Randomized phase II study using a non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2 in metastatic melanoma
- Conditions
- malignant melanomaskin cancer10040900
- Registration Number
- NL-OMON34085
- Lead Sponsor
- ederlands Kanker Instituut
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 45
• Patients must have metastatic melanoma with a resectable metastatic lesion of sufficient size (>= 3 cm) and must be willing to undergo such a resection for experimental purposes.
• Patients must be >= 18 years of age and must have measurable metastatic melanoma (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.
• Hematology: Absolute neutrophil count greater than 1.5 x 10^9/L without support of filgrastim.
Platelet count greater than 100 x 10^9/L.
Hemoglobin greater than 5 mmol/L.
• Chemistry
Serum ALAT/ASAT less than 3 times the upper limit of normal, unless patients have liver metastases (< 5 times ULN).
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.
• Serology:
Seronegative for HIV antibody.
Seronegative for hepatitis B antigen, and hepatitis C antibody.
Seronegative for lues.
• Life expectancy of less than three months.
• Patients with metastatic ocular or mucosal melanoma.
• Requirement for systemic steroid therapy.
• Patients who have a history of more than two CNS metastases.
• Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or shows 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.
• Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks.
• The following patients will be excluded because of inability to receive high dose interleukin-2:
History of coronary revascularization
Documented LVEF of less than 45% in patients with:
o Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2° or 3° heart block
Documented FEV1 less than or equal to 60% predicted for patients with:
o A prolonged history of cigarette smoking (greater than 20 pack/year within the past 2 years)
o 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.
• Women who are pregnant or breastfeeding.
• Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune disease requiring anti-TNF treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part I: Pilot study:<br /><br>To examine whether the logistics and timing of this complex treatment can be<br /><br>managed properly without delays for the patients. If necessary, this will be<br /><br>optimized before entering the RCT. In addition, the toxicity according CTC and<br /><br>response rate according RECIST 1.1 will be documented.<br /><br><br /><br>Part II: Randomized controlled phase II study:<br /><br>Primary endpoint: Increase in median progression free survival from 2 to 6<br /><br>months</p><br>
- Secondary Outcome Measures
Name Time Method <p>Part II: Randomized controlled phase II study:<br /><br>Secondary endpoint: Objective response rate (RECIST), 1-year PFS, median<br /><br>overall survival, toxicity.</p><br>