Clinical Trial: Viral Therapy in Treating Patients With Relapsed or Refractory Multiple Myeloma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1 Study of Reolysin Alone in Patients With Relapsed or Refractory Multiple Myeloma

Brief Summary: This pilot phase I trial studies the side effects and the best dose of giving viral therapy to patients with relapsed or refractory multiple myeloma. Viral therapy, such as wild-type reovirus, may be able to kill cancer cells without damaging normal cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine safety and tolerability of Reolysin in patients with relapsed multiple myeloma.

II. Obtain evidence of Reovirus replication by immunohistochemical co-localization of Reovirus and tubulin staining in marrow clot sections obtained on cycle 1 day 8.

SECONDARY OBJECTIVES:

I. Obtain preliminary data on response as determined by International Myeloma Working Group criteria after infusion of Reolysin as a single agent. (Clinical) II. Obtain pilot overall and progression free survival data for all treated patients. (Clinical) III. Assess neutralizing anti-reovirus assay (NARA) results on days 1, 8, 15, and once days 22-28 during cycle 1. (Correlative) IV. Assess feasibility of staining for RAF/MEK/ERK in CD138+ cells using marrow clot sections obtained from pre-treatment specimen. (Correlative) V. Cryopreserve PBMCs for future ancillary studies focused initially on lymphocyte subset(s) and myeloid derived suppressor cell changes after Reolysin infusion during cycle 1. (Correlative) VI. Cryopreserve CD138+-selected cells at screening and after treatment for future ancillary studies of genetic and epigenetic changes focused in part on endoplasmic reticulum (ER) stress. (Correlative)

OUTLINE: This is a dose-escalation study.

Patients receive wild-type reovirus IV over 60 minutes on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspirate at baseline and periodically during study for RAF/MEK/ERK expression and wild-type reovirus replication analysis b
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• Associated adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria and tolerability of wild-type reovirus [ Time Frame: Up to 4 weeks post-treatment ]
  The number and severity of toxicity incidents will indicate the level of tolerance for Reolysin in the treatment of relapsed/refractory multiple myeloma. Toxicities will be evaluated using the CTCAE v. 4 standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
• Maximum-tolerated dose level [ Time Frame: 28 days ]
  The number and severity of toxicity incidents will indicate the level of tolerance for Reolysin in the treatment of relapsed/refractory multiple myeloma. Toxicities will be evaluated using the CTCAE v. 4 standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

Original Primary Outcome:

• Associated adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria and tolerability of Reolysin
• Maximum-tolerated dose level
• Objective response rate

Current Secondary Outcome:

• Duration of response [ Time Frame: Up to 2 years ]
  Defined as the duration from first observation of partial response to the time of disease progression (taking as a reference for progressive disease the smallest measurements recorded since treatment started), with deaths due to other causes other than progression censored. This includes only patients with confirmed responses, and the date at which the response status was first observed rather than the date of confirmation is used as the start date.
• Objective response rate [ Time Frame: Up to 4 weeks post-treatment ]
  Will evaluate clinical benefit endpoint described as that portion of patients experiencing CR, VGPR, or PR. The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.
• Progression-free survival [ Time Frame: From start of treatment to disease progression or death, regardless of cause of death, whichever comes first, assessed up to 2 years ]
• Time to progression [ Time Frame: Time from the start of the treatment until the criteria for disease progression are met, assessed up to 2 years ]

Original Secondary Outcome:

• Duration of response
• Progression-free survival
• Time to progression

Dates:
Date Received: February 11, 2012
Date Started: April 2012
Date Completion:
Last Updated: April 14, 2015
Last Verified: December 2014