Natural Killer Cell Therapy (UD TGFbetai NK Cells) and Temozolomide for the Treatment of Stage IV Melanoma Metastatic to the Brain

Description

PRIMARY OBJECTIVES:

I. To confirm the safety and tolerability of UD TGFbetai NK cells in combination with temozolomide as a lymphodepleting agent in patients with melanoma metastatic to the brain and to determine the recommended phase 2 dose (RP2D). (Phase 1) II. To determine the intracranial response rate. (Phase 2)

SECONDARY OBJECTIVES:

I. To define the toxicities of UD TGFbetai NK cells when delivered with temozolomide as a lymphodepleting agent. (Phase 1) II. To define the pharmacokinetics (pK) associated with UD TGFbetai NK cells when used in combination with temozolomide as a lymphodepleting agent in patients with metastatic melanoma. (Phase 1) III. To determine the extracranial response rate. (Phase 2) IV. To determine progression free survival (PFS) (intracranial, extracranial, overall). (Phase 2) V. To assess overall survival (OS). (Phase 2) VI. To continue to assess the safety of temozolomide in combination with UD TGFbetai NK cells in a patient with melanoma metastatic to the brain. (Phase 2)

EXPLORATORY/CORRELATIVE OBJECTIVES:

I. To assess the phenotype and function of the UD TGFbetai NK cells and correlate with clinical outcomes.

II. To assess in vivo persistence of UD TGFbetai NK cells after adoptive transfer and correlate with clinical outcomes.

III. To assess immune status, inflammatory cytokine levels, and anti-melanoma cell activity.

OUTLINE: This is a phase I, dose-escalation study of UD TGFbetai NK cells followed by a phase II study.

Patients receive UD TGFbetai NK cells intravenously (IV) over 30 minutes on day 1 and temozolomide orally (PO) daily on days 1-5. Treatment with UD TGFbetai NK cells repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Cycles of temozolomide repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.