Vaccine Therapy With or Without Cyclophosphamide in Treating Patients With Recurrent or Refractory Multiple Myeloma

This phase I/II trial studies the side effects and best dose of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients with multiple myeloma that has come back (recurrent) or has not responded to previous treatment (refractory). 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, by stopping them from dividing, or by stopping them from spreading. Giving vaccine therapy together with cyclophosphamide may be a better treatment for multiple myeloma.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the confirmed response rate of MV-NIS alone in patients with relapsed or refractory multiple myeloma who have exhausted all therapeutic options. (Phase II, Cohort A) III. To evaluate the confirmed response rate of MV-NIS alone in patients who are relapsing from very good partial response (VGPR) or complete response (CR) and have not received myeloma directed therapy for at least 12 weeks. (Phase II, Cohort B)

SECONDARY OBJECTIVES:

I. To determine the safety and toxicity of the intravenous administration of an Edmonston vaccine strain measles virus engineered to express the thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the confirmed response rate of MV-NIS in patients with relapsed or refractory multiple myeloma. (Phase I) III. To further evaluate the adverse event profile of MV-NIS in patients with relapsed or refractory multiple myeloma. (Phase II) IV. To evaluate overall survival, failure-free survival and progression-free survival. (Phase II)

TERTIARY OBJECTIVES:

I. To determine the time course of viral gene expression and virus elimination, and the biodistribution of virally infected cells at various times points after infection with MV-NIS (when administered with or without cyclophosphamide) using 99m-technetium (Tc) gamma camera imaging. (Phase I and II) II. To assess virus replication, viremia, viral shedding in urine and respiratory secretions, and virus persistence after systemic administration of MV-NIS (when administered with or without cyclophosphamide). (Phase I and II) III. To monitor humoral responses to the injected virus. (Phase I and II) IV. To explore the anti-myeloma 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. (Phase I and II)

OUTLINE: This is a phase I, dose-escalation study of MV-NIS followed by a phase II study. Patients are assigned to 1 of 2 treatment arms (Stage 1 or Stage 2) in phase I and assigned to Stage 1 in phase II.

STAGE 1 (MV-NIS ALONE, closed to accrual on 12/17/2009 and reopened 10/13/2011): Patients receive MV-NIS intravenously (IV) over 1 hour on day 1.

STAGE 2 (MV-NIS AND CYCLOPHOSPHAMIDE, temporarily closed to accrual on 10/13/11): Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later.

After completion of study treatment, patients are followed up at 6 weeks, 12 weeks, and then every 3 months for 1 year.

Eligibility Criteria:
Inclusion Criteria:

* Myeloma relapsing from partial response or better

  * Patients relapsing \> 18 months from transplant if not on maintenance, or
  * If off maintenance, discontinued at least 6 months ago, or
  * If relapsing on maintenance, at least 3 years from transplant, or
  * Off prior myeloma therapy at least 6 months ago
  * Sufficient tumor burden that is assessable for response

    * Serum M-spike \>= 0.5 g/dL, or
    * If immunoglobulin A (IgA) myeloma, IgA \> 1000 mg/dL, or
    * Difference between involved and uninvolved free light chain (dFLC) \> 10 mg/dL, or
    * Urine M-spike \>= 200 mg/24 hours, or
    * Bone marrow plasmacytosis \>= 10%, or
    * Plasmacytoma \>= 2 cm in diameter
* Absolute neutrophil count (ANC) \>= 1000/uL
* Platelets (PLT) \>= 50,000/uL
* Hemoglobin \>= 8.5 g/dl
* Aspartate aminotransferase (AST) =\< 2 times upper limit of normal
* Creatinine \< 2 times upper limit of normal
* Total bilirubin =\< 1.5 x upper limit of normal
* International normalized ratio (INR) =\< 1.4 x ULN at the time of registration
* Ability to provide informed consent
* Willingness to return to Mayo Clinic Rochester for follow-up
* Life expectancy \>= 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
* Willingness to provide all biological specimens as required by the protocol
* Negative serum pregnancy test done =\< 7 days prior to registration for women of childbearing potential only
* Measles antibody titer on the BioRad Multiplex assay less than or equal to 1.0

Exclusion Criteria:

* Uncontrolled infection
* Active tuberculosis
* Any myeloma directed therapy within 12 weeks of registration including plasmapheresis or transfusion
* New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review
* Active central nervous system (CNS) disorder or seizure disorder
* Human immunodeficiency virus (HIV) positive test result
* Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-Food and Drug Administration \[FDA\] approved indication and in the context of a research investigation)
* Previous exposure to heat inactivated measles virus vaccine (this vaccine was given to some individuals between the years of 1963-1967)
* Any of the following:

  * Pregnant women or women of reproductive ability who are unwilling to use effective contraception
  * Nursing women
  * Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
* Evidence of chronic or acute graft versus host disease or on-going treatment for graft versus host disease from prior allogeneic stem cell transplantation
* Exposure to household contacts =\< 15 months old or household contact with known immunodeficiency