NCT02101944

Wild-Type Reovirus in Combination With Carfilzomib and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

Pilot Trial Evaluating Viral Protein Production From the Combination of Reolysin and Carfilzomib in Multiple Myeloma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• 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 when combined with carfilzomib and dexamethasone in treating patients with multiple myeloma that has come back following treatment (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as dexamethasone and carfilzomib, 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. A virus called wild-type reovirus may be able to kill cancer cells without damaging normal cells and seems to work best when given with chemotherapy. Giving wild-type reovirus with chemotherapy may be a more effective treatment than chemotherapy alone.

Detailed description

PRIMARY OBJECTIVES: I. Determine safety and tolerability, and define the maximum tolerated dose of pelareorep (Reolysin), carfilzomib and dexamethasone in patients with relapsed multiple myeloma. II. Obtain evidence of reovirus entry into myeloma cells via localization of reoviral ribonucleic acid (RNA) in multiple myeloma (MM) cells (in situ hybridization \[ISH\]), and active viral proliferation/replication via localization of reoviral capsid protein (immunohistochemistry \[IHC\]) in MM cells in cycle 1 day 9 bone marrow biopsies in all patients enrolled in dose escalation cohorts. SECONDARY OBJECTIVES: I. Obtain preliminary data on response as determined by International Myeloma Working Group criteria after protocol therapy. II. Obtain overall and progression free survival data for all treated patients. III. Assess cytokine arrays of peripheral blood obtained on days 1, 2, 9, 15 and once during days 22-28 of cycle 1, and day 1 of cycle 2 and each successive cycle to obtain exploratory data regarding inflammatory cytokine concentrations and their correlation with response. IV. Investigate pretreatment cycle 1 days 1 and 9 bone marrow aspirate interferon (IFN)-beta in MM cells as a potential marker of Reolysin resistance. V. Measure the induction of endoplasmic reticulum (ER) stress and autophagy markers to explore their respective roles in MM cell death following combination Reolysin and carfilzomib in patients treated in all dose escalation cohorts. VI. Evaluate pretreatment cycle 1 days 1 and 9 peripheral blood to explore the antiviral humoral response by measuring the production of neutralizing reoviral antibody (NARA) using a functional killing assay. VII. Obtain cycle 1 day 1 pretreatment and 1 and 4 hours after treatment, and pretreatment cycle 1 days 2 and 9 peripheral blood, and pretreatment cycle 1 days 1 and 9 bone marrow aspirate samples to investigate the role of carfilzomib in modulating the antiviral immune mediated response. OUTLINE: This is a dose escalation study of Reolysin. Patients receive dexamethasone intravenously (IV), carfilzomib IV over 30 minutes, and Reolysin IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks and then every 6 months thereafter.

Conditions

• Anemia
• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Carfilzomib	Given IV
DRUG	Dexamethasone	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Pelareorep	Given IV

Timeline

• Start date: 2014-12-09
• Primary completion: 2021-05-05
• Completion: 2024-05-07
• First posted: 2014-04-02
• Last updated: 2024-05-17

Locations

3 sites across 1 country: United States