Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma

Phase 3

Completed

• Conditions: Metastatic Melanoma
• Interventions: Procedure: Translational research; Drug: Ipilimumab infusion; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

• Registration Number: NCT02278887
• Lead Sponsor: The Netherlands Cancer Institute

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 Timeline

• Study First Submitted: 2014-06-03
• Study Start: 2014-09-23
• Study First Submitted QC: 2014-10-28
• Study First Posted: 2014-10-30
• Primary Completion: 2022-09
• Study Completion: 2023-12-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 168

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TIL treatment	Interleukin-2	non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2
Ipilimumab	Translational research	4 cycles of ipilimumab treatment, the standard treatment
Ipilimumab	Ipilimumab infusion	4 cycles of ipilimumab treatment, the standard treatment
TIL treatment	Translational research	non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2
TIL treatment	Cyclophosphamide	non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2
TIL treatment	Fludarabine	non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2

Primary Outcome Measures

Name	Time	Method
Progression free survival	3 years	Progression free survival according to RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Immune related progression free survival	3 years

Trial Locations

Locations (2)

Netherlands Cancer Institute; 🇳🇱 Amsterdam, NH, Netherlands

CCIT Department of Oncology and Haematology Herlev Hospital; 🇩🇰 Copenhagen, Denmark