Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, With or Without Cyclophosphamide, in Patients With Recurrent or Refractory Multiple Myeloma
- 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.
- 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 [closed to accrual as of 12/17/09]): 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
- 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.
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Angela Dispenzieri, MD
United States: Food and Drug Administration
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