Malignant Pleural EffusionPhase 1RIOT 4BNCT07443020
Fast TILs to Treat Metastatic Pleural Effusions From Epithelial or Mesothelial Primary Tumors
A Phase 1 study testing locally manufactured adoptive cellular therapy (ACT) product and Interleukin-2 (IL-2) in people with Malignant Pleural Effusion and Malignant Mesothelioma, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Malignant Pleural Effusion, Malignant Mesothelioma, Pleural Effusion, Malignant
- What is being tested?
- locally manufactured adoptive cellular therapy (ACT) product and Interleukin-2 (IL-2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- May 2026to Mar 2038
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 MUGA or echocardiography.
- No requirement for supplemental oxygen and no dyspnea immediately after effusion drainage.
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- ECOG Performance Status 0 or 1.
- Patients must have an expected survival > 12 weeks.
- Patients must be able to comprehend the risks and methods used in this clinical trial and independently consent to participate.
- Patients must consent to collection of demographic and clinical data.
Who cannot join
- Infection with 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.
- Patients currently being treated for bacterial, fungal or viral infection.
- Documented myocardial infarction within 6 months of study participation and/or symptomatic coronary artery or valvular disease or uncontrolled arrhythmia.
- Investigational drug use within 30 days before effusion collection.
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- Cytotoxic anti-cancer or radiation therapy administration within 2 weeks of effusion collection. The exclusion does not apply to patients receiving monoclonal antibody therapy targeting immune checkpoint molecules.
- Corticosteroid therapy > 10 mg of prednisone (biological equivalent) daily within 2 weeks before effusion collection.
- Immunosuppressive therapy that cannot be stopped for 4 weeks prior to effusion collection as deemed by the prescribing physician.
- Laboratory abnormalities that indicate clinically significant hematological, hepatobiliary, or renal disease:
- AST/SGOT > 2.0 times the upper limit of normal ALT/SGPT > 2.0 times the upper limit of normal Total bilirubin > 2.0 times the upper limit of normal, unless patient has Gilbert Syndrome (>3.0 times the upper limit of normal) Hemoglobin < 8 gm/dL or dependent upon transfusion to maintain ≥ 8 gm/dL White blood cell count < 2,000/mm3 Platelet count < 100,000/mm3 or dependent upon transfusion to maintain ≥ 100,000 mm3 Creatinine > 2.0 times the upper limit of normal or calculated creatinine clearance ≤ 40 mL/min.
- Pregnant or lactating females.
- Prior solid organ transplantation
- Patients who, in the opinion of the Investigator, will be non-compliant with study schedules or procedures.
- Patients who belong to a vulnerable population such as the homeless, the developmentally disabled and prisoners or have any condition that impairs their ability to provide informed consent or comply with study schedules or procedures.
- Patients with documented anaphylaxis as a result of penicillin allergy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
AHN West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Patrick Wagner, MD, 412-359-3731, patrick.wagner@ahn.org
AHN Clinical Trial Contact, 412-359-3731, clinicaltrials@ahn.org
About this study
Official title: Fast TILs to Treat Metastatic Pleural Effusions From Epithelial or Mesothelial Primary Tumors: A Phase I Trial (FAST TILS 2)
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.
Read the detailed description
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.
- Conditions
- Malignant Pleural Effusion, Malignant Mesothelioma, Pleural Effusion, Malignant, Metastasis to Pleura
- Being tested
- locally manufactured adoptive cellular therapy (ACT) product, Interleukin-2 (IL-2)
- Keywords
- metastasis to pleura, pleural infiltrating T cells, CliniMACS Prodigy, malignant mesothelioma, pleural effusion, malignant, Adoptive Cellular Therapeutic, immunotherapy, autologous tumor infiltrating lymphocytes (TIL)
- Medical subject headings
- Pleural Effusion, Malignant, Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
locally manufactured adoptive cellular therapy (ACT) productBiological
Also called ACT, Fast TIL
Single dose, intrapleural delivery (via indwelling pleural catheter) of adoptive cellular therapy (ACT) product derived from autologous pleural infiltrating T-cells.
Interleukin-2 (IL-2)Drug
Also called IL-2, Proleukin
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).
| Study group | Role | What they receive |
|---|---|---|
| locally manufactured adoptive cellular therapeutic (ACT) product | Experimental | 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). Receives: Biological: locally manufactured adoptive cellular therapy (ACT) product; Drug: Interleukin-2 (IL-2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
flow cytometry for cellular ACT identity
Measured: 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
Measured: 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
Measured: 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.
Measured: 5 years
Secondary outcomes (4)
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
Measured: 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
Measured: 30 days
To document the overall response rates to therapy
as measured by PET CT scan, using mRECIST criteria
Measured: 60 days
To document the complete response rates to therapy
as measured by PET CT scan, using mRECIST criteria
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2026
- Study startMay 2026 (estimated)
- Primary completionMar 2033 (estimated)
- Study completionMar 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural EffusionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Sponsor type
- University, hospital or other
- Collaborators
- AHN Cancer Institute (AHNCI)
- Responsible party
- Principal investigator, Patrick Wagner, MD, FACS, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Investigators
- Patrick Wagner, MD, Principal investigator, Allegheny Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07443020
- Sponsor's protocol ID
- 2025-289
- Other IDs
- RIOT 4B, Fast TILS 2
- Acronym
- RIOT 4B
- Status last verified
- Apr 2026
- First submitted
- 25 Feb 2026
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fast TILs to Treat Metastatic Pleural Effusions From Epithelial or Mesothelial Primary Tumors: A Phase I Trial (FAST TILS 2)
- ClinicalTrials.gov ID
- NCT07443020
- Acronym / sponsor ID
- RIOT 4B / 2025-289
- Conditions
- Malignant Pleural Effusion, Malignant Mesothelioma, Pleural Effusion, Malignant, Metastasis to Pleura
- Keywords
- metastasis to pleura, pleural infiltrating T cells, CliniMACS Prodigy, malignant mesothelioma, pleural effusion, malignant, Adoptive Cellular Therapeutic, immunotherapy, autologous tumor infiltrating lymphocytes (TIL)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)University, hospital or other
- Collaborators
- AHN Cancer Institute (AHNCI)
- Study start
- May 2026 (estimated)
- Primary completion
- Mar 2033 (estimated)
- Study completion
- Mar 2038 (estimated)
- First posted
- 2 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| locally manufactured adoptive cellular therapeutic (ACT) product | Experimental | Biological: locally manufactured adoptive cellular therapy (ACT) product, Drug: Interleukin-2 (IL-2)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). |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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 MUGA or echocardiography.
Key exclusion criteria (16 listed)
- Infection with 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.
- Patients currently being treated for bacterial, fungal or viral infection.
- Documented myocardial infarction within 6 months of study participation and/or symptomatic coronary artery or valvular disease or uncontrolled arrhythmia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| locally manufactured adoptive cellular therapy (ACT) productAlso: ACT, Fast TILSingle dose, intrapleural delivery (via indwelling pleural catheter) of adoptive cellular therapy (ACT) product derived from autologous pleural infiltrating T-cells. | Biological | locally manufactured adoptive cellular therapeutic (ACT) product |
| Interleukin-2 (IL-2)Also: IL-2, ProleukinLow 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). | Drug | locally manufactured adoptive cellular therapeutic (ACT) product |
Primary outcome
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
Time frame: 30 days
flow cytometry for cellular ACT identity
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
Time frame: 30 days
cytotoxicity assays for ACT potency
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device
Time frame: 30 days
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
Time frame: 5 years
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.
4 secondary outcomes
To document changes in the pleural fluid secretome secondary to local therapeutic ACT product infusion.
Time frame: 30 days
To document changes in the pleural cellular composition secondary to local therapeutic ACT product infusion
Time frame: 30 days
To document the overall response rates to therapy
Time frame: 60 days
To document the complete response rates to therapy
Time frame: 60 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Patrick Wagner, MD principal investigator
Allegheny Health Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing locally manufactured adoptive cellular therapy (ACT) product and Interleukin-2 (IL-2) in people with Malignant Pleural Effusion and Malignant Mesothelioma, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Patrick Wagner, MD (412-359-3731, patrick.wagner@ahn.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Document the feasibility of local manufacture of ACT product from drained pleural effusions using the CliniMACS Prodigy® device (time frame: 30 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.