NCT02354690

Vemurafenib and TIL Therapy for Metastatic Melanoma

T-cell Therapy in Combination With Vemurafenib for Patients With BRAF Mutated Metastatic Melanoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Inge Marie Svane · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Background: Adoptive T cell therapy with tumor infiltrating lymphocytes (TILs) has been reported to induce durable clinical responses in patients with metastatic melanoma. From patients own tumor material T cells are extracted, expanded and activated in vitro in a 4-6 weeks culture period. Before TIL infusion patients are preconditioned with a lymphodepleting chemotherapeutic regimen. After TIL infusion, patients are treated with IL-2 to support T cell activation and expansion in vivo. The BRAF inhibitor is an approved treatment of metastatic melanoma and functions by selectively inhibiting the BRAF mutated enzyme, consequently halting the proliferation of tumor cells. Furthermore, in vitro tests have shown that vemurafenib has immunomodulatory effects that are hypothesized to synergize with TIL therapy, which has been confirmed in animal studies. Objectives: * To evaluate safety and feasibility when combining vemurafenib and ACT with TILs. * To evaluate treatment related immune responses * To evaluate clinical efficacy Design: * Patients will be screened with a physical exam, medical history, blood samples and ECG. * Patients will start vemurafenib 960 mg BID and will continue during TIL preparation. * 7 days after start of vemurafenib, patients will undergo surgery to harvest tumor material for TIL production. * Patient stops vemurafenib and is admitted day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. * On day 0 patients receive TIL infusion and shortly after starts IL-2 infusion continually following the decrescendo regimen. * The patients will followed until progression or up to 5 years.

Conditions

• Metastatic Melanoma

Interventions

Type	Name	Description
DRUG	Vemurafenib	Vemurafenib is used to treat patients with BRAF mutated metastatic melanoma. Patients will start treatment in a dose of 960 BID 7 days before tumor harvest and ends at the day of admission (day -8).
DRUG	Lymphodepleting chemotherapy	First patients undergo lymphodepleting chemotherapy regimen consisting of cyclophosphamide 60 mg/kg for 2 days and fludarabine 25 mg/m2 for 5 days (constitutes day -7 to -1 of admission).
DRUG	TIL infusion	7 days after start of vemurafenib treatment, patients undergo surgery to removal of a tumor in order to isolate, activate and expand tumor infiltrating lymphocytes (TIL) to high numbers. In vitro preparation usually takes 4-6 weeks using the young TIL method. On day 0 patients receive an infusion of TIL (1x10e9-2x10e11 cells).
DRUG	Interleukin-2	After infusion of TILs, patients will receive interleukin-2 infusions according to the decrescendo regimen (18 MIU/m2 for 6 hours, 18 MIU/m2 for 12 hours, 18 MIU/m2 for 24 hours followed by 4,5 MIU/m2 for another 3 x 24 hours)

Timeline

• Start date: 2014-11-01
• Primary completion: 2018-12-31
• Completion: 2018-12-31
• First posted: 2015-02-03
• Last updated: 2020-03-23
• Results posted: 2020-02-24

Locations

1 site across 1 country: Denmark