This research study aims to evaluate the safety and effectiveness of a novel immunotherapy, Fast TIL, an Adoptive Cellular Therapeutic (ACT), to fight cancer that has spread to the pleura or pleural mesothelioma. The ACT product is created at AHN West Penn using the participant's pleural infiltrating T-cells (PIT). It is administered through a pleural catheter along with the drug Interleukin-2 (IL-2). Based on previous research it is believed that it may help fight the tumor and relieve symptoms. As a participant, their pleural fluid will be collected and the PIT cells will be isolated and expanded in the lab to create the ACT product. Before receiving the ACT product through their pleural catheter, they will undergo outpatient lymphodepleting chemotherapy. LDC is a standard procedure for many approved immunotherapy treatments Following the infusion, they'll receive IL-2 through the catheter for two days to stimulate the expanded PIT cells. The active treatment phase lasts about three weeks, with follow-up visits over five years at AHN West Penn Hospital, potentially requiring a hospital stay of up to six days. Blood samples will be taken to monitor their response. As this is a first-in-human study, treatment carries an unknown risk up to and including death from toxicity. However, the risks of similar immunotherapy treatments are well documented.
This is a first-in-human Phase 1 trial of short-term expanded pleural T cells to treat cancer metastatic to the pleura. Expanded cells will be delivered intrapleurally in combination with intrapleural IL-2, administered at a dose that ensures high local concentration while minimizing systemic exposure. Ancillary studies conducted in conjunction with the trial will leverage drained pleural effusions collected before and after intervention to determine why the intervention is succeeding or failing.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Single dose, intrapleural delivery (via indwelling pleural catheter) of adoptive cellular therapy (ACT) product derived from autologous pleural infiltrating T-cells.
Low dose Interleukin-2 (IL-2) will also be administered intrapleural at the dose of 20 milliliters (mL) at 1 x 10⁵ International Units (IU)/mL starting approximately 2 hours after ACT infusion and every 8 to 16 hours thereafter, as tolerated, for up to 4 doses (total 8 x 10⁶ IU).
AHN West Penn Hospital
Pittsburgh, Pennsylvania, United States
RECRUITINGDocument the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
flow cytometry for cellular ACT identity
Time frame: 30 days
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
cytotoxicity assays for ACT potency
Time frame: 30 days
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
flow cytometry for cellular ACT purity
Time frame: 30 days
To demonstrate the safety of intrapleural administration of the locally manufactured ACT product plus Interleukin 2 (IL-2) to study patients
incidence of Treatment-Emergent Adverse Events (Safety) of intrapleural administration of the locally manufactured ACT product, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: 5 years
To document changes in the pleural fluid secretome secondary to local therapeutic ACT product infusion.
changes in the pleural fluid secretome secondary to local therapeutic ACT product infusion using Luminex assays
Time frame: 30 days
To document changes in the pleural cellular composition secondary to local therapeutic ACT product infusion
changes in the pleural cellular composition secondary to local therapeutic ACT product infusion via flow cytometry
Time frame: 30 days
To document the overall response rates to therapy
as measured by PET CT scan, using mRECIST criteria
Time frame: 60 days
To document the complete response rates to therapy
as measured by PET CT scan, using mRECIST criteria
Time frame: 60 days
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