Clinical trial NCT02278887: Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Melanoma
Keywords: melanoma
TIL treatment
tumor infiltrating lymphocytes
ipilimumab
interleukin 2
non-myeloablative
randomization
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Copenhagen University Hospital at Herlev
First posted: 2014-10-30
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Progression free survival
timeFrame: 3 years
Secondary outcomes:
measure: Immune related progression free survival
timeFrame: 3 years
Other outcomes:
measure: Safety
timeFrame: 3 years
Locations:
city: Copenhagen
country: Denmark
facility: CCIT Department of Oncology and Haematology Herlev Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
state: NH
Study officials:
affiliation: The Netherlands Cancer Institute
name: John B.A.G. Haanen, Prof.
role: PRINCIPAL_INVESTIGATOR
References: