TILs & Low-Dose IL-2 Therapy Following Cyclophosphamide and Fludarabine in Pleural Mesothelioma Patients

January 8, 2023 updated by: University Health Network, Toronto

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tumor Infiltrating lymphocytes (TILs)

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).
Drug: Cyclophosphamide
Other Names:
  • Procytox
Drug: Fludarabine
Other Names:
  • Fludara
Biological: Autologous tumor infiltrating lymphocytes (TILs)
Biological: Interleukin-2
Other Names:
  • Proleukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of patients with a clinical response to the study treatment
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Marcus Butler, M.D., Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2015

Primary Completion (Actual)

October 1, 2020

Study Completion (Actual)

October 1, 2020

Study Registration Dates

First Submitted

April 8, 2015

First Submitted That Met QC Criteria

April 8, 2015

First Posted (Estimate)

April 13, 2015

Study Record Updates

Last Update Posted (Estimate)

January 10, 2023

Last Update Submitted That Met QC Criteria

January 8, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TILs-003-Meso

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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