metastasized melanoma gemetastaseerde huidkanker
Conditions
Interventions
Patients will be hospitalized to first receive chemotherapy during one week, then they will receive their own transduced T cells intraveneously, which will be followed by a low-dose of interleukin-2.
Sponsors
NKI-AVL
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients must be ≥ 18 years of age; 2. Patients must have inoperable stage IIIc or stage IV cutaneous melanoma (AJCC) progressing after at least two lines of therapy (DTIC, BRAF inhibitor, ipilimumab); 3. Patients must be HLA-A*0201 positive; 4. The primary tumor and/or metastasis have to be positive for MART-1 (>10% of tumor cells); 5. Patients with measurable disease (RECIST 1.1); 6. Patients must have a clinical performance status of ECOG 0 or 1; 7. 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; 8. Patients must be able to understand and sign the Informed Consent document; 9. Absolute neutrophil count greater than 1.5 x 109/L without support of filgrastim; 10. Platelet count greater than 100 x 109/L; 11. Hemoglobin greater than 5 mmol/L or 8.0 in g/dl; 12. Chemistry; 13. Serum ALAT/ASAT less than 3 times the upper limit of normal, unless patients have liver metastases (< 5 times ULN); 14. Serum creatinine normal range or clearance at 50 ml/min or higher; 15. 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; 16. Seronegative for HIV antibody; 17. Seronegative for hepatitis B antigen, and hepatitis C antibody; 18. Seronegative for lues.
Exclusion criteria
Exclusion criteria: 1. Life expectancy of less than three months; 2. Patients with metastatic ocular melanoma or mucosal melanoma; 3. Requirement for systemic steroid therapy; 4. Patients who have a history of more than two CNS metastases; 5. 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; 6. Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks; 7. Patients who have: history of coronary revascularization, documented LVEF of less than 45%, 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 history of cigarette smoking (greater than 20 pack/year within the past 2 years) and with symptoms of respiratory distress; 8. 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; 9. Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. A negative pregnancy test before inclusion in the trial is required for all women of child bearing potential; 10. Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune disease requiring anti-TNF treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety (CTCAE 4.0) of the TCR treatment; 2. Objective response rate according to RECIST 1.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. 1-year progression free survival (PFS) and median overall survival; 2. Efficacy of induction of tumor specific T cell responses (as measured by the persistence of Melan-A/MART1 specific T cells in peripheral blood samples at several time points following adoptive transfer and in tumor biopsies when possible). | — |
Contacts
Public ContactJohn B.A.G. Haanen
Plesmanlaan 121
Outcome results
None listed