Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma (TIL)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02278887
Recruitment Status : Recruiting
First Posted : October 30, 2014
Last Update Posted : January 12, 2018
Sponsor:
Collaborators:
Copenhagen University Hospital at Herlev
University of Manchester
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Tracking Information
First Submitted Date  ICMJE June 3, 2014
First Posted Date  ICMJE October 30, 2014
Last Update Posted Date January 12, 2018
Study Start Date  ICMJE September 2014
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2014)
Progression free survival [ Time Frame: 3 years ]
Progression free survival according to RECIST 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02278887 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2014)
Immune related progression free survival [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 28, 2014)
Safety [ Time Frame: 3 years ]
Adverse events will be assessed during treatment and follow-up
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma
Official Title  ICMJE Randomized Phase III Study Comparing a Non-myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Tumor Infiltrating Lymphocytes and Interleukin-2 to Standard Ipilimumab Treatment in Metastatic Melanoma
Brief Summary In this randomized controlled phase III study the investigators will evaluate whether TIL infusion preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 can result in an improved progression free survival when randomly compared to ipilimumab in 168 stage IV melanoma patients. A health technology assessment (HTA) will be performed to evaluate the impact of the TIL treatment on patients and organizational processes and cost-effectivity.
Detailed Description In this randomized controlled phase III study the investigators will evaluate whether TIL infusion preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 can result in an improved progression free survival when randomly compared to ipilimumab in 168 stage IV melanoma patients. A health technology assessment (HTA) will be performed to evaluate the impact of the TIL treatment on patients and organizational processes and cost-effectivity. This will be done via questionnaires at baseline, just after treatment and during follow-up. Also healthcare providers will be interviewed after 6 months after starting the trial.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Melanoma
Intervention  ICMJE
  • Procedure: Translational research
    Before during and at progression/regression biopsies and blood will be taken for translational research
    Other Names:
    • tumor tissue
    • blood
  • Drug: Cyclophosphamide
    The patient receives 2 days cyclophosphamide via IV to deplete T-cells.
    Other Name: chemotherapy
  • Drug: Fludarabine
    The patient receives 5 days fludarabine via IV to deplete T-cells.
    Other Name: chemotherapy
  • Drug: Interleukin-2
    After infusion of the TIL, the patient receives IL-2 to keep the TIL active.
    Other Name: Proleukin
  • Drug: Ipilimumab infusion
    In arm A patients will be treated with 4 infusion of ipilimumab
    Other Name: standard treatment
Study Arms  ICMJE
  • Active Comparator: Ipilimumab
    4 cycles of ipilimumab treatment, the standard treatment
    Interventions:
    • Procedure: Translational research
    • Drug: Ipilimumab infusion
  • Experimental: TIL treatment
    non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2
    Interventions:
    • Procedure: Translational research
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Drug: Interleukin-2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 6, 2016)
168
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2014)
162
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed unresectable AJCC stage III or stage IV melanoma
  • Patients must have metastatic melanoma with a resectable metastatic lesion(s) of sufficient size (≥ 2-3 cm in total) and must be willing to undergo such a resection for experimental purposes.
  • Patients should have received maximum one line of systemic therapy (except for ipilimumab) for unresectable or metastatic melanoma.[
  • Patients must be ≥ 18 years and ≤ 75 years of age and must have measurable disease by CT or MRI per RECIST 1.1 criteria (in addition to the resected lesion).
  • Patients must have a clinical performance status of ECOG 0 or 1.
  • Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen.
  • Patients must be able to understand and sign the Informed Consent document.

Exclusion Criteria:

  • Life expectancy of less than three months.
  • Patients with metastatic ocular/ mucosal or other non-cutaneous melanoma.
  • Adjuvant treatment with ipilimumab within 6 months prior to randomization.
  • Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to randomization.
  • Patients who have a more than two CNS metastases.
  • Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or show significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months.
  • All patients' toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less.
  • Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • Any active systemic infections, coagulation disorders or other active major medical illnesses.
  • Any autoimmune disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John B.A.G. Haanen, Prof. +31205126979 j.haanen@nki.nl
Listed Location Countries  ICMJE Denmark,   Netherlands
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02278887
Other Study ID Numbers  ICMJE M14TIL
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Netherlands Cancer Institute
Study Sponsor  ICMJE The Netherlands Cancer Institute
Collaborators  ICMJE
  • Copenhagen University Hospital at Herlev
  • University of Manchester
Investigators  ICMJE
Principal Investigator: John B.A.G. Haanen, Prof. The Netherlands Cancer Institute
PRS Account The Netherlands Cancer Institute
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP