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

November 14, 2023 updated by: The Netherlands Cancer Institute

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

168

Phase

  • Phase 3

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

  • Denmark
      • Copenhagen, Denmark
        • CCIT Department of Oncology and Haematology Herlev Hospital
  • Netherlands
    • NH
      • Amsterdam, NH, Netherlands, 1066CX
        • Netherlands Cancer Institute

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 to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • chemotherapy
Drug: Fludarabine
The patient receives 5 days fludarabine via IV to deplete T-cells.
Other Names:
  • chemotherapy
Drug: Interleukin-2
After infusion of the TIL, the patient receives IL-2 to keep the TIL active.
Other Names:
  • Proleukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 3 years
Progression free survival according to RECIST 1.1
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Immune related progression free survival
Time Frame: 3 years
3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: 3 years
Adverse events will be assessed during treatment and follow-up
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Netherlands Cancer Institute

Collaborators

Copenhagen University Hospital at Herlev

Investigators

  • Principal Investigator: John B.A.G. Haanen, Prof., The Netherlands Cancer Institute

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 (Actual)

September 23, 2014

Primary Completion (Actual)

September 1, 2022

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

June 3, 2014

First Submitted That Met QC Criteria

October 28, 2014

First Posted (Estimated)

October 30, 2014

Study Record Updates

Last Update Posted (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M14TIL

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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