Constitutive IL7R (C7R) Modified Banked Allogeneic CD30.CAR EBVSTS for CD30-Positive Lymphomas (CABAL2)

Constitutive IL7R (C7R) Modified Banked Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes (CD30.CAR-EBVSTs) in Patients With Relapsed or Refractory CD30-Positive Lymphomas

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.

Study Overview

• Status: Recruiting
• Conditions: Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Peripheral T-cell Lymphoma; Anaplastic Large Cell Lymphoma, ALK-Positive; Anaplastic Large Cell Lymphoma, ALK-negative; CD30-Positive Diffuse Large B-Cell Lymphoma; Anaplastic Large Cell Lymphoma, T Cell and Null Cell Type
• Intervention / Treatment: Biological: C7R.CD30.CAR-EBVST cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Premal Lulla, MD; Phone Number: 713-441-1450; Email: lulla@bcm.edu
• Study Contact Backup: Name: Vicky Torrano, RN; Phone Number: (832) 824-7821; Email: vtorrano@bcm.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
      • Contact: Premal Lulla, MD; Phone Number: 713-441-1450; Email: lulla@bcm.edu
      • Contact: Vicky Torrano, RN; Phone Number: 832-824-7821; Email: vtorrano@bcm.edu
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Texas Children's Hospital
      • Contact: Premal Lulla, MD; Phone Number: 713-441-1450; Email: lulla@bcm.edu
      • Contact: Vicky Torrano, RN; Phone Number: 832-824-7821; Email: vtorrano@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Phase; Four dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three 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 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

Biological: C7R.CD30.CAR-EBVST cells; The dose is based on the number of CD30.CAR- expressing cells. In our previous study the highest dose was 4 × 10^8 cells/m2 and we did not reach an MTD. On Day 0, patients will receive their planned dose of investigational T cell product by IV infusion over approximately 1 to 10 minutes in an expected volume of 1 to 50 mL.; Other Names: Allogeneic CR7.CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity (DLT)	Dose-limiting toxicity (DLT) is defined as any of the following considered possibly, probably, or definitely related to study cellular products: (1) Grade 5 event without disease progression; (2) CRS: Grade 4, or Grade 3 not improving to ≤Grade 2 within 72 hours despite therapy; (3) ICANS: Grade 4, or Grade 3 not improving within 72 hours despite therapy; (4) Grade ≥3 IEC-HS; (5) Grade ≥3 acute GvHD requiring corticosteroids and not resolving within 7 days, or steroid-refractory Grade 2 GvHD; (6) Grade 4 neutropenia or thrombocytopenia not resolving to ≤Grade 2 within 42 days, or Grade 3 thrombocytopenia with major bleeding; (7) Grade ≥3 vital organ toxicity (except transient hepatic/renal abnormalities resolving within 7 days); (8) other Grade 3 toxicities not resolving within 72 hours; (9) Grade ≥2 allergic reaction.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Anti-Tumor effect Objective Response (OR)	Objective response rate is defined as complete response and partial response	6 to 8 weeks post CTL infusion
Duration of response	Response duration will be measured from the time of initial response until documented tumor progression.	Up to 5 years
Stable disease (SD) rate	SD will be defined as the proportion of patients that have stable disease	6 to 8 weeks post CTL infusion
Duration of SD	Stable disease is measured from the start of the treatment until the criteria for progression are met.	Up to 5 years
Progression free survival (PFS)	PFS is defined as the time from treatment until objective tumor progression or death, whichever occurs first.	Up to 5 years

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: The Methodist Hospital Research Institute; Center for Cell and Gene Therapy, Baylor College of Medicine
• Investigators: Principal Investigator: Premal Lulla, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): July 27, 2028
• Study Completion (Estimated): June 27, 2043

Study Registration Dates

• First Submitted: December 11, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Actual): December 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: non-Hodgkin lymphoma; Hodgkin lymphoma; CD30-Positive Lymphoma; CD30 CAR
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma, T-Cell, Peripheral; Lymphoma, Large-Cell, Anaplastic
• Other Study ID Numbers: H-56523, CABAL2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No