Allogeneic CD30.CAR-EBVSTs in Patients With Relapsed or Refractory CD30-Positive Lymphomas

NCT04288726 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-46862 BESTA
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL) or classical Hodgkin lymphoma (cHL) (hereafter these 3 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study. In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins. The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients

Conditions

Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type; Classical Hodgkin Lymphoma

Keywords

CD30-Positive Lymphoma; Hodgkin lymphoma; non-Hodgkin lymphoma; CD30 CAR

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity rate (DLT) by CTCAE 5.0

  Any Grade 5 event, / Non-hematologic dose-limiting toxicity is any Grade 3 or Grade 4 non-hematologic toxicity that affects the cardiopulmonary system, or corresponds to neurotoxicity, or otherwise fails to return to Grade 2 within 72 hours, / Grade 2-4 allergic reaction to T-Cells, / Grade 3-4 GVHD, / Hematologic dose limiting toxicity is defined as any Grade 4 hematologic toxicity that fails to return to Grade 2 or baseline (whichever is more severe) within 14 days or within 28 days for patients with evidence of bone marrow disease.

  28 days

Secondary Outcomes (5)

• Rate of Anti-Tumor effect Objective Response (OR)

  6 to 8 weeks post CTL infusion

• Duration of response

  Up to 5 years

• Stable disease (SD) rate

  6 to 8 weeks post CTL infusion

• Duration of SD

  Up to 5 years

• Progression free survival (PFS)

  Up to 5 years

Study Arms (1)

Treatment Phase

EXPERIMENTAL

Four dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three to six patients will be enrolled at each dose level The dose is based on the number of CD.30 CAR-EBVT-expressing cells administered. The total number of dose levels evaluated will depend upon toxicities experienced. Dose level cohorts will be numbered sequentially. * 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

Biological: CD30.CAR-EBVST cells

Interventions

CD30.CAR-EBVST cells BIOLOGICAL

The dose is based on the number of CD30.CAR-expressing cells. In our previous study the highest dose was 2 × 10\^8 cells/m2 and we did not reach an MTD. This will be administered as a single infusion of the full dose for each level, which was already shown to be safe in the first 3 patients treated at dose level 3. Since we have not observed any dose limiting toxicities at the current dose level (Dose Level 3 as of June 2022), we propose to include a new higher dose level (8 × 10\^8).There will be a gap of 4 weeks between the first and second patient, and between the second and the third patient, on each dose level.

Also known as: Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes

Treatment Phase

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis and clinical course falling into one of the following categories:
• Hodgkin lymphoma
• Aggressive non-Hodgkin lymphoma
• ALK-negative anaplastic T cell lymphoma or other peripheral T-cell lymphoma
• ALK-positive anaplastic T cell lymphoma
• CD30-positive tumor as assayed in a CLIA certified Pathology Laboratory.
• Age 12 to 75.
• Bilirubin 2 times (or 3 times if the patient has Gilbert syndrome) or less than the upper limit of normal.
• AST 3 times or less than the upper limit of normal.
• Estimated GFR \> 70 mL/min.
• Pulse oximetry of \> 90% on room air
• EKG shows no significant arrhythmias
• Karnofsky or Lansky score of \> 60%.
• Available allogeneic T cells with ≥15% expression of CD30CAR determined by flow-cytometry.
• Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.

You may not qualify if:

• Received an investigational cell therapy or vaccine within the past 6 weeks.
• Received an investigational small molecule drug within the past 2 weeks.
• Received CD30 antibody-based therapy within the previous 4 weeks.
• Received gemcitabine-containing chemotherapy within the previous 12 weeks
• History of hypersensitivity reactions to murine protein-containing products.
• Pregnant or lactating.
• Tumor in a location where enlargement could cause airway obstruction (determined at the investigators' discretion).
• Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day of prednisone.
• Active significant, uncontrolled bacterial, viral or fungal infection.
• Symptomatic cardiac disease (NYHA Class III or IV disease).

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Carlos Ramos, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carlos Ramos, MD

CONTACT

832-824-4817; caramos@bcm.edu

Vicky Torrano

CONTACT

(832) 824-7821; vtorrano@bcm.edu-

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 26, 2020
• First Posted: February 28, 2020
• Study Start: September 16, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2037
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)