Tumor-Infiltrating Lymphocytes And Low-Dose Interleukin-2 Therapy Following Cyclophosphamide And Fludarabine In Patients With Melanoma

November 7, 2019 updated by: University Health Network, Toronto

Phase II Study Evaluating The Infusion Of Autologous Tumor-Infiltrating Lymphocytes (TILs) And Low-Dose Interleukin-2 (IL-2) Therapy Following A Preparative Regimen Of Non-Myeloablative Lymphodepletion Using Cyclophosphamide And Fludarabine In Patients With Metastatic Melanoma

This is a phase II clinical study for patients with metastatic (the cancer has spread to other parts of the body) melanoma. 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 which is an approved drug to treat melanoma. This study will see how useful this regimen is in treating metastatic melanoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

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 (Eligibility for TIL Evaluation):

  • Must have measurable, unresectable stage III or stage IV melanoma
  • Suitable tumor for collection
  • If tumor is suitable for collection, patient must be suitable for surgery
  • Patient must be 18 years of age or older
  • Performance status of ECOG 0 or 1
  • Life expectancy > 5 months from date of consent of TIL evaluation
  • Willing to be tested for transmissible diseases
  • For patients with a history of allergy to penicillin, gentamycin, streptomycin, or anti-fungals, the ability to generate TILs will be confirmed with the cell manufacturing laboratory

Inclusion Criteria (Eligibility for Treatment):

  • Signed and dated the informed consent
  • No brain metastases or stable brain metastases for 3 months following definitive treatment.
  • Life expectancy > 3 months from the date of consent for TILs treatment
  • TILs are suitable for use as determined by laboratory
  • More than 30 days since any prior systemic therapy at the time of the cell infusion, or more than six weeks since prior nitrosurea therapy. For patients with prior ipilimumab therapy, at least six weeks must elapse between the last ipilimumab dose and the start of study treatment. All side effects from previous treatment must have recovered to an acceptable grade level.
  • Adequate organ function
  • Must have positive EBV titres
  • 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.

Exclusion Criteria:

  • Requiring systemic steroid therapy
  • HIV positive
  • With active hepatitis B or hepatitis C, syphilis, or HTLV
  • 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 following study procedures.
  • Have no active underlying cardiac illnesses defined by positive stress test, LVEF<40% or ongoing life-threatening arrhythmias
  • Abnormal lung function test

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cyclophosphamide and Fludarabine followed by TILs and IL-2
Cyclophosphamide, i.v., 60mg/kg per day for 2 days and Fludarabine, i.v., 25mg/m2 per day for 5 days; then Tumor-Infiltrating Lymphocytes, i.v., 1x10^10 - 1.6x10^11 cells and Low-Dose Interleukin, i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week)
Drug: Cyclophosphamide
i.v., 60mg/kg per day for 2 days
Other Names:
  • CYTOXAN, PROCYTOX
Drug: Fludarabine
i.v., 25mg/m2 per day for 5 days
Other Names:
  • FLUDARA
Biological: Tumor-Infiltrating Lymphocytes
i.v., 1x10^10 - 1.6x10^11 cells
Biological: Low-Dose Interleukin
i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week)
Other Names:
  • Aldesleukin, Proleukin, Recombinant Human Interleukin 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Clinical response to treatment
Time Frame: 6 weeks after treatment
6 weeks after treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Number occurrences and severity of side effects
Time Frame: Starting at first dose of study treatment up to 10 years
Starting at first dose of study treatment up to 10 years
Number of patients with an immunity and no immunity to the study treatment
Time Frame: From start of study up to 10 years
From start of study up to 10 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: Butler Marcus, M.D., Princess Margaret Cancer Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

June 1, 2013

Primary Completion (ACTUAL)

April 1, 2018

Study Completion (ACTUAL)

April 1, 2018

Study Registration Dates

First Submitted

June 11, 2013

First Submitted That Met QC Criteria

June 18, 2013

First Posted (ESTIMATE)

June 21, 2013

Study Record Updates

Last Update Posted (ACTUAL)

November 8, 2019

Last Update Submitted That Met QC Criteria

November 7, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TILs-002-MEL

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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