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

NCT06090864 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LCCC2222-ATL
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hodgkin Lymphoma; Relapse; Refractory

Keywords

cellular therapy; CD30+

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Phase Ib Dose Limiting Toxicity

  Up to 6 weeks

• Overall Survival (OS)

  Up to 6 months

• Duration of Response (DOR)

  Up to 6 months

Study Arms (1)

ATLCAR.CD30

EXPERIMENTAL

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; Biological: Cell infusion

Interventions

Chemotherapy DRUG

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.

ATLCAR.CD30

Cell infusion BIOLOGICAL

ATLCAR.CD30.CCR4 cells infusion for the eligible subjects after depletion chemotherapy.

ATLCAR.CD30

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• Age ≥ 18 years at the time of consent.
• Karnofsky score of \> 60%
• The subject must have a diagnosis of Classical Hodgkin Lymphoma according to World Health Organization criteria.

You may not qualify if:

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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• Clinical trials at UNC Lineberger

MeSH Terms

Conditions

Hodgkin Disease; Recurrence

Interventions

Drug Therapy; Insulin Infusion Systems

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Drug Delivery Systems; Infusion Pumps; Equipment and Supplies; Artificial Organs; Surgical Equipment

Study Officials

• Natalie Grover, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Cheng

CONTACT

+1 919-445-4208; UNCImmunotherapy@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2023
• First Posted: October 19, 2023
• Study Start: April 25, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2031
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)