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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02278887
Recruitment Status : Active, not recruiting
First Posted : October 30, 2014
Last Update Posted : July 11, 2022
Sponsor:
Collaborator:
Copenhagen University Hospital at Herlev
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Procedure: Translational research Drug: Cyclophosphamide Drug: Fludarabine Drug: Interleukin-2 Drug: Ipilimumab infusion Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 23, 2014
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Ipilimumab

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Ipilimumab
4 cycles of ipilimumab treatment, the standard treatment
 Procedure: Translational research
Before during and at progression/regression biopsies and blood will be taken for translational research
Other Names:
  • tumor tissue
  • blood

Drug: Ipilimumab infusion
In arm A patients will be treated with 4 infusion of ipilimumab
Other Name: standard treatment
Experimental: TIL treatment
non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2
 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


Outcome Measures
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Primary Outcome Measures :
  1. Progression free survival [ Time Frame: 3 years ]
    Progression free survival according to RECIST 1.1


Secondary Outcome Measures :
  1. Immune related progression free survival [ Time Frame: 3 years ]

Other Outcome Measures:
  1. Safety [ Time Frame: 3 years ]
    Adverse events will be assessed during treatment and follow-up


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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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): NCT02278887


Locations
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Denmark
CCIT Department of Oncology and Haematology Herlev Hospital
Copenhagen, Denmark
Netherlands
Netherlands Cancer Institute
Amsterdam, NH, Netherlands, 1066CX
Sponsors and Collaborators
The Netherlands Cancer Institute
Copenhagen University Hospital at Herlev
Investigators
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Principal Investigator: John B.A.G. Haanen, Prof. The Netherlands Cancer Institute
More Information
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02278887    
Other Study ID Numbers: M14TIL
First Posted: October 30, 2014    Key Record Dates
Last Update Posted: July 11, 2022
Last Verified: July 2022
Keywords provided by The Netherlands Cancer Institute:
melanoma
TIL treatment
tumor infiltrating lymphocytes
ipilimumab
 interleukin 2
non-myeloablative
randomization
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Fludarabine
Ipilimumab
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
 Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents