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.
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 by immunohistochemistry. Blood and cryopreserved CD138+ selected cell samples are also collected for future ancillary studies. After completion of study treatment, patients are followed up for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Correlative studies
Given IV
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Associated adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria and tolerability of wild-type reovirus
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.
Time frame: Up to 4 weeks post-treatment
Maximum-tolerated dose level
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.
Time frame: 28 days
Duration of response
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.
Time frame: Up to 2 years
Objective response rate
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.
Time frame: Up to 4 weeks post-treatment
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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