ATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells

The Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) and CCR4 for Relapsed/Refractory CD30+ Hodgkin s Lymphoma

Despite the progress in the therapy, Hodgkin's Lymphoma (HL) remains fatal for more than 15% of patients. Even in patients who are cured, the morbidity of therapy is substantial and long-lasting. New therapeutic agents are required therefore not only to further reduce mortality but also to alleviate morbidity.

The majority of HL express the CD30 antigens. CD30 expression is routinely used for the diagnosis of HL. Preclinical observations support CD30 as a viable target of CAR-T therapy. This phase Ib/II study was conducted based on these observations.

The purpose of this study is to determine the tolerability of ATLCAR.CD30.CCR4 cells in subjects with Hodgkin's Lymphoma and identify a recommended dose for further.

This is a single-center, open-label phase Ib/II trial that uses a 3+3 design to identify a recommended phase 2 dose (RP2D) of ATLCAR.CD30.CCR4 cells in Hodgkin's Lymphoma. The phase II portion is designed to determine the PFS of ATLCAR.CD30.CCR4 in Hodgkin's Lymphoma.

Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments.

Study Overview

• Status: Recruiting
• Conditions: Hodgkin Lymphoma; Relapse; Refractory
• Intervention / Treatment: Drug: Chemotherapy; Biological: Cell infusion

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Catherine Cheng; Phone Number: +1 919-445-4208; Email: UNCImmunotherapy@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • Lineberger Comprehensive Cancer Center
      • Contact: Catherine Cheng; Phone Number: +1 919-445-4208; Email: UNCImmunotherapy@med.unc.edu
      • Contact: Natalie Grover, MD; Phone Number: 919-966-4431; Email: UNCImmunotherapy@med.unc.edu

Participation Criteria

Eligibility Criteria

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

Description

During the period of cell procurement and lymphodepletion, subjects will be eligible to receive standard-of-care therapy e.g., chemotherapy or radiation therapy to stabilize their disease if the treating physician feels it is in the subject's best interests. Eligibility must be maintained up until the subject is procured, receives lymphodepletion, or receives treatment for the subject to be considered eligible to proceed with the specific phase of the study.

Inclusion Criteria:

Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study. As these criteria are unchanging they will be evaluated at the time of initial enrollment and not continuously throughout the study.

1. Written informed consent and HIPAA authorization for release of personal health information explained to, understood by, and signed by the subject or legally authorized representative.
2. Age ≥ 18 years at the time of consent.
3. Karnofsky score of > 60%
4. The subject must have a diagnosis of Classical Hodgkin Lymphoma according to World Health Organization criteria.

Exclusion Criteria:

1. Subjects had major surgery within 28 days.
2. Subject received investigational agents or tumor vaccines within 3 weeks.
3. Subject received chemotherapy or radiation therapy within the previous 3 weeks.

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: ATLCAR.CD30; Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments

Drug: Chemotherapy; Subjects will receive a lymphodepletion regimen of bendamustine 70 mg/m2 IV and fludarabine 30 mg/m2 each as a daily infusion for 3 consecutive days prior to the ATLCAR.CD30.CCR4 cell infusion.; Biological: Cell infusion; ATLCAR.CD30.CCR4 cells infusion for the eligible subjects after depletion chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b adverse events	Toxicity will be graded as the number of participants with adverse events (AE) related to the administration of ATLCAR.CD30.CCR4 cells in subjects with CD30+ Hodgkin's Lymphoma. AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) are defined as at least possibly related to CAR.B7-H3T cell product administration.	Up to 6 weeks
Phase 1b Toxicity Cytokine Release Syndrome (CRS)	CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading related to the administration of ATLCAR.CD30.CCR4 cells in subjects with CD30+ Hodgkin's Lymphoma. Grade 1 - Mild: Fever ≥38^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death	Up to 6 weeks
Phase 1b Toxicity Immune effector cell-associated neurotoxicity syndrome (ICANS)	Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria related to the administration of ATLCAR.CD30.CCR4 cells in subjects with CD30+ Hodgkin's Lymphoma. Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).	Up to 6 weeks
Phase II Median Progression Free Survival (PFS)	Median PFS will be measured from the first day of lymphodepletion chemotherapy prior to ATLCAR.CD30.CCR4 cell infusion to progression (as defined by Lugano Criteria or death. Complete: Complete metabolic response on Positron emission tomography (PET) or the largest transverse diameter (LDi) of target nodes/masses ≤ 1.5 cm and no extra lymphatic disease on Computerized Tomography (CT). Partial: reduced uptake compared with baseline and residual mass(es) on PET and ≥50% decrease in the sum of the products of diameters (SPD) of nodes and extranodal sites on CT. No Response or Stable Disease: No metabolic response on PET or < 50% decrease from baseline in SPD, measurable nodes and extranodal sites; no criteria for the progressive disease are met on CT. Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new focus on PET, LDi>1.5 cm or by ≥ 50% from nadir.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the first day of lymphodepletion to date of death for any cause. Subjects who have not had an event will be censored at the date of last assessment documenting the subject was alive.	Up to 6 months
Duration of Response (DOR)	DOR is defined as the time from partial response (PR) or better to progressive disease (PD) per Lugano Criteria. Complete Response: Complete metabolic response on Positron emission tomography (PET) or Target nodes/nodal masses must be ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic of disease on Computerized Tomography (CT). Partial Response: Score of 4 or 5† with reduced uptake of any size on PET and ≥50% decrease in the sum of the products of diameters (SPD) of nodes and extranodal sites on CT. No Response or Stable Disease: No metabolic response on PET or < 50% decrease from baseline in SPD of nodes and extranodal sites; no criteria for the progressive disease are met on CT. Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma.	Up to 6 months
Phase Ib Dose Limiting Toxicity	The recommended phase 2 dose (RP2D) of ATLCAR.CD30.CCR4 cells will be determined based on the 3+3 dose finding rule as specified in the protocol for the tolerability of ATLCAR.CD30.CCR4 cells will be assessed using NCI-CTCAE v5 and ASTCT Consensus CRS Grading Criteria.; Grade 3-5 allergic reactions related to the CAR-T cell infusion.; A treatment-emergent Grade 3 CRS that does not improve to Grade 0-1 by 72 hours or Grade 4 CRS; Grade ≥3 ICANS that are unresponsive to the standard of care interventions and do not decrease to Grade ≤1 within 7 days or grade 4 ICANS of any duration that has evidence of cerebral edema and/or generalized convulsive status epilepticus.; Any treatment-emergent Grade 4 non-hematologic AE that does not resolve to Grade 2 within 7 days.; Any Grade 5 events are not due to the underlying malignancy.	Up to 6 weeks

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Natalie Grover, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• Clinical trials at UNC Lineberger

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 13, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: cellular therapy; CD30+
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Hodgkin Disease; Therapeutics; Surgical Equipment; Equipment and Supplies; Artificial Organs; Drug Delivery Systems; Infusion Pumps; Drug Therapy; Insulin Infusion Systems
• Other Study ID Numbers: LCCC2222-ATL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No