Clinical trial: NCT03910439
Section: Alternatives
Subsections: What Are The Benefits Of Being In The Study?|What Other Options Are There For You?

You might not benefit from being in this study. However, the potential benefits to you might be the shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer.

Before you decide whether or not to be in this study, we will discuss other options that are available to you. Instead of being in this study, you could:  
choose to be treated with surgery, radiation or with drugs without being in a study; these or may not include treatments already approved by the FDA for your disease choose to take part in a different study, if one is available choose not to be treated for cancer but you may want to receive comfort care to relieve symptoms.  
You should discuss with your doctor your other choices and their risks and benefits.
Clinical trial: NCT03910439
Section: Confidentiality
Subsections: Confidentiality Protections Provided In This Study|Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality|Privacy Act

Some of your health information, and/or information about your specimen, from this study will be kept in a central database for research. Your name or contact information will not be put in the database. Your test results will be identified by a unique code and the list that links the code to your name will be kept separate from your sample and health information. Your information may be given out if required by law. For example, certain states require doctors to report to health boards if they find a disease like tuberculosis. However, the researchers will do their best to make sure that any information that is released will not identify you.

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
The NIH and other government agencies, like the Food and Drug Administration (FDA),
which are involved in keeping research safe for people.  
National Institutes of Health Intramural Institutional Review Board Qualified representatives from EMD Serono, Inc., the pharmaceutical company who produces avelumab.  
When results of an NIH research study are reported in medical journals or at scientific meetings, the people who take part are not named and identified. In most cases, the NIH will not release any information about your research involvement without your written permission. However, if you sign a release of information form, for example, for an insurance company, the NIH will give the insurance company information from your medical record. This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance. If we share your specimens or data with other researchers, in most circumstances we will remove your identifiers before sharing your specimens or data. You should be aware that there is a slight possibility that someone could figure out the information is about you. Further, the information collected for this study is protected by NIH under a Certificate of Confidentiality and the Privacy Act.

To help us protect your privacy, the NIH Intramural Program has received a Certificate of Confidentiality (Certificate). With this certificate, researchers may not release or use data or information about you except in certain circumstances. NIH researchers must not share information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a court. The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used for auditing or program evaluation internally by the NIH; or 2. is required to be disclosed by Federal, State, or local laws, for example, when information must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA);
3. is for other research; 4. is disclosed with your consent.
The Certificate does not prevent you from voluntarily releasing information about yourself or your involvement in this research. The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or others including, for example, child abuse and neglect, and by signing below you consent to those  
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disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice and Acknowledgement of Information Practices consent.

The Federal Privacy Act generally protects the confidentiality of your NIH medical information that we collect under the authority of the Public Health Service Act. In some cases, the Privacy Act protections differ from the Certificate of Confidentiality. For example, sometimes the Privacy Act allows release of information from your record without your permission, for example, if it is requested by Congress. Information may also be released for certain research purposes with due consideration and protection, to those engaged by the agency for research purposes, to certain federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is involved in a lawsuit. However, NIH will only release information from your medical record if it is permitted by both the Certificate of Confidentiality and the Privacy Act.
Clinical trial: NCT03910439
Section: Duration of Study Involvement
Subsections: During The Study|How Long Will The Study Take?|How Long Will Your Specimens And Data Be Stored By The Nih?

Testing (screening) will have been performed under another consent or another protocol to determine whether you are eligible to take part in this study. If the screening tests show that you are eligible to take part, you may then receive treatment for research purposes. All participants will receive the same treatment on study. Avelumab will be administered to you through an IV (intravenous catheter, a small plastic tube that is put into a vein, usually in your arm) once every 2 weeks (on days 1 and 15) of every cycle. Radiation treatment will be administered to you only for 5 days during Cycle 2. After you complete 5 days of radiation treatment, you may continue treatment with avelumab alone unless your disease gets worse or you have unacceptable side effects. We will give you standard premedications before the avelumab infusions. These may include acetaminophen (Tylenol), nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen), an antihistamine (Benadryl), and in some cases histamine-2 blockers (Zantac). These are given to help prevent infusion related side effects. Your study doctor or a member of the study staff can explain these to you in more detail. You will also be asked to stay at the clinic for about 30 minutes after receiving avelumab for monitoring. Similar to the tests done at the beginning of the study, the following will be repeated during the study to see how you are doing and how the cancer may be responding to treatment:  
Review of medical history, and a physical exam (check weight and vitals), including obtaining information about how you function in your daily activities, side effects and symptoms, and review of medications Routine blood and urine tests Bone marrow testing and imaging:
o Bone marrow aspiration/biopsy will be done around day 15 of cycle 2 (after radiation treatment). This may also be repeated if needed to assess your response to treatment.  
o Imaging assessments:
You will have a [18F]-FDG PET/CT scan done at baseline (unless the [18F]-
FDG PET/CT performed at screening was with 28 days prior to starting first dose of avelumab), around day 15 of cycle 2, and one just prior to the end of your treatment. These may be replaced with CT and/or MRI scans.  
The [18F]-FDG PET/CT scans may be replaced with an MRI scan.  
An MRI creates pictures of the inside of your body using strong magnets instead of x-ray energy. At the time of each scan you will be asked to fill out a screening form to verify that it is safe for you to have the scan. You will also be asked to remove any metallic objects you may be wearing (for example, watches, earrings or piercings) and possibly to change into a hospital gown. Then you'll be asked to lie on a narrow bed that will move into the MRI scanner. Once you are comfortable, the table will be moved into the scanner (the scanner is a long, narrow tube that is open at each end). You will need to lie still on the table during the scan which will take about 30 minutes to complete. You will hear normal "hammering" or clicking and squealing noises during the scan. While in the scanner you will be fitted with earplugs or earmuffs to muffle the sound. You will be able to communicate with the technician running the scan the entire time and will be provided an emergency button to squeeze at any time if you decide you want the scan to stop.  
The [18F]-FDG PET/CT scans may be replaced with CT scans. The CT scanner is a doughnut-shaped machine that uses x-rays to create computer pictures showing the inside of your body. During the procedure, you will need to lie still on a table inside the CT machine. The table will move you in and out of the machine during the scan and you will be instructed to hold your breath. The scan itself will only take a few minutes to complete, the entire visit will take about 30 minutes.  
o X-rays will also be done of the sites of the cancer in the bones.  
Research questionnaires about quality of life (PROMIS)

If you agree to take part in this study, your involvement is expected to last for as long as the study treatment benefits you. We will continue to follow you in clinic or by phone, and may perform tests to see how you are doing, about every 3 months for the first year after treatment, and about every 6 months until year 5. We will continue to follow you at least yearly after that if your cancer has not come back, gotten worse, or you have not started any new treatment for your disease. If your cancer has worsened or you start another treatment, you will be contacted about every 3 months (by phone or in clinic if you continue to be seen here) to get information on any new medications, treatments, or procedures you are currently taking or have recently received for your cancer. You will be followed on this study for the rest of your life or until the study is stopped. This study is expected to involve at least 15 visits and may involve more depending upon how long you receive treatment. Visits usually take about 3 hours each, but should not take longer than 8 hours.

Your specimens and data may be stored by the NIH for as long as the study is open. When this study is closed, we may keep the samples for future research indefinitely.
Clinical trial: NCT03910439
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Risks And Discomforts Of Being In The Study?|Risks From Study Therapy Avelumab|Rare, And Serious In 100 People Receiving Avelumab, 3 Or Fewer May Have:|What Are The Risks Of Radiation From Being In The Study? Radiation Therapy|Overall Radiation Risk|Risks Of Other Procedures|What Are The Risks Related To Pregnancy?|Psychological Or Social Risks Associated With Return Of Incidental Or Secondary Findings|Privacy Risks Associated With Return Of Incidental Or Secondary Findings|Protections Against Misuse Of Genetic Information|Risks Of Storage And Sharing Of Specimens And Data

You should talk to your study doctor about any symptoms that you experience while taking part in the study. If you choose to take part in this study, there is a risk that the avelumab and radiation may not be as good as the usual approach for your treating your cancer or condition. You also may have the following discomforts:
Spend more time in the hospital or doctor's office.  
Be asked sensitive or private questions about things you normally do not discuss.  
May not be able to take part in future studies.
Avelumab and radiation therapy used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if changes occur that may affect your health. Here are important points about side effects:
The study doctors do not know who will or will not have side effects.  
Some side effects may go away soon, some may last a long time, and some may never go away.  
Some side effects may make it hard for you to have children.  
Some side effects may be mild. Other side effects may be very serious and even result in death.  
You can ask your study doctor questions about side effects at any time. Here are important ways to make side effects less of a problem:
If you notice or feel anything different, tell your study doctor. He or she can check to see if it is a side effect.  
Your study doctor will work with you to treat your side effects.  
Your study doctor may adjust the study drugs to try to reduce side effects.  
Below we show the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you.

Three types of risks are associated with avelumab: general signs and symptoms, reactions that occur during or following the infusion (infusion-related reactions), and immune side effects. In studies with humans, common and not very common risks and side effects related to avelumab included the following:
Common (In 100 people receiving avelumab, more than 20 and up to 100)
Fatigue (tiredness)
Occasional (In 100 people receiving avelumab, 4 to 20)

Avelumab may cause your immune system to attack normal organs and cause side effects in many parts of the body. These problems may include but are not limited to:  
Heart problems including inflammation and heart failure. Symptoms and signs of heart problem may include: Shortness of breath, swelling of the ankle and body Swelling and redness of the eye Intestinal problems (colitis) that can rarely lead to tears or holes in your intestine. Signs and symptoms of colitis may include: diarrhea or increase in bowel movements, blood in your stools or dark, tarry, sticky stools, severe belly pain or tenderness Liver problems (hepatitis) which can cause liver failure. Signs and symptoms of hepatitis may include: yellowing of your skin or the whites of your eyes, severe nausea or vomiting; drowsiness; pain in the right upper belly A condition with high blood sugar (diabetes) which leads to tiredness, frequent urination or excessive thirst which may require treatment with insulin Problem of the nerves that can cause paralysis. Signs and symptoms may include:
numbness, tingling of hands and feet; weakness of the arms, legs and facial muscle movement Inflammation of the brain (meningitis/encephalitis), which may cause: headache, confusion, sleepiness, seizures, and stiff neck Kidney problems, including nephritis and kidney failure requiring dialysis. Signs of kidney problems may include: decrease in the amount of urine, blood in your urine, ankle swelling Lung problems (pneumonitis and pleural effusion). Symptoms may include: new or worsening cough, chest pain, shortness of breath Myasthenia gravis, a disease that causes weakness in the skeletal muscles that worsens after periods of activity and improves after periods of rest. These muscles are responsible for functions involving breathing and moving parts of the body, including the arms and legs. Please let the study doctor know if you experience one of the following symptoms: weakness of the eye muscles, drooping of one or both eyelids, blurred or double vision, a change in facial expression, difficulty swallowing, shortness of breath, impaired speech, or weakness in the arms, hands, fingers, legs, and neck.
Allergic reactions or reactions in the context with the infusions of avelumab might occur during treatment. Although avelumab is a fully human protein the risk cannot be completely excluded. In general, these reactions are mild to moderate and can be handled with appropriate drugs, but in  
  
very rare cases severe to life-threatening and even fatal reactions might occur, which require advanced cardiac life support. For the prevention of infusion-related adverse effects and possible allergic reactions you will receive a premedication of an antihistamine drug (so-called H1 blocker) and acetaminophen 30 to 60 minutes before every infusion. There is a risk of tumor lysis syndrome due to tumor shrinkage. This complication is caused by the breakdown products of dying cells and includes elevated blood potassium, elevated blood phosphorus, elevated blood uric acid and elevated urine uric acid, low blood calcium, and consequent acute kidney failure. Special risks have been identified in similar trials utilizing drugs that inhibit the PD-1/L1 pathway in multiple myeloma using immunomodulatory drugs (pembrolizumab with lenalidomide or pomalidomide). Recently, an important risk has been identified with the combination of PD-1 inhibitors and immunomodulatory drugs in multiple myeloma. This current study is utilizing a PD-L1 inhibitor without an immunomodulatory drug. Therefore, the below, may not be applicable to the current study but serves only to inform.  
Two clinical trials evaluating KEYTRUDA® (pembrolizumab), a PD-1 inhibitor, in combination with an immunomodulatory agent (either pomalidomide or lenalidomide) in patients with multiple myeloma demonstrated an increased risk of death for patients receiving KEYTRUDA® (pembrolizumab). PD-1 inhibitors and immunomodulatory agents are classes of drugs which are used for the treatment of cancer.  
Keynote-183 was a randomized trial which evaluated pomalidomide and low-dose dexamethasone with or without pembrolizumab in patients with relapsed and refractory multiple myeloma. With the current information, on an average it is estimated that the risk of death in the pembrolizumab treated arm is 1.6 times that of the control arm.  
Keynote-185 was a randomized trial which evaluated lenalidomide and low-dose dexamethasone with or without pembrolizumab in patients with newly diagnosed multiple myeloma. With the current information, on an average it is estimated that Pembrolizumab doubles the risk of death compared to the control arm.  
Description of the causes of death: Some patients in these studies developed fatal, serious side effects, including inflammation of the heart(myocarditis), rash with peeling of skin and/or mucous membranes, heart attack, cardiac arrest, cardiac failure, bleeding of the heart lining, respiratory tract infection, respiratory failure, blood clots in the lungs, sepsis, multiple organ failure, suicide, and sudden death. Some of the causes of death are unknown at this time.  
At this time, it is unknown if the increased risk of death seen in the trials evaluating KEYTRUDA® (pembrolizumab), a PD-1 inhibitor, will be seen in trials of PD-L1 inhibitors (or "other PD1 inhibitors"), as they are different monoclonal antibodies that target the same pathway.  
Though the combination of treatments on this study is different from the studies in which the increased rate of deaths was observed, it is unclear if the agents on this study either alone or in combination may have similar risks.

In general, the radiation therapy you receive on this study can cause the following side effects regardless of the site that is being treated.  
- Tiredness  
- Lowered blood counts
- Skin reddening
- Mild ache at the site that received radiation  
- Nausea, vomiting - Diarrhea - Abdominal pain - Feelings of claustrophobia
- Skin irritation
- Sore throat and trouble swallowing
- Late or delayed side effects (the side effects noted above, but they occur after the radiation has completed)
These side effects tend to go away after the radiation therapy is completed. However, there are some long-term or chronic side effects that primarily affect the small bowel, liver, kidneys, and spinal cord. Many of these side effects take months to years to develop. Rarely, treatment with radiation may also lead to developing other types of cancer, usually years after receiving the treatment. It is possible that you may experience some, all, or none of the side effects described above. It is also possible that your specific treatment may cause some side effects that we cannot anticipate. For that reason, you will be watched closely while you are receiving treatment for any signs that might signal the earliest stage of toxicity so that we can treat them early.  
If any of these side effects occur, you must inform your study doctor immediately.

During a year in this research study, your tumor may be exposed to 5 Gy from radiation therapy, received over the course of 5 days for a total of 25 Gy. You will also receive a much smaller amount of radiation from scans used to plan your treatment and measure your progress. Additionally, tumor biopsies may be done by a specialist using a CT scanner to guide the biopsy needle into the tumor to ensure accuracy. The total scans include FDG-PET/CT scans (or CT scans), skeletal surveys, CT guided biopsies. The amount of radiation from these scans adds minimal additional risk to the higher radiation doses received in the course of treatment. This radiation has been reviewed by the NIH Radiation Safety Committee and deemed appropriate for this study.  
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You may not participate in this study if you are pregnant. If you are capable of becoming pregnant, we will perform a pregnancy test before exposing you to radiation. You must tell us if you may have become pregnant within the previous 14 days because the pregnancy test is unreliable during that time.

Blood draws may cause pain, redness, bruising or infection at the site of the needle stick.  
Rarely some people faint. The study team member may apply numbing cream to the area so that the needle stick won't hurt as much.  
Questionnaires: The questions asked on the questionnaires may make you feel uncomfortable. You are not required to answer questions that you do not want to answer.
Bone Marrow Aspiration and Biopsy: A numbing agent that can cause a stinging or burning sensation may be injected at the site of your bone marrow biopsy. The biopsy needle will go through the skin into the bone and may produce a brief, sharp pain. As the bone marrow liquid is taken from the bone, there may be a brief, sharp pain. Since the inside of the bone cannot be numbed, this procedure may cause some discomfort, however not all patients experience discomfort.  
o Likely: discomfort or pain, redness, swelling, and/or bruising at the site of the needle insertion.  
o Less likely: bleeding from site of the needle insertion. o Rare: significant infection or bleeding from this procedure, allergic reaction to the anesthetic, formation of a scar at the site of needle entry.  
Tumor biopsy: The likely side effects include discomfort or pain, redness, swelling, and/or bruising at the site of the needle insertion. Bleeding from the site of the needle insertion is a less likely risk. Rarely, significant infection or bleeding from this procedure, allergic reaction to the anesthetic, or formation of a scar at the site of needle entry occurs. If you will have sedation with the procedure, these risks will be discussed with you prior to the procedure. You will be asked to sign a separate consent form prior to any biopsy procedure.  
[
18F]-FDG PET/CT scans: There is a chance of developing an allergic reaction from the contrast material, which may cause symptoms ranging from mild itching or a rash to severe difficulty breathing, shock or rarely, death. The contrast material may also cause kidney problems. The study doctors will do a blood test prior to the test to confirm that it is safe you to receive the contrast.  
MRI scans (non DW-MRI): People are at risk for injury from the MRI magnet if they have some kinds of metal in their body. It may be unsafe for you to have an MRI scan if you have pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metal prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, tattoos, an implanted delivery pump, or shrapnel fragments. Welders and metal workers may have small metal fragments in the eye. You will be screened for these conditions before having any MRI scan. If you have a question about metal in your body, you should File in Section 4: Protocol Consent (1) Version Date: 11/20/2020 Page 13 of 22 CC ICF template v. 09.27.19 inform the staff. You will be asked to complete an MRI screening form before each MRI scan you have. In addition, all magnetic objects (like watches, coins, jewelry, and credit cards) must be removed before entering the MRI scan room. People with fear of confined spaces may become anxious during an MRI. Those with back problems may have back pain or discomfort from lying in the scanner. The noise from the scanner is loud enough to damage hearing, especially in people who already have hearing loss. Everyone having a research MRI scan will be fitted with hearing protection. If the hearing protection comes loose during the scan, you should let us know right away.  
There are no known long-term risks of MRI scans. DW-MRI scans: The DW-MRI scan requires you to remain still on your back for approximately 1½ hours. Even though adverse side effects are not anticipated, you should tell the doctors or nurses supervising the scan of any discomfort you experience during the scans.

If you are able to become pregnant, we will ask you to have a pregnancy test before starting this study. You will need to practice an effective form of birth control before starting study treatment, during study treatment, and for 30 days after you finish study treatment (the restricted period). If you become pregnant, there may be unknown risks to the fetus or unborn child, or risks that we did not anticipate. There may be long-term effects of the treatment being studied that could increase the risk of harm to a fetus. You must tell the study doctor if your birth control method fails during the restricted period. If you think or know you have become pregnant during the restricted period, please contact the research team member identified at the top of this document as soon as possible. If you are a sexually active person with a partner able to become pregnant, it is important that your partner not become pregnant during the restricted period. There may be unknown risks to a fetus or risks we did not anticipate. You and your partner must agree to use birth control if you want to take part in this study. If you think your partner has become pregnant during the restricted period, please contact the research team member identified at the top of this document as soon as possible. If you and your partner plan for your partner to become pregnant after the restricted period, please discuss this with the study team.

As part of the research study, it is possible that you could learn that you have genetic risks for another disease or disability. This may be upsetting and, depending on what you learn, might create a need to make challenging decisions about how to respond. Although your genomic information is unique to you, you share some genomic similarities with your children, parents, brothers, sisters, and other blood relatives. Therefore, learning your research results could mean something about your family members and might cause you or your family distress. Before joining the study, it may be beneficial to talk with your family members about whether and how they want you to share your results with them.

Although your genetic information is unique to you, you do share some genetic information with your children, parents, brothers, sisters, and other blood relatives. Consequently, it may be possible that genetic information from them could be used to help identify you. Similarly, it may be possible that genetic information from you could be used to help identify them. Patterns of genetic variation also can be used by law enforcement agencies to identify a person or his/her blood relatives.

This study involves genetic testing on samples. Some genetic information can help predict future health problems of you and your family and this information might be of interest to your employers or insurers. The Genetic Information Nondiscrimination Act (GINA) is a federal law that prohibits plans and health insurers from requesting genetic information or using genetic information. It also prohibits employment discrimination based on your health information. However, GINA does not address discrimination by companies that sell life insurance, disability insurance, or long-term care insurance. GINA also does not protect you against discrimination based on an already-diagnosed condition or disease that has a genetic component.

When we store your specimens and data, we take precautions to protect your information from others that should not have access to it. When we share your specimens and data, we will do everything we can to protect your identity, for example, when appropriate, we remove information that can identify you. Even with the safeguards we put in place, we cannot guarantee that your identity will never become known or someone may gain unauthorized access to your information. New methods may be created in the future that could make it possible to re-identify your specimens and data.
Clinical trial: NCT03910439
Section: Procedures
Subsections: What Will Happen During The Study?

If you decide to take part in this study, you may receive up to five doses of radiation therapy to all or several of the sites in your body where the disease is located. At the same time, you will receive avelumab (an IV infusion). You will receive treatment in cycles (each cycle is 4 week or 28 days long) on an outpatient basis in the NIH Clinical Center. You should not need to be admitted to the hospital unless needed for scheduling reasons, special testing, or your doctor feels that it is in your best interests. For the first cycle, you will receive avelumab alone. During cycle 2 you will receive both avelumab (2 doses each cycle, 2 weeks apart) together with radiation therapy (for five days in a row after the first dose of avelumab). From cycle 3 on, you will receive avelumab alone (2 doses each cycle, 2 weeks apart).
Clinical trial: NCT03910439
Section: Purpose of Research
Subsections: Key Information About This Research|Why Is This Study Being Done?

This consent form describes a research study and is designed to help you decide if you would like to be a part of the research study. You are being asked to take part in a research study at the National Institutes of Health (NIH). This section provides the information we believe is most helpful and important to you in making your decision about participating in this study. Additional information that may help you make a decision can be found in other sections of the document. Taking part in research at the NIH is your choice. You are being asked to take part in this study because you have multiple myeloma that has relapsed (come back) after initial treatment and has spread to other parts of your body (such as your soft tissue or bones). The purpose of this study is to find out if avelumab, when given together with radiation therapy, may help to treat your disease. We also hope to learn if giving these treatments together is safe. Avelumab works to treat cancer by helping your immune system to fight the cancer. Avelumab is considered investigational, which means that it has not been approved by the U.S. Food and Drug Administration (FDA) to treat multiple myeloma. However, the FDA has given us permission to use avelumab in this study. The radiation therapy used in this study is a standard type where a few doses of radiation are delivered to a few of the sites of your tumors. The tumor sites will be chosen by the study doctors based on their size and location in your body. We hope that the way we are giving the radiation in this study will kill cancer cells at the sites of the radiation. We also hope it causes your immune system to kill myeloma cells in other parts of your body with the help of the avelumab. Although the radiation therapy used in this study is standard care, it is not usually given by itself. There are also no other drugs known to work together with radiation therapy for your type of disease. There are other drugs that may be used for your disease, and these can be prescribed by your regular cancer doctor, even if you are not in this study. For example, there are several FDA approved therapies that you may have or have not received that have been associated with clinical benefit in some patients, such as: daratumumab alone or in combination with lenalidomide, bortezomib, or pomalidomide; elotuzumab in combination with lenalidomide; or, panobinostat in combination with bortezomib. You must have been previously treated with and have failed treatment due to your myeloma progressing, not be a candidate for (ineligible), or not be able to tolerate these other therapies. Other drugs your regular cancer doctor may have already tried or could give without being in a study are chemotherapy drugs not FDA approved to treat multiple myeloma, such as melphalan and cyclophosphamide. All of these other drugs have significant side effects including lowering of blood counts, numbness and tingling, nausea and vomiting, diarrhea, skin rashes, hair loss, inflammation of the bladder and lungs, infections, and secondary cancers. If you would prefer other drugs or treatments, you should consider not joining this study. If you decide to join this study, here are some of the most important things that you should know that will happen: - Before you begin the study, we will perform tests to find out whether you are eligible to participate (screening) that will include tests such as: a complete physical examination, blood and urine tests, bone marrow testing and imaging. - If you are eligible to receive treatment, you will receive avelumab. Avelumab is given by infusion (IV) in the NIH Clinical Center every 2 weeks. You will receive avelumab for two (2) doses, then, after the third dose of avelumab, you will receive radiation treatment each day for 5 days only. You may continue to receive avelumab every 2 weeks for as long as you do not have serious side effects and your disease is responding to the treatment. - You may experience side effects from taking part in this study. Some can be mild or very serious, temporary, long-lasting, or permanent, any may include death. Examples of some of the most common side effects that you may have from the avelumab include: tiredness, nausea, diarrhea, decreased appetite, and infusion reactions. Some of the other most common side effects that you may have from the radiation include: skin reddening and irritation, pain at the site(s) of radiation. - You will be seen regularly during the study. You will have clinical, laboratory, and imaging tests to see how you are doing and to assess your disease. We will also collect required samples from you (such as: blood, urine, bone marrow, and tumor biopsies) for both clinical and research purposes. - After the study treatment has ended, we will need to see you at the NIH Clinical Center about 30 days after the last dose. Then, again about every 3-6 months for up to about five (5) years to assess your health and to see how you are doing. If at any time your disease comes back or gets worse, we may continue to contact you by phone to see how you are doing for the rest of your life if you are no longer being seen at the NIH. Just as we do not know what side effects you might have, we cannot know if you may benefit from taking part in this study. If you do not benefit directly, this study and the results from our research may help others in the future. You are free to stop participating in the trial at any time. If you decide to stop, the study doctor may ask you to agree to certain tests to make sure it is safe for you to stop.  
The remaining document will now describe more about the research study. This information should be considered before you make your choice. Members of the study team will talk with you about the information described in this document. Some people have personal, religious, or ethical beliefs that may limit the kinds of medical or research treatments they would want to receive (such as blood transfusions). Take the time needed to ask any questions and discuss this study with NIH staff, and with your family, friends, and personal health care providers. If the individual being asked to participate in this research study is not able to give consent to be in this study, you are being asked to give permission for this person as their decision-maker. The term "you" refers to you as the decision-maker and/or the individual being asked to participate in this research, throughout the remainder of this document.

This is a research study. The purpose of this research study is to see if the study drug avelumab given with radiation therapy may help to treat multiple myeloma. We are asking you to join this research study because you have multiple myeloma that relapsed after initial treatment and has spread to your soft tissues and bones. The FDA has asked us to make sure that you understand that there are a number of different ways to treat multiple myeloma. You should ask your regular cancer doctor to explain to you the different kinds of treatment options for your cancer. If you join this study, your cancer will be treated with a drug that will activate your immune system to fight your cancer and with radiation therapy. Radiation therapy can be prescribed by your regular cancer doctor, even if you are not in this study.
Clinical trial: NCT03910439
Section: Voluntary Participation
Subsections: It Is Your Choice To Take Part In The Study

You may choose not to take part in this study for any reason. If you join this study, you may change your mind and stop participating in the study at any time and for any reason. In either case, you will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you must be taking part in a study or are being considered for a study. If you do choose to leave the study, please inform your study team to ensure a safe withdrawal from the research.
Clinical trial: NCT03910439
Section: Withdrawal from Study
Subsections: When You Are Finished Taking The Treatment|Early Withdrawal From The Study

When you have finished taking the study drugs, you will be asked to return for a safety follow-up visit within about 30 days. At this visit, your will be asked questions about your health, get a physical exam and undergo routine blood and urine tests and research samples. We may also perform evaluations of your cancer (such as blood, urine, or imaging tests). We will follow-up with you again at about 3 months after treatment. If you are unable to return for this visit, we will obtain the information from you by telephone and/or from your outside primary doctor.

Your doctor may decide to stop your therapy for the following reasons:
if he/she believes that it is in your best interest  
if your disease worsens or comes back during treatment if you have side effects from the treatment that your doctor thinks are too severe if you become pregnant
if you need to use medications that are not allowed on this study  
if the avelumab becomes unavailable if new information shows that another treatment would be better for you if you do not follow the study rules if the study is stopped for any reason
In this case, you will be informed of the reason therapy is being stopped. After therapy is stopped, we would like to see you for a safety visit 30 days after your last dose. You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your primary doctor first. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to EMD Serono, Inc. (the pharmaceutical company who produces avelumab), or designated representatives.