Metastatic Melanoma
Conditions
Keywords
melanoma, TIL treatment, tumor infiltrating lymphocytes, ipilimumab, interleukin 2, non-myeloablative, randomization
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.
Interventions
PROCEDURETranslational research
Before during and at progression/regression biopsies and blood will be taken for translational research
DRUGCyclophosphamide
The patient receives 2 days cyclophosphamide via IV to deplete T-cells.
DRUGFludarabine
The patient receives 5 days fludarabine via IV to deplete T-cells.
DRUGInterleukin-2
After infusion of the TIL, the patient receives IL-2 to keep the TIL active.
DRUGIpilimumab infusion
In arm A patients will be treated with 4 infusion of ipilimumab
Sponsors
Copenhagen University Hospital at Herlev
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | 3 years | Progression free survival according to RECIST 1.1 |
Secondary
| Measure | Time frame |
|---|---|
| Immune related progression free survival | 3 years |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety | 3 years | Adverse events will be assessed during treatment and follow-up |
Countries
Denmark, Netherlands
Outcome results
None listed