Back to resultsTILs & Low-Dose IL-2 Therapy Following Cyclophosphamide and Fludarabine in Pleural Mesothelioma Patients
Primary Purpose
Pleural Mesothelioma
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
Autologous tumor infiltrating lymphocytes (TILs)
Interleukin-2
Sponsored by
About this trial
This is an interventional treatment trial for Pleural Mesothelioma
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Princess Margaret Cancer Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tumor Infiltrating lymphocytes (TILs)
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Percentage of patients with a clinical response to the study treatment
Full Information
NCT ID
NCT02414945
First Posted
April 8, 2015
Last Updated
January 8, 2023
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT02414945
Brief Title
TILs & Low-Dose IL-2 Therapy Following Cyclophosphamide and Fludarabine in Pleural Mesothelioma Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
May 15, 2015 (Actual)
Primary Completion Date
October 2020 (Actual)
Study Completion Date
October 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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). 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pleural Mesothelioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tumor Infiltrating lymphocytes (TILs)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Procytox
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Type
Biological
Intervention Name(s)
Autologous tumor infiltrating lymphocytes (TILs)
Intervention Type
Biological
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
Proleukin
Primary Outcome Measure Information:
Title
Total number of adverse events for each event reported and the severity and attribution to study therapy of each event
Description
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.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Percentage of patients with a clinical response to the study treatment
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus Butler, M.D.
Organizational Affiliation
Princess Margaret Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
TILs & Low-Dose IL-2 Therapy Following Cyclophosphamide and Fludarabine in Pleural Mesothelioma Patients
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