Clinical trial: NCT01583686
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

Other options for treatment of your cancer include:
- Taking part in another study - Getting treatment or care for your cancer without being in a study
- 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, but instead 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: NCT01583686
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 - The Study Sponsor, Center for Cancer Research or their agents - Kite Pharma
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.

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  
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-0111 CONTINUATION: page 13 of 16 pages 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: NCT01583686
Section: Duration of Study Involvement
Subsections: When You Are Finished Taking The Drugs (Treatment) Recovery|Follow Up And Evaluation Of Experimental Regimen|Gene Therapy Long Term Follow Up (Retroviral Vectors)|This Consent Document Has Been Approved For Use From October 25, 2018 **Through May 06, 2019.**

After your last dose of IL-2, you will recover in the hospital until you are well enough to go home. This usually takes 7 to 21 days; 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. In addition to the laboratory tests to monitor your condition, we will remove approximately 9 teaspoons of blood three times per week to study the effects of this regimen on your immune system. 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 regimen. We will ask you to return to NIH approximately 6 and 12 weeks following treatment and then if you are responding to the treatment, every 3 months x 3, every 6 months x 2 years and then as determined by your physician. This visit will probably take 2 days. If your tumor shows evidence of shrinking, we will ask you to return for evaluation every month for several more months. If your tumor appears to be growing, we will look for other investigational therapies you may be eligible for, or refer you back to the care of your local physician. At some of your follow up visits, you may undergo leukapheresis 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.

Because we do not know the long term side effects of gene therapy, we will collect your blood over the next several years, frequently at first and then less frequently. If you return to your referring physician after treatment here we will ask you to have your physician send your blood specimens here for this testing. This testing will determine if the cells have grown or changed in your body. We will test your blood immediately after you receive the cells, and then at 3, 6 and 12 months (2 teaspoons each time). If all of the tests are normal and show no change, we will collect blood from you every year after that to store in case you develop symptoms later. According to FDA requirements, we need you to return annually to the NIH for a physical examination for five years after you receive the cells. After that time, we will be sending you a questionnaire to get information regarding your health for the next ten years, for a total follow up time period of 15 years. For this reason, we ask that you continue to provide us with a current address and telephone number, even after you complete this research study. At the time of your death, no matter the cause, we may request permission for an autopsy in order to obtain vital information concerning the safety of this experimental treatment approach. Please discuss this with your family to inform them of this request.

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: NCT01583686
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.  
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-0111 CONTINUATION: page 12 of 16 pages
Clinical trial: NCT01583686
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?|Gene Therapy Risk Of Cancer And Other Diseases|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 regimen can lead to long-term decrease in your immune function. It is also possible that you may lose your fertility following this experimental regimen. It is possible, although unlikely, that this experimental regimen 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.  
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-0111 CONTINUATION: page 7 of 16 pages

When retroviral vectors enter a normal cell in the body, the DNA of the vector inserts itself into the normal DNA in that cell; this process is called integration. Most integration is expected to cause no harm to the cell or to the patient. However, there is a chance that there may be some regions of the normal human DNA where integration of the viral vector's DNA may result in activation of neighboring genes. For example, if one of these genes were a growth factor, this may cause uncontrolled division of the cell, resulting in a cancer. This type of event has occurred in one animal study in mice where the vector integration site correlates with the occurrence of cancer in these mice. Five instances of a similar event have been reported in five children out of 22 who received a retroviral vector in two experimental gene transfer studies for X-linked Severe Combined Immunodeficiency (SCID) conducted in Europe, not under the jurisdiction of the U.S. Food and Drug Administration (FDA). While most of the children who participated in this clinical trial appear to have been cured of their disease, five children developed leukemia (a form of cancer of the blood) approximately 2-6 years after receiving the gene transfer regimen. The first patient had extensive testing done to determine the cause of the leukemia. A group of experts in this field have looked at all the test results, and concluded that the gene transfer caused the leukemia in the first child. One of the children died as a result of their leukemia. The risk of another cancer developing in you, including leukemia, is unknown, but you need to be aware of this possible risk. To monitor you for this risk we will be testing your blood 3 months after cell infusion, then at 6 and 12 months, and then annually thereafter. If we find that the cells we have given you grow out of control, chemotherapy will be given to you to kill the cells, given their risk of causing leukemia or a second cancer. This testing will be conducted on our protocol 09-C-0161, "Follow up Protocol for Subjects Previously Enrolled in NCI Surgery Branch Studies" to which you will be enrolled following treatment.  
STUDY NUMBER: 12-C-0111 CONTINUATION: page 11 of 16 pages

The aim of this study is to see if this 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 effect of this treatment on 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: NCT01583686
Section: Procedures
Subsections: What Will Happen If You Take Part In This Research Study?|Cell Harvest And Growth|Work Up|Catheter Insertion|Leukapheresis|Chemotherapy Regimen (Day -7 Through Day -3)|Cell Infusion And Il-2 Regimen (Day 0 Through Day 4)

The first few patients enrolled will participate in the Phase I portion of the study, called the "dose escalation" phase. The purpose of dose escalation is to determine the most effective yet safe dose of anti-mesothelin cells. There will be 10 dose levels of anti-mesothelin cells. The first patients enrolled get the smallest dose and the dose is increased when a level has been determined to be safe. If the first dose has too many side effects, patients enrolled will receive smaller doses. Discuss with your doctor which dose of anti-mesothelin cells you will be receiving. The major side effects of this experimental regimen (described below) that are most severe

You underwent a process called apheresis, while enrolled on our companion protocol 03-C-0277. This process obtained blood cells from you. Some of these cells will be grown in the lab and genetically modified to recognize a protein on your tumor cells. If your cells do not grow, unfortunately, you will not be able to receive the cell infusion. If that happens, we will look at alternative experimental treatments at the NIH Clinical Center or refer 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 regimen, you will undergo many tests. These include imaging procedures, heart and lung function tests, eye exams, and laboratory tests. If you are a woman, you will undergo a pregnancy test. You may be admitted to the hospital for these tests.  
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-0111 CONTINUATION: page 4 of 16 pages However, you will be allowed to leave on pass on the days that you are not having tests performed.

Prior to beginning the experimental regimen, 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 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 white blood cells may be used to help grow the cells.

After we have grown the anti-mesothelin cells to large numbers in the laboratory, you will be admitted to the hospital to begin your experimental regimen. You will be given two chemotherapy medicines, cyclophosphamide and fludarabine, to suppress your immune system so the anti-mesothelin cells can work without any interference from the cells in your immune system. (These medicines will not treat your cancer.) Animal experiments have indicated that this 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 -7 through Day -3). The side effects of these medicines are described on the following pages.

One to four days after the last dose of chemotherapy, you will be given the anti-mesothelin cells. The anti- mesothelin cells will be given in your catheter over 20-30 minutes. Within 24 hours after the anti- mesothelin cell infusion, you will be given low dose IL-2 through your catheter. High dose IL-2 is approved by the FDA for treatment of metastatic melanoma and metastatic renal cell cancer. The purpose of giving the IL-2 with this therapy is to keep the cells we give  
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-0111 CONTINUATION: page 5 of 16 pages you active for as long as possible so they will fight your tumor. The IL-2 will be given as a 15minute infusion every 8 hours for up to five days after the cell infusion (maximum number of doses is 15). Doses may be skipped or delayed depending on how well you tolerate the doses. The risks of the cells and IL-2 are described on the following pages. The day after you receive the anti-mesothelin cells, we will give you more G-CSF (filgrastim) as a shot or injection under the skin. This will continue until your white blood cell counts begin to return to normal.
Clinical trial: NCT01583686
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 have been diagnosed with metastatic cancer and the standard treatments available have not been effective. We have developed an experimental procedure for treating patients with cancer that uses blood cells found in their peripheral blood cells. We genetically modify these cells and grow them in the laboratory. We will be using the anti-mesothelin gene and a type of virus  
PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY  
- Adult Patient or - Parent, for Minor Patient  
NIH-2514-1 (07-09) P.A.: 09-25-0099  
File in Section 4: Protocol Consent (1)  
STUDY NUMBER: 12-C-0111 CONTINUATION: page 2 of 16 pages
(retrovirus) in making these special cells (anti-mesothelin cells). The anti-mesothelin cells target a protein called mesothelin. This receptor is located on some types of cancer, including the type of cancer you have been diagnosed with. By blocking mesothelin, we hope that these cells when infused will decrease the size of your tumors. However, it is possible that these cells will not have this effect. The anti-mesothelin cells will be given to you as an intravenous (IV) infusion. This type of experimental regimen is called "gene transfer" and is very closely monitored by the Food and Drug Administration (FDA) and other regulatory agencies. The risks of gene transfer will be described later in this document.

You are being asked to participate in this study because you have been diagnosed with cancer that has the mesothelin molecule on the surface of the tumors.

This study has the following stages outlined below: Stage 1 is performed under the screening protocol, 99-C-0128 Stage 2 is performed under the cell harvest protocol, 03-C-0277 Stages 3-6 are performed under this protocol  
| What          | Timeframe                                   | Location                            | Comments & Instructions   |                                                                                            |
|---------------|---------------------------------------------|-------------------------------------|---------------------------|--------------------------------------------------------------------------------------------|
| 1.            | Work up                                     | 1-2 weeks                           | Inpatient and             | Scans, x-rays, labs and other tests                                                        |
| out patient   | as needed                                   |                                     |                           |                                                                                            |
| 2.            | Cell                                        | 4-6 weeks                           | Inpatient or              | Leukapheresis                                                                              |
| Manufacturing | Outpatient                                  |                                     |                           |                                                                                            |
| 3.            | Chemotherapy                                | 1 week                              | Inpatient                 | Receive IV chemotherapy to  prepare your immune system for  the cells                      |
| 4.            | Cells and IL-2                              | 1-5 days                            | Inpatient and             | Receive anti-mesothelin cells, and                                                         |
| possibly ICU  | then IL-2 every 8 hours for up to  15 doses |                                     |                           |                                                                                            |
| 5.            | Recovery                                    | 1-3 weeks                           | Inpatient unit            | Recover from the effects of  chemotherapy and IL-2.                                        |
| 6.            | Follow -up                                  | Ongoing  until disease  progression | Outpatient                | Return to clinic for physical exam,  review of side effects, labs, scans  every 1-6 months |  
STUDY NUMBER: 12-C-0111 CONTINUATION: page 3 of 16 pages
Clinical trial: NCT01583686
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
- if you become pregnant
- if you have side effects from the treatment that your doctor thinks are too severe - if new information shows that another treatment would be better for you
In this case, you will be informed of the reason therapy is being stopped. You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your regular doctor first. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to 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.