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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by University Health Network, Toronto
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
First received: June 11, 2013
Last updated: July 8, 2015
Last verified: July 2015

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.

Condition Intervention Phase
Metastatic, Stage III or Stage IV, Melanoma
Drug: Cyclophosphamide
Drug: Fludarabine
Biological: Tumor-Infiltrating Lymphocytes
Biological: Low-Dose Interleukin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Clinical response to treatment [ Time Frame: 6 weeks after treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number occurrences and severity of side effects [ Time Frame: Starting at first dose of study treatment up to 10 years ] [ Designated as safety issue: Yes ]
  • Number of patients with an immunity and no immunity to the study treatment [ Time Frame: From start of study up to 10 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: June 2013
Estimated Study Completion Date: December 2023
Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Fludarabine
i.v., 25mg/m2 per day for 5 days
Other Name: 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 Name: Aldesleukin, Proleukin, Recombinant Human Interleukin 2


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01883323

Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Marcus Butler, M.D.    416-946-4628    marcus.butler@uhn.ca   
Principal Investigator: Marcus Butler, M.D.         
Sub-Investigator: Anthony Joshua, M.D.         
Sub-Investigator: David Hogg, M.D.         
Sponsors and Collaborators
University Health Network, Toronto
Principal Investigator: Butler Marcus, M.D. Princess Margaret Cancer Centre
  More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01883323     History of Changes
Other Study ID Numbers: TILs-002-MEL 
Study First Received: June 11, 2013
Last Updated: July 8, 2015
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by University Health Network, Toronto:
Stage III
Stage IV
Tumor-Infiltrating Lymphocytes
Low-Dose Interleukin-2

Additional relevant MeSH terms:
Nevi and Melanomas
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Fludarabine phosphate
Alkylating Agents
Analgesics, Non-Narcotic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 23, 2016