再発または難治性CD30陽性リンパ腫患者における同種CD30.CAR-EBVST

Earlier, healthy donors gave blood for us to make CD30.CAR-EBVST cells in the laboratory. These cells were grown and frozen and the investigators will select the donor which the investigators think is the best match for the patient. This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose of CD30.CAR-EBVST cells. Once the lower dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 4 dose levels are studied. If the side effects are too severe, the dose will be lowered or the T cell infusion will be stopped. Both the risks and benefits of this study may be dose related. The investigators don't know the best dose that will provide benefit while minimizing the risks.

To enroll on this study, patients will need to have recovered from toxic effects of previous chemotherapy and not be receiving any other investigational agents. Patients cannot have received an investigational cell therapy or vaccine within the past 6 weeks. Patients cannot have received an investigational small molecule drug within the past 2 weeks.

If patients agree to take part in this study, the investigators will ask the patients to adhere to the following study visits and procedure. After patients have signed the consent form, patients are required to come to the hospital for a series of standard medical screening tests, lymphodepletion chemotherapy with cyclophosphamide and fludarabine, infusion with CD30.CAR-EBVST cell treatment and follow-up visits (See details below).

1. Screening tests

   Screening tests include:

   • Blood tests [Human Leukocyte Antigen (HLA) testing] to help us identify the best match for patients from the banked CD30.CAR-EBVST cells.
   • Blood tests for viruses such as human immunodeficiency virus [HIV], human T cell lymphotropic virus [HTLV], hepatitis B virus and hepatitis C virus.
   • Tumor biopsy test to check the status of CD30.

   Once the investigators find that patients are eligible for this study, patients will be called for additional screening tests before treatment day. The screening tests include:

   • Physical examination
   • Vital signs tests to measure temperature, pulse, respiratory rate and blood pressure
   • Blood tests to measure blood cells, kidney and liver functions
   • Urine test
   • Pregnancy test for women of child-bearing potential
   • Measurements of tumor by routine imaging studies

2. Lymphodepletion chemotherapy Several studies suggest that the infused T cells need room to be able to multiply and grow to accomplish their functions and that this may not happen if there are too many other T cells in the blood stream. Because of that, if patients have NOT had a bone marrow or stem cell transplant recently, patients will receive treatment with cyclophosphamide and fludarabine (chemotherapy drugs) before patients receive the CD30.CAR-EBVST cells if patients doctor thinks this is appropriate. This is called "lymphodepletion". These drugs will decrease the numbers of patients own T cells before the investigators inject the CD30.CAR-EBVST cells. Although the investigators do not expect any effect on the patients tumor with the dose that the patients will receive, these drugs are part of many regimens that are used to treat lymphoma.

3. Treatment with CD30.CAR-EBVST cells

   Each patient will receive a total dose of CAR modified T cells according to the following dosing schedule:

   • Dose Level 1: 4 × 10^7 CD30.CAR-EBVST cells
   • Dose Level 2: 1 × 10^8 CD30.CAR-EBVST cells
   • Dose Level 3: 4 × 10^8 CD30.CAR-EBVST cells
   • Dose Level 4: 8 × 10^8 CD30.CAR-EBVST cells

   The CD30.CAR-EBVST cells will be infused via an IV line at the assigned dose. Before patients receive the infusion, they may be given a dose of acetaminophen or anti-histamine (Benadryl for example) to minimize any possible allergic reaction. The infusion of CD30.CAR-EBVST cells will take within 10 minutes. The investigators will follow patients in the clinic after each infusion for up to 3 hours. The patient will need to stay less than 2 hours away from the Medical Center for 4 weeks after the CD30.CAR-EBVST cell infusion so the investigator can monitor them for side effects.

4. Follow-up visits

On follow-up visits after treatment, patients will also receive a series of standard medical tests:

• Physical examination
• Vital sign tests to measure temperature, pulse, respiratory rate and blood pressure
• Blood tests to measure blood cells, kidney and liver functions
• Urine tests (if clinically necessary)
• Pregnancy test for women of child-bearing potential (if clinically necessary)
• Measurements of tumor by routine imaging studies

After infusion of CD30.CAR-EBVST cells,the patients blood will be collected on follow-up visits at week 1, week 2, week 3, week 4, week 6, week 8, every 3 months for 1 year, every 6 months for 4 more years. Blood samples and tumor biopsies will also be periodically collected, based on the patients doctor's discretion for exploratory tests in the laboratory. After 5 years, in the event there is suspected or new cancer is detected, additional blood sample will also be collected for additional tests. Patients will be followed annually for 15 years total after year 5.

To learn more about the way the CD30.CAR-EBVST cells are working and how long they last in the body, the investigators will draw blood. The total amount of blood collected on any day is about 4-18 teaspoons (18-87 ml). This volume is considered safe but may be decreased if the patients are anemic. Patients blood will be drawn from a central line if participants have one. The total blood drawn during the patients participation in this study will not exceed 110 teaspoons (546 ml).

The investigators will also look at any scans or biopsies patients have had as standard of care.