Clinical trial NCT06096038: Autologous CAR-T Cells Targeting CSPG4 in Relapsed/Refractory HNSCC
Official title: Administration of T Cells Expressing Chondroitin-Sulfate-Proteoglycan-4 Specific Chimeric Antigen Receptors (CAR) in Subjects With Head and Neck Squamous Cell Carcinoma (HNSCC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Head and Neck Cancer
Relapse
Recurrent
Refractory Cancer
Keywords: cellular therapy
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Bellicum Pharmaceuticals
name: National Cancer Institute (NCI)
First posted: 2023-10-23
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the CSPG4 antigen (iC9.CAR-CSPG4 T cells) in patients with head and neck cancer that came back after receiving standard therapy for this cancer. The iC9.CAR-CSPG4 treatment is experimental and has not been approved by the Food and Drug Administration.

How many (dose) of the iC9.CAR. CSPG4 T cells are safe to use in patients without causing too many side effects, and what is the maximum dose that could be tolerated will be investigated. The information collected from the study would help cancer patients in the future.

There are two parts to this study. In part 1, blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy.

The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD). Additionally, recommended phase 2 dose will be tested.

Eligible subjects will receive lymphodepletion chemotherapy standard followed by infusion of iC9-CAR.CSPG4 T cells. After treatment completion or discontinuation, subjects will be followed since involving gene transfer experiments.


Eligibility criteria: Inclusion Criteria:

Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study:

1. Written informed consent and HIPAA authorization for release of personal health information explained to, understood by and signed by the subject; subject given a copy of the informed consent form.
2. Age ≥ 18 years at the time of consent.
3. Karnofsky score of \> 60%
4. Histologically or cytologically confirmed stage recurrent/metastatic squamous cell carcinoma of the head and neck as defined by American Joint Committee on Cancer (AJCC). This includes squamous cancer of: oral cavity, oropharynx, hypopharynx and larynx.

Exclusion Criteria:

1. Subject with a history or current severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, uncontrolled arrhythmia, or myocardial infarction in the past 6 months.
2. Subject with a history of stroke or transient ischemic attack (TIA) within 12 months before procurement.
3. Subject with a history of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.

Primary outcomes:
measure: Toxicity: NCI-CTCAE
timeFrame: Up to 4 weeks
measure: Toxicity: Cytokine Release Syndrome (CRS)
timeFrame: Up to 4 weeks
measure: Toxicity: Immune effector cell-associated neurotoxicity syndrome (ICANS)
timeFrame: Up to 4 weeks
measure: Dose Limiting Toxicity
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: The recommended phase 2 dose (RP2D) of iC9-CAR.CSPG4
timeFrame: Up to 4 weeks
measure: Objective response rate
timeFrame: Up to 2 years
Other outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Feasibility of iC9-CAR.CSPG4 T cell therapy
timeFrame: From cell procurement to 4 weeks after iC9-CAR.CSPG4 T cell infusion.
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Jared Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References: