Clinical Trial: VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I Trial of Systemic Administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon, in Patients With Relapsed or Refractory Multiple Myeloma, Acute Myelo

Brief Summary: This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus carrying the human NIS and IFN beta genes (VSV-hIFNbeta-sodium iodide symporter [NIS]) in treating patients with multiple myeloma, acute myeloid leukemia, or T-cell lymphoma that has come back or does not respond to treatment. A virus, called VSV-hIFNbeta-NIS, which has been changed in a certain way, may be able to kill cancer cells without damaging normal cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of VSV-hIFNbeta-NIS in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, or T-cell lymphoma.

SECONDARY OBJECTIVES:

I. To determine the safety profile of VSV-hIFNbeta-NIS. II. To estimate clinical response rate in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, or T-cell lymphoma overall and by disease type.

III. To estimate progression-free and overall survival in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, or T-cell lymphoma overall and by disease type.

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 VSV-hIFNbeta-NIS using planar and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging.

II. To assess virus replication, viremia, viral shedding in urine and respiratory secretions, and virus persistence after systemic administration of VSV-hIFNbeta-NIS.

III. To characterize the pharmacodynamics (PD) of VSV-IFNbeta-NIS by way of measuring serum interferon-beta and also vesicular stomatitis virus (VSV)-real time (RT)-polymerase chain reaction (PCR) of VSV-IFNbeta-NIS.

IV. Assess CD8+ T cell (both general and VSV-IFNbeta-NIS specific) and natural killer (NK) cell responses.

V. Gene expression analysis pre- a
Sponsor: Mayo Clinic

Current Primary Outcome: Incidence of adverse events of grade 3 or higher assessed by the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ]

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns (by cohort and overall). Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The rate of grade 3 or higher non-hematologic adverse events, and the rate of grade 4 or higher adverse event (hematologic and non-hematologic) will be computed each with a 95% exact binomial confidence.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Clinical response [ Time Frame: Up to 1 year ]
    The number of responses (complete response [CR], very good partial response, partial response [PR], or minimal response for multiple myeloma; CR, CR with incomplete recovery, cytogenetic complete response, PR for AML; CR or PR for TCL) will be summarized by simple descriptive summary statistics.
  • Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 1 year ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).
  • Progression-free survival [ Time Frame: From registration to disease progression or death due to any cause, assessed up to 1 year ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).


Original Secondary Outcome: Same as current

Information By: Mayo Clinic

Dates:
Date Received: January 9, 2017
Date Started: April 4, 2017
Date Completion: January 2021
Last Updated: May 22, 2017
Last Verified: January 2017