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 (1 of 3 different
levels) 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 3 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 any tumor vaccines within the previous six 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 Patients will be given one injection of
CD30.CAR-EBVST cells. The CD30.CAR-EBVST cells will be injected into the vein through an
IV line at the assigned dose. Before patients receive the injection, patients may be
given a dose of acetaminophen or anti-histamine (Benadryl for example) to minimize any
possible allergic reaction. The injection of CD30.CAR-EBVST cells will take within 10
minutes. The investigators will follow patients in the clinic after each injection 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.
At the discretion of the study doctor, if patients have stable disease (the lymphoma did
not grow) or there is a reduction in the size of the patients lymphoma on imaging
studies at week 6 after T-cell infusion or on subsequent evaluations, then patients may
receive up to two additional doses of the CD30.CAR-EBVST cells at approximately 6 weeks
intervals if patients wish to. Lymphodepletion chemotherapy may also be administered
before additional doses of CD30.CAR-EBVST infusion. After each T-cell infusion, patients
will be monitored to ensure that participants don't have a reaction to the infusion.
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.
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.
Inclusion Criteria:
1. Diagnosis and clinical course falling into one of the following categories:
1. Hodgkin lymphoma
2. Aggressive non-Hodgkin lymphoma
3. ALK-negative anaplastic T cell lymphoma or other peripheral T-cell lymphoma
4. ALK-positive anaplastic T cell lymphoma
2. CD30-positive tumor as assayed in a CLIA certified Pathology Laboratory.
3. Age 12 to 75.
4. Bilirubin 2 times (or 3 times if the patient has Gilbert syndrome) or less than the
upper limit of normal.
5. AST 3 times or less than the upper limit of normal.
6. Estimated GFR > 70 mL/min.
7. Pulse oximetry of > 90% on room air
8. EKG shows no significant arrhythmias
9. Karnofsky or Lansky score of > 60%.
10. Available allogeneic T cells with ≥15% expression of CD30CAR determined by
flow-cytometry.
11. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.
12. Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 6 months after the study is concluded. The
male partner should use a condom.
13. Informed consent explained to, understood by and signed by patient or guardian.
Patient or guardian given a copy of the informed consent form.
Exclusion Criteria:
1. Currently receiving any investigational agents or received any tumor vaccines within
the previous six weeks.
2. Received CD30 antibody-based therapy within the previous 4 weeks.
3. History of hypersensitivity reactions to murine protein-containing products.
4. Pregnant or lactating.
5. Tumor in a location where enlargement could cause airway obstruction.
6. Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day
of prednisone.
7. Active significant, uncontrolled bacterial, viral or fungal infection.
8. Symptomatic cardiac disease (NYHA Class III or IV disease).
