Clinical trial: NCT01814046
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

If there are effective salvage regimens (regimens used when standard regimens have failed), you will be directed to undergo these regimens before participating in this protocol. Instead of being on this study, you have these options for treatment:
- Getting treatment or care for your cancer without being in a study - Taking part in another study
- Getting no treatment; or getting comfort care which is also called palliative care. This type of care helps reduce pain, tiredness, appetite problems, and other problems caused by 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: NCT01814046
Section: Confidentiality
Subsections: Will Your Medical Information Be Kept Private?

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
- The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.  
- NCI Institutional Review Board
- The study Sponsor (Center for Cancer Research) or their agent(s) - Lion Biotechnologies
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most the Web site will include a summary of the results. You can search this Web site at any time.
Clinical trial: NCT01814046
Section: Duration of Study Involvement
Subsections: When You Are Finished Taking The Drugs (Treatment) Recovery|Follow Up And Evaluation Of Experimental Regimen|This Consent Document Has Been Approved For Use From October 17, 2016 Through **October 16, 2017.**

You will recover in the hospital until you are well enough to go home. This usually takes 7-12 days after you have received cells or your last dose of aldesleukin; however, you may need to stay in the hospital for longer than this before you are well enough to go home. We will continue to give you support medications, do laboratory tests, and watch you closely for any side effects until we feel your condition is stable.  
STUDY NUMBER: 13-C-0093 CONTINUATION: page 5 of 14 pages In addition to the laboratory tests to monitor your condition, we will remove between 1 and 9 teaspoons of blood daily to study the effects of this regimen on your immune system. If you experience side effects in your kidneys, we will collect 1 additional teaspoon of blood and about 6 teaspoons of urine to see if we can determine the cause of these side effects. The maximum amount of blood for research is approximately 2.3 cups in 8 weeks.

You will need to continue to take Bactrim, an antibiotic, for at least 6 months following your treatment to prevent you from catching a certain type of pneumonia seen in patients who have low white blood cell counts. We will ask you to return to the NIH Clinical Center frequently after you are discharged approximately 6 and 12 weeks following treatment and then if you are responding to the treatment, every 3 months for the first year following treatment, every 6 months for the second year and then as determined by your physician. The first visit will probably take 2 days; the following visits may only take one day. At each visit you will have lab tests, imaging studies and a physical examination. At some of your follow up visits, you may undergo leukapheresis or have about 8 tubes of blood drawn (4 tablespoons) so that we can see the effect this therapy has had on your immune system and if the cells we gave you are still alive. If you are unwilling or unable to travel to the NIH Clinical Center we will contact you by phone or e-mail and we may ask you to send us lab, imaging, and physical exam reports.

Signature of Investigator Date Signature of Witness Date Print Name Print Name PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL **RESEARCH**
STUDY (Continuation **Sheet)**
- Adult Patient or - Parent, for Minor Patient NIH-2514-1 (07-09) P.A.: 09-25-0099 File in Section 4: Protocol Consent
Clinical trial: NCT01814046
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:  
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: 13-C-0093 CONTINUATION: page 10 of 14 pages  
- 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: NCT01814046
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?

The risks and discomforts of this research study can be significant. This experimental treatment can lead to long-term decrease in your immune function. It is also possible that you may lose your fertility following this experimental treatment. It is possible, although unlikely, that this experimental treatment may cause your death. We will discuss the side effects of this experimental treatment with you. You will be given medicines, transfusions, and treatments to prevent or treat the side effects including drugs to prevent and/or treat different types of infections. We will try to make you as comfortable as possible. You should talk to your study doctor about any symptoms that you experience while taking part in the study.

The aim of this study is to see if this new experimental treatment will cause your tumors to shrink. We do not know if you will receive personal medical benefit from taking part in this study. These potential benefits could include shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer. Because there is not much information about the Young TIL therapy effect on your type of cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may benefit others in the future who have cancer.
Clinical trial: NCT01814046
Section: Procedures
Subsections: What Will Happen If You Take Part In This Research Study? Before You Begin The Study Cell Harvest And Growth|Work Up|Catheter Insertion|Leukapheresis|Leukapheresis|During The Study Chemotherapy Regimen (Day -7 Through Day -1)|Cell Infusion And Aldesleukin Regimen (Day 0 Through Day 5)|Retreatment|Leukapheresis|Leukapheresis|Young Til Cell Infusion

You underwent a procedure, either surgery or a biopsy, to obtain pieces of your tumor so that we can grow the Young TIL from your tumor cells in the laboratory while enrolled on our companion protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols). The surgical procedure may involve liver resection either by laparoscopic or open surgical approaches. In 1 out of 5 patients, we are not able to successfully grow the cells for this procedure. If your cells do not grow, you will not be able to receive the cell infusion. If that happens, we will look at alternative treatments for you (best available care) or return you to the care of your referring physician. We usually know after about 4 weeks whether the cells will grow well enough to be used as an experimental treatment on this protocol. At the time we determine that your cells are not growing, we will inform you and discuss your options with you. Several medications are used during the preparation of your cell product, be sure to tell your doctor if you are allergic to any antibiotics.

Prior to receiving the experimental treatment, you will undergo many tests. These include imaging procedures, heart and lung function tests, and laboratory tests. If you are a woman, you will undergo a pregnancy test. You will also have a large catheter inserted into a vein and leukapheresis will be performed (see below). You may be admitted to the hospital for these tests. However, you will be allowed to leave on pass on the days that you are not having tests performed.

Prior to beginning the experimental treatment, you will have an intravenous (IV) catheter placed in your upper chest. The area will be numbed with an anesthetic before the catheter is put in. Although rare, putting these catheters in can sometimes cause collapse of a lung or cause bleeding. Lung collapse is treated by putting a tube into your chest for a few days to allow your lung to expand. Pressure is placed on any area that might bleed. Other IVs may be needed in one or both of your arms if we need to give you extra fluids, medicines, or nutrition.

Leukapheresis is a procedure that allows us to remove certain types of blood cells from you and return the rest of your blood. It is a very common procedure that is done routinely here at the NIH with very few risks. During leukapheresis, blood is removed from you through a needle in your arm, circulated through a machine that divides whole blood into red cells, plasma (the serum part), and lymphocytes (or white cells), and then the plasma and red cells are returned to you through a second needle in your other arm. The procedure takes between 3-4 hours to complete. The white blood cells may be used to help grow the cells. In addition to the STUDY NUMBER: 13-C-0093 CONTINUATION: page 4 of 14 pages leukapheresis you will undergo as part of your work up, we will also ask you to undergo one additional pheresis procedure between 4 and 6 weeks after your cell treatment to see the impact of this therapy on the immune system and see if the cells we gave you are still active.

During the leukapheresis procedure, you may have some tingling in your face and lips due to the medicine used to keep your blood from clotting during the procedure. The nurses may give you a calcium-containing antacid to chew that takes away this tingling. Rarely, people may experience lightheadedness or dizziness. We ask that you eat prior to the procedure to prevent this. Rare complications of this procedure are lowered blood pressure, bleeding or bruising where the needles are put in your arms.

After we have grown the Young TIL cells to large numbers in the laboratory, you will be admitted to the hospital to begin your experimental treatment. You will be given two chemotherapy medicines, cyclophosphamide and fludarabine, to make space in your immune system so the Young TIL can work without any interference from the cells in your immune system. These medicines may cause your tumor to shrink some, but this shrinkage is anticipated to be only partial and of small duration. The main purpose of the chemotherapy is to see if we can make the cells more effective in fighting cancer tumors. Animal experiments have indicated that chemotherapy can make the cells more effective in fighting cancer tumors, but it is not known whether this is true in humans. The cyclophosphamide will be given into your catheter over 1 hour for two days (Day -7 and Day -6) and the fludarabine will be given into your catheter for 30 minutes every day for the next five days (Day -5 through Day -1). The side effects of these medicines are described on the following pages.

All patients will be given the cells through their IV over 20-30 minutes one to four days after the last dose of chemotherapy. Within 24 hours after your cell infusion you will be given high dose aldesleukin through one of the IVs. It will be given as a 15-minute infusion about every 8 hours for up to five days after the cell infusion. Aldesleukin is a cell growth factor and it is thought that it will help the cells live longer in your body. No aldesleukin will be given if you refuse it or are not medically eligible to receive it. The day after your cells are infused, we will give you G-CSF (filgrastim) as a shot or injection under the skin every day to stimulate your bone marrow to produce blood cells until they increase to a sufficient number. We will watch you closely during this entire time for any side effects of this experimental regimen. We will discuss the side effects below and we will include in your care all the medicines and treatments to prevent as many of these side effects as we can and to make you as comfortable as we can.

If you have sustained stable disease or your tumor shrinks or disappears following the initial treatment and then recurs you may receive one additional treatment if you tolerated the treatment well and if all the side effects have resolved. You will receive the same medications and cell infusion on the same schedule as with the first treatment.

Leukapheresis is a procedure that allows us to remove certain types of blood cells from you and return the rest of your blood. It is a very common procedure that is done routinely here at the NIH with very few risks. During leukapheresis, blood is removed from you through a needle in your arm, circulated through a machine that divides whole blood into red cells, plasma (the serum part), and lymphocytes (or white cells), and then the plasma and red cells are returned to you through a second needle in your other arm. The procedure takes between 3-4 hours to complete. The white blood cells may be used to help grow the cells. In addition to the STUDY NUMBER: 13-C-0093 CONTINUATION: page 4 of 14 pages leukapheresis you will undergo as part of your work up, we will also ask you to undergo one additional pheresis procedure between 4 and 6 weeks after your cell treatment to see the impact of this therapy on the immune system and see if the cells we gave you are still active.

During the leukapheresis procedure, you may have some tingling in your face and lips due to the medicine used to keep your blood from clotting during the procedure. The nurses may give you a calcium-containing antacid to chew that takes away this tingling. Rarely, people may experience lightheadedness or dizziness. We ask that you eat prior to the procedure to prevent this. Rare complications of this procedure are lowered blood pressure, bleeding or bruising where the needles are put in your arms.

All Young TIL cells will be given through your catheter while we keep you in the patient care unit so we can watch you closely.  
Potential risks include:
- Fever, chills and shortness of breath, which are common and may last for a few hours
- Lung congestion causing shortness of breath
- Immune-type reaction, such as pharyngitis and vaginitis. *Note:* In similar clinical trials with cells targeting a melanoma protein, we have observed the following immune-mediated toxicities: loss of skin pigment (known as vitiligo), and inflammation of the eye (uveitis). The skin and the eye are all sites where that targeted melanoma protein is known to exist.  
- As this is a new experimental therapy, side effects that we do not anticipate that may cause your condition to deteriorate may be encountered. Any new information that becomes available during the course of this study will be shared with you.
Clinical trial: NCT01814046
Section: Purpose of Research
Subsections: Why Are You Being Asked To Take Part In This Study?

You are being asked to participate in this study because you have been diagnosed with metastatic ocular melanoma. How many people will take part in this Study? Up to 54 patients will be enrolled in this study. Description of Research Study Research Study Overview The Cell protocol has several stages:  
| Stage                                 | Timeframe                                                     | Location       | Comments & Instructions                                                                                        |                                   |         |      |               |
|---------------------------------------|---------------------------------------------------------------|----------------|----------------------------------------------------------------------------------------------------------------|-----------------------------------|---------|------|---------------|
| Work up                               | 1-2 weeks                                                     | Inpatient      | and                                                                                                            | Scans,                            | x-rays, | labs | leukapheresis |
| out patient                           | other tests as needed                                         |                |                                                                                                                |                                   |         |      |               |
| Chemotherapy                          | 1 week                                                        | Inpatient      | Receive IV chemotherapy to prepare  your immune system for the cells                                           |                                   |         |      |               |
| (day -7 to -1) Cells and  aldesleukin | 1-5 days                                                      | Inpatient      | and                                                                                                            | Receive the TIL cells IV and then |         |      |               |
| possibly ICU                          | high dose aldesleukin about every 8  hours for up to 15 doses |                |                                                                                                                |                                   |         |      |               |
| (Day 0-4) Recovery                    | 1-2 weeks                                                     | Inpatient unit | Recover from the effects of treatment                                                                          |                                   |         |      |               |
| Follow -up                            | Ongoing until  disease  progression                           | Outpatient     | Return to clinic for physical exam,  review of side effects, labs, scans  every 1-3 months for the first year. |                                   |         |      |               |  
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: 13-C-0093 CONTINUATION: page 3 of 14 pages
Clinical trial: NCT01814046
Section: Withdrawal from Study
Subsections: Stopping The Study

Your doctor may decide to take you off this study under the following circumstances:
- if he/she believes that it is in your best interest - if your disease comes back during treatment - if you become pregnant - if you experience side effects from the treatment that are considered too severe - if new information becomes available that shows that another treatment would be better for you In this case, you will be informed of the reason for that decision.
You can stop participating at any time. However, if you decide to stop participating in the study, we encourage you to talk to the study doctor and your regular doctor first. If you refuse to  
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: 13-C-0093 CONTINUATION: page 11 of 14 pages participate or withdraw from the protocol or at the completion of the protocol, we will attempt to offer you participation in other NIH protocols if these are available, or will refer you to your home physician for further management. 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 the Sponsor. 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.