- - Histologically confirmed unresectable or metastatic melanoma.
- - At least 1 PD-1 targeted immunotherapy and BRAF inhibition in case of BRAF mutated
- - Resectable tumor mass and measurable disease by CT or MRI per RECIST 1.1 criteria (in
addition to the resected lesion)
- World Health Organization (WHO) clinical performance Status (ECOG) 0-1.
- - Adequate organ function.
- - Patients of both genders must be willing to practice a highly effective method of
birth control during treatment and for five months after receiving the last dose of
nivolumab for women and seven months for men.
- - Patients must be able to understand and sign the Informed consent document.
- - Hematology: Absolute neutrophil count greater than 1.5 x 109/L without support of
Platelet count greater than 100 x 109/L. Hemoglobin greater than 5 mmol/L,
or 80 g/L.
- - Chemistry: Serum alanine aminotransferase (ALAT)/ aspartate transaminase (ASAT) less
than 3 times the upper limit of normal, unless patients have liver metastases (< 5
Serum creatinine clearance 50 ml/min or higher. Total Bilirubin less than
or equal to 20 micromol/L, except in patients with Gilbert's Syndrome who must have a
total bilirubin less than 50 micromol/L. Lactate dehydrogenase (LDH) ≤ 2x ULN.
- - Serology: Seronegative for HIV antibody.
Seronegative for hepatitis B antigen, and
hepatitis C antibody. Seronegative for syphilis.
- - Life expectancy of less than three months.
- - Patients with metastatic ocular/ mucosal or other non-cutaneous melanoma.
- - 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.
- - Uncontrolled central nervous system (CNS) metastases.
Controlled CNS metastases must
be for at least 4 weeks stable.
- - Documented Forced expiratory volume at one second (FEV1) less than or equal to 50%
predicted for patients with:
- A prolonged history of cigarette smoking (greater than 20 pack/year within the past 2
- Symptoms of respiratory distress.
- - 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
- - Contraindication for IL-2 or nivolumab (allergies etc.).
- - Any autoimmune disease: patients with a documented history of inflammatory bowel
disease, including ulcerative colitis and Crohn's disease are excluded from this study
as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis,
autoimmune thyroiditis (e.g. Hashimoto's disease), autoimmune hepatitis, systemic
progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune
vasculitis (e.g., Wegener's Granulomatosis).
Subjects with motor neuropathy considered
of autoimmune origin (e.g., Guillain-Barré Syndrome) are excluded from this study.
Patients with vitiligo are eligible to enter the study