Allogeneic CTL Study Version 1.00

Allogeneic CTL Study Version 1.00

Donor Treatment Consent August 15, 2008

CONSENT FORM

DONOR CONSENT

Most-closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation or Infection with Adenovirus, CMV and EBV after Hemopoietic Stem Cell Transplantation

Background

In this consent "you" refers to you or your child.
We are asking permission to take blood from you to grow a special type of T cell that fights viruses that may be given to a patient (recipient) who has had a blood or bone marrow transplant (BMT) for a type of blood cell cancer, other blood disease or a genetic disease. You may be being asked to do this because you have been a bone marrow donor in the past or because you have a common HLA type that may match many potential patients. As part of this research study, we are trying to learn if closely matched T cells might help to treat virus infections in BMT recipients. The T cells that we will make will have activity against three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) and adenovirus.

Adenovirus is a virus that just causes symptoms of a common cold normally but which can cause serious life-threatening infections in patients who have weak immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can gut, the liver, the pancreas and the eyes.

CMV is a virus that can also cause serious infections in patients with suppressed immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the intestinal tract, the liver and the eyes. Approximately two-thirds (2/3) of normal people harbor this virus in their body. In healthy people CMV rarely causes any problems because the immune system can keep it under control. If you and/or your donor are positive for CMV, you are at risk of developing CMV disease while your immune system is weak post transplant.

EBV is the virus that causes glandular fever or kissing disease. It is also normally controlled by a healthy immune system but when the immune system is weak can cause fevers, enlarged lymph nodes and some times develop into a type of cancer called lymphoma.

We plan to grow your T cells in the laboratory in a special way, to see if they can help treat infections with these viruses. This treatment with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from the transplant donor. However as it takes two to three (2-3) months to make the cells that approach is not practical when the recipient already has an infection. We want to find out if we can use CTLs that we have already made from another donor who matches as closely as possible and if they will last in your body and have activity against these viruses. These cells are called “trivirus specific CTLs” because they can attack all three (3) viruses.

Purpose

The purpose of this study is to obtain some of your blood to make trivirus specific CTLs so they would be available to potentially treat a recipient who had an infection with one of these viruses.

Procedures

You will be one of approximately (45) subjects to be asked to participate in this trial. The CTL lines will be made at Baylor College of Medicine and may be given to patients at several sites who are participating in the clinical trial. If a patient has an infection with one of the three (3) viruses their doctor will first look in a database to see if there is a CTL line that is a close match with them using HLA type which measures six (6) proteins on the surface of cells. If your CTL line is the best match it may be given to a patient but there is also a possibility your line may never be the best match and will never be given.

If you agree to be in this study you will first undergo the following evaluations:

1) a medical evaluation, a questionnaire that is given to blood donors.,
and a series of laboratory tests,

2) testing for diseases such as hepatitis and HIV (within seven (7) days of the blood collection), and

3) if a female of child bearing age, a pregnancy test.

These evaluations will determine if the recipient might experience unexpected risks from receiving your cells. You have the right to review your record and ask to change incorrect information. If your medical evaluation discloses any abnormalities, you will be informed. We may also be required by law to notify your state public health agency if you test positive for hepatitis B, hepatitis C, HIV or other infectious diseases.

If this assessment shows that you are a suitable donor, we will draw 40-80 mls of blood to make the CTL line. To do this we first infect blood cells called monocytes with a specially produced adenovirus gene that also carries part of the CMV gene. These monocytes with these new genes then stimulate the T cells. This stimulation will train the T cells to kill cells with this part of the CMV virus or with adenovirus. We then grow these CTLs with more stimulation with EBV infected cells (which we will make from donor blood by infecting them with EBV in the laboratory). We will also put the adenovirus that carries the CMV gene into these EBV infected cells so that they too have CMV and adenovirus proteins. These EBV infected cells will be treated with radiation so they cannot grow. By this type of culture we grow out T cells that can see and attack cells infected with EBV, adenovirus or CMV. Once we have made sufficient numbers of T cells we will test them to make sure they kill cells infected with these viruses and freeze them.

Any left over samples of tissues (blood) or the cell lines may be used to help research. The specimens may be kept for a long time or given to a third party. These specimens and information about your circumstances may be shared with other researchers. Although there will be a record identifying under what circumstances these specimens were obtained, under all circumstances your identity will be kept confidential.

You can see and get a copy of your research related health information. Your research doctor may be able to provide you with part of your information while the study is in progress and the rest of your information at the end of the study.

Potential Risks

Possible side effects from drawing blood may include pain or bruising at the site of the needle puncture. There is a very small risk of an infection at the site of the needle puncture. Also, it is possible that a person may faint when blood is drawn. Care will be taken to clean the site well and therefore decrease the risk of infection. Unforeseeable and/or unknown risks/discomforts may occur.
Once the blood sample has been obtained there is no risk to you from the laboratory work that will be done to the T-cells.

Potential Benefits

You have been told that you will receive no direct benefit from your participation in this study. However, your participation may help the investigators learn if CTLs from closely matched donors can treat infections in transplant patients.

Alternatives

You may choose not to participate in this study:

SubjectCosts and Payments

You will not be charged for any evaluations that are being done solely as part of your participation in this research project. You will have an opportunity to discuss any financial concerns with a financial counselor.

There could be considerable time and effort spent to develop a potential commercial product which is a significant commitment of resources on the part of this institution. Therefore, this institution does not plan to pay royalties to you should a commercial product be developed from your blood or tissue as a consequence of this research.

Subject Rights

Your signature on this consent form means that you have received the information about this study and that you agree to be a part of the study.
You will be given a copy of this signed form to keep. You are not giving up any of your rights by signing this form. Even after you have signed this form, you may change your mind at any time. Please contact the study staff if you decide to stop taking part in this study.
The investigator or sponsor may decide to stop you from taking part in this study at any time. You could be removed from the study for reasons related only to you (for example, if you move to another city, if you do not take your study medication, or if you have a serious reaction to your study medication) or because the entire study is stopped. The sponsor may stop the study at any time.
There may be unknown risks/discomforts involved. Study staff will update you in a timely way on any new information that may affect your health, welfare, or decision to stay in this study.
If you are injured because of this study, you will receive medical care that you or your insurance will have to pay for just like any other medical care. You will not be paid for the injury.
Your Health Information
We may be collecting health information that could be linked to you (protected health information). This protected health information might have your name, address, social security number or something else that identifies you attached to it. Federal law wants us to get your permission to use your protected health information for this study. Your signature on this form means that you give us permission to use your protected health information for this research study.
If you decide to take part in the study, your protected health information will not be given out except as allowed by law or as described in this form. Everyone working with your protected health information will work to keep this information private. The results of the data from the study may be published. However, you will not be identified by name.
People who give medical care and ensure quality from the institutions where the research is being done, the sponsor(s) listed in the sections above, representatives of the sponsor, agents of the Food and Drug Administration, and regulatory agencies such as the U.S. Department of Health and Human Services will be allowed to look at sections of your medical and research records related to this study. Because of the need for the investigator and study staff to release information to these parties, complete privacy cannot be guaranteed.
The people listed above will be able to access your information for as long as they need to, even after the study is completed.
If you decide to stop taking part in the study or if you are removed from the study, you may decide that you no longer allow protected health information that identifies you to be used in this research study. Contact the study staff to tell them of this decision, and they will give you an address so that you can inform the investigator in writing. The investigator will honor your decision unless not being able to use your identifiable health information would affect the safety or quality of the research study.

The investigator, and/or someone he/she appoints in his/her place will try to answer all of your questions. If you have questions or concerns at any time, or if you need to report an injury related to the research, you may speak with a member of the study staff: 832-824-4670 during the day and after hours.
Members of the Institutional Review Board for Baylor College of Medicine and Affiliated Hospitals (IRB) can also answer your questions and concerns about your rights as a research subject. The IRB office number is (713) 798-6970.

Your signature on this consent form attests to the fact that your child ______has, within limits imposed by age, maturity, and psychological state, given his/her assent (affirmative agreement) to participate in this research project.

Signature of Recipient Date

Signature of Investigator Date

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