Clinical trial: NCT01155583
Section: Alternatives
Subsections: 6. Alternatives To Participation

If you do not take part in this study, you have several alternatives to choose from, including the following that you should discuss with your doctor:  
x Getting treatment or care for your cancer without being in a study such as:
o Chemotherapy o Bone marrow or stem cell transplantation o Radiation therapy o High-dose myeloablative therapy - High-dose chemotherapy o Glucocorticoids like dexamethasone or prednisone with or without lenalidomide o Other anti-myeloma drugs like bortezomib (Velcade®) or thalidomide
(Thalomid®)
x Taking part in another study x Getting no treatment  
x 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, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
You should talk to your doctor about your choices for managing your healthcare needs before you decide if you will take part in this study
Clinical trial: NCT01155583
Section: Confidentiality
Subsections: 9. Privacy And Confidentiality|Authorization To Use Or Disclose (Release) Health Information That Identifies You For A Research Study

This section explains how your medical and health records might be used and disclosed if you agree to participate in this study. If you do not sign this form you will not be able to participate in this study. Every effort will be made to maintain the confidentiality of your study records. Agents of the United States Food and Drug Administration and Celgene Corporation, their agent or designee will be allowed to inspect sections of your medical and research records related to this study. The data from the study may be published; however, you will not be identified by name. In order to obtain lenalidomide free of charge from Celgene, your name, address, phone, date of birth and the fact that you are participating in this trial will be disclosed to Celgene and its agents or vendors that supply lenalidomide and administer the RevAssist® program. By signing this consent form you agree to this disclosure.

If you volunteer to participate in this research, your protected health information (PHI) that identifies you will be used or disclosed to *Frederic Reu, MD, Ehsan Malek, MD and SubInvestigators* and their research staff at Cleveland Clinic and University Hospitals Case Medical Center for the purposes of this research and to Case Western Reserve University for administration. The PHI that we may use or disclose (release) for this research may include your name, address, phone number, date of birth, Social Security number, information from your medical record, lab tests, or certain information relating to your health or condition.. Some of the tests and procedures done solely for this research study may also be placed in your medical record so other doctors know you are in this study. Upon completion of the study, you may have access to the research information that is contained in your medical record. In addition to the investigators and research staff listed above, your PHI may be looked at by other groups involved with the study such as the Cleveland Clinic Institutional Review Board, and the Case Comprehensive Cancer Center Protocol Review and Monitoring Committee. Your PHI may also be used by and/or disclosed (released) to:  
x Study supporter *(Celgene Corporation)*
x **The Food and Drug Administration** x **The Department of Health and Human Services**
x **Your insurance company**
x **The National Committee for Quality Assurance** x **The Cleveland Clinic and/or University Hospitals Case Medical Center**
Once your personal health information is released it may be re-disclosed and no longer protected by privacy laws. Your research information may be used and disclosed indefinitely, but you may stop these uses and disclosures at any time by writing to Frederic Reu, MD, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 or Ehsan Malek, MD at University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, Ohio 44106. Your participation in the research will stop, but any information previously recorded about you cannot be removed from the records and will continue to be used as part of this research. Also, information already disclosed outside the Cleveland Clinic cannot be retrieved. This will not affect your rights to treatment or benefits outside the research study. The Cleveland Clinic and/or University Hospitals will not use your information collected in this study for another research purpose without your written permission; unless the Cleveland Clinic Institutional Review Board (IRB) assures your privacy and confidentiality is protected. The IRB is a committee whose job it is to protect the safety and welfare of research subjects. By signing this informed consent form, you are authorizing such access to your research and medical record information. If you choose not to sign this consent form, you will not be able to participate in this research study. This Authorization does not have an expiration date.
Clinical trial: NCT01155583
Section: Duration of Study Involvement
Subsections: Duration|Long-Term Follow Up:

As long as your myeloma responds you may stay on study. Monitoring for toxicity and efficacy will be weekly during the first four weeks, then monthly for an additional eleven months, then every other month.

All participants will be followed by telephone contact for disease progression and overall survival every 3 months after study discontinuation for up to 3 years from entry.
Clinical trial: NCT01155583
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 4. Risks|Side Effects Of Any Grade Occurring In 10% Or More Of Patients|Serious Side Effects Occurring In 1% Or More Of Patients And Not Listed In Bold Above|Hematological Toxicity|Deep Vein Thrombosis And Pulmonary Embolism|Second New Cancers|Measures That May Be Used If White Blood Cells And/Or Platelets Are Lowered On Therapy|Possible Side Effects Of Blood Draws|Possible Side Effects Of Bone Marrow Aspiration And Biopsy|Radiation Risks (X-Ray/Chest X-Ray/Skeletal Survey):|Pregnancy Risk:|Pregnancy Risk - Males:|8. Research-Related Injury

There is always a risk involved in taking any drugs, but you will be carefully monitored for any problems and you are encouraged to report anything that is bothering you. There may be risks or side effects of the study drugs that are unknown or cannot be predicted at this time. You should not hesitate to report anything that upsets you or may be troubling you to your Study Doctor, even if you do not think it is connected to taking the study drugs. If you have any questions you should contact Dr. Frederic Reu at 216-636-0200 or Dr. Ehsan Malek at 216-844-3951. Everything possible will be done to prevent or reduce any discomfort or risk. You understand that there may be risks and discomforts that are unknown. You may experience all, some or none of these side effects listed. You will be asked to contact your study doctor for any problems or questions that arise at any time during your treatment, so that measures can be started to prevent or decrease serious problems. If, during the course of treatment, your doctor becomes aware of additional toxic or therapeutic effects, your doctor will discuss them with you.

*Side effects considered serious are *bolded.*  
x Fatigue or feeling tired; x Lack or loss of strength; x Problems falling asleep or staying asleep; x **Anemia** or a decrease in red blood cells that can cause tiredness; x **Neutropenia** or a decrease in white blood cells that can make you more prone to infections; x **Thrombocytopenia** or a decrease in platelets which can cause you to bruise or bleed easily; x Constipation or difficulty moving your bowels; x Diarrhea or loose/frequent bowel movements; x Nausea; x Loss of appetite; x **Back pain**;
x Joint pain; x Muscle cramps; x Swelling of the arms and legs; x **Fever**; x Cough; x **Shortness of breath** or difficulty catching your breath; x Upper respiratory infection; x Rash; x Itching and dry skin; x Dizziness; x Headache.

x Fever with neutropenia which is a decrease in white blood cells that help fight infections; x Pulmonary embolism or blood clot in or around the lungs; x Deep vein thrombosis or blood clots in larger blood vessels; x Atrial fibrillation or irregular heartbeat; x Pneumonia or an infection of the lungs; x Sepsis or an infection of the blood; x Dehydration or loss of water from the body, organ or body part, as from illness or lack of fluid; x Kidney failure or inability of the kidneys to remove waste from the body.
The following events have been reported from clinical studies and post-marketing experience:  
x Rare treatment-emergent adverse events of angioedema (an allergic skin disease which includes small areas of swelling involving the skin and/or the lining of the nose, mouth, stomach, and intestines) and serious skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). SJS and TEN are serious allergic skin reactions that begin as a rash in one area and later cover more of the body leading to separation of the top layer of skin (could be body-wide) which have been reported with lenalidomide during commercial use. These events have the potential to result in death. Medical journals have reported patients with allergic skin reaction with thalidomide who also developed the same type of reaction with lenalidomide.  
x Occasional adverse events such as atrial fibrillation (irregular heartbeat), myocardial infarction (heart attack), and congestive heart failure (condition where the heart becomes weak and cannot pump enough blood to the rest of the body) have been reported with the use of lenalidomide from clinical studies and post-marketing.  
x Tumor lysis syndrome (TLS) and tumor flare reaction (TFR) have commonly been observed in patients with Chronic Lymphocytic Leukemia (CLL), and uncommonly in patients with other lymphomas, who were treated with lenalidomide. There have been rare reports of TLS in patients with Multiple Myeloma (MM) treated with lenalidomide, and no reports in patients with Myelodysplastic Syndrome (MDS) treated with lenalidomide. Tumor lysis syndrome is a metabolic complication caused by the break-down products of dying cancer cells. Complications include hyperkalemia (high potassium), hyperphosphatemia (high phosphorus), hyperuricemia and hyperuricosuria (high uric acid in blood and urine), hypocalcemia (low calcium), and consequent acute uric acid nephropathy and acute renal failure (kidney damage). Tumor lysis syndrome can occur with or without treatment of cancer. Tumor flare reaction is a condition that
involves any of the following: increase in size of the cancerous lymph nodes, rash and slight fever.  
x The rare adverse event of rhabdomyolysis has been seen with lenalidomide treatment.  
This is a serious condition involving destruction of skeletal muscle that can lead to kidney damage. Signs and symptoms include dark, red or cola colored urine, muscle tenderness and stiffness, aching (myalgia) or weakness.

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.

According to researchers, patients with cancer have a higher risk for developing a second new cancer when compared to people without cancer. In clinical studies of newly diagnosed multiple myeloma, a higher number of second cancers were reported in patients treated with lenalidomide for a long period of time after induction therapy (treatment as first step to reducing the number of cancer cells) with or without bone marrow transplant than in patients who received placebo for a long period of time after induction therapy with or without bone marrow transplant Placebo treated patients experienced earlier progression of their myeloma in all of these trials and therefore went off study earlier. At this point it is not known if this explains the higher reported rate of secondary cancers in lenalidomide treated patients or if lenalidomide contributed to the development of secondary cancers. Patients should make their doctors aware of their medical history and of any concerns they may have regarding their own increased risk of other cancers.

Myeloma and previous therapy can limit platelet and white blood cell production by your bone marrow. Since both lenalidomide and azacitidine can potentially lower white blood cells and platelets your doctor may advise measures that make their administration safer without reducing their dose until an antimyeloma effect may improve your bone marrow function. Your doctor may advise the use of G-CSF, which helps the bone marrow produce white blood cells, if your white blood cells should drop while receiving azacitidine and / or lenalidomide. G-CSF can cause flu-like side effects that include fever, muscle, and bone aches. Platelet transfusions may be advised by your doctor if your platelets drop with the use of azacitidine and / or lenalidomide and your doctor feels that full doses of azacitidine and lenalidomide give you the best chance for getting the myeloma under control and thereby among other things may restore your bone marrow's ability to produce enough platelets. The risks of platelet transfusions would be discussed with you separately by your doctor. In general they include transfusions reactions which are usually mild and include rashes, fever, rigors, and muscle aches, but extremely rarely they can be severe and life threatening requiring hospital and intensive care unit admission. Other very rare side effects from platelet transfusions with today's blood product quality control are infections with bacteria or viruses.

The risk of blood drawing commonly includes discomfort, pain, redness, swelling, and/or bruising where the blood is taken from your arm. Sometimes bleeding can occur at the place where blood is drawn. Fainting and infection are rare occurrences.

With the bone marrow aspiration and biopsy you may feel a slight burning sensation with the local anesthetic. Pressure may be felt as the needle is inserted into the bone. There is a sharp sucking sensation as the marrow is aspirated, which lasts for only a few moments. There may be some bleeding, swelling, and bruises at the puncture site. More serious risks, such as serious bleeding or infection, are very rare. Bleeding may be stopped with direct pressure and a cool compress to the area as soon as possible to reduce swelling. Do not place ice directly on the skin.

While you are in this research study, chest x-rays and skeletal surveys (x-rays of the bones) may be used to evaluate your disease. The total amount of radiation that you will get from these tests is relatively small and is not likely to be harmful to you or affect your disease.

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 to 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. For this reason, lenalidomide is provided to patients under a special distribution program called **RevAssist®.** In order to participate in this study you must register into and follow the requirements of the RevAssist® 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: 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.  
* For the purposes of this study, a female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months).
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 Additional Effective Methods Hormonal (birth control pills, injections, implants) Diaphragm  
Intrauterine device (IUD) Latex condom Tubal ligation Cervical Cap  
Partner's vasectomy 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.  
Genetic Information Nondiscrimination Act (GINA) A Federal law, called the Genetic Information Nondiscrimination Act (GINA), effective May 21, 2010, generally makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information. This law generally will protect you in the following ways:  
x Health insurance companies and group health plans may not request your genetic information that we get from this research.  
x Health insurance companies and group health plans may not use your genetic information when making decisions regarding your eligibility or premiums.  
x Employers with 15 or more employees may not use your genetic information that we get from this research when making a decision to hire, promote, or fire you or when setting the terms of your employment.
Be aware that this new Federal law does not protect you against genetic discrimination by companies that sell life insurance, disability insurance, or long-term care insurance.

If you experience physical injury or illness as a result of participating in this research study, medical care is available at the Cleveland Clinic or elsewhere; however, the Cleveland Clinic has no plans to provide free care or compensation for lost wages. You are not waiving any legal rights by signing this form.  
If injury occurs as a result of your involvement in this research, medical treatment is available from University Hospitals or another medical facility but you/your medical insurance will be responsible for the cost of this treatment. A research injury is an injury that happens as a result of taking part in this research study. If you are injured by a medical treatment or procedure that you would have received even if you weren't in the study, that is not considered a "research injury". There are no plans for payment of medical expenses or other payments, including lost wages, for any research related injury. To help avoid injury, it is very important to follow all study directions. Further information about research-related injuries is available by contacting the Cleveland Clinic Institutional Review Board at *216-444-2924*.
Clinical trial: NCT01155583
Section: Procedures
Subsections: 3. Study Procedures

You will be asked to take lenalidomide every day on Days 1-21 of each 28-day cycle of therapy and dexamethasone once a week starting on Day 1 of each 28-day cycle (day 1, 8, 15, 22). You will find more information on how to take lenalidomide and dexamethasone on page 12 to 13 under "all patients". You will be given azacitidine by subcutaneous (under the skin) injection once or twice a week starting on Day 1 of each 28-day cycle. The dose of azacitidine and the number of times per week that you receive azacitidine will be determined by how many patients have been treated on the study before you start, and by the side effects seen in the patients treated before you. The first six 28 day cycles consist of combination therapy with azacitidine (Vidaza ®), lenalidomide (Revlimid ®), and dexamethasone, followed by maintenance with lenalidomide (Revlimid ®) alone until your myeloma stops responding. If your physician feels your myeloma would not be sufficiently controlled with lenalidomide (Revlimid ®) alone you may be offered to continue azacitidine (Vidaza ®) and/or dexamethasone beyond six 28 day cycles. Also, if your myeloma progresses while on maintenance therapy with lenalidomide (Revlimid ®), with or without dexamethasone, you may be offered to restart azacitidine (Vidaza ®) and if not already on it, dexamethasone too, if your physician thinks this may again control your myeloma. During the first 4 weeks you will have to come to the Cleveland Clinic and/or University Hospitals Case Medical Center weekly for toxicity evaluation including history, physical, and blood tests. Also, in order to determine if the study is appropriate for your participation and to obtain a new baseline status of your myeloma and of your organs that could possibly be affected by side effects, some tests must be done and you must meet certain criteria.  
These tests will include standard tests and research related tests.  
x Complete Physical Examination (measuring your heart rate, blood pressure, temperature, height, weight, and body surface area, inquire about prescription, over-thecounter medication, vitamins, nutritional supplements, natural and herbal products)
x Serum Chemistry (to check your general body functions) x Complete Blood Count (CBC) (to check your blood count) x Bone marrow biopsy and aspirate (to determine percent plasma cell involvement) x Skeletal survey (to detect any fractures or tumors of the bone; the standard set of X-rays includes X-rays of the skull, entire spine, pelvis, ribs, and legs)
x Electrocardiogram (to check your heart function) x For females of childbearing potential a pregnancy blood test x Thyroid function blood test x Myeloma blood and urine tests (from a 24hour urine collection)
Research related tests:
x Blood sample (three tablespoons) obtained during the routine blood draw x Bone marrow sample (8 teaspoons)
The charts below shows what will happen to you during the first cycle and future treatment cycles. The left-hand column shows the day in the cycle and the right-hand column tells you what to do on that day.  
| Cycle One:                                                                                                               |                                                                                        |                                                                                                                                                                                                                                                                                                                                                                       |
|--------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Day                                                                                                                      | What you do                                                                            |                                                                                                                                                                                                                                                                                                                                                                       |
| Screening- Anytime  within 7 days of  starting study                                                                     | x                                                                                      | Get physical examination, routine blood tests, Thyroid function  blood test, Myeloma blood and urine tests (from a 24hour urine  collection), Electrocardiogram, bone marrow biopsy/aspirate,  skeletal survey, and pregnancy tests for females of childbearing  potential 10 to 14 days before and again within 24 hours before  lenalidomide is prescribed for you. |
| Day 1  (if screening  assessments were  done within 7 days  of Day 1, they do  not need to be  repeated at Study  Day 1) | x                                                                                      | Get physical examination and routine blood tests                                                                                                                                                                                                                                                                                                                      |
| x                                                                                                                        | Bone marrow biopsy/aspirate                                                            |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Thyroid function blood test                                                            |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Myeloma blood and urine tests                                                          |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Pregnancy test for females of childbearing potential every week  for the first 28 days |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Research blood sample                                                                  |                                                                                                                                                                                                                                                                                                                                                                       |
| Day 8                                                                                                                    | x                                                                                      | Get physical examination and routine blood tests                                                                                                                                                                                                                                                                                                                      |
| x                                                                                                                        | Myeloma blood and urine tests                                                          |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Pregnancy test for females of childbearing potential every week  for the first 28 days |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Research blood sample                                                                  |                                                                                                                                                                                                                                                                                                                                                                       |
| Day 15                                                                                                                   | x                                                                                      | Get physical examination and routine blood tests                                                                                                                                                                                                                                                                                                                      |
| x                                                                                                                        | Myeloma blood and urine tests                                                          |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Pregnancy test for females of childbearing potential every week  for the first 28 days |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Research blood sample                                                                  |                                                                                                                                                                                                                                                                                                                                                                       |
| Day 22                                                                                                                   | x                                                                                      | Get physical examination and routine blood tests                                                                                                                                                                                                                                                                                                                      |
| x                                                                                                                        | Myeloma blood and urine tests                                                          |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Pregnancy test for females of childbearing potential every week  for the first 28 days |                                                                                                                                                                                                                                                                                                                                                                       |
| x                                                                                                                        | Research blood sample                                                                  |                                                                                                                                                                                                                                                                                                                                                                       |  
Discontinuation Procedures: Standard tests:  
x Complete Physical Examination (measuring your heart rate, blood pressure,  
temperature, height, weight, and body surface area, inquire about prescription, over-thecounter medication, vitamins, nutritional supplements, natural and herbal products)  
CCF IRB #: CC 902  
| Cycle 2:                                            |                                                                                                                                                                         |                                                  |
|-----------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------|
| Day                                                 | What you do                                                                                                                                                             |                                                  |
| Day 1                                               | x                                                                                                                                                                       | Get physical examination and routine blood tests |
| x                                                   | Bone marrow sample                                                                                                                                                      |                                                  |
| x                                                   | Myeloma blood and urine tests                                                                                                                                           |                                                  |
| x                                                   | Pregnancy test for females of childbearing potential every 28  days if you have regular or no menstrual cycles or every 14  days if you have irregular menstrual cycles |                                                  |
| x                                                   | Research blood sample                                                                                                                                                   |                                                  |
| Cycles 3-6:                                         |                                                                                                                                                                         |                                                  |
| Day                                                 | What you do                                                                                                                                                             |                                                  |
| Day 1                                               | x                                                                                                                                                                       | Get physical examination and routine blood tests |
| x                                                   | Thyroid function test (every 16 weeks)                                                                                                                                  |                                                  |
| x                                                   | Myeloma blood and urine tests                                                                                                                                           |                                                  |
| x                                                   | Pregnancy test for females of childbearing potential every 28  days if you have regular or no menstrual cycles or every 14  days if you have irregular menstrual cycles |                                                  |
| x                                                   | Research blood sample                                                                                                                                                   |                                                  |
| Maintenance Cycles 1-6: (every 2 months thereafter) |                                                                                                                                                                         |                                                  |
| Day                                                 | What you do                                                                                                                                                             |                                                  |
| Day 1                                               | x                                                                                                                                                                       | Get physical examination and routine blood tests |
| x                                                   | Thyroid function test (every 16 weeks)                                                                                                                                  |                                                  |
| x                                                   | Myeloma blood and urine tests                                                                                                                                           |                                                  |
| x                                                   | Pregnancy test for females of childbearing potential every 28  days if you have regular or no menstrual cycles or every 14  days if you have irregular menstrual cycles |                                                  |
Clinical trial: NCT01155583
Section: Purpose of Research
Subsections: 2. Purpose

You have been asked to participate in this research study because you have multiple myeloma that has relapsed after previous treatment or did nor respond to the last treatment. Current therapy for your disease includes lenalidomide (Revlimid ®), thalidomide (Thalomid ®), dexamethasone (e.g. Decadron ®), prednisone, bortezomib (Velcade ®), chemotherapeutic agents like cyclophosphamide (Cytoxan ®) or liposomal doxorubicin (Doxil ®) alone or in various combinations. The purpose of this research is to evaluate the use of azacitidine in combination with lenalidomide and dexamethasone for six 28-day cycles followed by maintenance with lenalidomide alone. This study will also seek to find an appropriate dose of azacitidine (one that is not too toxic) given once or twice a week in combination with lenalidomide and dexamethasone. Azacitidine can reactivate genes that cancer cells have shut down to grow better and live longer. It is approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome, a cancer of the blood. Laboratory and animal studies suggest that, by reactivating genes, azacitidine can overcome resistance of various cancers, including myeloma, to other therapies. Lenalidomide is a drug that is felt to exert anti-cancer effects by altering the immune system and the production of myeloma supporting molecules in the bone marrow, and by interfering with the development of tiny blood vessels that help support tumor growth. Lenalidomide is approved by the FDA for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior therapy. A study of azacitidine and lenalidomide in combination in patients with MDS has shown promising efficacy and good tolerability but the combination has not been tested in myeloma yet, making this initial study necessary. This study will enroll up to 40 patients, who will be monitored for toxicity and efficacy.
Clinical trial: NCT01155583
Section: Voluntary Participation
Subsections: 10. Voluntary Participation

Your participation in this research study is voluntary. Choosing not to participate will not alter your usual health care or involve any penalty or loss of benefits to which you are otherwise entitled. If you decide to join the study, you may withdraw at any time and for any reason without penalty or loss of benefits. If information generated from this study is published or presented, your identity will not be revealed. In the event new information becomes available that may affect the risks or benefits associated with this study or your willingness to participate in it, you will be notified so that you can decide whether or not to continue participating.
Clinical trial: NCT01155583
Section: Withdrawal from Study
Subsections: Termination Of Participation

You understand that your participation is voluntary and you may refuse to participate. You may discontinue your participation AT ANY TIME, without penalty or loss of benefits to which you are otherwise entitled. You also understand that the investigator has the right to withdraw you from the study AT ANY TIME. You understand that your withdrawal from the study may be for reasons related solely to you (e.g. not following study-related directions from the Investigator; a serious adverse reaction) or because the entire study has been terminated. You understand that the study or the Investigator's participation in the study may be terminated at any time.