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Trial record 1 of 1 for:    TILs-003-Meso
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TILs & Low-Dose IL-2 Therapy Following Cyclophosphamide and Fludarabine in Pleural Mesothelioma Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02414945
Recruitment Status : Completed
First Posted : April 13, 2015
Last Update Posted : January 10, 2023
Information provided by (Responsible Party):
University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Pleural Mesothelioma Drug: Cyclophosphamide Drug: Fludarabine Biological: Autologous tumor infiltrating lymphocytes (TILs) Biological: Interleukin-2 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 15, 2015
Actual Primary Completion Date : October 2020
Actual Study Completion Date : October 2020

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 Name: Procytox

Drug: Fludarabine
Other Name: Fludara

Biological: Autologous tumor infiltrating lymphocytes (TILs)
Biological: Interleukin-2
Other Name: Proleukin

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Percentage of patients with a clinical response to the study treatment [ Time Frame: 5 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02414945

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Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
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Principal Investigator: Marcus Butler, M.D. Princess Margaret Cancer Centre
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02414945    
Other Study ID Numbers: TILs-003-Meso
First Posted: April 13, 2015    Key Record Dates
Last Update Posted: January 10, 2023
Last Verified: January 2023
Additional relevant MeSH terms:
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Mesothelioma, Malignant
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents