UARK 2014-21 A Phase II Trial of Oncolytic Virotherapy by Systemic Administration of Edmonston Strain of Measles Virus

• Sponsor: University of Arkansas
• Information provided by (Responsible Party): University of Arkansas

Study Description

Brief Summary:

The purpose of this study is to determine the clinical efficacy of MV-NIS (measles virus-sodium iodide symporter) therapy for people with relapsed/refractory myeloma when given with cyclophosphamide

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: MV-NIS	Phase 2

Detailed Description:

The drug used in this trial is a modified version of the measles virus used to vaccinate children. The virus has been altered by having an extra gene (piece of DNA) added to it to allow a protein called NIS to be inserted into it. NIS is normally found in the thyroid gland ( a small gland in the neck) and helps the body concentrate iodine. Having this additional gene will make it possible to track where the virus goes in the body.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 16 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Oncolytic Virotherapy by Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, With Cyclophosphamide, in Patients With Recurrent of Refractory Multiple Myeloma
• Study Start Date: March 2015
• Estimated Primary Completion Date: August 2019
• Estimated Study Completion Date: August 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: MV-NIS + Cyclophosphamide	Drug: MV-NIS; one dose in conjunction with a 4 day course intravenously; Other Name: Recombinant Edmonston measles virus with human NIS gene

Outcome Measures

Primary Outcome Measures :

1. The effectiveness of MV-NIS therapy as measured by the International Myeloma Working Group (IMWG) guidelines [ Time Frame: 1 year ]
   The primary objective of this study is to assess the effectiveness of MV-NIS therapy for people with relapsed/refractory myeloma when given with cyclophosphamide

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Relapsed patients must have a confirmed MM diagnosis with high-risk disease as defined by GEP70 risk score ≥ 0.66 or GEP80 gene score of ≥ 2.48 or metaphase cytogenetic abnormalities or LDH ≥ 360 U/L due to MM (Rule out hemolysis, infection and contact PI for clarification if any doubt). Patients must have relapsed after auto-PBSCT followed by further chemotherapy
• ≥2 months must have elapsed after the last peripheral blood stem cell transplant prior to enrollment
• Zubrod ≤ 2, unless solely due to symptoms of MM-related (bone) disease
• Patients must have a platelet count of ≥ 20,000/µL within 45 days of registration, unless lower levels are explained by extensive BM plasmacytosis or extensive prior therapy
• Patients must be at least 18 years of age and not older than 75 years of age at the time of registration
• Participants must have preserved renal function as defined by a serum creatinine level of ≤ 3 mg/dL within 45 days of registration
• Participants must have an ejection fraction by ECHO or MUGA scan ≥ 40% within 45 days prior to registration
• Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, etc) and diffusion capacity (DLCO) > 50% of predicted within 45 days prior to registration. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, exception may be granted
• Patients must have signed an IRB-approved informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization form
• Patients must have anti-MV IgG titer of ≤ 0.5U/mL (Mayo clinic assay). Mayo Clinic will also assay the patients' IgM titer and perform a neutralizing antibody plaque-assay to determine recent MV exposure and the ability of the patients' circulating antibodies to inhibit MV propagation on Vero cells, respectively. While these tests are additional indicators of patient eligibility, final enrollment decision will be determined by IgG levels

Exclusion Criteria:

• Patients may not be positive for the Human Immunodeficiency Virus (HIV)
• History of poorly controlled hypertension, diabetes mellitus, or any other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol or could be considered to be an exclusion criterion deemed by the PI
• Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds three years as determined by the PI
• Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy test documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• Exposure to household contacts ≤ 15 months old or household contact with known immunodeficiency

Contacts and Locations

Contacts

Contact: Brittany Lehman; (501) 686-8274; blehman@uams.edu

Locations

United States, Arkansas

University of Arkansas for Medical Science; Recruiting

Little Rock, Arkansas, United States, 72205

Contact: Brittany Lehman 501-686-8274 blehman@uams.edu

Sub-Investigator: Faith Davies, MD

Sub-Investigator: Michele Fox, MD

Sub-Investigator: Gareth Morgan, MD, PhD

Sub-Investigator: Maurizio Zangari, MD

Sub-Investigator: Atul Kothari, MD

Sub-Investigator: Carolina Schinke, MD

Sub-Investigator: Juan Crescencio, MD

Sub-Investigator: Mary Burgess, MD

Sub-Investigator: Meera Mohan, MD

Sub-Investigator: Muthukumar Radhakrishnan, MD

Sub-Investigator: Pankaj Mathur, MD

Sub-Investigator: Sharmilan Thanendrajan, MD

Sub-Investigator: Sandra Susanibar-Adaniya, MD

Sub-Investigator: Shadiqul Hoque, MD

Sponsors and Collaborators

University of Arkansas

Investigators

• Principal Investigator: Frits Van Rhee, MD, Ph.D; University of Arkansas

More Information

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT02192775 History of Changes
• Other Study ID Numbers: 203081
• First Posted: July 17, 2014
• Last Update Posted: September 20, 2018
• Last Verified: September 2018

Keywords provided by University of Arkansas:

Measles virus; Sodium Iodide Symporter; Cyclophosphamide; Refractory multiple myeloma

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Measles; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Cyclophosphamide; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists