Clinical trial: NCT02659943
Section: Alternatives
Subsections: What Other Choices Do I Have If I Do Not Take Part In This Study?|Alternative Approaches Or Treatments

Instead of being in this study, you have these options:
- Getting treatment or care for your cancer without being in a study  
- Taking part in another study - Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite problems and other problems caused by the cancer. It does not treat the cancer directly. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
Please talk to your doctor about these and other options.

Prior to this, you have received many of the conventional therapies for your disease. Before deciding whether or not to participate in this clinical trial, you may consider other treatments such as:
- Other forms of chemotherapy, radiation, surgery, or immune therapies, without being in a study.  
- You may be eligible for other experimental therapies. - Another option is not to receive any further therapy at all, other than comfort care, also called palliative care. This type of care reduces tiredness, appetite problems and other problems caused by the cancer. It does not treat cancer directly. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
You should discuss with your referring doctor and the NIH doctors whether any of these treatments might represent a reasonable treatment option for your disease.
Clinical trial: NCT02659943
Section: Confidentiality
Subsections: How Will My Samples And Data Be Used?|Protections Against Misuse Of Genetic Information|Use Of Specimens And Data For Future Research|Genomic Data Sharing|Confidentiality Protections Provided In This Study Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality|Privacy Act

This study aims to perform laboratory studies (research) to better understand how the immune system fights cancer cells and to make more effective cell treatments. We plan to keep some of your specimens and data that we collect while you are participating on this study to use in our research labs. We will use some of the samples we collect (blood, tissue) to perform a number of genetic tests. This includes RNA sequencing on your samples. The human genome is the material in our cells that includes thousands of genes. Genes are the building blocks of our cells that make and maintain our body. A gene provides instructions to individual cells to make proteins through a middle step of making RNA. Proteins are the substances that are involved in all of our body's chemical processes. The purpose of RNA sequencing is to learn about the expression of different genes in your cancer cells and in your CAR T cells. Our goal is not to look into genetic abnormalities that could be inherited by you or passed along to your children, but in the course of studying gene expression, there is a slight chance that we could find evidence of an inherited disorder or a genetic disorder that could be passed along to your children. The slight possibility of this happening is covered below under "Incidental and Secondary Findings".  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020

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

To advance science, it is helpful for researchers to share information they get from studying human samples. They do this by putting it into one or more scientific databases, where it is stored along with information from other studies. A researcher who wants to study the  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
information must apply to the database and be approved. Researchers use specimens and data stored in scientific databases to advance science and learn about health and disease. We plan to keep some of your specimens and data that we collect and use them for future research and share them with other researchers. We will not contact you to ask about each of these future uses. These specimens and data will be stripped of identifiers such as name, address or account number, so that it may be used for future research on any topic and shared broadly for research purposes. Your specimens and data will be used for research purposes only and will not benefit you. It is also possible that the stored specimens and data may never be used. Results of research done on your specimens and data will not be available to you or your doctor. It might help people who have cancer and other diseases in the future. If you do not want your stored specimens and data used for future research, please contact us in writing and let us know that you do not want us to use your specimens and/or data. Then any specimens that have not already been used or shared will be destroyed and your data will not be used for future research. However, it may not be possible to withdraw or delete materials or data once they have been shared with other researchers.

As part of this research study, we will put your genomic data in a large database for broad sharing with the research community. These databases are commonly called data repositories. The information in this database will include but is not limited to genetic information, race and ethnicity, and sex. If your individual data are placed in one of these repositories, they will be labeled with a code and not with your name or other information that could be used to easily identify you, and only qualified researchers will be able to access them. These researchers must receive prior approval from individuals or committees with authority to determine whether these researchers can access the data. Summary information about all of the participants included in this study (including you) is being placed in a database and will be available through open access. That means that researchers and non-researchers will be able to access summary information about all the participants included in the study, or summary information combined from multiple studies, without applying for permission. The risk of anyone identifying you with this information is very low. NIH policies require that genomic data be placed in a repository for sharing. Therefore, we cannot offer you a choice of whether your data will be shared. If you do not wish to have your data placed in a repository, you should not enroll in this study.

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:  
- The NIH and other government agencies, like the Food and Drug Administration (FDA),
which are involved in keeping research safe for people.  
- National Institutes of Health Intramural Institutional Review Board
- The study Sponsor, NCI Center for Cancer Research, or their agent(s)
When results of an NIH research study are reported in medical journals or at scientific meetings, the people who take part are not named and identified. In most cases, the NIH will not release any information about your research involvement without your written permission. However, if you sign a release of information form, for example, for an insurance company, the NIH will give the insurance company information from your medical record. This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance.  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
If we share your specimens or data with other researchers, in most circumstances we will remove your identifiers before sharing your specimens or data. You should be aware that there is a slight possibility that someone could figure out the information is about you. Further, the information collected for this study is protected by NIH under a Certificate of Confidentiality and the Privacy Act.

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

The Federal Privacy Act generally protects the confidentiality of your NIH medical records we collect under the authority of the Public Health Service Act. In some cases, the Privacy Act protections differ from the Certificate of Confidentiality. For example, sometimes the Privacy Act allows release of information from your medical record without your permission, for example, if it is requested by Congress. Information may also be released for certain research purposes with due consideration and protection, to those engaged by the agency for research purposes, to certain federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is involved in a lawsuit. However, NIH will only release information from your medical record if it is permitted by both the Certificate of Confidentiality and the Privacy Act.  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020
Clinical trial: NCT02659943
Section: Duration of Study Involvement
Subsections: During The Study|When You Are Finished The Cell Infusion|Gene-Therapy-Specific Follow-Up

First, you will undergo an apheresis procedure that will remove cells from your blood. Apheresis is a procedure for obtaining certain blood cells, such as white blood cells, without removing most blood cells. It is a process persons undergo when giving routine platelet donations. Next, we will manipulate your cells in a laboratory so that they can recognize your lymphoma. We will grow your T cells in a laboratory. We will use a type of virus (lentivirus) to permanently change the genes of your T cells. The lentivirus will add a new gene to your T cells, so that your  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
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T cells will have a new receptor. This receptor will allow your T cells to target lymphoma cells that express the CD19 protein. Both your lymphoma cells and your normal B cells, which are a type of immune cell in your body, express CD19. This means that your T cells, which have been changed to express the new receptor, may kill both your lymphoma cells and your normal B cells. We hope that your T cells will decrease the amount of cancer you have. However, it is possible that these cells will not have this effect. If it is not possible after 2 attempts to prepare at least enough cells for you to get the number of cells required by the protocol, you will not be able to be treated on this protocol. This study will be conducted as a "dose escalation". The purpose of dose escalation is to determine the safe dose of anti-CD19 T cells. There will be four dose levels of anti-CD19 T cells. The first patients enrolled get the smallest dose and the dose is increased when a level has been determined to be safe. You can discuss this with the study doctors to find out which dose of anti-CD19 T cells you will be receiving. After you have had cells removed from your blood, you will receive two FDA approved drugs (chemotherapy) named cyclophosphamide and fludarabine, over a period of 3 days. The purpose of the chemotherapy is to enhance the activity of the anti-CD19 T cells. This is a standard chemotherapy regimen that is often used to treat certain types of leukemia. The chemotherapy can be administered on an outpatient basis, which means hospital admission is not necessary to receive this chemotherapy. If you have been removed from the protocol BEFORE receiving any protocol therapy, you may be eligible for re-enrollment in the study. Two days after the chemotherapy ends, you will be admitted to the hospital as an inpatient and receive the antiCD19 T cells. The anti-CD19 T cells will be given to you as a single intravenous (IV) infusion.  
You will need to have a "central line", and IV catheter (or tube) placed in a large vein in your arm or chest for this infusion. If you have a catheter or a port-a-cath in place already, this could possibly be used to receive the cell infusion. All patients that participate in this study will be required to stay in the hospital for close observation for at least 9 days after the cell infusion, and patients must stay within 60 minutes driving distance for 2 weeks after the cell infusion. This is because in our experience with similar treatments we have noticed side-effects including fevers, fatigue, low blood pressure, and others that have been most severe between 4 and 9 days after cell infusion. You will be closely watched during the anti-CD19 T cell infusion for signs of a reaction. While other types of genetically-modified T cells have been administered to many patients, infusion of anti-CD19 T cells is a new approach that is being evaluated in this protocol. There is always a chance that we will not be able to genetically-modify your cells or be able to grow the cells in the laboratory. If we are not able to successfully prepare the minimal number of cells that we believe are needed to help control the cancer in our first attempt to produce the cells, we will make a second attempt to produce the cells if you give us permission to do so even if you have already received the chemotherapy part of the protocol at the time. This second attempt to produce cells will probably not be necessary. For patients who still have detectable cancer after receiving anti-CD19 T cells the first time, repeated infusions might be possible. In order for a repeat infusion to be possible, you must not  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
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have experienced severe toxicities with their first infusion, and you must meet the original eligibility requirements for enrollment on the trial. Repeat treatments will also include the same chemotherapy as the first treatment.

You will need to come for a clinic visit two weeks and three weeks after your cell infusion, for blood work and a brief visit with one of our doctors. You will also need to return to clinic for evaluation of your overall health and your B-cell cancer 1, 2, 3, 6, 9 and 12 months after the cell infusion. If you have a fever of 100.5 degrees or higher within the first year after CAR T-cell infusion, you should report to your local health care facility for a complete blood count to make sure you do not have low blood counts, which can make infections life-threatening. After 12 months, follow up for patients with ongoing responses, which means the B-cell cancer has not progressed, will continue every 6 months for up to 3 years and then annually after your T-cell infusion. At the follow-up visits we will evaluate your general health, and we will assess your B-cell cancer. Blood will be drawn at all follow-up visits. Note that all of these follow-up visits are only required for patients with ongoing responses. If your B-cell cancer progresses, you will be removed from the study to pursue other options. As long as your B-cell cancer does not progress, we ask that you do not take any other treatments. We also ask that you do not take any corticosteroid medications such as prednisone or dexamethasone. If you do take other treatments or if you take corticosteroids, we will not be able to interpret the results of the anti-CD19 T cells, and you will be removed from the study. In addition, corticosteroids and some other medications including chemotherapy will damage the anti-CD19 T cells, so they might reduce the effectiveness of the T cells at eliminating cancer. You will also be followed by your home oncologist who will receive a detailed summary of your case and blood tests and other investigations that need to be performed and potential problems that may arise. We encourage early communication of any problems with us so that we can assist in deciding the best treatment approach.

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 receiving therapy 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 collect your blood sample right after you receive the cells, and then at 3, 6, and 12 months after treatment (2 teaspoons each time). We may also collect your blood over the next several years after 12 months if you have had any previous tests that show a lentivirus in your blood.. According to FDA requirements, we need you to return annually to the NIH or in some cases have an appointment with a physician close to your home 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  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
death, no matter the cause, we may request permission for an autopsy in order to obtain vital information concerning the safety of this experimental therapy approach. Please discuss this request with your family to inform them of your wishes.
Clinical trial: NCT02659943
Section: Participant Responsibilities
Subsections: Birth Control|Compensation, Reimbursement, And Payment Will You Receive Compensation For Participation In The Study?|Will You Receive Reimbursement Or Direct Payment By Nih As Part Of Your Participation?|Will Taking Part In This Research Study Cost You Anything?

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 therapy 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 4 months after you finish the last cell infusion. If you think that you or your partner is pregnant, you should tell your study doctor or nurse at once. If you are a man, you should not donate sperm during the study treatment and for 4 months after you finish the last cell infusion.  
Effective forms of birth control include:
- abstinence - intrauterine device (IUD) - hormonal [birth control pills, injections, or implants] - tubal ligation
- vasectomy

Some NIH Clinical Center studies offer compensation for participation in research. The amount of compensation, if any, is guided by NIH policies and guidelines. You will not receive compensation for participation in this study.  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020

Some NIH Clinical Center studies offer reimbursement or payment for travel, lodging or meals while participating in the research. The amount, if any, is guided by NIH policies and guidelines. On this study, the NCI will cover the cost for some of your expenses. Some of these costs may be paid directly by the NIH and some may be reimbursed after you have paid. Someone will work with you to provide more information.

NIH does not bill health insurance companies or participants for any research or related clinical care that you receive at the NIH Clinical Center.  
- If some tests and procedures are performed outside the NIH Clinical Center, 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 NIH Clinical Center.  
- Once you have completed taking part in the study, medical care will no longer be provided by the NIH Clinical Center.
Clinical trial: NCT02659943
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Potential Risks Of Cyclophosphamide:|Gene Therapy Risk Of Cancer And Other Diseases|Procedure Risks|Lumbar Puncture:|Apheresis:|What Are The Risks Of Radiation From Being In The Study?|Contrast Agent Enhanced Ct Scans Risks:|Non-Physical Risks Of Genetic Research Psychological Or Social Risks Associated With Return Of Incidental Or Secondary Findings|Privacy Risks Associated With Return Of Incidental Or Secondary Findings|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

Because the CD19 protein is found on normal B cells as well as on your cancer, the anti-CD19 T cells might cause a fleeting or prolonged decrease in the number of normal B cells. Because B cells are involved in protection against infections, this decrease in B cell number might lead to a greater risk of infections. We do not know if a decrease in normal B cells will cause problems with infections and several steps can be taken to deal with an increased risk of infection or actual infections. The anti-CD19 T cells we will be giving you have been modified to express the anti-CD19 part that targets the T cells to the cancer by using a virus (lentivirus). Although this lentivirus is not active, there is the rare possibility that it may cause infection. The cells could also cause you to develop another type of cancer in your blood cells, although we think this is very unlikely. Other gene-modified T cells have been given to hundreds of individuals before, and in no patient receiving T-cell gene therapy has an infection or cancer developed that was shown to be caused by the lentivirus used. Some patients died who were treated on different experimental protocols that included T cells genetically engineered to express an anti-CD19 receptor. Several other patients have received T cells genetically engineered to express an anti-CD19 receptor without significant adverse effects. Many patients receiving anti-CD19 CAR T cells at various institutions have developed fever and fatigue that can last for up to 2 weeks after cell infusion. Some patients that have received  
| PATIENT IDENTIFICATION      | Consent to Participate in a Clinical Research Study NIH-2977 (4-17) File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020                   |
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similar treatments have developed low blood pressure. A small number of patients developed a temporary decrease in heart function after participating in a similar study at this institute. Their heart function has subsequently returned to normal levels and the other participants in the study have not had decreased heart function. One participant on a different NCI anti-CD19 T-cell study developed tumor lysis syndrome, which is a release of toxic substances from tumor cells that are being destroyed. This tumor lysis syndrome was successfully treated and caused no long-term problems for the patient. Patients at risk of tumor lysis syndrome will receive medication to prevent this complication. Neurological toxicities such as a temporary loss of the ability to speak, temporary confusion, and temporary difficulty walking have occurred in several patients.  
| Potential risks of anti CD 19 T cells infusion include: Likely: Less Likely:   | Rare:                                                                                                                                                                                                                                                                               |    |          |
|--------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----|----------|
| -                                                                              | Fever                                                                                                                                                                                                                                                                               |    |          |
| -                                                                              | Chills                                                                                                                                                                                                                                                                              |    |          |
| -                                                                              | Shortness of breath (these  side effects may last a  few hours)                                                                                                                                                                                                                     |    |          |
| -                                                                              | Fatigue                                                                                                                                                                                                                                                                             |    |          |
| -                                                                              | Somnolence (excessive  sleeping)                                                                                                                                                                                                                                                    |    |          |
| -                                                                              | Low antibody levels  which might require  antibody replacement  infusions                                                                                                                                                                                                           | -  | Headache |
| -                                                                              | General feeling of being unwell  (malaise)                                                                                                                                                                                                                                          |    |          |
| -                                                                              | Lung congestion                                                                                                                                                                                                                                                                     |    |          |
| -                                                                              | Delayed low blood counts months  after infusion of T cells                                                                                                                                                                                                                          |    |          |
| -                                                                              | Rash and/or itching                                                                                                                                                                                                                                                                 |    |          |
| -                                                                              | Cytokine Release Syndrome (release  of substances from T cells that can  cause many side-effects) including o Fever o Fast heart rate o Low Blood Pressure o Possible intensive care unit  admission o Rare cases, death.                                                           |    |          |
| -                                                                              | Low blood pressure                                                                                                                                                                                                                                                                  |    |          |
| -                                                                              | Tumor lysis syndrome (rapid  breakdown of tumor that can cause  side-effects) o Possible intensive care unit  admission o Fast heart rate o Possible kidney damage that  will most likely be  temporary o Possible breathing problems  that might in rare cases  require mechanical | -  | Death    |
| -                                                                              | Delayed toxicity                                                                                                                                                                                                                                                                    |    |          |
| -                                                                              | Sudden stop in heart  function /abnormal  heart rhythm                                                                                                                                                                                                                              |    |          |
| PATIENT IDENTIFICATION                                                         | Consent to Participate in a Clinical Research Study NIH-2977 (4-17) File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020                                                                                                                                                                                                                                                                                          |    |          |
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| Likely:                                                                                           | Less Likely:                                                                                                     | Rare:   |
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| ventilation (breathing  machine)                                                                  |                                                                                                                  |         |
| -                                                                                                 | Temporary decreased cardiac  function                                                                            |         |
| -                                                                                                 | Temporary liver function test  elevation                                                                         |         |
| -                                                                                                 | Temporary decrease in blood counts                                                                               |         |
| -                                                                                                 | Temporary low calcium,  phosphorous, albumin in the blood                                                        |         |
| -                                                                                                 | Muscle inflammation and pain                                                                                     |         |
| -                                                                                                 | Increase in bleeding times                                                                                       |         |
| -                                                                                                 | Temporary neurological changes, ex:  confusion, difficulty speaking,  decreased balance, seizures, eye  floaters |         |
| -                                                                                                 | Fainting                                                                                                         |         |
| As this is a new experimental therapy, side effects that we do not anticipate that may cause your |                                                                                                                  |         |  
As this is a new experimental therapy, side effects that we do not anticipate that may cause your condition to worsen may be encountered.  
| Potential risks of Cyclophosphamide: Likely: Less Likely:   | Rare:                                           |    |                     |
|-------------------------------------------------------------|-------------------------------------------------|----|---------------------|
| -                                                           | Low blood counts                                | -  | Nausea and vomiting |
| -                                                           | Painful and bloody urination                    |    |                     |
| -                                                           | Sterility                                       |    |                     |
| -                                                           | Water retention                                 |    |                     |
| -                                                           | Hair loss                                       | -  | Heart damage        |
| -                                                           | Secondary leukemia (a different type of cancer) |    |                     |
| -                                                           | Skin rash                                       |    |                     |
| -                                                           | Bleeding                                        |    |                     |

| Potential risks of Fludarabine: Likely: Less Likely:   | Rare:                     |    |                                                                                       |
|--------------------------------------------------------|---------------------------|----|---------------------------------------------------------------------------------------|
| -                                                      | Low blood counts          | -  | Long-term reduction of  lymphocyte counts which could  increase the risk of infection |
| -                                                      | Infection                 | -  | Seizures, coma, blindness  and even death                                             |
| -                                                      | Inflammation in the lungs |    |                                                                                       |
| -                                                      | Kidney damage             |    |                                                                                       |  
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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 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 20 later developed leukemia and one died. Experts who looked at these cases thought that the gene therapy caused the leukemia in these children. Because you will be receiving a gene therapy that is very different from the gene therapy that these children received, the chance of this therapy causing a second cancer may be lower. In fact, hundreds of patients have received T-cell gene therapies similar to the one that you will receive without any of them developing a cancer that has been proven to be caused by the T-cell gene therapy. To watch you for this risk we will be testing your blood as described before.

Blood Draws: Blood will be drawn frequently during your treatment. Most of the blood draws will be to monitor your health during and after the lymphocyte infusion. In addition, some blood samples will be drawn for research purposes. Additional blood draws might be necessary to investigate T cell responses and serum cytokine levels in cases of clinical events such as rapid regressions of malignancy or toxicity. These samples will be used to study how your immune system is affected by the cell therapy, a graft-versus-tumor response and graft-versus-host disease (if it occurs). Some of the samples may be used for other or future research conducted by the investigational team or other researchers. In general, 20 to 70 ml of blood (4 to 12 teaspoons) will be drawn at each clinic visit or inpatient hospital day. Side effects of repeated blood sampling depend in part on how the blood is drawn. If through a central venous catheter, risks include contamination of the catheter which would result in a serious blood stream infection, requiring admission to the hospital and giving you antibiotics through the vein; if blood is drawn through a needle into your skin, side-effects could include pain and bruising in the area where the blood was drawn. Other side-effects can include lightheadedness, or rarely, fainting. If you have too much blood taken over a prolonged period, your red blood cell count may drop (this is called "anemia"). As a precaution, we will check your red blood cell level, and give you iron treatment or a blood transfusion if needed.  
Intravenous Catheter: In order to receive this treatment, you will need to have a central venous catheter. This catheter is placed under the skin of the chest wall and enters a major vein in the chest. There are several types of catheters including those which must be removed after each cycle of chemotherapy (temporary type) and those which may be kept for the duration of therapy (permanent type). These options will be discussed with you. The risks associated with placing some catheters include pain, bleeding, infection and collapsed lung. The long-term risks of the catheter include infection and clotting of your veins. If these occur, it may be necessary to remove the catheter. These risks will be explained to you in more detail at the time of insertion. Bone marrow aspiration and biopsy: A bone marrow biopsy is performed by inserting a needle into a bone of the hip. In the aspiration part of the procedure, a small amount of liquid bone  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
marrow is removed, and in the biopsy part, a tiny solid piece of bone marrow is removed. You may feel a pressure sensation when the needle is being inserted and a pulling sensation and brief pain as the marrow is withdrawn. The amount of marrow taken is very small and will not change your body's ability to form blood cells. Potential complications of this procedure are local bleeding, pain at the site, and infection. Both of these are very rare. Bleeding can be stopped by applying local pressure and an infection can be treated with antibiotics

There is very minor discomfort when the numbing medicine is injected into the skin. It may cause pain at the site where the needle goes in and the spinal fluid is taken. There is a small risk of infection or bleeding. A third or fewer patients may experience some headache while the body replenishes the fluid that is removed.

The risks of apheresis are similar to whole blood donation and include pain and bruising at the needle insertion site in the arms, lightheadedness, dizziness, nausea, and rarely fainting due to a rare reflex reaction to needle placement and to the temporary decrease in blood volume during apheresis. You may also feel tingling around your mouth or in your fingers caused by a blood thinner given during the procedure. The nurses will give you a calcium containing antacid to chew to reduce the tingling. All the symptoms usually go away within a few minutes of stopping the procedure. We ask that you eat a meal before coming to donate, and avoid caffeine, to prevent lightheadedness or dizziness that might occur. You will be asked to remain in the chair/bed for a few minutes after the donation is completed, and to sit down and relax for about 15 minutes after the donation. This is done so that staff can observe you to make sure that you feel entirely well before you leave our department. Optional Biopsies: You may be asked to undergo a biopsy for research purposes. Tumor biopsies can be performed as an outpatient surgical procedure or can be done by a specialist using the CT scanner or ultrasound machine to guide the biopsy needle into the tumor to ensure accuracy. There are risks associated with the biopsies, which can include pain and bleeding at the biopsy site. The biopsies to be performed are exclusively for research purposes and will not benefit you. It might help other people in the future. You will be asked at the time of the procedure if you are willing to have this biopsy.

During your participation in this research study, you may be exposed to radiation from CT scans of your neck, chest, abdomen and pelvis, CT guided biopsies and 18FDG-PET/CT scans each year. The amount of radiation exposure you will receive from these procedures is equal to approximately 19.9 rem. A rem is a unit of absorbed radiation. Every day, people are exposed to low levels of radiation that come from the sun and the environment around them. The average person in the United States receives a radiation exposure of 0.3 rem per year from these sources. This type of radiation is called "background radiation." This study will expose you to more radiation than you get from everyday background radiation.  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
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No one knows for sure whether exposure to these low amounts of radiation is harmful to your body. The CT scans and 18FDG-PET/CT scans that you get in this study will expose you to the roughly the same amount of radiation as 66.3 years' worth of background radiation. Being exposed to too much radiation can cause harmful side effects such as an increase in the risk of cancer. The risk depends on how much radiation you are exposed to. Please be aware that about 40 out of 100 people (40%) will get cancer during their lifetime, and 20 out of 100 (20%) will die from cancer. The risk of getting cancer from the radiation exposure in this study is 2.0 out of 100 (2.0%) and of getting a fatal cancer is 1.0 out of 100 (1.0%). You may not participate in this study if you are pregnant. If you can become pregnant, we will perform a pregnancy test before exposing you to radiation. You must tell us if you may have become pregnant within the previous 14 days because the pregnancy test is unreliable during that time

If contrast dye is used, there is a chance of developing an allergic reaction from the contrast material, which may cause symptoms ranging from mild itching or a rash to severe difficulty breathing, shock or rarely, death. The contrast material may also cause kidney problems. The study doctors will do a blood test prior to the test to confirm that it is safe you to receive the contrast. For IV contrast if used: You may feel discomfort when the contrast material is injected. You may feel warm, flushed, get a metallic taste in your mouth or, rarely, may make you vomit or feel sick to your stomach. For oral contrast if used: You may experience vomiting, nausea, cramping, bloating, constipation or diarrhea after drinking the contrast.

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

Although your genetic information is unique to you, you do share some genetic information with your children, parents, brothers, sisters, and other blood relatives. Consequently, it may be possible that genetic information from them could be used to help identify you. Similarly, it may be possible that genetic information from you could be used to help identify them. Patterns of File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020 genetic variation also can be used by law enforcement agencies to identify a person or his/her blood relatives.

The aim of this study is to see if this experimental (anti-CD19 T cells infusion) 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 drug's effect on your cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may help others in the future who have cancer.
Clinical trial: NCT02659943
Section: Procedures
Subsections: Description Of Research Study What Will Happen If You Take Part In This Research Study? Before You Begin The Study|Tests For Research|Research Blood Samples|Lumbar Puncture|Bone Marrow Biopsies|Tumor Sampling|Ct Scan|Pet Scan

You will need to have the following exams, tests or procedures to find out if you can be in the study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the study. However, there are some extra exams, tests and procedures that you will need to have if you take part in this study. If you have had some of them recently, they may not need to be repeated. These tests include:
- Physical examination
- Routine blood and urine tests
- Blood tests for viruses and other disease causing organisms - Echocardiogram and EKG of your heart
- Bone marrow biopsy
- CT scan (head, neck, chest, abdomen and pelvis) and/or PET scan, and MRI of your head

An important part of this study is testing the effects of this treatment on your tumor and immune system. The following blood samples and tests will be done while you participate in this study:

Blood will be drawn frequently during your treatment. Most of the blood draws will be to monitor your health during and after the cell infusion. In addition, some blood samples will be drawn for research purposes. Additional blood draws might be necessary to investigate T cell responses and serum cytokine levels in cases of clinical events such as rapid regressions of malignancy or toxicity. These samples will be used to study how your immune system is affected by the cell therapy. In general, 4 tablespoons will be drawn at each clinic visit or every Monday, Wednesday, and Friday during the inpatient stay. On one occasion before the treatment a larger amount of blood (8 tablespoons) will be drawn. The NIH has set a limit on the maximum amount of blood that can be taken for research. This limit is based on your age. For adults, no more than 37 tablespoons can be taken over an 8-week period.

File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
If you have a form of B cell malignancy that has a tendency to spread to the lining of the brain or spinal cord (called the leptomeninges) or if there is any concern that this might have occurred, you may also require a lumbar puncture to determine whether you would require special therapy that should not be delayed while participating on an experimental protocol. The procedure is done with local anesthesia to numb the skin in the lower back, and a very thin needle is used to draw fluid from the area below the spinal cord. Approximately one-to-three teaspoons of the fluid that bathes the spinal cord (called the cerebrospinal fluid) would be removed and examined for tumor cells.

Before you begin treatment on this protocol a bone marrow biopsy will be scheduled. For the other B-cell cancers, you may need one if you are in remission to make sure there is also no cancer in your bone marrow. These biopsies are required for participation on the study to evaluate your tumor but also for research tests.

Before or at the end of cell therapy, we may ask your permission to perform a biopsy of your cancer. If we can safely perform a biopsy without general anesthesia or significant risk of danger or discomfort to you, a sample may be removed through a surgical procedure or with a needle biopsy. The specific details would be described to you by the surgeon and you will be asked to sign a separate consent for the procedure. The primary risks are pain from the needle insertion and a slight risk of infection, bleeding, or injury to the nearby tissue. The biopsy will be performed under sterile conditions to prevent infections. We may also ask your permission to perform a biopsy for research. The tissue from this biopsy will be used to determine whether there is evidence of an immune response to the tumor or to determine if a newly discovered tumor is actually B-cell cancer. Any biopsies would only be performed with your permission, and if the biopsy is determined to be safe by the Principal Investigator of this trial and the additional physician or physicians that would actually perform the biopsy. Some of the samples may be used for other or future research conducted by the investigational team or other researchers. This future research might directly study malignancy of the same type that you have, or it could focus on other areas of research.

You may have a CT (Computed Tomography) scan of areas as needed for disease assessment) at 1-month, 2-month, 3-month, 4-month, 6-month, 9-month and 12 months after T cell infusion. This may include areas such as the neck, chest, abdomen and pelvis. If is necessary, we may use contrast agent enhanced CT scans. The CT scanner is a doughnut-shaped machine that uses xrays to create computer pictures showing the inside of your body. During the procedure, you will need to lie still on a table inside the CT machine. The table will move you in and out of the machine during the scan and you will be instructed to hold your breath. The scan itself will only take a few minutes to complete, the entire visit will take about 30 minutes.

File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
You may have PET (Positron Emission Tomography) scan at 1-month, 2-month, 3-month, 4month, 6-month, 9-month and 12-months if needed to stage disease. The PET scanner is a doughnut-shaped machine that uses x-rays combined with a dose of a radioactive substance (tracer) to create computer pictures showing the inside of your body. Before the scan, you will have a radioactive substance injected into your arm after which, you will need to wait for approximately 30 minutes for the substance to be absorbed. After 30 minutes, you'll lie on a narrow, padded table and be positioned for the scan. The scan itself is painless and won't make much noise. During this time, you will need to lie very still. It will take about another 30 minutes to complete.
Clinical trial: NCT02659943
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

The immune system plays many important roles in the body such as helping the body fight infections. The immune system is also known to affect cancer cells. "T" lymphocytes, or T cells, are a type of white blood cell and a major component of the immune system. T cells have been shown to be capable of recognizing and destroying a number of different tumors, particularly types of leukemias or lymphomas. Unfortunately, most tumors have developed ways of escaping  
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the monitoring by the immune system for foreign or abnormal cells and continue to grow in an uncontrolled manner. Thus, we are looking at ways to manipulate the immune system, in particular, the T cell component, so that it will more efficiently recognize and kill tumor cells. You have been diagnosed with a B cell cancer (such as: non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and B-cell acute lymphoblastic leukemia) that has not been controlled by other therapies, meaning that the cancer cells have continued to grow or, if you did achieve a remission, the cancer has recurred after or during treatment. Unfortunately, many B cell cancers quickly develop resistance to standard treatment options and ultimately become completely resistant to conventional drug or antibody therapy. Thus, there is a need to find new approaches for the treatment of B cell cancers. You should discuss with your referring doctor and the NIH doctors other treatment options that might be available to you so that you feel that you have made the best choice for your disease at this time.
Clinical trial: NCT02659943
Section: Voluntary Participation
Subsections: It Is Your Choice To Take Part In The Study

You may choose not to take part in this study for any reason. If you join this study, you may change your mind and stop participating in the study at any time and for any reason. In either case, you will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you must be taking part in a study or are being considered for a study. If you do choose to leave the study, please inform your study team to ensure a safe withdrawal from the research.
Clinical trial: NCT02659943
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  
File in Section 4: Protocol Consent (3) Protocol Number: 16-C-0054 Version Date: 09/17/2020  
- if your disease comes back during treatment
- if you have side effects from the treatment that your doctor thinks are too severe - if new information shows that another treatment would be better for you
- if the study doctor decides to end the study
- if you become pregnant
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 Dr. Kochenderfer or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases cannot be recalled and destroyed.