Clinical trial: NCT01572493
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

Instead of being in this study, you have these options:
- 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.
Clinical trial: NCT01572493
Section: Confidentiality
Subsections: Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality

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.  
- National Cancer Institute Institutional Review Board - Regulatory agencies in the United States
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.

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-0113 CONTINUATION: page 10 of 13 pages To help us protect your privacy, we have obtained a Certificate of Confidentiality. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, except as explained below. You should also know that there are several circumstances in which the Certificate does not provide coverage. These include when information:  
- will be used for auditing or program evaluation internally by the NIH; or
- must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA).  
- is necessary for your medical treatment and you have consented to this disclosure;
- is for other research.
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible as evidence or used for any purpose in any action, suit, or proceeding without your consent. You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. If an insurer, employer, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information. The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others.
Clinical trial: NCT01572493
Section: Duration of Study Involvement
Subsections: During The Study|When You **Are Finished Taking The Drugs (Treatment)**

You will be admitted to the inpatient unit for the rhIL-15 infusion. If you do not already have a functional implanted central venous catheter in place, we will insert a small, flexible tube known as a "PICC line" or a similar type of intravenous device into one or two of your veins for the drug to be given and for the multiple blood samples planned for this study. Depending on your dosing schedule, you will spend approximately 12 or 6 days in the hospital for treatment and monitoring of your condition. You will be closely monitored during the treatment. If you develop side effects such as fever, chills, decreased blood pressure, blood test abnormalities, decrease in hemoglobin (red blood cells), rash or an allergic reaction, you will be treated as needed with IV fluids or solutions, transfusion, nausea and vomiting and diarrhea medications, ibuprofen (Motrin), acetaminophen (Tylenol) or antihistamines (Benadryl). If you tolerate the treatment well, you will be free to walk around the unit and the hospital building, but you will not be allowed outside the Clinical Center complex while you are being treated. While you are at the Clinical Center, we will also perform study tests and procedures to see how the study drug is affecting your body. Please see below for more details. Standard procedures being done because you are in this study; these may be done more often because you are in the study:
- Medical history and physical exam  
- Measurement of vital signs - CT scans of the chest, abdomen and pelvis to identify your tumor locations and size - EKG to check your heart  
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-0113 CONTINUATION: page 4 of 13 pages
- Standard blood tests

After you are done taking rhIL-15, we would like to do the following tests before you leave the study:  
- History and physical exam - Standard blood tests - Research blood tests for antibodies against rhIL-15
If your treatment is stopped after 2 or 4 cycles because your disease remains unchanged, we would like to continue to follow you to see how long your disease remains stable. We will ask you to come to the Clinical Center for routine exams and x-rays every 2 months for the first 6 months after you stop taking rhIL-15 (3 visits) and then every 3 months thereafter for up to 2 years after your start of treatment. If your disease worsens or you start another treatment, the follow-up would end.
Clinical trial: NCT01572493
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: NCT01572493
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks **Or Discomforts Of Participation** What Side Effects Or Risks Can I Expect **From Being In This Study?**|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen. Side effects may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Some side effects may go away soon after you stop taking rhIL-15. In some cases, side effects can be serious, long lasting, may never go away, or may result in death. rhIL-15 has been given to 19 patients as a short (30 minute) IV infusion in a trial that has been completed and to 25 patients participating in this trial as of April 2016. The treatment in this trial has been tolerated fairly well with some exceptions: One patient whose cancer had spread to the lungs had breathing problems and required oxygen treatment. Two patients who were treated at the highest dose level of rhIL-15 (4 mcg/kg) had serious side effects including one patient who died from complications caused by blood vessel blockage. The first patient developed diarrhea, most likely due to a change in her liquid feeding tube preparation and treatment with antibiotics that were given for a suspected infection. The diarrhea led to an interruption of the patient's rhIL-15 treatment. The rhIL-15 was restarted after the patient's diarrhea decreased. Soon afterwards the patient developed abdominal pain and other problems that required the patient be taken to surgery. During the surgery the patient was discovered to have multiple areas of her stomach as well as her small and large bowel that had decreased blood flow. The area of involvement was too large to allow removal of all the damaged areas. At that time, the rhIL-15 treatment was permanently discontinued. The patient was given additional antibiotics, IV fluids and blood pressure medicine to support her during this period. The patient eventually died as a consequence of this event. In all the patients previously  
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-0113 CONTINUATION: page 6 of 13 pages treated in any of the rhIL-15 trials, we have had 2 or 3 patients with a few loose stools of short episodes (approximately 1 day) of diarrhea that did not appear related to or worsened by the rhIL-15 treatment. Although we do not entirely understand the exact cause of this event, it appears that rhIL-15 contributed to this serious toxicity. The second patient had periods of confusion related to the rhIL-15 treatment that eventually cleared up after the rhIL-15 was stopped. This patient had a large amount of cancer in his liver and we believe that added to his confusion. We will no longer treat patients with a large amount of cancer in their liver and we will stop treatment in any patient who has even mild diarrhea. We believe these changes will allow us to treat patients at higher dose levels for the upcoming patients.  
There have been 2 patients who had significant bleeding episodes (the first patient bled from one of the airways in the lung and the second patient bled from the small bowel). In both cases, it is possible that the bleeding was caused by other factors, including tumor; but it is also possible that rhIL-15 was a contributing factor. To reduce the chance that future patients will experience these events, changes have been made to the requirements that patients must meet in order to enroll on this study. The changes include performing extra blood tests and disappearance of side effects from previous cancer treatments. The doctor going through this consent with you will describe these events and other toxicities seen in patients previously treated on this protocol in greater detail. Based on observations from all the rh IL-15 clinical trials to date, the known characteristics of this class of drug (interleukins) and the safety studies of rhIL-15 carried out in monkeys, the following side effects may be expected or theoretically possible:
Possible:  
- Abnormal heartbeat
- Decreased red blood cells (anemia) which may require blood transfusion
- Pain in belly - Low blood pressure which may cause feeling faint
- Chills
- Fatigue/Tiredness - Fever
- Lowered numbers of a type of infection-fighting white blood cells (granulocytes)
- Increased or decreased numbers of blood immune cells (lymphocytes)
- Low albumin (blood protein)
- Liver blood test abnormalities
- Swelling of arms, legs  
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-0113 CONTINUATION: page 7 of 13 pages
- Swelling and redness at the site of the medication injection  
- Severe blood infection
- Bruising, bleeding
- Infection, especially when white blood cell count is low - Muscle weakness
- Dizziness, headache
- Shortness of breath - Dry skin - Rash - Fluid in the organs which may cause low blood pressure, shortness of breath, swelling of ankles
- Diarrhea - Nausea and vomiting
- High blood pressure which may cause blurred vision
- Increased heart rate - Decreased platelets (cells that help with blood clotting)
- Immune responses against rhIL-15 - Decreased blood oxygen level
- Blood chemistry (electrolyte) abnormalities
Risks of blood sampling: The blood samples collected as part of this study are not expected to produce any important decrease in the total amount of blood in your body. Side effects may include pain and discomfort, bruising, and rarely inflammation of the vein, bleeding or infection. Additionally, some patients can experience light-headedness or fainting.  
Risks of a central line: In order to receive this therapy, you may need to have an intravenous catheter placed. This catheter is usually placed in the arm, chest or neck area into a major vein inside your chest. The catheter may be used for infusion of rhIL-15 and for drawing blood. It is usually inserted under local anesthesia. The risks associated with the procedure include pain, bleeding, infection, inflammation and puncture of the underlying lung. Lung puncture can result in lung collapse, which might require that a chest tube be placed into the chest cavity (usually for a day or two) to help the lung re-inflate. The long-term risks of the catheter include infection and clotting of the vein in which the catheter sits. If these occur, it may be necessary to remove the catheter. These risks will be explained to you in more detail at the time of the insertion.  
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-0113 CONTINUATION: page 8 of 13 pages

Taking part in this study may not have any effect on your disease or benefit for your general condition. 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 the pain caused by your 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: NCT01572493
Section: Procedures
Subsections: What Will Happen If You **Take Part In This Research Study?** Before You Begin The Study|Tests And Procedures That Are Being Done To See How The Study Is Affecting Your Body:

You will need to have examinations, tests and procedures to see if you qualify for the study.  
Many of these tests are performed as part of your regular medical care or during the prior treatments for your cancer. You will be asked to sign a separate consent describing the tests you will need to have done. These tests need to be performed within 28 days before you enroll in this study. After all of these examinations are performed and we determine you are eligible for the trial, you will be asked to sign this informed consent agreeing to participate in this research study.

- Blood tests to measure changes in the number and percentages of specific sets of white blood cells (lymphocytes) that make up your immune system and the production of other cytokines in your blood that result from the rhIL-15 treatment
- Blood tests to measure the amount of rhIL-15 in your blood over time; these will be collected during the first treatment cycle only
- Blood tests for antibodies to check whether your immune system is reacting against rhIL15
Clinical trial: NCT01572493
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Why Are You Being Asked To Take Part In This Study?|Description Of Research Study

You are being invited to participate in a research study on the effects of an investigational new drug called recombinant human interleukin-15 (rhIL-15). rhIL-15 is not yet approved by the Food and Drug Administration (FDA). rhIL-15 is a man-made version of a small protein (cytokine) that is naturally produced in your body by certain white blood cells and increases the activity and strength of the immune system. Patients with cancer can have a weak immune system. This weakness can be caused by the cancer itself, or by treatments such as radiation, chemotherapy or other drugs that work against the immune system. It is hoped that rhIL-15 can "boost" or strengthen patients' immune systems and restore immune responses against cancer.  
STUDY NUMBER: 12-C-0113 CONTINUATION: page 2 of 13 pages In this study, rhIL-15 will be given through a vein continuously (without a break) for 10 days
(240 hours) or 5 days (120 hours). This is called a continuous intravenous infusion. In the first trial of rhIL-15 in humans, rhIL-15 was given through a vein for 30 minutes each day for 12 days in a row. This study will see if rhIL-15 given continuously for 10 or 5 days gives a better boost in the immune system.

You are being asked to take part in this study because there are no treatments that are very effective for the cancer you have. We want to find out what effects; good and/or bad, rhIL-15 has on you and your cancer.

The purpose of this study is to test the safety of different doses of rhIL-15 when given as a continuous infusion for 10 or 5 days. When you are enrolled in the study, you will be assigned to a Group of 3-6 patients and you will receive rhIL-15 treatment at the dose level assigned to that Group. The first group of patients entering the study will receive the lowest dose of rhIL-15 planned for this trial. If these patients tolerate the treatment well (no unacceptable side effects); then new groups of 3-6 patients will be enrolled and treated with higher doses of rhIL-15. Initial groups of patients will be treated with the 10-day schedule. After the group of patients on the 10day schedule is finished then new groups of 3-6 patients will be treated with the 5-day schedule to identify the highest dose that can be safely given with this shorter schedule. For the 10-day treatment groups, rhIL-15 will be given about every 42 days for Cycles 1 and 2, then every 28 days for Cycle 3 and beyond unless you have unacceptable side effects or your disease gets worse. CT scans will be performed before you start treatment and after each treatment cycle for the first 2 cycles to see if the treatment is shrinking your tumor. For the 5-day treatment groups, rhIL-15 will be given every 21 days and the first set of CT scans to check for response will be performed after the second cycle. If there is evidence of improvement in your scans and you do not have unacceptable side effects, you may continue rhIL-15 treatment. For the 10-day treatment group, the initial decision about whether to continue treatment will be made after 2 cycles of treatment and for the 5-day treatment group, the initial decision about whether to continue treatment will be made after 4 cycles so patients treated with both schedules will receive an equal number of doses to demonstrate their tumor is sensitive to rhIL-15. If you continue treatment beyond Cycle 3 or 5, you will have CT scans after every other cycles (4, 6, 8 etc.). If your scans show worsening of your disease or the CT scans are unchanged after any 2 cycles of treatment in a row, rhIL-15 treatment will be stopped. Patients who stop treatment for side effects or no improvement in their disease will continue routine follow-up outpatient assessments unless they choose to start another treatment or withdraw from the trial. During treatment, we will perform routine blood tests to determine the effects of rhIL-15  
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-0113 CONTINUATION: page 3 of 13 pages treatment on your normal organ function and investigational tests to examine the effect of the treatment on your immune system. It is possible that you will be asked to have an additional CT scan to document a significant response to the rhIL-15 at least 28 days after the initial CT scan which showed the improvement. This is not a common practice and would expose you to slightly greater amount of radiation than normal. You are free to refuse this additional scan if you are concerned about the additional radiation exposure with this scan.
Clinical trial: NCT01572493
Section: Withdrawal from Study
Subsections: Stopping Therapy

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 and you need to have a different 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
- if the study drug, rhIL-15 is no longer available
- if the FDA, other health authority, the NIH or the Biopharmaceutical Development Program (the makers of the study drug) decide to end the study
- if you do not follow the study requirements (for instance, if you are not coming for your study visits when scheduled).  
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.  
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-0113 CONTINUATION: page 9 of 13 pages 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 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.