Clinical trial: NCT02153905
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 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, 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: NCT02153905
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.
- NCI Institutional Review Board  
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:14-C-0110 CONTINUATION: page 13 of 16 pages  
- The study Sponsor, Center for Cancer Research or their agents
- Our research collaborator, Kite Pharma, Inc.
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 Website 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 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: NCT02153905
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)

After your last dose of aldesleukin, 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. 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 treatment. 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 x 3, then every 6 months x 2 years and then as determined by your physician. The follow up visits will probably take 1-2 days. 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 email and we may ask you to send us lab, imaging, and physical exam reports. 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.

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.
Clinical trial: NCT02153905
Section: Participant Responsibilities
Subsections: Birth Control

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. 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 four months after your blood tests show no evidence of the cells. In addition, male participants should not donate sperm during this time period. If you think that you or your partner is pregnant, you should tell your study doctor or nurse at once. Effective forms of birth control include:  
- Abstinence
- Intrauterine device (IUD)
- Hormonal [birth control pills, injections, or implants]
- Tubal ligation
- Vasectomy
Clinical trial: NCT02153905
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are The Costs Of Taking Part In This Study?

If you choose to take part in the study, the following will apply, in keeping with the NIH policy:  
- You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.  
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.  
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Clinical trial: NCT02153905
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 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.  
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:14-C-0110 CONTINUATION: page 7 of 16 pages 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.

We are unsure if this type of gene therapy will cause you to become sick in the future. It is possible that it may cause your immune system or nerves not to work well or cause a sickness of  
| 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:14-C-0110 CONTINUATION: page 11 of 16 pages your blood cells or even a cancer (for example leukemia). We do not know if you will develop any of these disorders, but you need to be aware of this possible risk. Children in France and England received gene therapy for a particular disease of the immune system. Most of the children were cured, but 5 children out of 22 later developed leukemia and one died. Experts who looked at these cases thought that the gene therapy caused the leukemia in these children. 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.

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: NCT02153905
Section: Procedures
Subsections: Cell Harvest And Growth|Work-Up|Catheter Insertion|Leukapheresis|During The Study The Following Procedures Will Be Performed Under This Protocol: Chemotherapy Regimen (Day -7 Through Day -3)|Cell Infusion And Aldesleukin Regimen (Day 0 Through Day 5)|Retreatment|Cell Infusion|Aldesleukin (Il-2)|Medications

You underwent a process called "apheresis", while enrolled on our companion protocol 03-C0277 (Cell harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols). This process obtained certain types of 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 (anti-MAGE-A3). 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 treatment, you will undergo many tests. These include imaging procedures, heart and lung function tests, eye exams, and laboratory tests. If you have received ipilimumab (also called Yervoy, MDX-010) or any antibody therapy that could affect an anti cancer immune response and have experienced any GI toxicities, you will have a colonoscopy and biopsies to make sure your colon is normal since these drugs may have caused damage to your colon that may worsen with aldesleukin treatment. If you are a woman, you will undergo a pregnancy test. 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  
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:14-C-0110 CONTINUATION: page 4 of 16 pages 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 white blood cells may be used to help grow the cells and after the treatment, you will have leukapheresis so that we can test your cells. In addition to the 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 regimen to see the impact of this therapy on the immune system and see if cells we gave you are still active.

After we have grown the anti-MAGE-A3 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 suppress your immune system so the anti-MAGE-A3 cells can work without any interference from the cells in your immune system. (These medicines will not treat your cancer; although they may cause your tumor to shrink for a short period of time.) 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 five days (Day - 7 through Day -3). The side effects of these medicines are described on the following pages. After you have completed the chemotherapy regimen you will receive the cell infusion.

One to four days after the last dose of chemotherapy, you will be given the anti-MAGE-A3 cells. The anti-MAGE-A3 cells will be given in your intravenous catheter over 30 minutes. Within 24 hours after the anti-MAGE-A3 cell infusion, you will be given high dose aldesleukin through your intravenous catheter. Aldesleukin is approved by the FDA for treatment of metastatic melanoma and metastatic renal cell cancer. The purpose of giving the aldesleukin with this therapy is to keep the cells we give you active for as long as possible so they will fight your tumor. The aldesleukin will be given as a 15-minute infusion about every 8 hours for up to five days after the cell infusion (maximum number of doses is 15). Doses may be skipped or delayed STUDY NUMBER:14-C-0110 CONTINUATION: page 5 of 16 pages depending on how well you tolerate the doses. The risks of the cells and aldesleukin are described on the following pages. The day after you receive the anti-MAGE-A3 cells, we will give you 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. 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 your tumor shrinks or disappears following the initial treatment and then stops shrinking or recurs, you may receive additional treatments if you tolerated the treatment well and if all the side effects have resolved. The second treatment will not begin prior to 6- 8 weeks after your last dose of aldesleukin.  
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:14-C-0110 CONTINUATION: page 6 of 16 pages

The cells we will be giving you have been modified with a retrovirus that has the gene for antiMAGE-A3 incorporated in the retrovirus. The cells could cause you to develop another type of cancer, such as leukemia or lymphoma, although this has never been seen in any gene therapy trial involving lymphocytes. These specific gene-modified cells have not been given to patients and thus we do not know what the specific side effects will be. In 2 prior studies using different parts of the MAGE gene, four patients died. In one of these studies, two patients of 9 who received this treatment died from neurological toxicities, probably due to the treatment. We stopped that study but continued research to try to determine the cause of the side effects from the treatment. In the other study which took place at another institution 2 patients died from cardiac toxicities. The anti-MAGE-A3 is different from the MAGE used in the earlier trials and we do not anticipate that this anti-MAGE-A3 will cause the same side effects. Potential risks include:  
- Fever, chills and shortness of breath, which may last for a few hours (common)
- Lung congestion causing shortness of breath
- Autoimmune reaction such as loss of skin pigment (known as vitiligo) or inflammation of the eye (uveitis) which may require the use of steroid eye drops.  
- As this is a new experimental therapy which has not been given to patients, 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.  
- You will be treated on this gene transfer protocol with a viral vector that was manufactured at the NCI Surgery Branch Vector Production Facility before May 2016.  
An internal review of the facility that made the vector for this protocol determined that the facility needed to be closed due to manufacturing issues. We know of no additional risks related to the previously produced vector for patients who have received cells with vectors made in this facility as the vectors were extensively tested by outside experts. Therefore, the IRB has determined that the potential benefit to you outweighs the potential risks.  
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:14-C-0110 CONTINUATION: page 8 of 16 pages

When aldesleukin is given through an intravenous catheter, it can make you feel like you have the flu. It can also cause confusion and mental status changes making you unable to make sound decisions. Prior to beginning treatment, we will ask you to complete a Durable Power of Attorney so that a person of your choosing can make health care decisions for you in case you develop these side effects. In our experience giving aldesleukin to over 2,000 patients we have found that these side effects go away within a few days of stopping the aldesleukin.

The side effects of cyclophosphamide, fludarabine, high dose aldesleukin and some of the other medications you will receive are listed below:  
| Cyclophosphamide and Fludarabine Side Effects Common Less Common   | Rare                                                                                                                                                                                                                                                                                                           |    |               |    |              |
|--------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----|---------------|----|--------------|
|                                                                   | Changes in blood counts  including: low red cell  count (causing fatigue and  shortness of breath), low  platelet count (increasing  the risk of bleeding and  bruising), decrease in  white blood cells  (increasing the risk of  infection and the need for  treatment with antibiotics  or other treatment) |    |               |    |              |
|                                                                   | Loss of appetite, nausea,  vomiting,                                                                                                                                                                                                                                                                           |    |               |    |              |
|                                                                   | Diarrhea, stomach pain                                                                                                                                                                                                                                                                                         |    |               |    |              |
|                                                                   | Mouth sores                                                                                                                                                                                                                                                                                                    |    |               |    |              |
|                                                                   | Hair loss                                                                                                                                                                                                                                                                                                      |    |               |    |              |
|                                                                   | Fatigue                                                                                                                                                                                                                                                                                                        |    |               |    |              |
|                                                                   | Muscle or joint aches                                                                                                                                                                                                                                                                                          |   | Bleeding      |   | Heart damage |
|                                                                   | Infection                                                                                                                                                                                                                                                                                                      |   | Lung damage   |    |              |
|                                                                   | Bladder irritation with  bloody urine                                                                                                                                                                                                                                                                          |    |               |    |              |
|                                                                   | Severe allergic reaction  (difficulty  breathing/swelling)                                                                                                                                                                                                                                                     |    |               |    |              |
|                                                                   | Headache or dizziness                                                                                                                                                                                                                                                                                          |    |               |    |              |
|                                                                   | Sweating                                                                                                                                                                                                                                                                                                       |    |               |    |              |
|                                                                   | Swelling of arms or legs                                                                                                                                                                                                                                                                                       |    |               |    |              |
|                                                                   | Skin changes, rash, blisters                                                                                                                                                                                                                                                                                   |    |               |    |              |
|                                                                   | Weakness                                                                                                                                                                                                                                                                                                       |    |               |    |              |
|                                                                   | Hearing loss                                                                                                                                                                                                                                                                                                   |   | Kidney damage |    |              |
|                                                                   | Inflammation of the eye  resulting in blindness                                                                                                                                                                                                                                                                |    |               |    |              |
|                                                                   | Inflammation of nervous  system resulting in death                                                                                                                                                                                                                                                             |    |               |    |              |
|                                                                   | Epstein Barr Virus  Lymphoma. This can be  fatal (Two patients on  other studies in the  Surgery Branch developed  EBV lymphoma, and both  died as a result of this  disease.)                                                                                                                                 |    |               |    |              |
|                                                                   | Loss of fertility                                                                                                                                                                                                                                                                                              |    |               |    |              |
|                                                                   | Death due to  complications resulting  from suppression of the  immune function which  resulted in a severe  infection                                                                                                                                                                                         |    |               |    |              |  
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  
for  
  
NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study STUDY NUMBER:14-C-0110 CONTINUATION: page 9 of 16 pages  
| Aldesleukin (IL-2) Side Effects Common Less Common                                     | Rare                                                                                                                                                                                                                |                           |                                                                                     |
|----------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------|-------------------------------------------------------------------------------------|
|                                                                                       | Fever, chills, and fatigue                                                                                                                                                                                          |                          | Decrease in thyroid  function that may require  daily thyroid hormone  replacement. |
|                                                                                       | Abnormal kidney and liver  function that can be  severe.                                                                                                                                                            |                           |                                                                                     |
|                                                                                       | Abnormal heartbeats or  low blood pressure that  may require treatment in  the ICU.                                                                                                                                 |                           |                                                                                     |
|                                                                                       | Breathing problems which  may need monitoring in  ICU and insertion of a  breathing tube.                                                                                                                           |                          | Bowel perforation (a hole)  requiring longer  hospitalization or surgery.           |
|                                                                                       | Autoimmune disease,  where your immune  system attacks cells in  organs of your body.  Should this occur, you will  be treated with steroids to  stop the immune response.                                          |                           |                                                                                     |
|                                                                                       | Damage to the heart  muscle or heart attack                                                                                                                                                                         |                           |                                                                                     |
|                                                                                       | Loss of blood flow to the  extremities due to  medicines used to treat  very low blood pressure  and shock. In one instance  a patient had to have her  lower arm amputated after  treatment with these  medicines. |                           |                                                                                     |
|                                                                                       | Aldesleukin is mixed with  human albumin which  could cause an allergic  reaction or potentially  transmit viral infections,  although we have not had  this occur.                                                 |                           |                                                                                     |
|                                                                                       | Lowered platelet and red  blood cell levels that may  require transfusions                                                                                                                                          |                           |                                                                                     |
|                                                                                       | Significant fluid retention  causing weight gain (as  much as 20 pounds).                                                                                                                                           |                           |                                                                                     |
|                                                                                       | Low blood pressure                                                                                                                                                                                                  |                           |                                                                                     |
|                                                                                       | Increased heart rate                                                                                                                                                                                                |                           |                                                                                     |
|                                                                                       | Shortness of breath                                                                                                                                                                                                 |                           |                                                                                     |
|                                                                                       | Low urine output                                                                                                                                                                                                    |                           |                                                                                     |
|                                                                                       | Swelling in your  extremities,                                                                                                                                                                                      |                           |                                                                                     |
|                                                                                       | Fluid in your lungs that  can require oxygen                                                                                                                                                                        |                           |                                                                                     |
|                                                                                       | Dry mouth, nausea,  vomiting and diarrhea;                                                                                                                                                                          |                           |                                                                                     |
|                                                                                       | Rash, itching; and changes  in skin or hair  pigmentation, called  vitiligo;                                                                                                                                        |                           |                                                                                     |
|                                                                                       | Changes in mental status,  including confusion,  difficulty sleeping or vivid  dreams; this can be severe  and require sedation and  monitoring in the ICU                                                          |                           |                                                                                     |
| Support Medications - Side Effects Common Less Common                                  | Rare                                                                                                                                                                                                                |                           |                                                                                     |
| Filgrastim (To increase production of white blood cells)  Bone Pain  Severe headache |                                                                                                                                                                                                                    | Severe breathing problems |                                                                                     |
| 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                                                                                           |                           |                                                                                     |
Clinical trial: NCT02153905
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

We have developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol we are modifying the patient's white blood cells with a retrovirus that has the gene for anti-MAGE-A3 incorporated in the retrovirus. So far, MAGE-A3 has been found only on tumor cells. The purpose of this study is to see if these particular tumor-fighting cells can cause tumors to shrink and to be certain the treatment is safe. However, it is possible that these cells will not  
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:14-C-0110 CONTINUATION: page 2 of 16 pages have this effect. 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-MAGE-A3 cells. There will be 5 dose levels of anti-MAGE-A3 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-MAGE-A3 cells you will be receiving. This is the first time these cells will be given to humans. Since this is a phase I/II trial, it is unlikely that you will receive any benefit.

You are being asked to participate in this study because you have been diagnosed with cancer that has the MAGE-A3 molecule on the surface of the tumors.

This study has several stages as outlined below:  
- Stage 1 is performed under the companion protocol, 99-C-0128 (Evaluation for NCI
Surgery Branch Clinical Research Protocols), to which you have already enrolled.  
- Stage 2 is performed under the companion protocol, 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols), to which you have already enrolled.  
| Stage                  | Timeframe                                                                                                                 | Location   | Comments & Instructions   |                                                                       |
|------------------------|---------------------------------------------------------------------------------------------------------------------------|------------|---------------------------|-----------------------------------------------------------------------|
| 1.                     | Work-up                                                                                                                   | 1-4 weeks  | Inpatient or              | Scans, x-rays, labs, other tests as                                   |
| outpatient             | needed                                                                                                                    |            |                           |                                                                       |
| 2.                     | Cell                                                                                                                      | 4-6 weeks  | Inpatient or              | Leukapheresis                                                         |
| Manufacturing          | Outpatient                                                                                                                |            |                           |                                                                       |
| 3.                     | Chemotherapy                                                                                                              | 5 days     | Inpatient                 | Receive IV chemotherapy to  prepare your immune system for  the cells |
| (Days -7 to -3)        |                                                                                                                           |            |                           |                                                                       |
| 4.                     | Cells and  aldesleukin (Days 0-5)                                                                                         | 1-5 days   | Inpatient and             | Receive the anti-MAGE-A3 cells                                        |
| possibly ICU           | IV and then high dose  aldesleukin about every 8 hours  for up to 15 doses                                                |            |                           |                                                                       |
| 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 |            |                           |                                                                       |  
- Stages 3-6 are performed under this protocol.
STUDY NUMBER:14-C-0110 CONTINUATION: page 3 of 16 pages  
| Stage   | Timeframe   | Location                            | Comments & Instructions   |                                                                                                                 |
|---------|-------------|-------------------------------------|---------------------------|-----------------------------------------------------------------------------------------------------------------|
| 5.      | Recovery    | 1-3 weeks                           | Inpatient unit            | Recover from the effects of  treatment                                                                          |
| 6.      | 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. |  
What will happen if you take part in this research study?
Clinical trial: NCT02153905
Section: Voluntary Participation
Subsections: For Nih 2514-2, Minor Patient'S Assent To Participate In A Clinical Research Study

STUDY NUMBER:14-C-0110 CONTINUATION: page 10 of 16 pages  
|                                                                                                                                                                                                                           | Rupture of your spleen                      |                                                                          |                           |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------|--------------------------------------------------------------------------|---------------------------|
| Bactrim (To prevent a specific type of pneumonia)  Fever  Nausea, vomiting   Skin rash with itching   Reduced number of white  blood cells   Allergic reaction Fluconazole (To prevent fungal infections)   Headache |                                            | A skin disorder called  Stevens Johnson Syndrome,  which can be fatal    |                           |
|                                                                                                                                                                                                                           | Liver damage which may  be permanent        |                                                                          |                           |
|                                                                                                                                                                                                                           | Nausea, vomiting, diarrhea,  abdominal pain |                                                                          |                           |
|                                                                                                                                                                                                                           | Itching                                     |                                                                          |                           |
| Acyclovir and Valacyclovir                                                                                                                                                                                                 |                                            | Temporary decrease in  kidney function which may  not cause any symptoms |                           |
|                                                                                                                                                                                                                           | Nausea, vomiting, diarrhea,  constipation   |                                                                          |                           |
|                                                                                                                                                                                                                           | Pain and irritation at place  of injection  |                                                                         | Skin rash, hives, itching |
|                                                                                                                                                                                                                           | Tremors, dizziness,  Confusion, seizures    |                                                                          |                           |
|                                                                                                                                                                                                                           | Fatigue                                     |                                                                          |                           |
|                                                                                                                                                                                                                           | Blood in the urine                          |                                                                          |                           |
| Prior to and throughout this study you will undergo many tests to determine the size and extent                                                                                                                            |                                             |                                                                          |                           |  
Prior to and throughout this study you will undergo many tests to determine the size and extent of your tumor, as well as the impact of the treatment. Multiple blood tests will be performed and some of your serum and lymphocytes will be stored for future testing. Blood and tissue samples collected from you may be stored and used in the future to study scientific questions related to this protocol. If there are any risks to you or your family associated with these future scientific studies which are not covered in this consent form, your consent will be obtained before such studies are performed. If your disease progresses or recurs after this experimental treatment, then you will no longer receive treatment in this protocol, though you may be eligible to be considered for other protocols at the National Cancer Institute, NIH or referred elsewhere for treatment.
Clinical trial: NCT02153905
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  
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:14-C-0110 CONTINUATION: page 12 of 16 pages  
- 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.