Clinical trial: NCT00520130
Section: Alternatives
Subsections: Alternative Treatment

To be eligible for this study, you must have already received the standard treatment for your disease, but there are other options other than participating on this trial:
- You may consider other treatments such as other forms of chemotherapy, radiation, surgery, or immune therapies. In some cases, you may be eligible for an autologous bone marrow or stem cell transplant, in which your own stem cells are returned to your body following high dose chemotherapy treatment.  
- Taking part in another research study - Instead of participating in a research study such as this, you may also be eligible to receive a standard allogeneic stem cell transplant with high dose chemotherapy and/or radiation therapy to completely wipe out your bone marrow before donor cells are transplanted.  
- Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite problems, and other problems caused by cancer. It does not treat the cancer directly, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
STUDY NUMBER: 07-C-0195 CONTINUATION: page 23 of 27 pages
- Another option is not to receive any further treatment at all.  
You should discuss with your referring doctor and your doctors at the NCI whether or not any of these other treatments might be a reasonable choice for your disease.
Clinical trial: NCT00520130
Section: Confidentiality
Subsections: Use Of Specimens And Data For Future Research|Use Of Specimens And Data For Future Research|Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality|Use Of Specimens And Data For Future Research|Use Of Specimens And Data For Future Research

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 STUDY NUMBER: 07-C-0195 CONTINUATION: page 22 of 27 pages 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 they 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.

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 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.  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 26 of 27 pages

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:  
- The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.  
- National Cancer Institute Institutional Review Board - We may share data from this study with a blood and bone marrow registry called: The Center for International Blood and Marrow Transplant Research (CIBMTR). The CIBMTR (Hwww.cibmtr.org) is committed to respecting your privacy and the data we share with is sent without revealing any personal information. The information that is sent to the CIBMTR is combined with information from other transplant centers to better understand how transplants work and to improve patient care.
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most the Web site will include a summary of the results. You can search this Web site at any time.

To help us protect your privacy, we have obtained a Certificate of Confidentiality. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, except as explained below. You should also know that there are several circumstances in which the Certificate does not provide coverage. These include when information:  
- will be used for auditing or program evaluation internally by the NIH; or
- must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA).  
- is necessary for your medical treatment and you have consented to this disclosure;
- is for other research.
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible as evidence or used for any purpose in any action, suit, or proceeding without your consent.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 25 of 27 pages You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. If an insurer, employer, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information. The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others.

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 STUDY NUMBER: 07-C-0195 CONTINUATION: page 22 of 27 pages 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 they 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.

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 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.  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 26 of 27 pages
Clinical trial: NCT00520130
Section: Duration of Study Involvement
Subsections: Frequent Follow-Up At The Nci In The First Year After Transplant

If you are in good health after the three month period after your transplant, you will then be allowed to return home to the care of your primary physician. You will be required to return to the NIH monthly until approximately six months after transplantation so you can be monitored for late transplant complications including GVHD and infection. Thereafter you will be seen at NIH at 9, 12, 18 and 24 months after your transplant and then every year following your transplant, unless an earlier visit is required, per the study doctors. After 5 years after the transplant, you will no longer be asked to return to NIH. We will still contact you by phone annually. At each visit when you return to NIH, you will have a physical exam and blood draws (approximately 4-10 teaspoons of blood will be taken). During some visits you may have a bone marrow aspirate and biopsies, and other appropriate tests (for example: CT, MRI, PET scan) to monitor disease status. Study-related medications will be provided by the NIH during your hospital stay and after you leave the NIH.
Clinical trial: NCT00520130
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are The Costs Of Taking Part In This Study?

If you choose to take part in the study, the following will apply, in keeping with the NIH policy:  
- You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.  
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.
STUDY NUMBER: 07-C-0195 CONTINUATION: page 24 of 27 pages  
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Clinical trial: NCT00520130
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Other Risks From Allogeneic Sct Include:|Potential Benefits Of Participation

Risk of Death from Allogeneic SCT: Patients undergoing allogeneic SCT are at risk of dying from the transplant procedure and its possible complications. In some studies of allogeneic SCT, as many as half of the patients have died as a direct result of the transplant or its complications. In transplant studies similar to this one, up to 50 percent of patients have died from the transplant procedure. The risk of death or other complications can vary greatly, depending on the age of the patient, the way the transplant is performed, and other factors.

Veno-Occlusive Disease (VOD) - A severe liver complication known as VOD occurs in less than 5 percent of allogeneic transplants. VOD is a chemotherapy side effect that causes blood vessels in the liver to be blocked. Severe VOD can lead to liver failure and death.  
Graft Rejection: There is a chance that you may reject your donor's stem cells. If that were to happen, you would most likely recover your own blood cells. However, there is the rare possibility that your own cells may not recover. This may result in prolonged low blood counts, which may result in infection or bleeding and may lead to death. In this event, we would attempt to support you with transfusions, growth factors and antibiotics until your own blood counts recover. A blood test will be performed at 14, 28, 42, 70 and 98 days after your transplant to find out if your body has accepted the donor cells. If no donor cells can be found, then we will conclude that you rejected them. In that case, your blood counts will probably return to the same levels as before the transplant in about 2 to 3 weeks. You will receive the growth factor filgrastim to help the cells engraft. In the event that your cells do not engraft, we may ask your donor to donate more cells.  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 13 of 27 pages Graft-Versus-Host Disease (GVHD): You will be at risk for the development of GVHD for the rest of your life after transplantation. GVHD occurring within the first 100 days after transplantation is referred to as acute GVHD. Acute GVHD most commonly attacks the liver, intestines, and skin. Symptoms of skin GVHD may be as mild as a rash with itching, or as severe as blistering and loss of the skin. Symptoms of intestinal GVHD may be as mild as heartburn and mild diarrhea, or as severe as cramping abdominal pain and bloody diarrhea. Liver GVHD may be as mild as slight disturbances in liver function, or severe as jaundice (yellowing of the skin) with liver failure. Mild GVHD (skin rash only) can be treated with steroid creams that you apply on your skin. Severe GVHD can be very dangerous and needs to be treated aggressively. Treatment of severe GVHD initially includes weakening of the immune system, usually with intravenous (I.V.) steroids. Weakening of the immune system increases the risk of infection. A delayed form of GVHD, known as chronic GVHD, may occur after day 100 post-transplant. Some degree of chronic GVHD affects about half of patients after transplantation. It most commonly attacks the skin, the liver and the intestines, but it may also affect other organs such as the lungs, eyes, muscles, joints, and the bone marrow. Symptoms of chronic GVHD may include dryness of the mouth and eyes, a loss of appetite, weakness, hair loss, weight loss, liver damage (including yellowing of the skin), and lung damage leading to shortness of breath and cough. Patients with severe chronic GVHD are also at increased risk of infection and death. Chronic GVHD is also treated with drugs that weaken the immune system such as steroids. Taking steroids may increase your risk of infection.  
Late Transplant Complications: There are other potential complications that can occur long after transplantation. These complications could affect any organ in the body including the heart, lungs, kidneys, liver, muscles, and brain. Rarely, patients who receive an allogeneic SCT are at risk for developing a second cancer such as leukemia or lung cancer. Other complications are also possible following your transplant. The most common complication is infections. Because you will be receiving drugs (e.g. cyclosporine) that weaken the immune system, you are at greater risk to develop infections from uncommon organisms. These infections can be life-threatening, and could cause death. There is about a 40 percent chance of death from complications of conventional allogeneic bone marrow transplants. Although we will use new/unconventional ways to try to reduce these odds, it is possible that our approach may not work or that it may even increase the chances of death. There is also the risk of complications that cannot be predicted.  
Bone Marrow Aspiration and Biopsy: This procedure usually causes only mild pain for a short time at the biopsy site. Very rarely, bleeding or an infection may occur at the biopsy site.  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 14 of 27 pages Blood Draws: Side effects of blood draws include pain and bruising in the area where the needle was placed, lightheadedness and rarely, fainting. When a large amount of blood is drawn, your red blood cell count may drop causing anemia. Anemia can cause a lack of energy and other symptoms. Transfusions of red blood cells are sometimes needed to treat anemia.  
Central Venous Catheter: Side effects of placing a central venous line in your chest wall include bleeding, bruising, blood clot, or pain in the area of insertion. This line will be placed by physicians with experience in this procedure. These physicians will discuss the above risks at the time of the line insertion. Rarely, placement of a central venous catheter can result in a collapsed lung. If a collapsed lung occurs, it may require hospitalization and temporary insertion of a plastic tube in your chest to re-expand the lung.  
Skin Punch Biopsies: Whenever possible, we will perform biopsies on covered areas of the body. There may be minor bleeding right after the procedure and this can easily be controlled by applying pressure on the spot for a few minutes. Rarely, a bruise might form and this eventually goes away on its own. Sometimes a small infection may occur at the biopsy site. This can usually be treated with topical antibiotics. On the very rare occasion that a larger or deeper infection occurs, oral antibiotics may be needed for 710 days. An infection can be recognized by redness, soreness, and pus at the site. It generally starts 2 days or more after the procedure and does not clear up in another couple of days. These biopsy/excision sites generally heal very well, leaving red, white, dark or skin-colored flat scars. Sometimes, the scar that forms may be a bit thicker than usual. Rarely, a keloid (large, painful or itchy scar) may form. Keloids are more likely to form on the chin, earlobes, chest and upper backs of Blacks and Asians between adolescence and the 30's.  
Oral mucosa biopsy: There may be minor bleeding, bruising, numbness and slight swelling.  
There is also the possibility of infection. Mouth sores have occurred in some patients, but this is uncommon.  
Induction **Chemotherapy:** As described previously, the type of induction chemotherapy you will receive depends on the type of disease you have. Some patients will receive fludarabine, cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone (called: EPOCH-F), while others will receive fludarabine, cytarabine, and filgrastim (called: FLAG). In addition, some patients will receive rituximab, as discussed before. It is important for you to know that this type of induction chemotherapy is likely to reduce your white blood cells for many days. This will place you at increased risk of infection. Such infections can be very serious and may result in death. For this reason, if you develop a fever higher than 101° F, you must see your doctor immediately. If necessary, you will be treated with antibiotics. Also, this chemotherapy will likely cause your platelet count to fall. This may place you at increased risk of bleeding. If your platelet count becomes dangerously low, you will receive platelet transfusions. The chemotherapy may also cause you to develop a low red blood cell count, called anemia. Anemia can cause a lack of energy and other symptoms. Transfusions of red blood cells are sometimes STUDY NUMBER: 07-C-0195 CONTINUATION: page 15 of 27 pages needed to treat anemia. Because the induction chemotherapy on this protocol is a new combination of drugs, there is a chance that unexpected toxic effects will occur. The following are known specific risks of each drug used within the specific regimen that you will receive:

The chemotherapy you receive may cause improvement in your cancer, although it is not likely to result in a cure by itself. The allogeneic SCT may improve the chance that your disease will enter into a long remission and possibly be cured. However, you should understand that this cannot be guaranteed. All of the evaluations, tests, and hospitalizations that you receive at the NIH will be free of charge to you. In addition, your participation in this study may contribute to understanding and developing new ways of using allogeneic SCT for the treatment of cancer.
Clinical trial: NCT00520130
Section: Procedures
Subsections: What Will Happen If You Take Part In This Research Study?|Pre-Transplant Evaluation|The Central Venous Catheter|Induction Chemotherapy|Transplantation Of The Blood Stem Cells From Your Donor|Transplant Procedures

The following will be done as part of this research study (details are included in later sections):  
- First, we must establish proof of a full genetic match (8/8 HLA genes) or partial genetic match (7/8 HLA genes) between you and your potential unrelated donor.  
- We will arrange to have your donor's stem cells collected at a center in cooperation with the National Marrow Donor Program.
STUDY NUMBER: 07-C-0195 CONTINUATION: page 6 of 27 pages
- You will receive one, two, or three cycles of "induction chemotherapy" (based on the type of disease you have; described below) to treat your disease and to weaken your immune system. If the study doctors feel your immune system is already weakened and your disease is well controlled you will not receive "induction chemotherapy".  
- After you have finished receiving induction chemotherapy, you will receive 4 days of reduced-intensity transplant chemotherapy, also called the "conditioning regimen," to prepare you for the transplant.  
- Two days after this transplant chemotherapy, you will receive the transplant with your unrelated donor's stem cells and immune cells.  
- Before and after the transplant you will receive one of two possible combinations of drugs
(AC or TMS) to prevent GVHD. The regimen you receive is randomly decided ("flip of a coin") at the time you agree to participate on the study.  
- You will be hospitalized approximately 3-4 weeks after your transplant.  
- When the study doctors think your condition is stable, you will be discharged from the hospital and be seen frequently at the NIH as an outpatient.  
- You will continue on medications at home to lower the risk of GVHD and infections.  
- You may receive additional cells from the donor, also called a "donor lymphocyte infusion" or DLI, after the transplant, these additional cells are given to help to rebuild or enhance your immune system.  
- You will visit our clinic regularly for the first six months after the transplant, and then less often for at least five years.

Once it is determined that you have a potential donor, you will be seen at the NIH Clinical Center, at which time you will have a complete medical history and physical examination in the NCI Medical Oncology Clinic. Members of the transplant team will review your medical history and explain the transplant procedure. A blood sample will also be used to check the health of your kidneys and liver. We will also test for exposure to a variety of infections, including hepatitis B and C, syphilis, and a virus called cytomegalovirus (CMV). As part of this study, we will test you for infection with the human immunodeficiency virus (HIV), the virus that causes AIDS. If you are infected with HIV you will not be able to participate in this study. We will tell you what the results mean, how to find care, how to avoid infecting others, how we report newly diagnosed HIV infection, and the importance of informing your partners at possible risk because of your HIV infection. You will also be tested for the following viruses: hepatitis A, HTLV-1 and -2, adenovirus, Epstein-Barr virus, herpes simplex virus, and the parasite Toxoplasma. A total of approximately 4-12 teaspoons of blood will be collected. If the study doctor feels it is necessary, you will have a PPD skin test (to test for tuberculosis). You will be asked to collect your urine for 24 hours to measure your kidney function. If you are a woman, you will have a urine test for pregnancy. If you are a woman who is breast-feeding or pregnant, you may not take part in this study because we don't know how the transplant will affect your baby or unborn  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 7 of 27 pages child. If you think that you or your partner is pregnant, you should tell your study doctor or nurse immediately. In addition, you will have a special breathing test, a test for heart health, and several X-ray studies, including a CT scan of your chest, abdomen, pelvis, and possibly your neck. You will have a CT scan or MRI of your head. If you have lymphoma, we will obtain a test called a positron emission tomography (PET) scan. You may also have a bone marrow aspiration and biopsy. This test is performed by numbing the iliac (hip) bone with a local numbing medicine called lidocaine. A small cut will be made in the skin, a needle is inserted into the hip bone, and about two tablespoons of liquid samples are removed from the bone marrow through the needle. A small fragment of the bone marrow may also be removed with the needle. If you are at risk of having your cancer involve the brain or central nervous system, you may also have a spinal tap (also known as a lumbar puncture). This test is performed by numbing an area over the lower portion (lumbar) of your spine with a numbing medicine called lidocaine. A thin needle is then inserted into your spinal canal and a small amount (about 5 tablespoons) of spinal fluid is removed. You will also be seen by a dentist, and meet with a social worker. You will be encouraged to name someone as your "durable power of attorney". This should be someone whom you trust to make medical decisions for you if you become physically or mentally unable to make your own treatment decisions. You should know that being in this study may keep you from being in other research studies that limit the number or types of treatments that you are allowed to have received previously.

If you do not already have one before you enroll in this study, you will receive an intravenous (I.V.) line placed in the upper part of your chest and tunneled under the skin into a neck vein. This line is called a central venous catheter that can be used throughout your transplant procedure and follow-up treatment. This kind of catheter is sometimes called a "Hickman catheter". If the catheter becomes infected or clogged, it can be replaced. It will be flushed once daily to prevent clogging. The nursing staff will teach you how to do this yourself. The catheter will be used to give you chemotherapy, your transplant, DLI (if needed), blood transfusions (if needed), and other medications such as antibiotics. It can also be used for drawing blood samples for tests. Since blood will be drawn often during your treatment, the catheter will make it easier and less painful.

In this study you will receive one, two, or three cycles of "induction chemotherapy" to treat your disease and to weaken your immune system. For patients with chronic lymphocytic leukemia, prolymphocytic leukemia, multiple myeloma, and most forms of lymphoma, this chemotherapy will include the following drugs: fludarabine, cyclophosphamide, etoposide, doxorubicin, STUDY NUMBER: 07-C-0195 CONTINUATION: page 8 of 27 pages vincristine, and prednisone (also called: "EPOCH-F"). Patients with lymphoblastic lymphoma, acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and other "pre-leukemic" diseases will receive induction chemotherapy with fludarabine, cytarabine, and filgrastim (also called: "FLAG"). Patients with certain forms of lymphoma and leukemia may also receive a drug called rituximab. Each of these medications have been approved by the Food and Drug Administration (FDA). The study doctors will test a biopsy specimen from your cancer to help them decide if you should receive rituximab with your induction chemotherapy. To start, you will receive common doses of these drugs for five days followed by a 16-day (EPOCH-F) or 23-day (FLAG) rest period (this time period is 1 cycle). The EPOCH-F regimen is generally given in outpatient setting. The FLAG regimen is given in the hospital, so you will be admitted as an inpatient, and you will remain in the hospital until your blood counts recover, usually 3 to 4 weeks. The effect of the chemotherapy on your immune system and on your disease will determine how many cycles of induction chemotherapy you receive. If blood tests show that your immune system is weakened enough after one cycle, you will go directly to the transplant. If your immune system is not very weakened and your disease is not growing after one cycle of induction chemotherapy, you will receive one or two more cycles (5 days of the same chemotherapy you received for cycle 1, followed by 16 (EPOCH-F) or 23 (FLAG) days of rest per cycle). If your disease grows in spite of the induction chemotherapy then the induction chemotherapy will be stopped, and you will be removed from the study. If your white blood cell count remains low for a long time after induction chemotherapy, meaning your immune system has weakened, you will go directly to the transplant. At most, you will receive 3 cycles of chemotherapy.

Before you begin your induction chemotherapy, your unrelated donor will have had a medical examination by a doctor in the National Marrow Donor Program (NMDP) network that includes extensive testing to make sure they do not have any of the following: HIV, Hepatitis B, Hepatitis C, and possible infectious diseases that may be transmitted by stem cell donation. The donor's exam will also ensure that they remain available and are physically well enough to undergo the donation procedure. The NMDP will notify NIH if there are any abnormalities that increase the risk of transmitting infectious diseases to you during the transplant. These findings will be discussed with you. The donor's medical clearance will be verified by the NIH study doctor before you receive any chemotherapy. The stem cells from your donor will be given to you within 48 hours from the time of their donation. This means that your conditioning chemotherapy will begin prior to the donor's cells being collected. The donor will receive daily injections of a medication that stimulates the stem cells to be released from the bone marrow and into the bloodstream. One or two days before your transplant, the donor will have these cells removed through a process called apheresis. The donor will have blood removed through an intravenous catheter and circulated through a machine which separates the peripheral blood stem cells. These cells are removed, and the rest STUDY NUMBER: 07-C-0195 CONTINUATION: page 9 of 27 pages of the blood is returned through the catheter. This collection occurs at the NMDP apheresis center closest to the donor. The cells are hand-carried by a trained courier to NIH. Once they arrive at NIH, the cells will be infused through your catheter within 24 hours. In rare cases, the stem cells may be frozen before they are given to you. Unrelated donor transplants are confidential and the identity of the donor will be anonymous. This means that you will not know who your donor is or where they are. You will know the age and gender of the donor and any history or medical exam findings that could possibly change the risk of your transplant. Likewise, the donor will not know who you are or where you are. He/she will know your age, gender, and the type of disease that you have. The donor will be given basic updates about your condition 30 days, 6 months, and 1 year after your transplant. The only information they will receive is whether or not the stem cells "engrafted" (taken hold), and if you have been discharged from the hospital. The donor will also be notified in the event of your death. Depending on the policy of the particular donor center, you may be able to communicate without revealing your identities in an anonymous manner with your donor beginning at the time of your transplant. In some cases, if both you and the donor agree, you may be able to learn who your donor is after one year. There are some cases when a donor and patient may never communicate or meet. Your transplant coordinator will tell you the details of if and how you may contact the donor once the donor has completed his or her medical exam.

You will be admitted into the hospital approximately seven days before transplantation to the NCI's Experimental Transplantation Unit at the NIH Clinical Center. You will receive 4 days of transplant chemotherapy called the "conditioning regimen," which will permit you to accept your donor's stem cells. This regimen uses fludarabine and cyclophosphamide at higher doses than were given as part of induction chemotherapy. Two days after completing this chemotherapy, you will receive the stem cell transplant. Your donor's stem cells will be infused through your central venous catheter. This is referred to as "day 0". While you are in the hospital for your transplant, you will be monitored very closely for possible complications, which are described below. You will receive drugs to help prevent and/or treat infection, growth factors (G-CSF), blood transfusions, and intravenous nutrition (if needed). Blood will be drawn frequently during your treatment. Your blood will be tested to monitor your health during and after the chemotherapy and transplant procedure. In general, 4 to 10 teaspoons of blood will be drawn an average of 2 to 3 times per week. Some blood will be drawn for research purposes. In general, 3 to 4 tablespoons of blood will be drawn for research on average of once per week for the first 100 days after transplant.  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 10 of 27 pages The average time you will stay in the hospital is three to four weeks after transplant, but it could be longer if there any complications. You will receive one of two combinations of drugs to prevent GVHD before and after your transplant. The combination of drugs that you will receive is randomly assigned at the time of enrollment onto the study. One of the possible combinations of drugs to help prevent GVHD that you may receive contains drugs called: tacrolimus, methotrexate, and sirolimus. Beginning three days before you receive the stem cell transplant, you will receive the drugs tacrolimus and sirolimus to help prevent GVHD. Sirolimus is given by mouth once a day for approximately six months after transplant. Tacrolimus is given either through an I.V. or by mouth once a day for approximately six months after transplant. Methotrexate is given for four doses intravenously (through the vein) before you are discharged from the hospital, shortly after the transplant. The other possible combination of drugs to prevent GVHD that you may receive contains alemtuzumab and cyclosporine. Alemtuzumab is started eight days before your stem cell transplant and is given for five daily doses through an I.V. Cyclosporine is given through an I.V. the day before the transplant. Cyclosporine is given either through an I.V. or by mouth every day for approximately six months after transplant. Once the stem cells have taken hold and you are strong enough, you will be discharged from the hospital and followed closely as an outpatient. You will be required to remain in the Washington, D.C. area for approximately three months after transplantation so the NIH doctors can monitor you in case of any complications. You may require re-admission to the hospital for complications. You will be followed by the doctors in the NCI clinic for the first six months after transplant, and then you will be followed less frequently for at least five years. After the transplant, if tests show that your blood and immune cells have not fully converted to your donor's type ("mixed chimerism"), then the drugs you are taking to prevent GVHD (depending on which arm that you are assigned to), will be lowered to help change your blood and immunity to full donor chimerism. Sometimes a donor lymphocyte infusion (DLI) may be given to you intravenously (I.V.) to reach a state of full donor chimerism, as described above. If your cancer is still present or grows after the transplant, cyclosporine or tacrolimus may be reduced in an attempt to permit a stronger graft-versus-tumor effect. After this, if there are no signs of significant GVHD, then you may receive one or more DLI at increasing doses. These DLI are intended to "boost" your new immune system and can enhance the graft-versus-tumor effect in some, but not all, patients. DLI can sometimes lead to the development of GVHD, so we will monitor you very closely for signs of GVHD after these infusions. If you experience significant GVHD after a DLI, we will give you treatment for GVHD, but you will not receive any further DLI. You may also be eligible to receive chemotherapy or other standard therapy STUDY NUMBER: 07-C-0195 CONTINUATION: page 11 of 27 pages
(like radiation therapy or immune therapies) after the transplant if your cancer requires further treatment. This therapy can be given alone or combined with DLI. If we are required to stop this study because too many patients have serious side effects, we will continue to provide care for you according to the study protocol. The skin and mouth are the two organs most commonly affected by chronic GVHD. In order to better understand chronic GVHD, the following tests will be performed.  
- Punch Skin Biopsy: This is performed so that a piece of skin may be examined under the microscope to get a closer look at what is going on in your skin and for diagnostic purposes. After cleaning the skin with alcohol and/or another antiseptic, a local numbing medicine (Lidocaine with or without epinephrine)--similar to what a dentist injects to numb your gums--is injected into the planned biopsy site. A sharp instrument which looks like a miniature cookie-cutter is used to remove a round plug of skin about the size of a pencil eraser. The biopsy site may be left open or may be closed by putting in one or two stitches, and a small dressing is applied. Sometimes more than one such skin sample may be needed. You will be expected to keep the dressing over the biopsy site dry for 1 to 2 days. Thereafter, the dressing may be changed daily until the suture(s) are ready to come out, usually in 7 days. Depending on circumstances, the suture(s) may be removed by one of us, by your own doctor and/or your doctor's assistant.  
- Oral mucosa biopsy: The procedure is done in a similar manner as a skin biopsy, except that a dressing cannot be applied, because it is not possible to keep the area dry enough to keep the dressing on.  
- Collection of saliva (natural mouth fluid). We will collect saliva from you after swabbing your tongue with a solution that tastes like lemon juice. We will collect the saliva that pools in your mouth, the saliva that collects under your tongue, and the saliva that comes into the mouth next to your upper back teeth. The techniques we use are non-invasive, and investigators at NIH have been collecting saliva with these methods for more than 20 years. This is a simple procedure that does not have any risks or discomforts. We will use saliva samples to study in our laboratory factors that may be associated with the development of GVHD including the types of bacteria that live in the mouth. We believe these studies will help us understand more about oral GVHD and lead to better treatments for this painful condition.  
These tests will be performed on in all patients at the time of start of decrease of medicines that suppress your immune system, prior to the time a clinical diagnosis of chronic GVHD is made. If you do not develop GVHD, these tests will be performed for the second time at 6 months post transplant. It is important for you to know that both the skin and mouth biopsies are being performed for research purposes to help us with our understanding of chronic GVHD. They would not routinely be performed unless they were needed to confirm the presence of chronic GVHD.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 07-C-0195 CONTINUATION: page 12 of 27 pages
Clinical trial: NCT00520130
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Why Are You Being Asked To Take Part In This Study?

We are conducting a study of allogeneic stem cell transplantation from HLA-matched unrelated, volunteer donors for cancers of the blood and immune system. Because you have one of the cancers with which we are concerned, and an HLA-matched unrelated donor has been identified, we are inviting you to participate in this pilot trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation (abbreviated RIST).  
PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH **STUDY**
- Adult Patient or - Parent, for Minor Patient NIH-2514-1 (07-09)
P.A.: 09-25-0099 File in Section 4: Protocol Consent (1)
STUDY NUMBER: 07-C-0195 CONTINUATION: page 2 of 27 pages The cancers with which are concerned include non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, acute lymphocytic leukemia, NK cell neoplasms, and T-cell neoplasms (e.g. adult T-cell leukemia lymphoma, hepatosplenic T-cell lymphoma and enteropathy associated T-cell lymphoma). It also includes pre-cancerous blood conditions including myelodysplasia, idiopathic myelofibrosis, polycythemia vera, and chronic myelomonocytic leukemia.

This research study is for patients who do not have an HLA-matched sibling and who have had a potential HLA-matched unrelated donor identified through one of the bone marrow donor registries such as the National Marrow Donor Program. To be eligible to participate on this study you must match on 8/8 or 7/8 HLA markers with your potential unrelated donor to enroll in the study.
Clinical trial: NCT00520130
Section: Withdrawal from Study
Subsections: Stopping Therapy

Your doctor may decide to stop your therapy for the following reasons:
- If he/she believes that it is in your best interest - If your disease comes back after 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
In this case, you will be informed of the reason therapy is being stopped. Participation in this research study is voluntary. You may stop your participation in the study at any time. There are no penalties for withdrawing from the study. However, if you withdraw after the transplant chemotherapy ("conditioning regimen") without receiving the infusion of donor stem cells, you would be at high risk for serious complications, including death. 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. Pavletic 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.