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.
Patients with symptomatic, biopsy-proven malignant to the pleura, or mesothelioma with pleural effusions. Patients must have received and be refractory to available standard of care (SOC) therapy specific to their cancer type and must have exhausted or failed available standard of care with clinical benefit.
Patients will be ≥ 18 and < 80 years of age.
Female patients of childbearing potential must have a negative urine or serum pregnancy test and if sexually active must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), an injectable contraceptive (such as Depo-Provera), or an oral contraceptive. Active contraception should continue for at least 12 months after ACT administration. Male participants must be willing to practice birth control from the time of enrollment on this study and for 4 months after receiving the preparative regimen.
Cardiac ejection fraction ≥ 0.45 by Multiple-Gated Acquisition (MUGA) or echocardiography.
Patients with breast, kidney, lung, pancreatic, prostate, ovarian, rare cancers, and melanoma.
Infection with Human Immunodeficiency Virus (HIV) and active viral replication. Patients with an undetectable viral load on Anti-retroviral Therapy (ART) can be considered for participation on this protocol.
Infection with hepatitis B and active viral replication.
Infection with hepatitis C and active viral replication.
Single group
locally manufactured adoptive cellular therapy (ACT) product
Biological/VaccineSingle dose, intrapleural delivery (via indwelling pleural catheter) of adoptive cellular therapy (ACT) product derived from autologous pleural infiltrating T-cells.
Interleukin-2
DrugLow 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).
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
flow cytometry for cellular ACT identity
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
cytotoxicity assays for ACT potency
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
flow cytometry for cellular ACT purity
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.
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
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
To document the overall response rates to therapy
as measured by PET CT scan, using mRECIST criteria
To document the complete response rates to therapy
as measured by PET CT scan, using mRECIST criteria
Click on the lead sponsor to view all of their trials.
David Bartlett, MD
Lead sponsor
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
Sponsor institution
Miltenyi Biotec, Inc.
Collaborator
Iovance Biotherapeutics, Inc.
Collaborator
UPMC Hillman Cancer Center
Collaborator
