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

Phase 1
18 Years
Open (Enrolling)
Light Chain Deposition Disease, Refractory Multiple Myeloma

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Trial Information

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


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.


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

After completion of study treatment, patients are followed up for 4 weeks.

Inclusion Criteria:

- Patient must have relapsed or refractory myeloma that fits or did fit IMWG diagnostic
criteria for symptomatic myeloma (although new or worsening end-organ damage is not
required to be eligible) as defined below:

- Presence of ≥ 10% clonal bone marrow plasma cells

- Presence of serum and/or urinary measurable monoclonal protein or light chains

- Evidence of any end-organ damage criteria listed below [at any time] attributed
to the patient's myeloma:

- Hypercalcemia: Serum calcium > 11.5 mg/dL

- Renal insufficiency: Serum creatinine > 2 mg/dL

- Anemia > 2 g/dL below the lower limit of normal or a hemoglobin value < 10

- Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures

- Subject must have measurable disease defined as any of the following:

- Serum monoclonal protein > 500 mg/dL by protein electrophoresis

- > 200 mg of monoclonal protein in the urine on 24-hour electrophoresis

- Serum immunoglobulin free light chain ≥ 100 mg/L AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio

- Patients must have received at least one prior antineoplastic therapy and must have

- No standard therapy is available or patient declines such options

- Prior autologous and/or allogeneic transplant is permitted although transplant must
have occurred greater than 90 days prior to registration

- Adverse events from prior therapy must have recovered to no greater than grade 1 with
the exception of grade 2 neuropathy

- Prior radiation is permitted; however, at least 4 weeks must have elapsed since the
completion of prior radiation therapy and patients must have recovered from all
radiation-associated toxicities to no greater than grade 1 at the time of

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%);
patients with lower performance status based solely on bone pain secondary to
multiple myeloma will be eligible

- Life expectancy of greater than 3 months

- Absolute neutrophil count (ANC) ≥ 1,000/μL

- Platelet count ≥ 50,000/μL

- Hemoglobin > 8 g/dL

- Total bilirubin < 1.5 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times the
institutional upper limit of normal.

- Able to understand and willing to sign a written informed consent document

- Patients must be able to avoid direct contact with pregnant or nursing women,
infants, and immunocompromised individuals during the five days of Reolysin treatment
and for two days after

- Patients must not have known immunodeficiency virus (HIV) infection or active
hepatitis B or C infections

- For patients with a history of congestive heart failure, systolic cardiac function
must be assessed at screening and left ventricular ejection fraction (LVEF) ≥ 50%

- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL prior to starting therapy and
prior to beginning another course (if applicable)

- FCBP and men must agree to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry and for the duration of study

- The patient must be willing to comply with fertility requirements as below:

- Male patients must agree to use an adequate method of contraception for the
duration of the study and for 90 days afterwards

- Female patients must be either postmenopausal, free from menses ≥ 2 years,
surgically sterilized, willing to use two adequate barrier methods of
contraception to prevent pregnancy, or agree to abstain from heterosexual
activity starting with screening and for 90 days afterwards

- Patients must agree not to donate blood or sperm/ova during the course of taking
protocol therapy and for at least 4 weeks after stopping treatment

- No patients who have had chemotherapy or radiotherapy within 4 weeks prior to
entering the study

- Patients may be receiving concomitant therapy with bisphosphonates and low-dose
corticosteroids (e.g., prednisone up to but no more than 10 mg by mouth daily or
its equivalent) for symptom management and comorbid conditions; doses of
corticosteroid should be stable for at least 7 days prior to study treatment

- No patients who are receiving any other investigational agents

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric
illness/social situations that would limit compliance with study requirements

- Pregnant women are excluded from this study

- No patients with a "currently active" second malignancy that, in the opinion of the
principal investigator, will interfere with patient participation, increase patient
risk, shorten survival to < 1 year, or confound data interpretation

- No POEMS syndrome

- No concurrent use of complementary or alternative medicines that, in the opinion of
the principal investigator, would confound the interpretation of toxicities and/or
antitumor activity of the study drug

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Associated adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria and tolerability of wild-type reovirus

Outcome Description:

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.

Outcome Time Frame:

Up to 4 weeks post-treatment

Safety Issue:


Principal Investigator

Craig Hofmeister

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2012

Completion Date:

Related Keywords:

  • Light Chain Deposition Disease
  • Refractory Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



The Ohio State University Medical CenterColumbus, Ohio  43210