Metastatic Melanoma
Conditions
Keywords
melanoma, tumor infiltrating lymphocytes, interleukin-2
Brief summary
Prior preclinical and clinical studies have shown that tumors from patients with advanced melanoma contain tumor-infiltrating lymphocytes (TIL) with anti-tumor reactivity. These TIL can be expanded in the laboratory to large numbers, and reinfused to the patient. Using a chemotherapy regimen that selectively kills lymphocytes, a single institution Phase II study of 35 patients showed a 51% objective response rate to TIL and interleukin-2 injection. In the present trial we would like to investigate whether we can achieve similar results in a Hadassah Phase II study, and to determine the feasibility of applying this approach to patients with advanced melanoma who currently have few treatment options.
Interventions
BIOLOGICALtumor infiltrating lymphocytes
Patients will have a melanoma metastasis resected and cultured in IL-2 in vitro. Tumor infiltrating lymphocytes from these cultures will be assessed for tumor reactivity and those with such activity will be further expanded and adoptively transferred. Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 mg/kg/day x2 days IV)and fludarabine (25 mg/mE2/day IV x5days). Following this regimen, patients will receive an intravenous adoptive transfer of at least 10E9 tumor-reactive lymphocytes followed by high dose IL-2 (720,000 IU/kg/dose IV every 8 hours for up to 15 doses).
Sponsors
Hadassah Medical Organization
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have metastatic melanoma with a resectable metastatic lesion of sufficient size and be willing to undergo such a resection for experimental purposes. For HLA-A0201+ patients, lesions must be \> 1.5 cm in diameter and for HLA-A0201- patients, lesions must be \> 3 cm in diameter. * Patients must be \> 18 years of age and must have measurable metastatic melanoma (in addition to the resected lesion). * Patients of both genders must be willing to practice birth control during treatment and for four months after receiving the preparative regimen. * Clinical performance status of ECOG 0, 1. * Absolute neutrophil count greater than 1000/mm3 without support of filgrastim. * Platelet count greater than 100,000/mm3. * Serum ALT/AST less than three times the upper limit of normal. * Serum creatinine less than or equal to 1.6 mg/dl. * Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl. * Patients must be able to understand and sign the Informed Consent document
Exclusion criteria
* Tumor/TIL Harvest
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the response rate of this approach when administered in our hospital | Two years |
Countries
Israel
Contacts
Primary ContactMichal Lotem, MD
Outcome results
None listed