


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myeloma specific T cell and achievement and maintenance of complete remission at 1 year post-
transplant 
2.3. Patient Eligibility  
Patients must meet specified eligibility criteria outlined in section 2.3.1 and 2.3.2 to be registered 
on the study. All questions regarding eligibility criteria should be directed to the protocol 
coordinator at 301-251-1161. 
 
2.3.1. Patient Inclusion Criteria 
1. Patients successfully enrolled in Segment A of BMT CTN 1401  
 
2. Patients eligible for randomization per Patient Eligibility Criteria for Randomization in 
Chapter 2 of BMT CTN 1401  
 
3. Patients with and available bone marrow aspirate material remaining at the BIDMC 
protocol-defined laboratory and/or BMT CTN Biorepository that was collected at the 
time of initial enrollment on BMT CTN 1401 
  
2.3.2. Patient Exclusion Criteria  
1. Patients unable or unwilling to undergo bone marrow aspiration or peripheral blood 
sampling  
 
2. Patients unable or unwilling to provide informed consent for participation on the ancillary 
study  
2.4. Study Procedures  
Patients who agree to participate in the ancillary study will provide additional blood and bone 
marrow samples during the course of the parent clinical trial as described below. For additional 
information on collection and shipment of the required samples, refer to the BMT CTN 1401 
Research Sample Information Guide.  
2.4.1. Peripheral Blood Collection  
Prior to cycles 1, 2, and 4 of maintenance, 10 mL of peripheral blood will be analyzed for 
Characterization of peripheral blood T cells with respect to clonality, TCR analysis, and 
neoantigen recognition and plasma analysis for immunoregulatory microRNA signature. This 
sample is collected in addition to the correlative study samples collected at these time points for 
the BMT CTN 1401 parent trial.  
At the time of progression, 40 mL of peripheral blood will be analyzed for characterization of 
marrow infiltrating T cells with respect to clonality, TCR analysis quantifying T cell subsets, and 
neoantigen recognition and plasma analysis for immunoregulatory microRNA signature. This 
sample is an additional collection time point for the ancillary study only. Samples at time of disease 
progression should only be collected on patients who have not yet completed their follow up on 
the BMT CTN 1401 parent trial. 


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2.4.2. Bone Marrow Aspirate Collection  
At time of initial tumor collection 4 mL of bone marrow aspirate are stored in the BMT CTN 
Bioprepository for patients that consent to provide samples for future research. These samples will 
be obtained from the biorepository for genomic analysis of tumor cells for immune regulatory 
signature and determination of neoantigen targets. No additional samples are required at this 
timepoint.  
At time of randomization & prior to cycle 9 of maintenance 4 mL of bone marrow aspirate will 
be collected for characterization of marrow infiltrating T cells with respect to clonality, TCR 
analysis quantifying T cell subsets, and neoantigen recognition, assessment of density of antigen 
expression by myeloma cells and subsets of immunoregulatory cells and, plasma analysis for 
immunoregulatory microRNA signature. This sample is collected in addition to the correlative 
study samples collected at these time points for the BMT CTN 1401 parent trial. 
At the time of disease progression 5 mL of bone marrow aspirate will be collected for genomic 
analysis of tumor cells for immune regulatory signature and determination of neoantigen targets, 
characterization of marrow infiltrating T cells with respect to clonality, TCR analysis quantifying 
T cell subsets, and neoantigen recognition, plasma analysis for immunoregulatory microRNA 
signature. This sample is an additional collection time point for the ancillary study only. Samples 
at time of disease progression should only be collected on patients who have not yet completed 
their follow up on the BMT CTN 1401 parent trial.  
2.5. Participant Risks  
Risks of the BMT CTN 1401 procedures are described in the parent clinical trial protocol. This 
ancillary study involves additional sampling of bone marrow and peripheral blood at the time these 
procedures are performed for other indications.   Risks of additional sampling include bruising and 
pain at the site of sample acquisition. 
 
 
 
 


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CHAPTER 3 
 
3. STUDY ENDPOINTS 
3.1. Ancillary Testing 
3.1.1.  Characterization of the immunologic response to the neoantigens 
Bone marrow mononuclear cells will be isolated from aspirate samples obtained at enrollment to 
the parent study (1401) by ficoll density centrifugation and segregated into CD38+ plasma cell 
fraction and CD38- nonmalignant cells. Whole Genome Sequencing (WGS) and RNA sequencing 
will be performed on malignant plasma cell and normal cell fractions tumor samples to characterize 
the tumor associated mutational burden. Putative neoantigens will be identified based on the 
computational algorithms established by Dr. Bhasin. Putative antigens arising from mutational 
events are further evaluated by algorithms predicting proteasome cleavage, transport through TAP 
transporter and MHC affinity. The peptides with a proteasome cleavage site at their C terminal but 
not in the center and with high/moderate TAP binding affinity will be used for MHC binding 
analysis. The MHC binding analysis will be performed using HLAPred (combination of 
Propred/Propred1) and IEDB consensus prediction methods. The peptides that are predicted 
high/moderate binders by both IEDB (IC50 <500nM) and HLAPred (Score > Threshold 3%) 
algorithms will be used for CTL epitope prediction using CTLPred. Candidate immunogenic 
peptides will be synthesized and used as antigens for pulsing autologous antigen presenting cells 
and testing their immunogenic potential in vitro using standard T cell assays.  Peptides will be 
pulsed onto PBMCs collected prior to cycle 1, 2, and 4 of maintenance.  The prevalence of antigen 
specific T cells will be quantified by measuring the percentage of CD4 and CD8 T cells that 
express IFNγ by intracellular FACS analysis.  The potential role of antigenic drift in tumor immune 
escape will be assessed with respect to presence of the identified neo-antigens in samples obtained 
at disease progression.  Immune response to neo-antigens and shared antigens will be compared 
between patients undergoing vaccination and lenalidomide maintenance alone, and who do and do 
not achieve CR following vaccination to correlate response with clinical outcome.  
3.1.2. Assessment of T cell clonality and function 
T cells will be isolated at baseline and following treatment and will be subjected to RNA seq to 
identify patterns of clonality as previously described.  We will perform a computational algorithm 
to extract of TCR repertoires from bulk RNA-Seq data for quantitative analysis.  Single cell 
analysis of cytokine expression will be assessed to further characterize the functional status of T 
cells. 
3.1.3. Characterization of the immune landscape 
The immunologic landscape in the peripheral blood and bone marrow will be interrogated for the 
bone marrow and peripheral blood sample drawn prior to cycle 1 maintenance therapy and prior 
to cycle 9 of maintenance. We will use a quantitative flow cytometry based analysis (QiFiKIT, 
Agilent) to determine the actual antigen density on the surface of MM cells. We will assess specific 
immune and tumor related cellular parameters.  Effector cells will be characterized including CD4+ 
and CD8+ α/β T cells, γ/δ T cells, NK (CD3-CD56+) cells and B cells (CD19). Effector T cells will 


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be further analyzed for the presence and temporal changes in naïve (Tn: CD45RA+,CCR7+) 
effector memory (Tem: CD45RA-CCR7+) central memory (Tcm; CD45RA-CCR7-) and terminally 
differentiated effector T cells (TEMRA; CD45RA+CCR7-) T cell activation markers including 
HLA-DR, CD25, CD69, CD38, CD137, Granzyme B. Regulatory cells including Tregulatory 
(CD25+CD25+CD127dimFoxp3+) B regulatory cells (CD19+CD38+CD24+IL-10+) and Myeloid 
derived Suppressor Cells (MDSC; CD11b+CD33+ CD38+ CD14+ or CD15+) will be quantified as 
well as expression levels of immune checkpoint receptors PD-1, LAG3, TIM-3, CTLA-4, BTLA, 
TIGIT, CD47 and GITR.  MM cells will be isolated from the bone marrow samples by their typical 
markers CD138, CD38, CD56 and analyzed for the potential markers for immune escape (PDL-1 
PDL-2 (ligand PD-1), GAL-9 (ligand TIM3), HVEM ( ligand BTLA), Sirp1a (ligand CD47) and 
CD155 (ligand TIGIT)) and immune resistance (survivin, Xiap1, MCL-1 and NOTCH). 
 
3.1.4. Genomic analysis to assess myeloma associated immunoregulatory pathways and clonal 
evolution 
Malignant plasma cells will be isolated from bone marrow aspirate samples obtained at time of 
enrollment in the parent 1401 study as previously described.   Expression patterns of a previously 
identified panel of immune regulatory pathways will be determined.   Similarly clonal evolution 
as evidenced by mutational pattern will be determined in patients demonstrating evidence of 
disease relapse.  
3.1.5. Noncoding RNAs as predictors of response 
Noncoding RNAs such as microRNAs (miRNA) are critical mediators of oncogenesis and are now 
being investigated as immunoregulatory molecules. We have demonstrated that miR200c and 
miR34a modulate tumor expression of PDL1 and recruitment of MDSCs into the bone marrow 
microenvironment, respectively. Using a panel of 60 miRNA families identified by the Slack lab 
as having immunoregulatory properties, we will examine how their pattern of expression at 
baseline is predictive of subsequent immune and clinical response and how alterations in 
expression correlated with disease progression and immune escape. Serum obtained from bone 
marrow and peripheral blood samples will be assessed using the Abcam Firefly platform to 
quantify levels of the target miRNA families.  
3.2. Definition of Disease Status  
3.2.1. Assessment of Disease Status  
Patient disease status will be assessed per Chapter 3 of the BMT CTN 1401 parent trial.  
3.2.2. Disease Assessment Comparison  
The parent trial will assess the rates of VGPR or better (VGPR, nCR, CR and sCR) responses at 
specific time points in all arms. The ancillary study will perform immunologic and genomic 
analysis to further characterize the immunologic response, immune landscape, and 
immunoregulatory features of the myeloma cells at baseline.  These findings will be compared 
between patients randomized to the Vaccine/GM-CSF/Lenalidomide arm and patients randomized 
to the Lenalidomide/GM-CSF or Lenalidomide Alone arms and will be correlated with 
achievement of CR, maintenance of CR at 1 year and PFS.   


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3.2.3. Progression-Free and Overall Survival  
The event for PFS and OS are defined in the BMT CTN 1401 parent clinical, and the same 
definition is used for the ancillary study.  
 
 
 


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CHAPTER 4 
 
4. PATIENT ENROLLMENT AND EVALUATION 
4.1. Screening and Enrollment Procedures  
Patients meeting eligibility criteria defined in Chapter 2 will be consented prior to Randomization 
on BMT CTN 1401. Patients that are eligible will proceed with randomization on the BMT CTN 
1401 parent trial. The Segment B enrollment form will include a question regarding participation 
on this ancillary study. A separate ancillary study enrollment form is not required. Once the patient 
is randomized on the BMT CTN 1401 parent trial, a schedule of assessments will be generated 
which will include any required data collection for the ancillary study.  
4.2. Patient Evaluations and Assessments  
4.2.1. Data Reporting  
Sample collection will be tracked in GlobalTrace and on the Specimen Acquisition Form in 
AdvantageEDC for all required samples. Detailed procedures regarding specimen collection 
schedules and data entry will be found in the BMT CTN 1401 Research Sample Information Guide 
and the BMT CTN 1401 Forms Guide. 
4.2.2. Adverse Event Reporting  
Any adverse events that may occur as a result of a bone marrow aspiration or peripheral blood 
draw performed as a part of the Ancillary study will be captured through the mechanism specified 
in the parent trial.  
4.2.3. Follow Up Schedule  
4.2.3: FOLLOW UP SCHEDULE  
Study Visit 
Target Day  
Tumor Cell 
Collection1  
No additional sample needed at this 
timepoint2  
Randomization1 
±14 days from date of randomization  
Start of Maintenance1 
Cycle 1 
≤ 33 days prior to initiation of 
maintenance 
Cycle 21 
≤ 3 days prior to Day 1 of Cycle 2 
Cycle 41 
≤ 3 days prior to Day 1 of Cycle 4 
Cycle 91 
≤ 3 days prior to Day 1 of Cycle 9 
Disease Progression4 
≤ 14 days after date of progression 
1Corresponds to existing BMT CTN 1401 Study Visit 
2Sample will be obtained from BMT CTN Biorepository  
3In the case that a sample is collected and then Maintenance therapy is delayed 
more than 14 days, the Prior to Cycle 1 sample should be recollected if 
possible. 
4Corresponds to new study visit for this ancillary study 
 


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4.2.4. Schedule of Assessments  
The sample collection schedule for this ancillary study is outlined below and in Table 4.3.4.  
1. Bone Marrow Aspirate: A bone marrow aspirate will be collected and shipped to the 
BIDMC Lab as outlined below:  
a. Prior to randomization (4mL)   
b. Prior to Cycle 9 of maintenance (4mL)  
c. At the time of disease progression (5mL)  
 
2. Peripheral Blood: A peripheral blood sample will be collected and shipped to the 
BIDMC Lab as outlined below:  
a. Prior to cycles 1, 2, and 4 of maintenance (10mL) 
b. At time of disease progression (40mL) 


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TABLE 4.2.4: Sample Collection Time Points 
Sample Collection 
Tumor Cell 
Collection 
(At 
Enrollment) 
Pre- 
Randomization 
Cycles of maintenance 
Disease 
Progression 
1 
2 
4 
9 
Bone Marrow Aspirate 
X1 
X 
 
 
 
X 
X 
Total Marrow Volume (mL) 
4mL 
4mL 
 
 
 
4mL 
5mL 
Peripheral Blood 
 
 
X 
X 
X 
 
X 
Total Blood Volume (mL) 
 
 
10 mL 
10 mL 
10 mL 
 
40mL 
1 No additional sample required. Sample will be obtained from remaining material at BIDMC lab and/or BMT CTN Biorepository  
 
 
 
 
 


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CHAPTER 5 
 
5. STATISTICAL CONSIDERATIONS 
5.1. Study Design and Objectives  
5.1.1.  Primary Objective  
Determine the impact of therapy on the expansion of T cells recognizing tumor associated neo-
antigens and compare response between patients randomized to the Vaccine/GM-
CSF/Lenalidomide arm and patients randomized to the Lenalidomide/GM-CSF or Lenalidomide 
Alone arms.  
5.1.2. Secondary Objectives  
Correlate of neoantigen T cell response with expansion of myeloma specific T cell and 
achievement and maintenance of complete remission at 1 year post-transplant 
Characterize T cell clonality and TCR identity following therapy 
Assess measures of the immune landscape and correlated with expansion of myeloma specific T 
cell and achievement and maintenance of complete remission at 1 year post-transplant 
Characterize myeloma cell expression of immunoregulatory pathways by genomic analysis and 
correlate with expansion of myeloma specific T cell and achievement and maintenance of complete 
remission at 1 year post-transplant 
Characterize the presence of immunoregulatory noncoding RNAs and correlate with expansion of 
myeloma specific T cell and achievement and maintenance of complete remission at 1 year post-
transplant 
5.2. Sample Size and Power Calculations  
Accrual to this study is limited to patients participating in the BMT CTN 1401 trial. The target 
accrual for this study is 188 patients. Assuming 30% of patients will not proceed to randomization, 
we plan for approximately 66 patients randomized to the vaccine arm and 33 randomized to one 
of two control arms. Based on the prior cooperative group studies, we anticipate approximately 
40% of patients will achieve CR and sCR at 1 year. In the prior phase II study of patients 
undergoing post-transplant vaccination in the absence of lenalidomide maintenance, CR was 
achieved in 29% and 54% of patients at 100 days and 1 year post-transplant respectively. Given 
that we anticipate that lenalidomide maintenance will enhance vaccine efficacy, we will consider 
the experimental arm of vaccine/GM-CSF + maintenance promising if the CR rate at 1 year is 
improved from 40% to 60%. A sample size of 66 patients (132 total) randomized to the vaccine 
arm and the combined no-vaccine arms will have 85% power to detect this improvement in the CR 
rate at 1 year from 40% to 60%, using a two-sample comparison of proportions with a one-sided 
type I error of 10%.  


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5.3. Analysis of the Primary Endpoint  
The Ancillary study will compare the expansion of peripheral blood T cells recognizing neo-
antigens (prior to vaccination to peak treatment levels) in patients receiving the DC/MM fusion 
vaccine as compared to standard maintenance patients. We will quantify neo-antigen specific T 
cells by determining expression of IFNg in response to exposure to neoantigen peptides in samples 
obtained prior to and following study therapy.  We hypothesize that vaccination will result in the 
significant expansion of these T cells in contrast to patients receiving nonvaccine maintenance 
therapy.  Of note, lenalidomide may amplify the presence of the T cell population somewhat via 
nonspecific immune stimulation of tumor specific populations that are observed during post-
transplant lymphopoietic reconstitution.   
The primary endpoint of log 10 peak change in tumor reactive T cells from baseline will be 
compared across the 3 groups using analysis of variance, and if significant then two-sample t-tests 
will be conducted for each pairwise comparison to determine whether the vaccine and nonvaccine 
groups are different from one another. A secondary analysis of peak change in tumor reactive T 
cells will be done by comparing the proportions of patients who experience >10-fold increase in 
IFNγ expression, using a chi-squared test. Myeloma reactive T- cell response profiles over time 
will be compared between the treatment groups using linear mixed models for repeated measures 
data. Peak immune response as well as most recent immune response will be compared between 
those in CR and those not in CR at each assessment, using a two-sample t-test, to assess the 
relationship between immune response and clinical response. Peak and most recent immune 
response will also be considered as time-dependent covariates in a Cox proportional hazards model 
to assess their impact on progression-free survival.  
We will assess whether there is a 2 fold difference in the percentage of the vaccine and nonvaccine 
groups achieving a minimum 10-fold increase of T-cell recognizing neoantigens, keeping power 
= 
85%, 
alpha  
= 
0.10, 
using 
2-sided 
Fisher's 
exact 
test. 
 
For instance, if 3 out of 15 pts (20%) in non-vaccine group have at least 10-fold increase of T-cell 
recognizing  neoantigens", then with 85% power and at alpha = 0.10 we can say vaccine group 
will have 66% of patients that have "at least 10-fold increase of T-cell recognizing  neoantigens" 
and detecting a difference of about 46% (20% vs 66%) between non-vaccine group (n1 = 15) and 
vaccine 
group 
(n2 
= 
30) 
. 
 
Table 5.3: Power = 85%, alpha = 0.10 and 2-sided Fisher exact test, d = at least 2-fold increase 
(post / pre >= 2) of T-cell recognizing neoantigens in non-vaccine group.  
   
S1 
S2 
S3 
S4 
S5 
S6 
S7 
S8 
Vaccine/GM-
CSF/Lenalidomide 
31% 
46% 
57% 
66% 
73% 
78% 
84% 
89% 
Non-Vaccine 
Group1 
d 
= 
0/15 
(0%) 
d=1/15 
(7%) 
d=2/15 
(13%) 
d=3/15 
(20%) 
d=4/15 
(27%) 
d=5/15 
(33%) 
d=6/15 
(40%) 
d=7/15 
(47%) 
1Includes patents randomized to both the Lenalidomide/GM-CSF arm and the Lenalidomide Alone arm.  


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5.4.  Analysis of the Secondary Endpoints  
Additional exploratory analyses will be conducted in a similar fashion to examine a number of 
secondary immunologic endpoints, including: 1) clonality assessment and TCR identification of T 
cells, 2) T cell cytokine expression 3) immune landscape analysis 4) genomic analysis of tumor 
immunoregulatory pathways 5) patterns of immunoregulatory microRNA expression. In each case, 
log transformations will be considered to induce normality, and if still non-normal then 
nonparametric tests will be used. Profiles of these secondary immunologic endpoints will be 
described at each time point for each group using summary statistics and compared between the 
vaccine and non-vaccine groups using mixed models for repeated measures data. The correlation 
between the immune environment measures and the myeloma specific T-cell response will be 
assessed and reported using Spearman rank correlation at each time point.    
Correlation between immune parameters and clinical outcome as measured by achievement and 
maintenance of CR at 1 year and PFS will be similarly determined. After the PFS and CR data is 
analyzed in the parent trial, they will be available for analysis in this ancillary study.  
 
 


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ANCILLARY STUDY REFERNCES  
 
1. Bolli, N., et al., Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat 
Commun, 2014. 5: p. 299 
2. Melchor, L., et al., Single-cell genetic analysis reveals the composition of initiating clones and 
phylogenetic patterns of branching and parallel evolution in myeloma. Leukemia, 2014. 28(8): p. 1705-15. 
3. Uttenthal, B., et al., Wilms' Tumour 1 (WT1) peptide vaccination in patients with acute myeloid leukaemia 
induces  short-lived WT1-specific immune responses. Br J Haematol, 2014. 164(3): p. 366-75.  
4. Kuball, J., et al., Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in 
combination with  MontanideISA51 and CpG7909. Cancer Immunol Immunother, 2011. 60(2): p. 161-71. 
5. Gong, J., et al., Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and 
breast  carcinoma cells. Proc Natl Acad Sci U S A, 2000. 97(6): p. 2715-8. 
6. Avigan, D., Dendritic cell-tumor fusion vaccines for renal cell carcinoma. Clin Cancer Res, 2004. 10(18 Pt 
2): p.  6347S-52S.  
7. Rosenblatt J et al. Individualized vaccination of AML patients in remission is associated with induction of 
antileukemia immunity and prolonged remissions. Sci Transl Med. 2016 Dec 
8. Rosenblatt, J., et al., Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral 
antitumor  immune responses in patients with multiple myeloma. Blood. 117(2): p. 393-402. 19 
9. Rosenblatt, J., et al., Vaccination with dendritic cell/tumor fusions following autologous stem cell 
transplant induces immunologic and clinical responses in multiple myeloma patients. Clin Cancer Res, 
2013. 19(13): p. 3640-8.   
 
 


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APPENDIX L 
 
REFERENCES 
 


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1 Ratta, M. et al. Dendritic cells are functionally defective in multiple myeloma: the role of 
interleukin-6. Blood 100, 230-237 (2002). 
 
2 Sharma, A., Khan, R., Joshi, S., Kumar, L. & Sharma, M. Dysregulation in T helper 1/T helper 
2 cytokine ratios in patients with multiple myeloma. Leuk Lymphoma 51, 920-927, 
doi:10.3109/10428191003699563 (2010). 
 
3 Joshua, D. E., Brown, R. D., Ho, P. J. & Gibson, J. Regulatory T cells and multiple myeloma. 
Clin Lymphoma Myeloma 8, 283-286, doi:10.3816/CLM.2008.n.039 (2008). 
 
4 Beyer, M. et al. In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T 
cells in patients with multiple myeloma. Blood 107, 3940-3949, doi:10.1182/blood-2005-09-
3671 (2006). 
 
5 Prabhala, R. H. et al. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth 
and inhibits immune function in multiple myeloma. Blood 115, 5385-5392, doi:10.1182/blood-
2009-10-246660 (2010). 
 
6 Nielsen, H. et al. Immune dysfunction in multiple myeloma. Reduced natural killer cell activity 
and increased levels of soluble interleukin-2 receptors. APMIS 99, 340-346 (1991). 
 
7 Avigan, D. et al. Fusion cell vaccination of patients with metastatic breast and renal cancer 
induces immunological and clinical responses. Clin Cancer Res 10, 4699-4708 (2004). 
 
8 Gong, J. et al. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic 
cells and breast carcinoma cells. Proc Natl Acad Sci U S A 97, 2715-2718. (2000). 
 
9 Gong, J., Chen, D., Kashiwaba, M. & Kufe, D. Induction of antitumor activity by immunization 
with fusions of dendritic and carcinoma cells. Nat Med 3, 558-561. (1997). 
 
10 Vasir, B. et al. Fusion of dendritic cells with multiple myeloma cells results in maturation and 
enhanced antigen presentation. Br J Haematol 129, 687-700 (2005). 
 
11 Gong, J. et al. Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice 
immunized with fusions of dendritic and carcinoma cells. Proc Natl Acad Sci U S A 95, 6279-
6283. (1998). 
 
12 Gong, J. et al. Immunization against murine multiple myeloma with fusions of dendritic and 
plasmacytoma cells is potentiated by interleukin 12. Blood 99, 2512-2517. (2002). 
 
13 Rosenblatt, J. et al. Vaccination with dendritic cell/tumor fusion cells results in cellular and 
humoral antitumor immune responses in patients with multiple myeloma. Blood 117, 393-402, 
doi:10.1182/blood-2010-04-277137 (2011). 
 
                                                 


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14 Rosenblatt, J. et al. Vaccination with dendritic cell/tumor fusions following autologous stem 
cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin 
Cancer Res 19, 3640-3648, doi:10.1158/1078-0432.CCR-13-0282 (2013). 
 
15 McCarthy, P. L. et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N 
Engl J Med 366, 1770-1781, doi:10.1056/NEJMoa1114083 (2012). 
 
16 Luptakova, K. et al. Lenalidomide enhances anti-myeloma cellular immunity. Cancer 
Immunol Immunother 62, 39-49, doi:10.1007/s00262-012-1308-3 (2013). 
 
17 Davies, F.E. et al, Thalidomide and immunomodulatory derivative augment natural killer cell 
cytotoxicity in multiple myeloma. Blood, 210-216 (2001) 
 
18 WAI, L.E. et al, Distinct roles for the NK cell-activating receptors in mediating interactions 
with dendritic cells and tumor cells. J Immunol, 222-229, doi: 10.4049/jimmunol.1002597 
(2010). 
 
19 BGM Durie et al. International uniform response criteria for multiple myeloma. Leukemia 
(2006) 1-7.