NCT03467516

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Metastatic Uveal Melanoma

A Phase 2 Study to Evaluate the Efficacy and Safety of Adoptive Transfer of Autologous Tumor Infiltrating Lymphocytes in Patients With Metastatic Uveal Melanoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Sponsor: Udai Kammula · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 2 study in which the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with metastatic uveal melanoma will be evaluated. Metastatic uveal melanoma (UM) carries a poor prognosis with estimated survival of 4-6 months. There are no known effective systemic therapies. Metastatic UM is classified as an "orphan" disease and there are currently few clinical trial options for these patients. Thus, novel systemic approaches are desperately needed. A recent pilot study has found that administration of autologous tumor infiltrating lymphocytes (TIL) generated from resected metastases can induce objective tumor response and durable complete response in metastatic uveal melanoma patients. These encouraging results require confirmation to determine if this immunotherapy is of future benefit in treating this disease.

Detailed description

STUDY DESIGN The Phase 2 study will be conducted in conjunction with companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) as described below: Cell Preparation: Patients with evaluable metastatic uveal melanoma who have lesions that can be resected with minimum morbidity will undergo resection of tumor. TIL will be obtained while enrolled on the companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies). Separate tumor procurements may be performed under a protocol to obtain TIL if initial tumor procurements could not successfully generate TIL. The TIL will be grown and expanded for this trial according to standard operating procedures submitted in the IND. The TIL will be assessed for potency by interferon-gamma release. Treatment Phase: Once cells exceed the potency requirement and are projected to exceed the minimum number specified in the COA, the patient will be registered on this study and receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10\^11 lymphocytes (minimum of 1x10\^9 cells) and administration of high-dose intravenous aldesleukin. It is anticipated that TIL that meet the COA will not be achievable in approximately 20% of patients who undergo resection. These patients may undergo a second resection to grow TIL, if another suitable lesion exists. Approximately 6 weeks (+/- 2 weeks) after TIL administration, patients will undergo a complete tumor evaluation and evaluation of toxicity and immunologic parameters. Patients will receive one course of treatment. The start date of the course will be the start date of the chemotherapy; the end date will be the day of the first post-treatment evaluation. Patients may undergo a second treatment. Patients will receive no other experimental agents while on this protocol.

Conditions

• Uveal Neoplasms
• Melanoma, Uveal

Interventions

Type	Name	Description
BIOLOGICAL	Tumor Infiltrating Lymphocytes (TIL)	TIL infusion intravenously through a central vein catheter over 20-30 minutes. Folowed by Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of TIL infusion and continuing for up to a maximum of 6 doses.

Timeline

• Start date: 2018-05-14
• Primary completion: 2027-07-31
• Completion: 2027-12-31
• First posted: 2018-03-16
• Last updated: 2025-07-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study