This study involves patients with diffuse large B cell lymphoma (DLBCL), natural killer/T-cell lymphoma (NKTL), or classical Hodgkin lymphoma (cHL) (referred to collectively as lymphoma) whose disease has returned or not responded to treatment.

Previous research combined antibodies and T cells to treat cancer. Antibodies bind to foreign substances, and T cells are infection-fighting white blood cells that can kill tumor cells. Both approaches have shown promise but have not been sufficient to cure most patients. In prior studies, an antibody targeting CD30, a protein found on some T cells and cancer cells, was joined to T cells through gene transfer to create CD30.CAR T cells.

Another study showed encouraging responses using CD30.CAR T cells made from a patient's own blood and returned to the same patient (autologous cells). In an ongoing study, patients have been treated with CD30.CAR T cells derived from healthy donors (allogeneic cells), allowing use of banked cells without individualized manufacturing. This approach has shown promising clinical activity with no safety concerns to date.

In this study, investigators are evaluating CD30.CAR-EBVST cells modified with an additional molecule called C7R, which has been shown in laboratory studies to enhance anti-cancer effects. The study aims to assess the safety and effectiveness of these allogeneic, banked C7R-modified CD30.CAR-EBVST cells and determine whether they may help treat lymphoma.

As an added safety measure, the modified T cells include a marker called iC9. If significant side effects occur, patients may receive rimiducid, which can eliminate the infused T cells. Rimiducid is not yet FDA approved but has been tested in patients without significant side effects.

This is a Phase 1 dose-escalation study evaluating allogeneic C7R.CD30.CAR-EBVST cells in patients with relapsed or refractory CD30-positive lymphoma.

Participants are treated in sequential cohorts at one of four dose levels of C7R.CD30.CAR-EBVST cells. Treatment begins at the lowest dose level, and subsequent cohorts are treated at higher dose levels if the preceding dose is determined to be safe. If significant toxicity is observed, dose escalation may be halted, reduced, or discontinued. The relationship between dose level and both safety and potential clinical benefit is evaluated.

Prior to treatment, participants undergo screening evaluations including laboratory testing, imaging studies, and confirmation of CD30 expression. Human leukocyte antigen (HLA) testing is performed to identify the most appropriate partially matched cell line from a bank of allogeneic C7R.CD30.CAR-EBVST products.

Participants may receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine prior to infusion, as clinically appropriate, to reduce endogenous lymphocytes and support expansion of the infused cells.

C7R.CD30.CAR-EBVST cells are administered as a single intravenous infusion at the assigned dose level. Premedication may be given to reduce the risk of infusion-related reactions. Participants are monitored in the clinical setting following infusion and are required to remain within close proximity to the treatment center for a defined period to allow for monitoring of potential adverse events.

Following treatment, participants undergo scheduled follow-up evaluations including physical examinations, laboratory testing, and imaging studies to assess safety and disease status. Blood samples are collected at multiple time points after infusion to evaluate persistence of the infused cells. Tumor assessments are performed using imaging and, when clinically indicated, biopsy.

Participants are followed longitudinally after treatment, with more frequent assessments early after infusion and less frequent long-term follow-up, for up to 15 years after the most recent infusion.

Inclusion Criteria:

1. Diagnosis and clinical course falling into one of the following categories:

   1. Hodgkin lymphoma
   2. CD30+ aggressive B-cell 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 less than or equal to 2 times the upper limit of normal (except for Gilbert syndrome, where the criteria will be Bilirubin less than or equal to 3 times the upper limit of normal).

5. AST less than 3 times the upper limit of normal.

6. Estimated GFR > 70 mL/min.

7. Pulse oximetry of > 90% on room air

8. Karnofsky or Lansky score of > 60%.

9. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.

10. 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.

11. 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. Received an investigational cell therapy or vaccine within the past 6 weeks.
2. Received an investigational small molecule drug within the past 2 weeks.
3. Received anti-CD30 antibody-based therapy within the previous 4 weeks.
4. History of hypersensitivity reactions to murine protein-containing products.
5. Pregnant or lactating.
6. Tumor in a location where enlargement could cause airway obstruction (determined at the investigators' discretion).
7. Current use of systemic corticosteroids at a dose equivalent to or higher than 10 mg/day of prednisone.
8. Active significant, uncontrolled bacterial, viral or fungal infection.
9. Symptomatic cardiac disease (NYHA Class III or IV disease).