Pleural MesotheliomaPhase 1/2NCT02414945
TILs & Low-Dose IL-2 Therapy Following Cyclophosphamide and Fludarabine in Pleural Mesothelioma Patients
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Autologous tumor infiltrating lymphocytes (TILs) in people with Pleural Mesothelioma, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This is a phase I and II clinical study for patients with malignant pleural mesothelioma (a type of cancer affecting the lining of the lung). Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pleural Mesothelioma
- What is being tested?
- Cyclophosphamide, Fludarabine and Autologous tumor infiltrating lymphocytes (TILs)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteCanada
- Study dates
- 15 May 2015to Oct 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to sign and date the informed consent form.
- Must have measurable stage I-IV malignant pleural mesothelioma at the time of investigational treatment.
- May have 3 or fewer asymptomatic brain metastases.
- Patient age: ≥ 18 years.
- Clinical performance status of ECOG 0 or 1.
- Life expectancy > 3 months from the date of consent.
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- Laboratory analyses of tumor-infiltrating lymphocytes (TILs) from the patient must demonstrate that the TILs are suitable for use in protocol treatment
- More than 30 days has elapsed since any prior systemic therapy at the time of the cell infusion, or more than six weeks since prior nitrosurea therapy. All toxicities must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less
- Adequate organ function
- Women of child-bearing potential must have a negative pregnancy test. Patients of both genders must be willing to practice birth control during treatment and for 6 months post completion of IL-2 treatment.
- Patients must have adequate respiratory function in the opinion of the treating thoracic physician
Who cannot join
- Ongoing or prior use systemic steroid therapy within 4 weeks before the TILs infusion will be excluded.
- Known HIV positive patients will be excluded.
- Active hepatitis B or hepatitis C, syphilis, or HTLV will be excluded.
- Must not have any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, uncontrolled psychiatric disorders, or other conditions that may affect compliance with the trial.
- Must have no active underlying cardiac illnesses defined by positive stress test, LVEF <40% or ongoing life threatening arrhythmias.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study Evaluating the Infusion of Tumor-Infiltrating Lymphocytes (TILs) & Low-Dose Interleukin-2 (IL-2) Therapy Following a Preparative Regimen of Non-myeloablative Lymphodepletion Using Cyclophosphamide & Fludarabine in Patients With Malignant Pleural Mesothelioma
This is a phase I and II clinical study for patients with malignant pleural mesothelioma (a type of cancer affecting the lining of the lung). Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down.
Prior to the cell infusion, patients will receive a two drugs cyclophosphamide and fludarabine to prepare the body to receive the TILs. After cell infusion, patients will receive low-dose interleukin-2 therapy. This study will see how safe and useful this regimen is in treating malignant pleural mesothelioma.
Read the detailed description
The investigational infusion product consists of autologous, in vitro-expanded tumor-infiltrating lymphocytes (TILs). The target number of cells for infusion is between 1 x 1010 and 1.6 x 1011. The cells are given intravenously over a 20-30 minute infusion.
Prior to infusion of TILs, patients will receive a preparative regimen of cyclophosphamide (60 mg/kg/day x 2 days intravenously) and fludarabine (25 mg/m2/day x 5 days intravenously).
After the cell infusion, patients will receive low-dose interleukin-2 (IL-2) therapy (125,000 IU/kg/day subcutaneously for 2 weeks with a 2 day break between each week. The goal for the total number of doses is 9-10).
Because confusion is a possible side effect of IL-2 administration, a Durable Power of Attorney will be signed by the patient to identify a surrogate to make decisions if a patient becomes unable to make decisions.
- Conditions
- Pleural Mesothelioma
- Being tested
- Cyclophosphamide, Fludarabine, Autologous tumor infiltrating lymphocytes (TILs), Interleukin-2
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Procytox
FludarabineDrug
Also called Fludara
Autologous tumor infiltrating lymphocytes (TILs)Biological
Interleukin-2Biological
Also called Proleukin
| Study group | Role | What they receive |
|---|---|---|
| Tumor Infiltrating lymphocytes (TILs) | Experimental | Lymphodepleting preparative regimen: Cyclophosphamide, intravenously, at 60mg/kg/day x 2 days, and Fludarabine, intravenously at 25mg/m2/day x 5 days
Autologous tumor infiltrating lymphocytes (TILs): Intravenously at 1x10^10 - 1.6x10^11 cells
Low-dose interleukin-2: Subcutaneously at 125,000 IU/kg per day, for 2 weeks (2 days rest between each week). Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Autologous tumor infiltrating lymphocytes (TILs); Biological: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total number of adverse events for each event reported and the severity and attribution to study therapy of each event
To determine the feasibility and safety of chemotherapy in combination with infusion of tumor-infiltrating lymphocytes followed by low-dose interleukin-2 in patients with malignant pleural mesothelioma.
Measured: 5 years
Secondary outcomes (1)
Percentage of patients with a clinical response to the study treatment
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2015 (estimated)
- Study start15 May 2015
- Primary completionOct 2020
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marcus Butler, M.D., Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02414945
- Sponsor's protocol ID
- TILs-003-Meso
- Status last verified
- Jan 2023
- First submitted
- 8 Apr 2015
- Last updated
- 10 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study Evaluating the Infusion of Tumor-Infiltrating Lymphocytes (TILs) & Low-Dose Interleukin-2 (IL-2) Therapy Following a Preparative Regimen of Non-myeloablative Lymphodepletion Using Cyclophosphamide & Fludarabine in Patients With Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT02414945
- Acronym / sponsor ID
- TILs-003-Meso
- Conditions
- Pleural Mesothelioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 15 May 2015 (actual)
- Primary completion
- Oct 2020 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 13 Apr 2015 (estimated)
- 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 is a phase I and II clinical study for patients with malignant pleural mesothelioma (a type of cancer affecting the lining of the lung). Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down.
Prior to the cell infusion, patients will receive a two drugs cyclophosphamide and fludarabine to prepare the body to receive the TILs. After cell infusion, patients will receive low-dose interleukin-2 therapy. This study will see how safe and useful this regimen is in treating malignant pleural mesothelioma.
Detailed description
The investigational infusion product consists of autologous, in vitro-expanded tumor-infiltrating lymphocytes (TILs). The target number of cells for infusion is between 1 x 1010 and 1.6 x 1011. The cells are given intravenously over a 20-30 minute infusion.
Prior to infusion of TILs, patients will receive a preparative regimen of cyclophosphamide (60 mg/kg/day x 2 days intravenously) and fludarabine (25 mg/m2/day x 5 days intravenously).
After the cell infusion, patients will receive low-dose interleukin-2 (IL-2) therapy (125,000 IU/kg/day subcutaneously for 2 weeks with a 2 day break between each week. The goal for the total number of doses is 9-10).
Because confusion is a possible side effect of IL-2 administration, a Durable Power of Attorney will be signed by the patient to identify a surrogate to make decisions if a patient becomes unable to make decisions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tumor Infiltrating lymphocytes (TILs) | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Autologous tumor infiltrating lymphocytes (TILs), Biological: Interleukin-2Lymphodepleting preparative regimen: Cyclophosphamide, intravenously, at 60mg/kg/day x 2 days, and Fludarabine, intravenously at 25mg/m2/day x 5 days Autologous tumor infiltrating lymphocytes (TILs): Intravenously at 1x10^10 - 1.6x10^11 cells Low-dose interleukin-2: Subcutaneously at 125,000 IU/kg per day, for 2 weeks (2 days rest between each week). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Able to sign and date the informed consent form.
- Must have measurable stage I-IV malignant pleural mesothelioma at the time of investigational treatment.
- May have 3 or fewer asymptomatic brain metastases.
- Patient age: ≥ 18 years.
- Clinical performance status of ECOG 0 or 1.
Key exclusion criteria (5 listed)
- Ongoing or prior use systemic steroid therapy within 4 weeks before the TILs infusion will be excluded.
- Known HIV positive patients will be excluded.
- Active hepatitis B or hepatitis C, syphilis, or HTLV will be excluded.
- Must not have any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, uncontrolled psychiatric disorders, or other conditions that may affect compliance with the trial.
- Must have no active underlying cardiac illnesses defined by positive stress test, LVEF <40% or ongoing life threatening arrhythmias.
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 |
|---|---|---|
| CyclophosphamideAlso: Procytox | Drug | Tumor Infiltrating lymphocytes (TILs) |
| FludarabineAlso: Fludara | Drug | Tumor Infiltrating lymphocytes (TILs) |
| Autologous tumor infiltrating lymphocytes (TILs) | Biological | Tumor Infiltrating lymphocytes (TILs) |
| Interleukin-2Also: Proleukin | Biological | Tumor Infiltrating lymphocytes (TILs) |
Primary outcome
Total number of adverse events for each event reported and the severity and attribution to study therapy of each event
Time frame: 5 years
To determine the feasibility and safety of chemotherapy in combination with infusion of tumor-infiltrating lymphocytes followed by low-dose interleukin-2 in patients with malignant pleural mesothelioma.
1 secondary outcome
Percentage of patients with a clinical response to the study treatment
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
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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. This study is not recruiting at the moment.
Marcus Butler, M.D. principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Autologous tumor infiltrating lymphocytes (TILs) in people with Pleural Mesothelioma, run by University Health Network, Toronto at 1 site in Canada.
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 11 inclusion and 5 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: finished, as of the sponsor's last update on 10 Jan 2023. 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 Canada. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total number of adverse events for each event reported and the severity and attribution to study therapy of each event (time frame: 5 years). 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 10 Jan 2023.