Constitutive IL7R (C7R) Modified Banked Allogeneic CD30.CAR EBVSTS for CD30-Positive Lymphomas

Description

This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 4 different levels) of C7R.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, 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 C7R.CD30.CAR-EBVST cells if patient’s 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 C7R.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 C7R.CD30.CAR-EBVST cells

Each patient will receive a total dose of CAR modified T cells as detailed below. Dose level cohorts will be numbered sequentially:
* Dose Level 1: 4 × 10^7 C7R.CD30.CAR-EBVST cells
* Dose Level 2: 1 × 10^8 C7R.CD30.CAR-EBVST cells
* Dose Level 3: 4 × 10^8 C7R.CD30.CAR-EBVST cells
* Dose Level 4: 8 × 10^8 C7R.CD30.CAR-EBVST cells

The C7R.CD30.CAR-EBVST cells will be infused via an IV line at the indicated 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 investigators will follow patients in the clinic after each infusion for at least 3 hours. The patient will need to stay less than 2 hours away from the Medical Center for 4 weeks after the C7R.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 C7R.CD30.CAR-EBVST cells, the patients blood will be collected on follow-up visits at week 1, week 2, week 3, week 4, week 8, every 3 months for 1 year, every 6 months for 4 more years then yearly for a total of 15 years (all of these dates are counted from the first infusion). In the event of repeat infusions, for each repeat infusion the calendar will reset, and the follow-up visits will be timed by counting from the date of the most recent T-cell infusion. A tumor biopsy may be done within 4 weeks after the initial C7R.CD30.CAR-EBVST cell infusion. The investigators will also look at any scans or biopsies patients have had as standard of care.

Participants may ask their treating team for a list of potential research costs patients are responsible for and where they are done.