RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vaccine therapy together with cyclophosphamide may be an effective treatment for multiple myeloma.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy when given with or without cyclophosphamide in treating patients with recurrent or refractory multiple myeloma.

OBJECTIVES:

Primary

• Determine the safety and toxicity of Edmonston vaccine strain oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma.
• Determine the maximum tolerated dose of MV-NIS when administered with or without cyclophosphamide in these patients.

Secondary

• Determine the time course of viral gene expression and viral elimination, and the biodistribution of virally infected cells at various time points after treatment with these regimens using iodine I 123 gamma camera imaging.
• Assess viral replication, viremia, viral shedding in urine and respiratory secretions, and viral persistence after treatment with these regimens.
• Monitor humoral responses to MV-NIS in these patients.
• Explore the antimyeloma efficacy (i.e., clinical response rate, time to progression, progression-free survival, duration of response) of the virus using standard myeloma response criteria as well as immunoglobulin free light chain measurements.

OUTLINE: This is a dose-escalation study of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS). Patients are stratified according to receipt of cyclophosphamide during study treatment (yes vs no). Patients are initially accrued to part 1. Once the maximum tolerated dose (MTD) of MV-NIS alone is determined, subsequent patients are accrued to part 2.

• Part 1 (MV-NIS alone): Patients receive MV-NIS IV over 30 minutes on day 1. Cohorts of 3-6 patients receive escalating doses of MV-NIS until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
• Part 2 (MV-NIS and cyclophosphamide): Patients receive cyclophosphamide IV over 30 minutes on day -1 and MV-NIS IV over 30 minutes on day 1.

Cohorts of 3-6 patients receive escalating doses of MV-NIS* in combination with cyclophosphamide until the MTD is determined. The MTD of MV-NIS is defined as in part 1.

NOTE: *Starting dose of MV-NIS is the MTD determined in part 1.

Blood and bone marrow samples are obtained for research studies, including flow cytometry, at baseline and at week 6. Serial measurements of viral RNA in mononuclear cells are conducted in samples of blood, saliva, and urine on days 3, 8, and 15 and are tested for viral replication by quantitative reverse transcriptase-polymerase chain reaction. Measles virus-specific immunity is evaluated at baseline and on day 42.

After the completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of recurrent or refractory multiple myeloma

  • Previously treated with ≥ 2 nonoverlapping chemotherapeutic combinations

    • Thalidomide and corticosteroids are considered chemotherapy
  • No known standard therapy that is definitely capable of extending life expectancy exists

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8.5 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 2 times ULN
• Creatinine < 2 times ULN
• INR ≤ 1.4 times ULN
• Thyroid-stimulating hormone 0.3-5.0 mlU/L
• Free thyroxine 0.8-1.87 ng/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
• No uncontrolled infection
• No active tuberculosis

• No clinically significant cardiac condition or illness, including any of the following:

  • New York Heart Association class III-IV congestive heart failure
  • Known symptomatic coronary artery disease
  • Symptoms of coronary artery disease on systems review
  • Cardiac arrhythmia (atrial fibrillation or supraventricular tachycardia)
• No active CNS disorder or seizure disorder
• No HIV positivity
• No allergy to iodine (not including reactions to IV contrast materials)
• No exposure to household individuals ≤ 15 months of age or to any household individual with known immunodeficiency

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior allogeneic hematopoietic stem cell transplantation
• No prior exposure to heat-inactivated measles virus vaccine
• More than 3 weeks since prior and no other concurrent chemotherapy
• More than 4 weeks since prior and no other concurrent immunotherapy
• More than 4 weeks since prior biologic therapy
• No concurrent radiotherapy
• No other concurrent ancillary investigational therapy, including drugs, biologicals, or gene therapy, for therapeutic intent or symptomatic control
• Concurrent bisphosphonates as maintenance therapy allowed