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’ - Lymphodepletion, TIL and Interleukin 2

Phase 1

• Conditions: Patients with metastatic (stage IV) melanoma will be randomized to either treatment arm A (dacarbazine) or treatment arm B (TIL) after metastasectomy and feasibility of culturing of TIL.; MedDRA version: 12.1Level: LLTClassification code 10053571Term: Melanoma

• Registration Number: EUCTR2010-021885-31-NL
• Lead Sponsor: KI-AV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-23
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•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.
Laboratory Parameters (Note: patients may undergo resection with lab values outside of the parameters listed below if it is anticipated that the resection will correct the abnormality).
•Hematology:
Absolute neutrophil count greater than 1.5 x 109/L without support of filgrastim.
Platelet count greater than 100 x 109/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. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
Seronegative for hepatitis B antigen, and hepatitis C antibody.
Seronegative for lues.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•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:
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:
A prolonged history of cigarette smoking (greater than 20 pack/year within the past 2 years)
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 illnesses, such as active autoimmune disease requiring anti-TNF treatment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Feasibility study (n=5 patients)<br>To examine whether the logistics and timing of this complex treatment can be managed properly without delays for the patients. If necessary this will be optimized before starting the RCT. In addition, toxicity (according CTCAE v. 3.0) and response rate (according RECIST version 1.1) will be measured.<br><br>Randomized phase II clinical trial:<br>Primary objective: Improvement of progression free survival compared to standard dacarbazine chemotherapy<br>;Secondary Objective: Randomized phase II clinical trial:<br>Secondary objective(s): Objective response rate according to RECIST version 1.1, 1-year PFS, median overall survival, toxicity.;Primary end point(s): The primary endpoint of the randomized controlled phase II trial is PFS improvement from 2 months in DTIC arm to 6 months in the TIL treatment arm.