Clinical trial NCT06090864: ATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells
Official title: The Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) and CCR4 for Relapsed/Refractory CD30+ Hodgkin s Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hodgkin Lymphoma
Relapse
Refractory
Keywords: cellular therapy
CD30+
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2023-10-19
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1b adverse events
timeFrame: Up to 6 weeks
measure: Phase 1b Toxicity Cytokine Release Syndrome (CRS)
timeFrame: Up to 6 weeks
measure: Phase 1b Toxicity Immune effector cell-associated neurotoxicity syndrome (ICANS)
timeFrame: Up to 6 weeks
measure: Phase II Median Progression Free Survival (PFS)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Phase Ib Dose Limiting Toxicity
timeFrame: Up to 6 weeks
measure: Overall Survival (OS)
timeFrame: Up to 6 months
measure: Duration of Response (DOR)
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Natalie Grover, MD
role: PRINCIPAL_INVESTIGATOR
References: