Clinical trial: NCT03958656
Section: Alternatives
Subsections: What Are The Benefits Of Being In The Study?|Are There Any Potential Benefits To Others That Might Result From Research?|What Other Options Are There For Me?

You might not benefit from being in this study. However, the potential benefit could include shrinking of your multiple myeloma if the cell infusion is accepted by your body or lessening of your symptoms, such as pain, that are caused by the cancer.

In the future, other people might benefit from this study because the knowledge gained from this study may help in developing treatments for those who have this cancer.

Before you decide whether or not to be in this study, we will discuss other options that are available to you. Instead of being in this study, you could:
choose to be treated with other forms of chemotherapy, antibody-drug therapy (such as daratumumab), radiation, stem cell or bone marrow transplantation, or immune therapies. File in Section 4: Protocol Consent (1) Version Date: 04/14/2020 Page 13 of 20 choose to take part in a different study, if one is available choose not to be treated for cancer but you may want to receive comfort care to relieve symptoms.  
You should discuss with your doctor your other choices and their risks and benefits.
Clinical trial: NCT03958656
Section: Confidentiality
Subsections: Confidentiality Protections Provided In This Study|Will My Medical Information Be Kept Private?|Will You Save My Specimens Or Data For Use In Other Research Studies?|Other Important Information Confidentiality

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

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:  
The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.  
National Institutes of Health Intramural Institutional Review Board Qualified representatives from Bellicum Pharmaceuticals, Inc, the pharmaceutical company that produces Rimiducid
This study is protected by a Certificate of Confidentiality (Certificate). With this certificate, researchers may not release or use data or information about you except in certain circumstances. Please refer to the Other Important Information section near the end of this consent form for more information on this type of protection.

As part of this study, we are obtaining data and specimens (such as: blood, bone marrow biopsies) from you. We plan to use these specimens and data for studies going on right now, as well as studies in the future. These studies may provide additional information that will be helpful in understanding multiple myeloma, or other diseases or conditions. This could include studies to develop other research tests, treatments, drugs, or devices, that may lead to the development of a commercial product by the NIH and/or its research or commercial partners. There are no plans to provide financial compensation to you if this happens. Also, it is unlikely that we will learn anything from these studies that may directly benefit you. By agreeing to let us use your specimens and data, you give the NIH any rights you may have in the specimens and data. We may share your specimens and data with other researchers. They may be doing research in areas similar to this research or in other unrelated areas. These researchers may be at NIH, other research centers and institutions, or industry sponsors of research. In addition to the use and sharing of your specimens and data described above, we might remove any information from your specimens and data that can identify you such as name, address, or File in Section 4: Protocol Consent (1) Version Date: 04/14/2020 Page 15 of 20 medical record number, and then use the specimens and data for additional research studies at the NIH or other places. If we do this, we might not contact you to ask your permission or otherwise inform you. If you change your mind and do not want us to store and use your specimens and data for future research, you should contact the research team member identified at the top of this document. We will do our best to comply with your request but cannot guarantee that we will always be able to destroy your samples. For example, if some research with your specimens and data has already been completed, the information from that research may still be used. Also, for example, if the specimens and data have been shared already with other researchers, it might not be possible to withdraw the samples and data. Please place your initials in the blank next to Yes or No for each of the questions below: My specimens and data (blood and bone marrow) may be stored and used for future research as described above.  
_____ Yes _____ No  
  
 Initials Initials
My specimens and data (blood and bone marrow) may be shared with other researchers and used by these researchers for future research as described above.  
_____ Yes _____ No  
  
 Initials Initials

When results of an NIH research study are reported in medical journals or at scientific meetings, the people who take part are not named and identified. In most cases, the NIH will not release any information about your research involvement without your written permission. However, if you sign a release of information form, for example, for an insurance company, the NIH will give the insurance company information from your medical record. This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance. If we share your specimens or data with other researchers, in most circumstances we will remove any information that shows your identity before sharing them. You should be aware that there is a slight possibility that someone could figure out the information is about you. To help us protect your privacy, the NIH Intramural Program has received a Certificate of Confidentiality (Certificate). NIH researchers must 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. NIH researchers will use the Certificate to resist any demands for information that would identify you, except as explained below. There are several circumstances in which the Certificate does not provide protection. These include when information:
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 necessary for your medical treatment and you have consented to this disclosure; 4. is for other research; 5. is disclosed with your consent In addition, identifiable, sensitive information collected or compiled during research and 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 does not prevent you from voluntarily releasing information about yourself or your involvement in this research. If an insurer, medical care provider, or other person obtains your written consent for us to disclose the research information, then the researchers will not use the Certificate to withhold that information. 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. The protections of the Certificate apply to all copies of the identifiable, sensitive information collected or compiled during the research. Therefore, if an NIH investigator shares a copy of your identifiable, sensitive information with any other investigator or institution (whether a collaborator on this study, or researcher conducting secondary research in the future) that party must generally agree to comply with the disclosure restrictions under the Certificate described above. Additionally, the Federal Privacy Act generally protects the confidentiality of your NIH medical records. 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. However, NIH will only release information from your medical record if it is permitted by both the Certificate of Confidentiality and the Privacy Act.
Clinical trial: NCT03958656
Section: Duration of Study Involvement
Subsections: When You Are Finished Taking The Drugs (Treatment)|Gene Therapy Long Term Follow Up (Retroviral Vectors)|How Long Will The Study Take?

You will need to come for a clinic visit two weeks after your cell infusion, for blood work, urine tests, 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 multiple myeloma 1, 2, 3, 4, 6, 9 and 12 months after the cell infusion. These visits will also include a health and multiple myeloma assessment including blood test, urine tests, and possible disease imaging. You will have imaging done using PET scan at 2, 4, 6, 12, 18, 24, 30 and 36 months after cell-infusion. If you have a certain type of multiple myeloma tumor, you may also need to have imaging done using a CT scan at your visits. File in Section 4: Protocol Consent (1) Version Date: 04/14/2020 Page 6 of 20 After 12 months, follow up for patients with ongoing responses, which means the multiple myeloma has not progressed, will continue every 6 months for up to 3 years after your T-cell infusion. At the follow-up visits we will evaluate your general health, and we will assess your multiple myeloma. Blood will be drawn at all follow-up visits. Note that all these follow-up visits are only required for patients with ongoing responses. If your multiple myeloma progresses, you will be removed from the study to pursue other options. As long as your multiple myeloma 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 including corticosteroids, we will not be able to interpret the results of the anti-SLAMF7 T cells, and you will be removed from the study. You will then 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.

You will be followed on a separate NCI protocol\# 15C0141 if you leave the CAR protocol. There will be a consent process for the separate protocol. Because we do not know the long-term side effects of gene therapy, we will ask you to take part in long term follow up for the next 15 years. The Food and Drug Administration (FDA) requires that people who receive gene therapy be watched even after they complete the study. We will ask you questions about your health and ask you to have a physical exam every year. We will also collect your blood over the next several years. If you return to your referring doctor after treatment here we will ask you to have your doctor send us a copy of your physical exam and your blood samples. We will collect blood samples right after you receive the cells, and at 3, 6 and 12 months after treatment, and then every year after that (2 teaspoons each time). This testing will help us learn if the cells have grown or changed in your body. 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 therapy approach. Please discuss this request with your family to inform them of your wishes.

If you agree to take part in this study, your involvement is expected to last for *3 years:*
You may be seen in the clinic two weeks after your cell infusion, for blood work, urine tests, and a brief visit with one of our doctors. Then to return to clinic for evaluation of your overall health and your multiple myeloma 1, 2, 3, 4, 6, 9 and 12 months after the cell infusion After 12 months, follow up for patients with ongoing responses, which means the multiple myeloma has not progressed, will continue every 6 months for up to 3 years after your Tcell infusion.  
Your involvement on the Gene Therapy Long Term Follow Up Study will be 15 years once you are off treatment in this study.
Clinical trial: NCT03958656
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Risks And Discomforts Of Being In The Study? Risks Of Study Drugs|Gene Therapy Risk Of Cancer And Other Diseases:|Procedure Risks Blood Draws:|Bone Marrow Aspiration And Biopsy:|Risks From Mri, Pet, And Ct Scan|What Are The Risks Of Radiation From Being In The Study?|What Are The Risks Related To Pregnancy?|Risks Of Storage And Sharing Of Samples And Data

Because the SLAMF7 protein is found on normal plasma cells as well as on your cancer, the antiSLAMF7 T cells might cause a fleeting or prolonged decrease in the number of normal plasma cells. SLAMF7 is also found on a proportion of other immune cells of the body that fight infections-NK cells, CD8+ T cells, dendritic cells, monocytes and B cells. NK cells and CD8+ T cells play important roles controlling viral infections while plasma cells make antibodies that are involved in protection against infections. We do not know if a decrease in these cells will cause problems with infections and several steps can be taken to deal with an increased risk of infection or actual infections. These include giving antibiotics or antiviral therapy, antibodies intravenously, which is a standard treatment given to many patients with immune deficits or turning on the safety switch by administering the drug Rimiducid to stop the CAR T cells from functioning. The anti-SLAMF7 T cells we will be giving you are exposed to a type of virus (retrovirus) in order to insert the anti-SLAMF7 gene that gives the T cells the ability to recognize multiple myeloma. Although this retrovirus is not active, there is the rare possibility that it may cause infection. This has never happened to any of the hundreds of patients who received T cells that were modified with similar viruses. The anti-SLAMF7 T cells could also cause you to develop another type of cancer in your blood cells, although we think this is very unlikely because it has never happened in the hundreds of patients who have received genetically-modified T cells. Patients who have received CAR T cells aimed at targets other than SLAMF7 have experienced a variety of side-effects. Most of these patients have developed fever and fatigue that can last for up to 2 weeks after cell infusion. Some patients that have received similar treatments have developed low blood pressure. In a minority of patients low blood pressure and a temporary decrease in kidney function also occurred. In some other clinical trials aimed at different targets, patients developed temporary confusion, headaches, or weakness. One patient developed severe, but temporary, muscle twitching. Three patients developed a temporary inability to speak, which resolved completely after a few days. Rarely patients developed a temporary decrease in heart function. Heart function has almost always subsequently returned to normal levels. Less likely, patients developed tumor lysis syndrome, which is a release of toxic substances from tumor cells that are being destroyed. Tumor lysis syndrome is very rare, and has not caused no long-term problems for the patients on CAR T-cell studies at the NIH. Patients at risk of tumor lysis syndrome on the anti-SLAMF7 T-cell study will receive medication to prevent this complication. In addition, the safety switch can be turned on which we anticipate will control these side-effects. Chemotherapy is part of this protocol. The chemotherapy part of this study can cause decreased blood count, nausea, and hair loss. The decreased blood counts due to chemotherapy can lead to infections and bleeding.  
| Potential risks of anti-SLAMF7 T cells infusion include: Likely: Less Likely:   | Rare:                                                                                                                                                                                                                     |    |                         |
|---------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----|-------------------------|
|                                                                                | Fever                                                                                                                                                                                                                     |    |                         |
|                                                                                | Chills                                                                                                                                                                                                                    |    |                         |
|                                                                                | Fatigue                                                                                                                                                                                                                   |    |                         |
|                                                                                | Low  immunoglobulin  levels ( susceptibility  to infection)                                                                                                                                                               |   | Headache                |
|                                                                                | General feeling of being unwell (malaise)                                                                                                                                                                                 |    |                         |
|                                                                                | Temporary decreased kidney function                                                                                                                                                                                       |    |                         |
|                                                                                | Temporary weakness or difficulty  speaking                                                                                                                                                                                |    |                         |
|                                                                                | Low blood pressure                                                                                                                                                                                                        |    |                         |
|                                                                                | Fainting                                                                                                                                                                                                                  |    |                         |
|                                                                                | Tumor lysis syndrome (rapid breakdown  of tumor that can cause side-effects)                                                                                                                                              |   | Muscle pain,  twitching |
|                                                                                | Death                                                                                                                                                                                                                     |    |                         |
|                                                                                | Permanent kidney  damage                                                                                                                                                                                                  |    |                         |
|                                                                                | Other neurologic  problems                                                                                                                                                                                                |    |                         |
|                                                                                | Coma                                                                                                                                                                                                                      |    |                         |
|                                                                                | Temporary liver  damage                                                                                                                                                                                                   |    |                         |
|                                                                                | Extreme  weakness of the  arms and legs                                                                                                                                                                                   |    |                         |
|                                                                                | Muscle damage                                                                                                                                                                                                             |    |                         |
|                                                                                | Long-term  debilitation                                                                                                                                                                                                   |    |                         |
|                                                                                | Difficulty  breathing                                                                                                                                                                                                     |    |                         |
|                                                                                | Increased risk of  cytomegalovirus  (CMV) and  Epstein-bar virus  (EBV) infections.                                                                                                                                       |    |                         |
|                                                                                | Possible intensive care unit  admission                                                                                                                                                                                   |    |                         |
|                                                                                | Fast heart rate                                                                                                                                                                                                           |    |                         |
|                                                                                | Possible kidney damage that will  most likely be temporary                                                                                                                                                                |    |                         |
|                                                                                | Possible breathing problems that  might in rare cases require  mechanical ventilation  (breathing machine)                                                                                                                |    |                         |
|                                                                                | Cytokine release syndrome (release of  substances from T cells that can cause  many side-effects) including  Fever  Fast heart rate  Low Blood Pressure  Possible intensive care unit  admission  Rare cases, death. |    |                         |
|                                                                                | Temporary decreased cardiac function, or  abnormal heart rhythms                                                                                                                                                          |    |                         |
|                                                                                | Prolonged (a month or more) low blood  counts including low white blood cells and  platelets                                                                                                                              |    |                         |
|                                                                                | Temporary changes in bleeding tests                                                                                                                                                                                       |    |                         |
|                                                                                | Temporary changes in liver function tests                                                                                                                                                                                 |    |                         |
| PATIENT IDENTIFICATION                                                          | Consent to Participate in a Clinical Research Study NIH-2977 (4-17) File in Section 4: Protocol Consent (1) Version Date: 04/14/2020 Page 9 of 20 IRB NUMBER: 19C0102 IRB APPROVAL DATE: 06/16/2020                       |    |                         |  
| Likely:                                                                                        | Less Likely:                                              | Rare:   |
|------------------------------------------------------------------------------------------------|-----------------------------------------------------------|---------|
|                                                                                               | Temporary low calcium, phosphorous,  albumin in the blood |         |
|                                                                                               | Increased risk of infection                               |         |
| There is no information available at this time to guide us in how humans might respond to this |                                                           |         |  
There is no information available at this time to guide us in how humans might respond to this type of cell infusion. 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                             |   | Heart damage |
|                                                            | Painful and bloody urination |   | Secondary leukemia (a different type of cancer) |    |              |
|                                                            | Sterility                    |   | Skin rash                                       |    |              |
|                                                            | Water retention              |   | Bleeding                                        |    |              |
|                                                            | Hair Loss                    |    |                                                 |    |              |  
| Potential risks fludarabine: Likely: Less Likely:   | Rare:                                                                                                                                                                                                |    |                                                                                         |    |                               |
|-----------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----|-----------------------------------------------------------------------------------------|----|-------------------------------|
|                                                    | Low blood counts                                                                                                                                                                                     |   | Long-term reduction of  lymphocyte counts which  could increase the risk of  infection. |   | Damage to the nervous  system |
|                                                    | Causing seizures, coma,  vision loss, and even  death                                                                                                                                                |    |                                                                                         |    |                               |
|                                                    | Infection                                                                                                                                                                                            |    |                                                                                         |    |                               |
| PATIENT IDENTIFICATION                              | Consent to Participate in a Clinical Research Study NIH-2977 (4-17) File in Section 4: Protocol Consent (1) Version Date: 04/14/2020 Page 10 of 20 IRB NUMBER: 19C0102 IRB APPROVAL DATE: 06/16/2020 |    |                                                                                         |    |                               |  
| Likely:   | Less Likely:   | Rare:  Inflammation in the lungs  Kidney damage   |
|-----------|----------------|-----------------------------------------------------|  
| Potential risks Rimiducid: Likely: Less Likely:   | Rare:                                        |    |    |
|---------------------------------------------------|----------------------------------------------|----|----|
|                                                  | Facial flushing                              |   | Allergic reactions  including anaphylactoidlike reactions or  pseudoallergy    |
|                                                  | Liver injury                                 |    |    |
|                                                  | Fevers                                       |    |    |
|                                                  | Urticaria                                    |    |    |
|                                                  | Nervous system  disorders such as  confusion |    |    |

The risks of gene therapy causing new disease are unknown. It is possible that the gene therapy may cause an immune system, blood, or neurological disorder, or cause a new cancer in your blood cells to develop. It is unknown 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. The disease these children had was very different from the disease that you have. These children did not receive CAR T cells, they received a different type of cells. In these children, stem cells were genetically modified (in contrast to the research offered in this trial where T cells are genetically modified). Most of the children were cured, but 5 out of 22 children developed leukemia and one died. Experts who examined this case thought that the gene therapy caused the leukemia in these children. To monitor you for this risk we will be testing your blood as previously described.

Side effects of drawing blood include pain and bruising in the area where the blood was drawn, lightheadedness, or rarely fainting due to transient lowering of blood pressure. If you feel dizzy, you should lie down for a few minutes to avoid hurting yourself if you fall. Infection at the blooddrawing site could also occur.

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 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 are very rare. Bleeding can be stopped by applying local pressure and an infection can be treated with antibiotics.

You may have allergic reaction to contrast used to perform MRI or CT scan. You may feel uncomfortable to stay still for about an hour during an MRI. For radiation risk associated with CT scans and PET scans, please, see next paragraph.

During your participation in this research study, you will be exposed to radiation from CT scans of your neck, chest, abdomen and pelvis, CT-Guided biopsies and 18FDG-PET/CT scans. The amount of radiation exposure you will receive from these procedures is equal to approximately 15.6 rem. A rem is a unit of absorbed radiation.  
Every day, people are exposed to low levels of radiation that come from the sun and the environment around them. The average person in the United States receives a radiation exposure of 0.3 rem per year from these sources. This type of radiation is called "background radiation." This study will expose you to more radiation than you get from everyday background radiation. No one knows for sure whether exposure to these low amounts of radiation is harmful to your body. The CT scans, CT-Guided biopsies and 18FDG-PET/CT scans that you get in this study will expose you to the roughly the same amount of radiation as 52 years' worth of background radiation. Being exposed to too much radiation can cause harmful side effects such as an increase in the risk of cancer. The risk depends on how much radiation you are exposed to. Please be aware that about 40 out of 100 people (40%) will get cancer during their lifetime, and 20 out of 100 (20%) will die from cancer. The risk of getting cancer from the radiation exposure in this study is 1.6 out of 100 (1.6%) and of getting a fatal cancer is 0.8 out of 100 (0.8%).

If you are able to become pregnant, we will ask you to have a pregnancy test before beginning this study. You will need to practice an effective form of birth control before starting study treatment, during study treatment, and for at least 4 months after your last research treatment (the restricted period). If you become pregnant, there may be unknown risks to the fetus or unborn child, or risks that we did not anticipate. There may be long-term effects of the treatment being studied that could increase the risk of harm to a fetus. You must tell the study doctor if your birth control method fails during the restricted period,. If you think or know you have become pregnant during the restricted period,, please contact the research team member identified at the top of this document as soon as possible. If you are a sexually active person with a partner able to become pregnant, it is important that your partner not become pregnant during the restricted period,. There may be unknown risks to a fetus or risks we did not anticipate. You and your partner must agree to use birth control if you want to take part in this study. If you think your partner has become pregnant during the restricted period,, please contact the research team member identified at the top of this document as soon as possible.

When we store your specimens and data, we take precautions to protect your information from others that should not have access to it. When we share your specimens and data, we will do everything we can to protect your identity, for example, when appropriate, we remove information that can identify you. Even with the safeguards we put in place, we cannot guarantee that your identity will never become known or someone may gain unauthorized access to your information. New methods may be created in the future that could make it possible to re-identify your data or samples.
Clinical trial: NCT03958656
Section: Procedures
Subsections: What Will Happen During The Study? Before You Begin The Study|During The Study Therapy|Additional Research Testing|Imaging Assessments:

If you decide to take part in this study, before receiving treatment, you will have several tests performed to check whether the trial is suitable for you. This is called the Screening Period. Your doctor will review your medical history and the drugs that you are currently taking to determine whether you can participate in this trial. Some of these tests or procedures are part of regular care and may be done even if you are not being considered to join the study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These tests will be performed on a separate screening protocol\# 01C0129 and include a medical history and physical examination, routine blood tests, pregnancy test in women who can have children (pregnant women are not allowed to take part), blood tests for viruses, taking a sample of your bone marrow, scans to assess your disease and tests of your heart function. We may also need to collect all your urine over a 24-hour period.

Once it is determined that you are eligible to participate in the study, and you agree to participate by signing the study consent, 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 people undergo for routine platelet donations. Some people need an IV (intravenous catheter, a small plastic tube that is put into a vein) inserted into each arm for this collection and some people need a temporary special apheresis "central line" just for the one-day collection. Next, we will manipulate your cells in a laboratory so that they can recognize your multiple myeloma. Specifically, we will genetically modify your T cells and grow them in the laboratory so that they can recognize and destroy cells that have a certain protein, signaling lymphocyte activation molecule 7 (SLAMF7) on the surface. Your multiple myeloma cells express the SLAMF7 protein on the surface. This SLAMF7 protein will serve as a target for the anti-SLAMF7 T cells. Most of your normal cells do not express SLAMF7; however, they are present in normal plasma cells and NK cells, parts of your immune system. To prevent too much damage to your normal cells, the T cells will be genetically modified to encode a gene for a "safety switch" protein in addition to the SLAMF7 protein. This safety switch can be turned on by giving an infusion of a drug called Rimiducid. We have incorporated this safety switch to stop toxicity of this therapy. By turning on the safety switch, the genetically modified T cells that recognize your multiple myeloma cells will no longer function and will die. Rimiducid, the drug that turns on the safety switch, will only be infused in certain circumstances: severe infections not controlled by antibiotics or antiviral medications, prolonged low blood counts with and without complications and severe cytokine release syndrome. There may be other severe instances where the medication will be infused. This study will be conducted as a "dose escalation". The purpose of dose escalation is to determine the safe dose of anti-SLAMF7 T cells. There are four dose levels of anti-SLAMF7 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 antiSLAMF7 T cells you will be receiving.  
After you have had cells removed from your blood, you will receive 2 FDA approved drugs (chemotherapy) named cyclophosphamide and fludarabine. These drugs will be given to you through a "central line" (or tube) placed in a large vein in your arm or chest once a day for 3 days. The two drugs are given one after the other with each infusion lasting about 30 minutes. The purpose of the chemotherapy is to enhance the activity of the anti-SLAMF7 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. Three days after the chemotherapy ends, you will be admitted to the hospital as an inpatient where. you will receive the anti-SLAMF7 T cells. The anti-SLAMF7 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. This may be the same "central line" that was used for the chemotherapy. You will receive the commercially-available, common drugs acetaminophen and diphenhydramine as premedications prior to the CAR T cells. All patients that participate in this study will be required to stay in the hospital for close observation and testing 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 6 and 9 days after cell infusion. You may have to stay in the hospital longer to manage these side effects if they occur. During this time-period, you must be willing to agree to intensive care treatment that can include drugs that support your blood pressure, chest compressions, a machine to assist your kidneys, and being attached to a breathing machine. You will be closely watched during the anti-SLAMF7 cell infusion for signs of a reaction. While other types of genetically-modified T cells have been administered to many patients, infusion of anti-SLAMF7 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 minimum number of cells that we believe are needed to help control the tumor 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. If a second attempt to produce cells is necessary, it might require a second apheresis. For patients who still have disease after receiving anti-SLAMF7 T cells the first time, repeated infusions might be possible. In order for a repeat infusion to be possible, you must not have experienced severe side effect with your 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. A maximum of 2 total treatments can be given to any one patient. 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. 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. If a cancer is suspected, but not definite, you may have subsequent evaluation here at NIH or at your home institution per standard of care. These might include additional testing such as, bone marrow biopsies, or other imaging tests.

In addition to performing the tests described above, we will also do tests for purposes of research. These are being done to help us to find out if you have cancer, evaluate your emotional and physical wellbeing, and to study possible markers in your blood. The studies include:

a computed tomographic scan (CT) that produces a picture of your body using a small amount of radiation (if you are not pregnant and do not have allergy to CT contrast)  
Positron emission tomography (PET)/CT scans which combine two different types of scanners to get better image of your tumor before starting the study treatment, approximately 1 scan/year.
**Tumor Sampling:** In very rare instance, before or after of cell therapy, we may ask your permission to perform a research 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 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 multiple myeloma. Any biopsies would only be performed with your permission, and if the biopsy is determined to be safe by the Principle 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.
Clinical trial: NCT03958656
Section: Purpose of Research
Subsections: Key Information About This Research|Why This Study Is Being Done?

This consent form describes a research study and is designed to help you decide if you would like to be a part of the research study. You are being asked to take part in a research study at the National Institutes of Health (NIH). This section provides the information we believe is most helpful and important to you to in making your decision about participating in this study. Additional information that may help you make a decision can be found in other sections of the document. Taking part in research at the NIH is your choice. You are being asked to take part in this study because you have been diagnosed with multiple myeloma, a blood cell cancer, that has not been controlled with standard therapies … The purpose of this study to determine if a personalized immune treatment is safe. The use of anti-SLAMF7 CAR T cells and Rimiducid used in this study is considered investigational, which means that it has not been approved by the U.S. Food and Drug Administration (FDA) to treat Multiple Myeloma. However, the FDA has given us permission to use anti-SLAMF7 CAR T cells in this study. There are other drugs that may be used to treat your disease, and these can be prescribed/given by your regular cancer doctor, even if you are not in this study. These may include, for instance, dexamethasone, standard chemotherapy or tocilizumab. While all the other therapies have their own side effects, CAR T-cell therapy can cause cytokine release syndrome (CRS) which is associated with high-fevers and feeling very sick, which may be different than some of the therapies, and it is expected that if the CAR T-cells cause cytokine-release syndrome, Patients sometimes need to go the an intensive care unit for close observation and intensive treatments. If you decide to join this study, here are some of the most important things that you should know that will happen: First, we will separate and collect your T cells from your blood. Your whole blood will go through a machine that separates blood into different parts (this will take 3-4 hours). Your T cells will be grown with viruses that carry the CAR genes that lead cells to recognize SLAM7, a protein often found in blood cells. The viruses will put the CAR gene into your collected T cells. These CAR T cells will then be grown in a laboratory at the NIH for 7 to 9 days. You will be given three days of low-dose standard chemotherapy before getting the CAR T cells. Chemotherapy creates an environment in your body where the T cells will be active and multiply. You will receive your CAR T cells by an intravenous (IV) infusion while in the hospital at the NIH three days after chemotherapy. You will be in the hospital for at least 9 days or longer, if there are complications. You may experience side effects from taking part in this study. Some can be mild or very serious, temporary, long-lasting, or permanent, any may include death. Some of the most important side effects that you may have include:  
- Cytokine release syndrome (CRS): Cytokines are substances released from cells that can cause many side effects such as fever, fast heart rate, low blood pressure etc.  
- Tumor lysis syndrome (rapid breakdown of tumor that can cause side-effects such as fast heart rate, possible kidney damage that will most likely be temporary, shortness of breath etc.)
- Headache - Temporary muscle weakness or difficulty speaking - Temporary decreased kidney function - Tiredness, fever, chills - Increased risk of infection May have rare incidence of increased risk of cytomegalovirus (CMV) and Epstein-bar virus
(EBV) infections.  
- Temporary changes in liver function tests - Temporary abnormal heart rhythm - Prolonged (a month or more) low blood counts including low white blood cells (leading to infection) and platelets (leading to bruising)
To increase the safety of this therapy, we have included a safety switch that can stop the CAR T cells with a medication. The medication is called Rimiducid. We will stop your CAR T cells if you develop severe side effects that are not controlled by standard medications or if you have a severe or life-threatening viral infection. There may be other serious situations where we will decide to give you the medication to stop the CAR T cells. You will be seen often during the study. You will have laboratory, and imaging tests to see how you are doing and to assess your disease. We will also collect required samples from you (such as: blood and bone marrow biopsies). After you finish your CAR T cell treatment we would like to see you at the NIH Clinical Center monthly for 4 months then at 6, 9 and 12 months, and finally every 6 months up to 3 years to assess your health and to determine what impact, if any, the cell therapy had on your disease. After the study follow-up period has ended, long-term follow up will be requested. During the long-term follow-up, we would like to contact you one time each year until 15 years after your CAR T-cell infusion. Just as we do not know what side-effects you might have, we cannot know if you may benefit from taking part in this study. If you do not benefit, this study and the results from our research may help others in the future. We will cover the cost for some of your expenses, such as travel, lodging and/or meals. Someone will work with you to review your costs of taking part and what we will support. You are free to stop participating in the trial at any time. If you decide to stop, the study doctor may ask you to agree to certain tests to make sure it is safe for you to stop. The remaining document will now describe more about the research study. This information should be considered before you make your choice. Members of the study team will talk with you about the information described in this document. Some people have personal, religious, or ethical beliefs that may limit the kinds of medical or research treatments they would want to receive (such as blood transfusions). Take the time needed to ask any questions and discuss this study with NIH staff, and with your family, friends, and personal health care providers. If the individual being asked to participate in this research study is not able to give consent to be in this study, you are being asked to give permission for this person as their decision-maker. The term "you" refers to you as the decision-maker and/or the individual being asked to participate in this research, throughout the remainder of this document.

This is a research study. The purpose of this research study is to see if it is safe to give anti-SLAM7 CAR T cells T cells to people with multiple myeloma We are asking you to join this research study because you have been diagnosed with multiple myeloma that has not been controlled with standard therapies, meaning that the cancer cells are growing despite your prior treatments or, if you did achieve a remission, the cancer has come back after your most recent treatment. Anti-SLAM7 CAR T cells and Rimiducid are considered investigational, which means that they have not been approved by the U.S. Food and Drug Administration (FDA) to treat multiple myeloma. There may be other standard therapies your myeloma will respond to.
Clinical trial: NCT03958656
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: NCT03958656
Section: Withdrawal from Study
Subsections: Early Withdrawal From The Study

Your doctor may decide to stop your therapy for the following reasons:
if new information shows that another treatment would be better for you. if you do not follow the study rules if he/she believes that it is in your best interest if you have side effects from the treatment that your doctor thinks are too severe if you develop problems such as an infection or other severe illness during or after the protocol chemotherapy before the CAR T-cell infusion if you become pregnant if you need to receive any other treatment for your disease if the study doctor decides to end the study 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 Bellicum Pharmaceuticals, Inc. -the manufacturer of Rimiducid - 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.