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

NCT02414945 | Completed Phase 1 DMC

• 1 other identifier: TILs-003-Meso
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Pleural Mesothelioma

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Secondary Outcomes (1)

• Percentage of patients with a clinical response to the study treatment

  5 years

Study Arms (1)

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).

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Autologous tumor infiltrating lymphocytes (TILs); Biological: Interleukin-2

Interventions

Cyclophosphamide DRUG

Also known as: Procytox

Tumor Infiltrating lymphocytes (TILs)

Fludarabine DRUG

Also known as: Fludara

Tumor Infiltrating lymphocytes (TILs)

Autologous tumor infiltrating lymphocytes (TILs) BIOLOGICAL

Tumor Infiltrating lymphocytes (TILs)

Interleukin-2 BIOLOGICAL

Also known as: Proleukin

Tumor Infiltrating lymphocytes (TILs)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Marcus Butler, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2015
• First Posted: April 13, 2015
• Study Start: May 15, 2015
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2020
• Last Updated: January 10, 2023

Record last verified: 2023-01

Locations

CA (1)