Clinical trial: NCT04185220
Section: Alternatives
Subsections: What Other Options Are There For You?

Before you decide whether or not to be in this study, we will discuss the other options that are available to you. Instead of being in this study, you could:  
Get treatment or care for your cancer without being in a study. These can be prescribed by your regular cancer doctor, even if you are not in this study. Some of the other treatments were able to shrink tumors and delay progression of disease in some people, but none has been shown to prolong life. Your study doctor can talk to you more about these other treatment options, how they are given and their possible side effects.  
Take part in another study Get 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.
Clinical trial: NCT04185220
Section: Confidentiality
Subsections: Will Your Specimens Or Data Be Saved For Use In Other Research Studies?|Confidentiality Protections Provided In This Study|Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality|Privacy Act

As part of this study, we are obtaining specimens and data from you. We plan to use these specimens and data for studies going on right now, as well as studies in the future. These studies may provide additional information that will be helpful in understanding T-cell leukemias and lymphomas or other diseases or conditions. This could include studies to develop other research tests, treatments, drugs, or devices, that may lead to the development of a commercial product by the NIH and/or its research or commercial partners. There are no plans to provide financial compensation to you if this happens. Also, it is unlikely that we will learn anything from these studies that may directly benefit you. By agreeing to let us use your specimens and data, you give the NIH any rights you may have in the specimens and data. We may share your specimens and data with other researchers. They may be doing research in areas similar to this research or in other unrelated areas. These researchers may be at NIH, other research centers and institutions, or industry sponsors of research: We may put your research data in a large database for broad sharing with the research community. These databases are commonly called data repositories. These data repositories might or might not be located at the NIH. The information in this database could include but is not limited to genetic information, ethnicity and sex. If your individual research data is placed in one of these repositories, it will not be labeled with your name or other information that could be used to easily identify you, and only qualified researchers will be able to look at your data. These researchers must receive prior approval from individuals or committees to access the data. In addition to the use and sharing of your specimens and data described above, we might remove any information from your specimens and data that can identify you such as name, address, or medical record number, and then use the specimens and data for additional research studies at the NIH or other places. If we do this, we might not contact you to ask your permission or otherwise inform you. If you change your mind and do not want us to store and use your specimens and data for future research, you should contact the research team member identified at the top of this document. We will do our best to comply with your request but cannot guarantee that we will always be able to destroy your specimens. For example, if some research with your specimens and data has already been completed, the information from that research may still be used. Also, for example, if the specimens and data have been shared already with other researchers, it might not be possible to withdraw the specimens and data. Please place your initials in the blank next to Yes or No for each of the questions below: My specimens and data may be stored and used for future research as described above.  
_____ Yes _____ No  
  
 Initials Initials
My specimens and data may be shared with other researchers and used by these researchers for future research as described above. Initials Initials  
  
_____ Yes _____ No  
  
  
NIH policies require that your clinical and other study data be placed in an internal NIH database that is accessible to other NIH researchers for future research. These researchers will not have access to any of your identifiers, such as your name, date of birth, address, or medical record number; and your data will be labeled with only a code. We cannot offer you a choice of whether your data to be placed in this database or not. If you do not wish to have your data placed in this database, you should not enroll in this study.

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

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:  
The NIH and other government agencies, like the Food and Drug Administration (FDA),
which are involved in keeping research safe for people.  
National Institutes of Health Intramural Institutional Review Board Qualified representatives from Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis (DCTD), NCI, who supplies the rhIL-15.
When results of an NIH research study are reported in medical journals or at scientific meetings, the people who take part are not named and identified. In most cases, the NIH will not release any information about your research involvement without your written permission. However, if you sign a release of information form, for example, for an insurance company, the NIH will give the insurance company information from your medical record. This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance. If we share your specimens or data with other researchers, in most circumstances we will remove your identifiers before sharing your specimens and data. You should be aware that there is a slight possibility that someone could figure out the information is about you. Further, the information collected for this study is protected by NIH under a Certificate of Confidentiality and the Privacy Act.

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

The Federal Privacy Act generally protects the confidentiality of your NIH medical information that we collect under the authority of the Public Health Service Act. In some cases, the Privacy Act protections differ from the Certificate of Confidentiality. For example, sometimes the Privacy Act allows release of information from your record without your permission, for example, if it is requested by Congress. Information may also be released for certain research purposes with due consideration and protection, to those engaged by the agency for research purposes, to certain federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is involved in a lawsuit. However, NIH will only release information from your medical record if it is permitted by both the Certificate of Confidentiality and the Privacy Act.
Clinical trial: NCT04185220
Section: Duration of Study Involvement
Subsections: During The Study|When You Are Finished Taking The Drugs (Treatment)|How Long Will The Study Take?|How Long Will Your Specimens And Data Be Stored By The Nih?

If the screening process shows that you are eligible for the study, and you choose to be in it, you may need to have a few additional standard tests completed if not done recently. You will also have additional samples collected for research tests. You will come to the NIH Clinical Center for treatment and procedures. The treatment will be given in the inpatient setting for the first week of the first cycle and then in the outpatient setting at the Clinical Center for the remainder of the study. You will be given IL-15 as a continuous intravenous infusion as described in section "What will happen during the study?", over a 24-hour period. Your dose of IL-15 will be assigned depending on what dose level is open at the time of your enrollment (gradually increasing doses during the dose escalation or the maximum tolerated dose during the dose expansion portion). Mogamulizumab is also an IV infusion and will be given to you over about a 1-hour period. A midline catheter may need to be inserted for each IL-15 infusion and maintained for the duration of the infusion. If you receive part of the treatment as an outpatient, you will get training on how to maintain the midline catheter and the ambulatory infusion pump before being discharged from the hospital. For the first five days of each cycle, you will need to report to the day hospital each day for an IL-15 bag change. Each IL-15 infusion is expected to start between 8am and 8pm, and bags will be replaced at the same time each day; however, if for any reason IL-15 infusion begins after hours (8pm-8am), you will need to come into the hospital during the night for nursing staff to manage the pump. We will give you standard pre-medications before the IL-15 and mogamulizumab infusions. These may include acetaminophen (Tylenol), nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen) and/or an antihistamine (Benadryl). These are given to help prevent infusion related side effects. Your study doctor or a member of the study staff can explain these to you in more detail. Because of the unknown side effects, we will ask you to stay at the clinic for an additional 30 minutes after your mogamulizumab infusion so we may monitor you. Similar to the tests done at the beginning of the study, the following will be repeated during the study to see how you are doing and how the cancer may be responding to treatment:  
Review of medical history, and a physical exam (check weight and vitals), including obtaining information about how you function in your daily activities, side effects and symptoms, and review of medications Routine blood and urine tests Bone marrow testing and imaging:
o Bone marrow testing will be repeated at the end of study treatment if needed to confirm response, if and only if other tests show a complete response.  
o Tumor imaging (such as, CT scan, PET/CT) will be done to assess the sites of your disease every 8 weeks during treatment An MRI of the brain and lumbar puncture
File in Section 4: Protocol Consent (1) Version Date: 11/16/2020 Page 7 of 25 is only required in participants with neurological symptoms. In participants with disease primarily on their skin, clinical photography and evaluation by a dermatologist will be used to assess the disease sites present on the skin, Other body areas may be imaged if clinically indicated. If your disease does not progress, follow-up imaging may be done every 60 days for the first 6 months after treatment, then every 90 days for 2 years and then every six months for another 2 years and then annually until you start another treatment, your disease progresses or the study ends.

When you finish taking the experimental therapy, we will ask you to come to the clinic for followup visits and assessments at about the following times after treatment: every 60 days for the first 6 months, then every 90 days for 2 years and then every six months for another 2 years. After almost 5 years we may contact you by phone or by email to see how you are doing until you start another treatment, your disease progresses, or the study ends. Only in certain cases, a participant may be asked to come in annually indefinitely. These clinic visits will include having required blood samples collected for routine analysis and for research, and may include CT or PET/CT scans. Visits usually take about 3 hours but should take no longer than 8 hours.

If you agree to take part in this study, your involvement will last for at least four years. HOW MANY PEOPLE WILL PARTICIPATE IN THIS STUDY? Approximately 20 people will participate in this study at the NIH.

Your specimens and data will be stored at NIH as long as the study is open. When this study is closed, we may keep the data and any samples that are leftover for future research indefinitely.
Clinical trial: NCT04185220
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Risks And Discomforts Of Being In The Study?|Risks Of Il-15|Other Risks Seen With Il-15 That Are Possibly Related To The Drug Include:|Risk Of Mogamulizumab|Rare, And Serious|Other Study Risks|Radiation Exposure From Imaging|Radiation Exposure In People Capable Of Becoming Pregnant|Mri Risks|Risks|Psychological Or Social Risks Associated With Return Of Incidental Or Secondary Findings|Privacy Risks Associated With Return Of Incidental Or Secondary Findings|Protections Against Misuse Of Genetic Information|What Are The Risks Related To Pregnancy?|What Are The Benefits Of Being In The Study?|Are There Any Potential Benefits To Others That Might Result From The Study?|Risks Of Storage And Sharing Of Specimens And Data

If you choose to take part in this study, there is a risk that the recombinant human IL-15 may not be as good as the usual approach for your cancer or condition at shrinking or stabilizing your cancer. You also may have the following discomforts:  
Spend more time in the hospital or doctor's office.  
Be asked sensitive or private questions about things you normally do not discuss.  
May not be able to take part in future studies.
The recombinant human IL-15 used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will test your blood and will let you know if changes occur that may affect your health. There is also a risk that you could have side effects from the study drug(s)/study approach. Here are important things to know about side effects:
The study doctors do not know who will or will not have side effects.  
Some side effects may go away soon, some may last a long time, and some may never go away.  
Some side effects may make it hard for you to have children. Some side effects may be mild. Other side effects may be very serious and even result in death.
You can ask your study doctor questions about side effects at any time. Here are important ways to make side effects less of a problem:  
If you notice or feel anything different, tell your study doctor. He or she can check to see if it is a side effect.  
Your study doctor will work with you to treat your side effects.  
Your study doctor may adjust the study drugs to try to reduce side effects.
The tables below show the most common and the most serious side effects doctors know about. Keep in mind that there might be other side effects doctors do not yet know about. If important new side effects are found, the study doctor will discuss these with you.

You may have side effects from the IL-15 while on the study. We pay close attention to any side effects you have. However, we don't know all the side effects that may happen. Side effects may be mild or very serious. We may give you medicines to help lessen side effects. Many side effects go away soon after you stop taking the IL-15. In some cases, side effects can be serious, long lasting, or may never go away. It is possible that IL-15 could increase the growth of your leukemic cells, that is the IL-15 could make your cancer worse. There also is a risk of death. Please talk to us about any symptoms you have while you are in the study.  
  
In studies with humans, common and not very common risks and side effects related to the IL-15 included the following:  
| POSSIBLE, SOME MAY BE SERIOUS   |
|---------------------------------|  
|    | Anemia (low red blood cells) which may require blood transfusion   |
|-----|--------------------------------------------------------------------|  
Abnormal heartbeat Pain in belly Diarrhea, nausea, vomiting Chills, tiredness, fever Swelling of arms, legs 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 High blood pressure which may cause blurred vision Low blood pressure which may cause feeling faint Increases in blood levels of liver function tests, which may indicate damage to the liver.

Chest pain bronchopulmonary hemorrhage and diffuse alveolar hemorrhage (bleeding in the lungs)
Confusion, psychosis (i.e., delusions, hallucinations)
Kidney failure - signs of kidney problems may include: decrease in the amount of urine, blood in your urine, ankle swelling. Severe kidney failure requiring hemodialysis has occurred when IL-15 was given with mogamulizumab, and may have been caused by IL15-associated capillary leak syndrome (fluid in the organs which may cause low blood pressure, shortness of breath, swelling of ankles).  
Papilledema (changes in vision due to increased pressure in the brain)
Uveitis (inflammation of the eye - symptoms may include redness, pain, blurred vision)  
File in Section 4: Protocol Consent (1) Version Date: 11/16/2020 Page 11 of 25  
Pneumonitis (inflammation of the lungs) - symptoms may include new or worsening cough, chest pain, shortness of breath.  
Inflammation of the lining of the first part of the small intestine symptoms may include nausea, vomiting, stomach burning, pain, indigestion Liver damage which may cause yellowing of eyes and skin, swelling and may result in liver failure Decreases in blood levels of albumin, phosphorus (these are standard blood tests)
Low number of white blood cells, cells that help fight infection (lymphopenia, leukopenia, neutropenia)
Low platelets, cells that help blood to clot (thrombocytopenia)  
Low blood oxygen - symptoms may include changes in skin color, confusion, cough, fast heartbeat, shortness of breath Immune related adverse events: hives, hypothyroidism and production of autoantibodies
- symptoms made include joint pain, tiredness fever, rashes, allergy-type symptoms, muscle weakness

You may have side effects from the mogamulizumab while on the study. Mogamulizumab may cause serious side effects that can be severe or life-threatening including skin problems, infusion reactions, infections, autoimmune problems, and complications from stem cell transplant. Please talk to us about any symptoms you have while you are in the study. In studies with humans, common and not very common risks and side effects related to the mogamulizumab included the following:  
| OCCASIONAL, SOME MAY BE SERIOUS                               |
|---------------------------------------------------------------|
| In 100 people receiving mogamulizumab, from 4 to 20 may have: |  
Nausea Tiredness, fever Flu-like symptoms including chills, body aches, muscle pain  
  
Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of  
  
  
  
breath, swelling of the face or throat Infection, especially when white blood cell count is low  
  
 Muscle weakness Damage to organs (lungs, heart, others) which may cause shortness of breath Rash, skin changes

In 100 people receiving mogamulizumab, 3 or fewer may have:
Chest pain Heart attack, heart failure which may cause shortness of breath, swelling of ankles,  
  
  
  
cough or tiredness Damage to organs in the body when donor cells attack host organs which may cause yellowing of eyes and skin, itchy dry skin, diarrhea Kidney damage which may require dialysis Severe skin rash with blisters and peeling which can involve mouth and other parts of the body

Blood draws: The possible side effects of drawing blood include pain, bleeding, bruising, dizziness, light-headedness, fainting and, on rare occasions, local blood clot formation or infection with redness and irritation of the vein.  
EKG: Some skin irritation can occur where the EKG (also referred to as ECG) electrodes are placed. Once the electrodes are placed, the test will begin, is completely painless, and generally takes less than a minute to perform. After the test, the electrodes are removed.  
Imaging/scans: CT, PET and/or MRI scans are used to monitor your disease while you are in this study. CT and PET scans expose you to radiation and the amount depends on the number of body areas scanned. In addition, CT, PET and MRI scans may involve use of contrast (oral and/or IV) so that the cancer may be seen better on the images. In the small group of patients who have a reaction, the most common symptoms are nausea, pain in the  
vein where the contrast was given, headache, a metallic or bitter taste in the mouth, and a warm or flushing feeling that lasts from 1-3 minutes. Rarely, these symptoms may require treatment. In very rare cases, people have had more severe allergic reactions that result in skin rashes, shortness of breath, wheezing, or lowering of the blood pressure. If you have had a reaction in the past, be sure to tell your doctor or nurse about it. Please ask the study doctor if you have questions about the risks of these scans. If done, MRI scans do not involve radiation risk. The scans that you will receive during this study are considered standard for your type of disease.  
Bone marrow biopsy: A numbing agent that can cause a stinging or burning sensation may be injected at the site of your bone marrow biopsy. The biopsy needle will go through the skin into the bone and may produce a brief, sharp pain. As the bone marrow liquid is taken from the bone, there may be a brief, sharp pain. Since the inside of the bone cannot be numbed, this procedure may cause some discomfort, however not all people experience discomfort. The possible side effects associated with a bone marrow biopsy include pain, bleeding, bruising, and infection, as well as a reaction to the numbing agent.  
Tumor biopsy: The likely side effects include discomfort or pain, redness, swelling, and/or bruising at the site of the needle insertion. Bleeding from the site of the needle insertion is a less likely risk. Rarely, significant infection or bleeding from this procedure, allergic reaction to the anesthetic, or formation of a scar at the site of needle entry occurs. If you will have sedation with the procedure, these risks will be discussed with you prior to the procedure. You will be asked to sign a separate consent form prior to any biopsy procedure.  
Midline Catheter Insertion: A non-tunneled central catheter is a soft tube a doctor puts into a vein leading to your heart. It is a way to take blood samples or give you fluids, medicines, or nutrients over a long period of time. Possible side effects include pain, bleeding, bruising, and, on rare occasions, swelling in your arm, chest, neck, or face on the same side as your catheter or infection.

During your participation in this research study, you will be exposed to radiation from CT of the neck, chest, abdomen, and pelvis, and from FDG PET/CT of the torso and the extremities. The amount of radiation exposure you will receive from these procedures is equal to approximately 12.7 rem. A rem is a unit of absorbed radiation.  
Every day, people are exposed to low levels of radiation that come from the sun and the environment around them. The average person in the United States receives a radiation exposure of 0.3 rem per year from these sources. This type of radiation is called "background radiation." This study will expose you to more radiation than you get from everyday background radiation. No one knows for sure whether exposure to these low amounts of radiation is harmful to your body. The CT and FDG PET/CT that you get in this study will expose you to the roughly the same amount of radiation as 42 years' worth of background radiation. Being exposed to too much radiation can cause harmful side effects such as an increase in the risk of cancer. The risk depends on how much radiation you are exposed to. Please be aware that about 40 out of 100 people (40%) will get cancer during their lifetime, and 20 out of 100 (20%) will die from cancer. The risk of  
getting cancer from the radiation exposure in this study is 1.3 out of 100 (1.3%) and of getting a fatal cancer is 0.6 out of 100 (0.6%).

You may not participate in this study if you are pregnant. If you are able to become pregnant, we will perform a pregnancy test before exposing you to radiation. You must tell us if you may have become pregnant within the previous 14 days because the pregnancy test is unreliable during that time.

Your doctor may want you to get a magnetic resonance imaging (MRI) scan. We will obtain pictures of your brain for this study. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, you will lie on a table that can slide in and out of the cylinder. We will place soft padding or a coil around your head. You will be in the scanner about 45 minutes. You may be asked to lie still for up to 15 minutes at a time. While in the scanner you will hear loud knocking noises, and you will be fitted with earplugs or earmuffs to muffle the sound. You will be able to communicate with the MRI staff at all times during your scan, and you may ask to be moved out of the machine at any time. It is very important for the experiment that you do not move your head or body inside the scanner. We will use padding around your head to help keep it in place. We may place a bar in your mouth to help keep your head still. People are at risk for injury from the MRI magnet if they have some kinds of metal in their body. It may be unsafe for you to have an MRI scan if you have pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metal prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, tattoos, an implanted delivery pump, or shrapnel fragments. Welders and metal workers may have small metal fragments in the eye. You will be screened for these conditions before having any MRI scan. If you have a question about metal in your body, you should inform the staff. You will be asked to complete an MRI screening form before each MRI scan you have. In addition, all magnetic objects (like watches, coins, jewelry, and credit cards) must be removed before entering the MRI scan room. People with fear of confined spaces may become anxious during an MRI. Those with back problems may have back pain or discomfort from lying in the scanner. The noise from the scanner is loud enough to damage hearing, especially in people who already have hearing loss. Everyone having a research MRI scan will be fitted with hearing protection. If the hearing protection comes loose during the scan, you should let us know right away. There are no known long-term risks of MRI scans.

The risks of an IV catheter include bleeding, infection, or inflammation of the skin and vein with pain and swelling. Mild symptoms from gadolinium infusion occur in fewer than 1% of those who receive it and usually go away quickly. Mild symptoms may include coldness in the arm during the injection, a metallic taste, headache, and nausea. In an extremely small number, fewer than one in 300,000 people, more severe symptoms have been reported including shortness of breath, wheezing, hives, and lowering of blood pressure. You should not receive gadolinium if you previously had an allergic reaction to it. You will be asked about such allergic reactions before gadolinium is given. People with kidney disease are at risk for a serious reaction to gadolinium contrast called "nephrogenic systemic fibrosis" which has resulted in a very small number of deaths. A blood test of your kidney function may be done within the month before an MRI scan with gadolinium contrast. You will not receive gadolinium for a research MRI scan if your kidney function is not normal or if you received gadolinium within the previous month. Most of the gadolinium contrast leaves the body in the urine. However, the FDA recently issued a safety alert that indicates small amounts of gadolinium may remain in the body for months to years. The effects of the retained gadolinium are not clear. At this time, retained gadolinium has not been linked to health risks in people whose kidneys work well. T Some types of gadolinium contrast drugs are less likely to remain than others. In this study, we will use the gadolinium contrast drugs that are less likely to remain. We will also give you additional information called a "Medication Guide." Upon request, we will give you individual information about retained gadolinium we see on your studies.

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

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

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

If you are capable of becoming pregnant, we will ask you to have a pregnancy test before beginning this study. If you are a woman who is breast feeding or pregnant, you may not take part in the study because we don't know how this medicine would affect your baby or your unborn child. There may be long-term effects of the treatment being studied that could increase the risk of harm to a fetus. If you are a woman who can become pregnant or are the partner of a woman who can become pregnant, you will need to practice an effective form of birth control before starting study treatment, during study treatment, and for six (6) months after you finish study treatment. You must tell the study doctor if your birth control method fails during the restricted period. If you think that you or your partner is pregnant, you should tell your study doctor or nurse at once. Men should also not donate sperm during the restricted period.

You might not benefit from being in this study. 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. Talk to your doctor about other approved agents and treatments that are available to you and that may provide clinical benefit without taking part in this study.

In the future, other people might benefit from this study because of the knowledge gained from the study drug combination or the results of the research studies.

When we store your specimens and data, we take precautions to protect your information from others that should not have access to it. When we share your specimens and data, we will do everything we can to protect your identity, for example, when appropriate, we remove information that can identify you. Even with the safeguards we put in place, we cannot guarantee that your identity will never become known or someone may gain unauthorized access to your information. New methods may be created in the future that could make it possible to re-identify your specimens and data.
Clinical trial: NCT04185220
Section: Procedures
Subsections: What Will Happen During The Study?|Screening|Additional Research Testing

If you decide to take part in this study, you will be asked to:
Receive IL-15 as a continuous intravenous infusion (civ) over 24 hours on days 1-5 of a 28-day cycle, together with intravenous infusion (IV) of mogamulizumab. Mogamulizumab will be given at a set dose on days 1, 8, 15 and 22 of cycle 1 and only on days 1 and 15 of all cycles that follow (up to 6 cycles total). Mogamulizumab will be infused over at least 1 hour.  
In order to confirm that the doses are safe, participants will be enrolled in groups:
o Dose escalation group: First, a groups of 3-6 study participants will receive IL-15 and mogamulizumab. The dose of IL-15 will be escalated (or increased) in a new group of participants, as long as it is safe to do so, until the best dose of IL-15 is found. All participants will receive the same dose of mogamulizumab. Each group of participants will be checked closely for side effects for at least 4 weeks before enrolling at the next higher dose of IL-15 with mogamulizumab.  
o Dose expansion group: Once the dose of IL-15 with mogamulizumab is determined, up to 9 more participants will receive IL-15 dose with mogamulizumab to learn more about the drugs and their effect on the types of cancer being studied.
All participants will be given treatment on an inpatient basis for the first week of the first cycle, and on an outpatient basis for subsequent weeks and cycles unless decided otherwise by the physician, based on clinical judgement. Treatment can continue for up to 6 (28-day) cycles. You will only be eligible for outpatient treatment if you have a caregiver to accompany you and help you manage the ambulatory infusion pump.  
If IL-15 needs to be discontinued, you may be able to continue on mogamulizumab alone if your doctor thinks this is appropriate. Your study team will discuss this with you.  
Another way to find out what will happen to you during the study is to read the chart below. Start  
 reading at the left side and read across to the right, following the lines and arrows:

Before you begin the study, you will have several tests performed to check whether the study is suitable for you. Some of these will be done before signing the informed consent document for this study. This is called screening. Your doctor will review your medical history and the drugs that you are currently taking as well as the previous treatments of your disease to determine whether you can participate in this study. A previously collected blood sample or small part of your tumor tissue (depending on your disease) that was collected from any previous surgery or biopsy will be tested at NCI to confirm your diagnosis. If no sample is available or if additional sample is needed to confirm your diagnosis, a fresh blood sample or biopsy will be taken. A biopsy will also be done prior to treatment if there is not enough tissue available from your diagnostic biopsy for study purposes (seeing whether the target of mogamulizumab can be found on the surface of the tumor cell; the results of this test will not affect your eligibility). Any leftover tissue may be stored for future research studies, but a biopsy will not be performed solely for these studies. You will be told if this mandatory biopsy is needed. Some of these tests or procedures are part of regular care and may be done even if you are not being considered to join the study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. The following tests and procedures will be performed prior to starting treatment:  
Your medical history, including previous cancer treatments, any current or previous medications (prescription, supplement, and over-the-counter medicines), will be reviewed. If you have medical records from another clinic or hospital, you will be asked to get copies of these records, or your study doctor may be able to request them on your behalf.  
A complete physical examination will be performed that will include your vital signs
(blood pressure, pulse, body temperature, and respiratory rate) and recording your height and weight, and evaluation of your ability to carry out daily activities.  
Blood and urine tests will be collected to:
o measure your liver, kidney, and thyroid function, red and white blood cells, platelets, electrolytes and others; o measure how well your blood clots; o test for human T-lymphotropic virus (HTLV) and Hepatitis B infection o test for human immunodeficiency virus (HIV) infection. This is the virus that causes AIDS. If you are infected with HIV you will not be able to participate in this study. We will tell you what the results mean, how to find care, how to avoid infecting others, how we report HIV infection, and the importance of informing your partners at possible risk because of your HIV infection.  
o run routine tests done in people with your type of cancer to confirm your diagnosis and the status of your disease.
If you have received a live vaccine within 30 days of starting study treatment, you will not be able to immediately participate. Examples of live vaccines include but are not limited to: the intranasal influenza vaccine known as Flu-Mist, measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine.  
For females of child-bearing potential, a pregnancy test will be done (urine or blood sample). You will not be able to participate if you are pregnant or you are breast feeding because we don't know how this medicine would affect your baby or your unborn child.  
Pulmonary function test to test how well your lungs function.  
An electrocardiogram (EKG) and echocardiogram (ECHO) to check your heart function.
Bone marrow testing and imaging will be done to check your disease, as needed.  
o A bone marrow aspiration and/or biopsy will be done prior to starting treatment if not done within the last 3 months since completing the last treatment received to confirm the stage and status of your disease. These are done by numbing your hipbone using a small needle containing local anesthesia, and then a needle will be put into the hipbone, and a small amount of bone marrow will be taken out through the needle o Imaging will include a CT scan of neck, chest, abdomen and pelvis, and a PET/CT
scan of the torso. Other body areas may be imaged if clinically indicated. For
participants with suspected involvement of disease in the central nervous system, an MRI of the brain will be taken.

In addition, the following research samples will be collected, and some are optional:
Blood Samples: Blood will be collected for required research studies to learn more about how IL-15 and mogamulizumab affect your cancer at the beginning of the study prior to starting treatment, during the first cycle of treatment, and at about the same time as each imaging assessment. If at any time your doctor thinks you have responded or may have progressed during or after treatment, we will again collect samples. Optional blood samples may be obtained more frequently throughout the treatment cycles depending upon the days that you are seen in the clinic. You will be told which samples are required and which are optional.  
Cheek Swab or Saliva Samples: A required cheek swab and/or saliva sample to collect normal tissue will be done, likely at the beginning of the study only. To obtain a cheek swab, a small brush is rubbed against the inside of the cheek to wipe off some cells. To obtain saliva, a special collection tube will be used and it may take a few minutes to collect the saliva.
Tumor Biopsies: A biopsy will be mandatory prior to treatment if we do not have sufficient material from your prior biopsies to perform some research studies. All other biopsies are an optional part of the study and you will only be asked to do so if it is felt to be safe. We will ask you to undergo a tumor biopsy during the first Cycle of treatment and again if your disease should progress during or after treatment on this study. The tissue is being collected for special research tests. Your doctor or the study team will discuss the biopsies with you. The biopsies to be performed are exclusively for research purposes and will not benefit you. They might help other people in the future. You may agree to biopsies now and change your mind later. If at any time you do not want to have a biopsy done, please tell us. Usually tissue can be obtained safely and comfortably with local anesthesia. If you require sedation before undergoing a biopsy, you will be informed of the risks and you will be asked to sign an additional consent prior to undergoing the procedure. Biopsies will NOT be done on this study if they require general anesthesia. We may ask that you have ultrasound to help clearly locate your tumor when doing a biopsy.  
All of your samples collected for research purposes on this study may be used to look for specific changes in the DNA in tumors that could be used to develop new ways of diagnosing and treating cancer. DNA (also called deoxyribonucleic acid) in the cells carries genetic information and passes it from one generation of cells to the next - like an instruction manual. Normal tissue contains the DNA (instructions) that you were born with, DNA in tumor cells has changed - or mutated - and we think that change in the DNA is what causes tumors to form and to grow. To look at your DNA, we may do what is called "whole genome sequencing." This where we will do special tests in the lab to look at the entire sequence, or order, of how your DNA is put together. This is what makes you unique. To determine which parts of the DNA have mutated, we will compare the DNA in your tumor cells to DNA from your normal cells. We will then analyze the results from similar tumors to see if there are any changes in the DNA that are common to a particular type of tumor. To examine the tumor and normal tissue we may use several different techniques depending on the type of tissue we collect. These could include growing cell lines (cells which keep dividing and growing in the laboratory, sometimes for years allowing us to continually study those cells), xenograft studies (placing or growing cells in another animal, such as mice), and looking in detail at the parts of the genes that produce specific proteins. However, you should know that the analyses that we perform in our laboratory are for research purposes only; they are not nearly as sensitive as the tests that are performed in a laboratory that is certified to perform genetic testing or testing for routine clinical care. For these reasons, we will not give you the results of the research tests done on your research samples in most cases. There may be exceptions to what we share with you and this is described later in this consent form in the section for "Return of research results".
Clinical trial: NCT04185220
Section: Purpose of Research
Subsections: Key Information About This Research|Why Is This Study Being Done?

This consent form describes a research study and is designed to help you decide if you would like to be a part of the research study. You are being asked to take part in a research study at the National Institutes of Health (NIH). This section provides the information we believe is most helpful and important to you to in making your decision about participating in this study. Additional information that may help you make a decision can be found in other sections of the document. Taking part in research at the NIH is your choice. You are being asked to take part in this study because you have relapsed adult T-cell leukemia/lymphoma (ATLL) or mycosis fungoides/Sézary syndrome (MF/SS), that has not responded to standard treatments.  
The purpose of this study is to test whether the combination of IL-15 and mogamulizumab can be used safely in people with your disease. Mogamulizamab used by itself is approved to treat people with relapsed or refractory mycosis fungoides or Sezary syndrome, but not ATLL. The combination of the 2 drugs has not been used before. We will also look at if they are effective in treating your disease. The goals of this study are to determine the safe dose of IL-15 when combined with mogamulizumab to be used in humans, to identify the side effects of the combination treatment and its effects on your immune system, and to determine if this treatment has activity against your cancer. Recombinant human interleukin 15 (IL-15) is considered investigational, which means that it has not been approved by the U.S. Food and Drug Administration (FDA) to treat ATLL or mycosis fungoides/ Sézary syndrome (MF/SS). However, mogamulizumab is approved for the treatment of relapsed and/or refractory mycosis fungoides/ Sézary syndrome after at least 1 prior  
File in Section 4: Protocol Consent (1) Version Date: 11/16/2020 Page 1 of 25  
failed therapy. In clinical trials, up to 50% of patients with MF/SS had improvement in skin lesions after treatment with mogamulizumab. It also delayed disease progression by 7 months on average but hasn't been shown to prolong life. We are testing it in this research study to see whether giving recombinant human interleukin 15 (IL-15) in combination with mogamulizumab will improve outcome of therapy for your disease. Since IL-15 and mogamulizumab have never before been given together, this treatment is considered investigational, or experimental. The FDA has given us permission to use IL-15 and mogamulizumab together in this study. There are other drugs and treatments that may be used for your disease, and these can be prescribed by your regular cancer doctor, if you are not in this study. These drugs all work in different ways in the body as compared to IL-15 and mogamulizumab, and with different side effects. In clinical trials, they were able to shrink tumors in 20-30% of patients, and delayed progression of disease in a majority of patients by 2-3 months, but none of the other available treatments has been shown to prolong life. If you would prefer other drugs or treatments, you should consider not joining this study. If you decide to join this study, here are some of the most important things that you should know that will happen:  
In the first groups of participants enrolled (dose escalation), we want to find out the highest dose of IL-15 that is safe to use with mogamulizumab. We will test increasing doses of IL-15 in small groups. We also want to find out what kind of side effects IL-15 and mogamulizumab might cause. After the first part is done, we will enroll additional participants in a second portion of the study (dose expansion) to learn more about whether IL-15 and mogamulizumab can shrink your tumor(s).  
Before you begin the study, we will perform tests to find out whether you are eligible to participate (screening) that will include tests such as: a complete physical examination, blood and urine tests, bone marrow testing and imaging. Some of these may be done on a separate screening protocol before signing the informed consent document for this study.  
If you are eligible to receive treatment, during the study, both drugs will be administered as intravenous infusions for up to six cycles of 28 days each. You will receive IL-15 over the course of the first five days of each cycle, and mogamulizumab on days 1, 8, 15 and 22 of cycle 1 and only on days 1 and 15 of all cycles that follow.  
You will be required to be hospitalized at the NIH Clinical Center for one week to receive the first cycle of IL-15. As long as you are accompanied by a caregiver or unless decided otherwise by the doctor, you will have the option of receiving the remaining cycles as an outpatient, but will still need to report to the hospital each day for the first five days of each cycle.  
You may experience side effects from taking part in this study. Some can be mild or very serious, temporary, long-lasting, or permanent, and may include death. Examples of some of the side effects that you may have include: changes in blood counts (such as low red or white cells), gastrointestinal (such diarrhea, nausea, vomiting), rashes, fatigue, and infections. Since this is the first time that IL-15 and mogamulizumab are administered together, there may be side effects that we cannot predict.  
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You will be seen regularly during the study. You will have clinical, laboratory, and imaging tests to see how you are doing and to see if the treatment is having any effect on your disease. We will also collect required samples from you (including blood, bone marrow, and tumor biopsies) for both clinical and research purposes.  
After the study treatment has ended, we will need to see you at the NIH Clinical Center periodically for up to about four (4) years to assess your health and to determine what impact, if any, the study drugs may have had on your disease. After this time, we may contact you to see how you are doing for the rest of your life.
Just as we do not know what side effects you might have, we cannot know if you may benefit from taking part in this study. If you do not benefit directly, this study and the results from our research may help others in the future. You are free to stop participating in the trial at any time. If you decide to stop, the study doctor may ask you to agree to certain tests to make sure it is safe for you to stop.  
The remaining document will now describe more about the research study. This information should be considered before you make your choice. Members of the study team will talk with you about the information described in this document. Some people have personal, religious, or ethical beliefs that may limit the kinds of medical or research treatments they would want to receive (such as blood transfusions). Take the time needed to ask any questions and discuss this study with NIH staff, and with your family, friends, and personal health care providers. If the individual being asked to participate in this research study is not able to give consent to be in this study, you are being asked to give permission for this person as their decision-maker. The term "you" refers to you as the decision-maker and/or the individual being asked to participate in this research, throughout the remainder of this document.

This is a research study. The purpose of this research study is to develop a new treatment for adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides/Sézary syndrome (MF/SS), that is more effective than existing therapies. We are asking you to join this research study because you have relapsed and/or refractory ATLL or mycosis fungoides/ Sézary syndrome for which no standard therapy exists, or standard therapy has failed. IL-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 IL-15 can "boost" or strengthen your immune system as it fights against cancer. In fact, in other clinical trials, all of the patients who received IL-15 showed an increase in the number of their immune system cells. In some of the patients, the growth was dramatic. We hope the same is true in this study. Mogamulizumab is a monoclonal antibody that works by attaching to a protein on your tumor cells and marking the tumor cell for destruction by other cells of the immune system. Monoclonal antibodies are purified proteins that are specially made to attach to pieces of foreign substances (such as cancer cells). Recent evidence shows that IL-15 boosts the number of immune system cells which are responsible for destroying tumor cells with antibodies attached. Recombinant human interleukin 15 (IL-15) is considered investigational, which means that it has not been approved by the U.S. Food and Drug Administration (FDA) to treat ATLL and mycosis fungoides/ Sézary syndrome (MF/SS). However, mogamulizumab is approved for the treatment of relapsed and/or refractory mycosis fungoides/ Sézary syndrome after at least 1 prior failed therapy. In clinical trials, up to 50% of patients with MF/SS had improvement in skin lesions after treatment with mogamulizumab. It also delayed disease progression by 7 months on average but hasn't been shown to prolong life. We are testing it in this research study to see whether giving recombinant human interleukin 15 (IL-15) in combination with mogamulizumab will improve outcome of therapy for your disease. Since IL-15 and mogamulizumab have never before been given together, this treatment is considered investigational, or experimental. The FDA has given us permission to use IL-15 and mogamulizumab together in this study
Clinical trial: NCT04185220
Section: Voluntary Participation
Subsections: It Is Your Choice To Take Part In The Study

You may choose not to take part in this study for any reason. If you join this study, you may change your mind and stop participating in the study at any time and for any reason. In either case, you will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you must be taking part in a study or are being considered for a study. If you do choose to leave the study, please inform your study team to ensure a safe withdrawal from the research.
Clinical trial: NCT04185220
Section: Withdrawal from Study
Subsections: Early Withdrawal From The Study

Your doctor may decide to stop your therapy for the following reasons:  
if he/she believes that it is in your best interest if your disease worsens or comes back during treatment if you have side effects from the treatment that your doctor thinks are too severe if you become pregnant if the IL-15 or mogamulizumab becomes unavailable if new information shows that another treatment would be better for you if you do not follow the study rules if the study is stopped for any reason
In this case, you will be informed of the reason therapy is being stopped. After therapy is stopped we would like to see you for a safety visit 30 days after your last dose. You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your 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 Division of Cancer Treatment and Diagnosis (DCTD) or designated representatives.