Track topics on Twitter Track topics that are important to you
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.
- 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 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.
Primary Purpose: Treatment
Multiple Myeloma and Plasma Cell Neoplasm
oncolytic measles virus encoding thyroidal sodium iodide symporter, cyclophosphamide, reverse transcriptase-polymerase chain reaction, flow cytometry, immunologic technique, laboratory biomarker analysis, biopsy
Mayo Clinic Cancer Center
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:39:30-0400
This randomized phase II trial studies how well oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) compared to investigator's choice chemotherapy works in treating...
This phase I/II trial studies the side effects and best dose of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) infected mesenchymal stem cells and to see how w...
This phase I trial studies the side effects and the best dose of a vaccine therapy in treating patients with malignant peripheral nerve sheath tumor that cannot be removed by surgery (unre...
This is a pilot imaging study for women whose tumors express NIS [Na+I- symporter, sodium iodide symporter]. Eligibility is limited to the presence of strong (3+) and/or plasma membrane st...
The goal of this proposal is to perform first-in-man evaluation of the imaging probe F-18 tetrafluoroborate (BF4) as a PET imaging biomarker for expression of the human sodium/iodide sympo...
We observed local homology between human pendrin and sodium/iodide symporter (NIS), that was absent in the NIS-homologous sodium/monocarboxylate transporter or apical iodide transporter (AIT) which, h...
Oncolytic virus therapy is a promising new option for cancer. It utilizes genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming norm...
Attenuated measles virus (MV) strains are promising agents currently being tested against solid tumors or hematologic malignancies in ongoing phase I and II clinical trials; factors determining oncoly...
The activating mutation BRAF is a frequent genetic event in papillary thyroid carcinomas (PTC). Mutation BRAF is associated with the loss of a sodium/iodine symporter (NIS), and subsequent radioiodide...
An iodide transport defect (ITD) in the thyroid gland was determined to cause congenital dyshormonogenic hypothyroidism with goiter (CDHG) in 2 members of a family of Shih-Tzu dogs. Strikingly, both d...
A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had measles or been immunized with live measles vaccine and have no serum antibodies against measles. Children are usually immunized with measles-mumps-rubella combination vaccine. (From Dorland, 28th ed)
The type species of MORBILLIVIRUS and the cause of the highly infectious human disease MEASLES, which affects mostly children.
Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.
Agents that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS which are concentrated in the thick ascending limb at the junction of the LOOP OF HENLE and KIDNEY TUBULES, DISTAL. They act as DIURETICS. Excess use is associated with HYPOKALEMIA and HYPERGLYCEMIA.
A defective variant of MEASLES VIRUS that has been isolated from the brain tissue of patients with subacute sclerosing panencephalitis.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...