Phase I/II 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

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of measles virus encoding the human 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. (Phase II) 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 alone 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 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-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. Part 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. Part 2 (MV-NIS AND CYCLOPHOSPHAMIDE): Patients receive cyclophosphamide IV over 30 minutes 2 days before MV-NIS IV is administered over 1 hour on day 1. After completion of study treatment, patients are followed up every 3 months for 1 year.

Who is eligible to participate?

Inclusion Criteria: - Relapsed or refractory myeloma previously treated with 2 or more non-overlapping chemotherapeutic combinations (note: Thalidomide and corticosteroids are considered chemotherapeutic agents) - 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 virus titers (measles neutralizing antibody) < 0.5 Exclusion Criteria: - Availability of known standard therapy that is definitely capable of extending life expectancy (patients who are on maintenance therapy with bisphosphonates are not excluded) - Uncontrolled infection - Active tuberculosis - Chemotherapy =< 3 weeks prior to study registration - Immunotherapy =< 4 weeks prior to study registration - Biologic therapy =< 4 weeks prior to study registration - New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT]) - 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 - Allergy to iodine (this does not include reactions to intravenous contrast materials) - 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 - Prior allogeneic hematopoietic stem cell transplantation - Exposure to household contacts =< 15 months old or household contact with known immunodeficiency

Last updated:

10/27/2014

NCT ID:

NCT00450814

IRB Number:

06-005263