EBV Specific T-Lymphocytes for Treatment of EBV-Positive Lymphoma

The patient will donate blood in order to make C7R-EBV T cells. Depending on how long ago the cells were generated, they have been frozen. To get the C7R to be made by the T-cell, the investigators inserted a gene into the T-cell. This is done using certain parts of a virus (known as a retrovirus) that can carry the gene into the T cells. Because patients receive cells with a new gene in them, they will befollowed for a total of 15 years to see if there are any long term side effects of gene transfer.

When they are enrolled in this study, patients are assigned a dose of C7R EBV T cells. The assigned dose of cells is based on body weight and height. Patients will receive the C7R EBV T cells and may also receive cyclophosphamide and fludarabine (these are standard chemotherapy medicines). The chemotherapy medicines may be given before the T cells to make space in the blood for the T cells to grow after receiving them.

If a patient receives chemotherapy medicines, these drugs will be given through an i.v. needle inserted in the patient's vein or central line) for 2 days and then fludarabine alone on the third day. The patient will be given an injection of C7R EBV T cells into the vein through an IV line at the assigned dose.

Patients may receive Benadryl and Tylenol. The infusion will take between 1 and 10 minutes. The investigators will then monitor the patient in the clinic or hospital for about 2 hours. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital. Patients should plan to stay in Houston for up to 2 weeks after the infusion so the investigators can monitor them for side effects.

Patients will have follow-up visits with the clinic (at scheduled visits weeks 2 and 6, and nursing follow-up at weeks 1, 2, 4, and 6; months 3, 6, 9, and 12; and annually for the next 15 years). Patients will have scheduled disease evaluations after the T-cell injection (at week 6 +/- 2 weeks and then as clinically needed). After the disease re-evaluation, if the patient's disease has not gotten worse, or if in the future it seems he/she might benefit, they may be eligible to receive one additional dose of the T cells. The dose will be at the same dose level as the patient's first infusion and separated by at least 6 weeks such that the investigators can make sure that the patient has no severe side effects between infusions. If the patient receives an additional dose of C7R EBV T-cells, they will need to stay in Houston for up to 2 weeks after the infusion as well so the investigators can monitor them for side effects.

Medical tests before treatment--

Before being treated, the patient will receive a series of standard medical tests:

• Physical exam
• Blood tests to measure blood cells, kidney and liver function
• Measurements of the tumor by routine imaging studies. The investigators will use the imaging studies that have been used in the past to best assess the patient's tumor (Computer Tomogram (CT) or Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET/CT) and/or Bone Scan).

Medical tests during and after treatment--

The patient will receive standard medical tests when they are getting the infusions and afterwards:

• Physical exams
• Blood tests to measure blood cells, kidney and liver function
• Measurements of the tumor by routine imaging studies approximately 6 weeks after the infusion.

To learn more about the way the C7R EBV T cells are working and how long they last in the body, an extra amount of blood will be obtained on the day that chemotherapy starts, the day of the T-cell infusion(s) and at the end of the T-cell infusion(s), 1, 2, 4, 6 weeks after the T-cell infusion(s) and every 3 months for the 1st year, and annually for the next 15 years and possibly at additional time points. The amount of blood taken will be based on the patient's weight with up to a maximum of 60 mL (12 teaspoons) of blood to be obtained at any one time. For children, the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon) per 1 kg (2 lbs) of body weight on any one day. This volume is considered safe, but may be decreased if the patient is anemic (have a low red blood cell count).

If the patient has a procedure where tumor samples are obtained, like a repeat bone marrow evaluation or tumor biopsy, the investigators request a sample to be used for research purposes. Patients will receive supportive care for any acute or chronic toxicities, including blood components or antibiotics, and other intervention as appropriate.