Clinical trial: NCT01675141
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

Maintenance use of lenalidomide is not yet standard of care. In general, after you have completed the initial therapy (also called induction therapy), you may be monitored closely with no therapy (often referred to as "observation") or you may consider maintenance therapy. Instead of being in this study, you have these options:
- Close observation without any treatment
- Getting treatment or care for your cancer without being in a study
- Taking part in another study
- Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite problems and other problems caused by the cancer. It does not treat the cancer directly. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
Please talk to your doctor about these and other options.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 12-C-0192 CONTINUATION: page 9 of 17 pages Risks or Discomforts of Participation What side effects or risks can I expect **from being in this study?**
Clinical trial: NCT01675141
Section: Confidentiality
Subsections: Will Your Medical Information Be Kept Private?

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 National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 12-C-0192 CONTINUATION: page 13 of 17 pages
- National Cancer Institute Institutional Review Board
- Qualified representatives from Celgene, the pharmaceutical company who produces 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.
Clinical trial: NCT01675141
Section: Duration of Study Involvement
Subsections: During The Study

If the exams, tests and procedures show that you can be in the study, and you choose to take part, then you will need the following tests and procedures.  
- Physical exam - Blood work to assess for disease status and biomarkers (immune cells) - Urine collection - Bone marrow biopsy and aspirate to assess the status of your myeloma - Urine or blood pregnancy tests in women of child bearing potential - Bone series (X-rays of all of your bones)  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 12-C-0192 CONTINUATION: page 4 of 17 pages If you agree to donate extra blood, urine and bone marrow aspirate samples, you will be asked to give the following amounts at the time points listed in the Study Chart and the samples will be used for research purposes only.  
- Research blood samples (about 3 tablespoons) - Research urine samples (about 2 ounces) - Research bone marrow aspirate (about 2 teaspoons)
The research blood samples, bone marrow aspirate, and urine are not mandatory. If you agree to provide research samples, they will be stored for use in research studies that may be done in the future. The treatment consists of one drug (lenalidomide) given during 28 day cycles. Lenalidomide tablets will be given from days 1-21 of every 28 day cycle. Treatment cycles will continue until your disease progresses, you develop intolerable side effects or you complete two years of lenalidomide treatment. You will be required to take aspirin or other medication to prevent blood clots while taking lenalidomide.
Clinical trial: NCT01675141
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are The Costs Of Taking Part In This Study?

If you choose to take part in the study, the following will apply, in keeping with the NIH policy:
- You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.  
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.  
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Clinical trial: NCT01675141
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Does This Study Involve? Pregnancy Risk:|Pregnancy Risk - Males:|Hematological Toxicity|Deep Vein Thrombosis (Dvt) And Pulmonary Embolism (Pe)|Second Primary Malignancies (Spm)|Other Risks|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

Lenalidomide is related to thalidomide. Thalidomide is known to cause severe life-threatening human birth defects. Findings from a monkey study indicate that lenalidomide caused birth defects in the offspring of female monkeys who received the drug during pregnancy. If lenalidomide is taken during pregnancy, it may cause birth defects or death of an unborn baby. Females must not become pregnant while taking lenalidomide. You have been informed that the risk of birth defects is unknown. If you are female, you agree not to become pregnant while taking lenalidomide. Lenalidomide is present at very low levels in human semen of healthy men for three days after stopping the drug according to a study. For some men, such as men with kidney problems, lenalidomide may be present in semen for more than three days. Because of the risk of birth defects, all patients taking lenalidomide must read the following statements that apply to them according to gender and menopausal status. For these reasons, lenalidomide is provided to patients under a special distribution program called REMS®. For these reasons, lenalidomide is provided to patients under a special distribution program called **REMS®**. In order to participate in this study you must register into and follow the requirements of the 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. Pregnancy Risk - Females:  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 12-C-0192 CONTINUATION: page 7 of 17 pages If you are a female of childbearing potential*, you will be required to have two negative pregnancy tests: the first test within 10-14 days before lenalidomide is prescribed and the second test within 24 hours before lenalidomide is prescribed.  
You will be required to use TWO reliable forms of birth control, one highly effective method and one additional effective method at the same time or practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) while participating in this study; and 3) for at least 28 days after discontinuation from the study. The following are the acceptable birth control methods:  
Highly Effective Methods
- Intrauterine device (IUD)
- Hormonal (birth control pills, injections, implants)
- Tubal ligation
- Partner's vasectomy
- Additional Effective Methods
- Latex condom
- Diaphragm
- Cervical Cap
You must not breastfeed a baby while you are participating in this study and for at least 28 days after you have been discontinued from the study. Females of childbearing potential 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 discontinuation from the study. 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 discontinuation from the study.  
If you have any reason to suspect you are pregnant, you must IMMEDIATELY stop taking lenalidomide and tell your doctor.

Lenalidomide is detected in trace quantities in human semen according to a study. The risk to the fetus in females of child bearing potential whose male partner is receiving lenalidomide is unknown at this time. For these reasons male patients receiving lenalidomide must use a latex condom during any sexual contact with a pregnant female or with a female of childbearing potential while you are participating in this study and for at least 28 days after stopping therapy, even if you have had a successful vasectomy. You must NEVER donate blood, sperm, or semen while you are participating in this study and for at least 28 days after you have stopped therapy.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 12-C-0192 CONTINUATION: page 8 of 17 pages

Lenalidomide is associated with significant neutropenia (decrease in white blood cells that help fight infection) and thrombocytopenia (decrease in platelets that help with blood clotting). You will have your blood counts checked frequently when starting treatment with lenalidomide.

Lenalidomide has demonstrated an increased risk of deep vein thrombosis (blood clots in larger blood vessels) and pulmonary embolism (a blood clot in or around the lungs) in some people with certain medical conditions. The study staff will ask you about any health conditions you may have that may increase your chance of developing blood clots. The risk of blood clots may also be increased when lenalidomide is combined with other drugs known to cause blood clots such as steroids, other forms of cancer drugs, hormone replacement therapy, birth control pills and erythropoietin (a drug given to help increase the red cell count). You should let your doctor know if you take birth control pills or hormone replacement therapy. You may be asked to take a blood thinner such as aspirin if your doctor feels that you are at increased risk for blood clots. If your platelet count becomes low, the blood thinners may need to be stopped temporarily. You will be instructed on the signs and symptoms of DVT and PE, including shortness of breath, chest pain or swelling of the arm and or leg, and if symptoms of DVT or PE occur you should contact your study doctor, healthcare provider or get emergency medical care promptly.

Higher incidences of SPM were observed in controlled trials of patients with multiple myeloma receiving lenalidomide. Patients with multiple myeloma treated with lenalidomide in studies including melphalan and stem cell transplantation had a higher incidence of second primary malignancies, particularly acute myelogenous leukemia (AML) and Hodgkin lymphoma, compared to patients in the control arms who received similar therapy but did not receive lenalidomide. Your doctor will monitor for the development of second malignancies. You and your doctor should take into account both the potential benefit of lenalidomide and the risk of second primary malignancies when considering treatment with lenalidomide.

Lenalidomide has been shown to increase the level of digoxin in the blood in some patients. Please tell your doctor if you are taking digoxin.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
  
STUDY NUMBER: 12-C-0192 CONTINUATION: page 12 of 17 pages

The aim of this study is to see if this experimental use of lenalidomide will cause your tumors to shrink. We do not know if you will receive personal, medical benefit from taking part in this study. These potential benefits could include shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer. Because there is not much information about the drug's effect on your cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may help others in the future who have cancer.
Clinical trial: NCT01675141
Section: Procedures
Subsections: What Will Happen If You **Take Part In This Research Study?** Before You Begin The Study|Blood Draws:|Bone Marrow Aspiration And Biopsy:|Optional Biopsy

Before you begin the study, if you decide to take part, some procedures and tests will need to be performed to determine if you qualify for the study. Appointments for these tests will be made by your doctor. These tests are part of regular cancer care and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor. You will have:
- History and physical examination - Blood work to assess for disease status and biomarkers (immune cells) - Urine laboratory tests - 24 hour-urine sample may be required (you will be notified if this applies to you). - A bone survey (series of x-rays of all of your bones) - A bone marrow procedure to obtain aspirate and core biopsy is required for the diagnosis of MM and can provide important additional information. We will request that you undergo such a biopsy.  
- Urine or blood pregnancy test
You will be asked if you would like to provide extra research samples of blood, urine and bone marrow aspirate. These studies are optional and will be used to learn more about myeloma. Whenever possible, if you have given permission, these samples will be collected at the same time as the when routine cancer care testing is done. You do not have to give these research samples in order to participate in this trial. You will not have to pay for the costs of collecting and analysis of these research samples. You will be asked at the end of this consent form to indicate your choice about giving additional research samples of blood, urine and bone marrow aspirate.

Side effects of drawing blood include pain and bruising in the area where the blood was drawn, lightheadedness, or rarely fainting due to transient lowering of blood pressure. If you feel dizzy, you should lie down for a few minutes to avoid hurting yourself if you fall. Infection at the blood-drawing site could also occur.

You may feel a pulling sensation and brief discomfort as the marrow is withdrawn and a pressure sensation when the needle is being inserted. The amount of marrow taken is very small and will not change your body's ability to form blood cells. Potential complications of this procedure are local bleeding, pain at the site, and infection. Both of these are very rare. Bleeding can be stopped by applying local pressure and an infection can be treated with antibiotics.

Bone marrow biopsy procedure entails having an area in the back of your hip numbed with a local anesthetic, and a large bone marrow needle inserted into the hipbone. Bone marrow aspirate is obtained, and a core biopsy is obtained. The needle is removed. The risks of the bone marrow procedure include pain, bleeding, infection of the skin or tissues, and allergy to the local anesthetic. You may have some soreness at the site for a day or so after the procedure. You may be asked to sign a separate consent for each of the bone marrow procedures. The biopsy to be performed is exclusively for research purposes and will not benefit you. It might help other people in the future. Even if you sign "yes" to have the biopsy you can change your mind at any time. Please read each sentence below and think about your choice. After reading each sentence, circle and initial the answer that is right for you. The decision to participate in this part of the research is optional, and no matter what you decide to do, it will not affect your care. I agree to have the tumor biopsy for the research tests in this study. Yes No Initials_________
Clinical trial: NCT01675141
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Description Of Research Study

Multiple Myeloma (MM) is rarely curable, but it is treatable. Initial therapy (also known as induction therapy) directed at controlling symptoms and reducing the myeloma cells, is generally continued until the response reaches a plateau. At that time the individual may be monitored closely with no therapy (often referred to as 'observation') or the individual may consider the use PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY
- Adult Patient or - Parent, for Minor Patient NIH-2514-1 (07-09) P.A.: 09-25-0099 File in Section 4: Protocol Consent (1)
STUDY NUMBER: 12-C-0192 CONTINUATION: page 2 of 17 pages of maintenance therapy. The maintenance therapy is given to try to extend the response achieved by induction therapy for as long as possible. Research is showing that lenalidomide maintenance therapy may delay the time for myeloma cells to start to grow and possibly improve survival. Lenalidomide is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that support tumor growth. It may reduce or prevent the growth of cancer cells. The primary purpose of the current study is to evaluate the long-term effect of lenalidomide on immune cells, when given alone. This study will also look at the effects of extended treatment on your MM and your own immune system. Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of MM in combination with dexamethasone. However, the use of lenalidomide as a single agent after induction therapy is still considered experimental.

We will test your MM response status before you enter into the study. If the disease is stable or responsive after the most recent therapy, you will receive maintenance treatment with the study drug lenalidomide. During this maintenance treatment, you will receive lenalidomide every day for 21 days of repeated 28 day cycles. You may continue to receive lenalidomide until we determine your disease has progressed, you develop intolerable side effects or you complete two years of lenalidomide treatment. At periodic time points while you are receiving lenalidomide, you will be required to provide blood samples to assess for immune cells (NK, NKT, and T cells).  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 12-C-0192 CONTINUATION: page 3 of 17 pages
Clinical trial: NCT01675141
Section: Withdrawal from Study
Subsections: When You Are Finished Taking The Drugs (Treatment)|Stopping Therapy

After you complete the treatment portion of the study, you may be asked to return to the Clinical Center for follow-up visits every 3-6 months for as long as you are participating in the study. Follow-up visits will be optional and consist of routine labs and clinic visit with history and physical exam. If your disease comes back or worsens, we may ask you to have optional research blood, urine, or bone marrow biopsy. You may have follow up visits at more frequent intervals if your doctors and the study team feel it is needed.

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 comes back during treatment
- if you have side effects from the treatment that your doctor thinks are too severe
- if new information shows that another treatment would be better for you
In this case, you will be informed of the reason therapy is being stopped. 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 regular 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 Celgene or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases cannot be recalled and destroyed.