A Phase 1 Study of Reolysin Alone in Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1 Study of Reolysin Alone in Patients With Relapsed or Refractory Multiple Myeloma
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.
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:
Subject must have measurable disease defined as any of the following:
Patients must have received at least one prior antineoplastic therapy and must have progressed
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 registration
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 participation
The patient must be willing to comply with fertility requirements as below:
No patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
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