NCT03605719

Dexamethasone, Carfilzomib, & Nivolumab With Pelareorep for Relapsed/Refractory Multiple Myeloma

PD1 Blockade and Oncolytic Virus in Relapsed Multiple Myeloma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of wild-type reovirus (pelareorep) when given together with dexamethasone, carfilzomib, and nivolumab in treating patients with multiple myeloma that has come back (relapsed). Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. A virus, called pelareorep, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Giving dexamethasone, carfilzomib, and nivolumab with pelareorep may work better in treating patients with multiple myeloma.

Detailed description

PRIMARY OBJECTIVES: I. Identify maximum tolerated dose of pelareorep in combination with other antineoplastic agents. II. Identify whether the combination of carfilzomib and nivolumab lead to a safety profile different than what has been reported with either agent independently. SECONDARY OBJECTIVES: I. Assess the relative roles of immune-mediated and direct cytotoxic myeloma cell killing. II. Understand the clinical benefit of nivolumab in programmed death-ligand 1 (PD-L1) positive multiple myeloma (MM) cells. OUTLINE: This is a dose-escalation study of pelareorep. Patients are assigned to 1 of 3 arms. ARM 1: Patients receive dexamethasone intravenously (IV) on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM 3 (expansion cohort): Patients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for a minimum of 4 weeks once off treatment or at least 100 days after the last nivolumab dose, then every 6 months after.

Conditions

• Recurrent Plasma Cell Myeloma

Interventions

Type	Name	Description
DRUG	Carfilzomib	Given IV
DRUG	Dexamethasone	Given IV
BIOLOGICAL	Nivolumab	Given IV
BIOLOGICAL	Pelareorep	Given IV

Timeline

• Start date: 2018-10-24
• Primary completion: 2022-10-10
• Completion: 2022-10-10
• First posted: 2018-07-30
• Last updated: 2023-10-06

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study