VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT03017820|
Recruitment Status : Recruiting
First Posted : January 11, 2017
Last Update Posted : June 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Previously Treated Myelodysplastic Syndrome Recurrent Adult Acute Myeloid Leukemia Recurrent Anaplastic Large Cell Lymphoma Recurrent Angioimmunoblastic T-cell Lymphoma Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma Recurrent Mycosis Fungoides Recurrent Plasma Cell Myeloma Recurrent T-Cell Non-Hodgkin Lymphoma Refractory Anaplastic Large Cell Lymphoma Refractory Angioimmunoblastic T-cell Lymphoma Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma Refractory Mycosis Fungoides Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified Refractory Plasma Cell Myeloma Refractory T-Cell Non-Hodgkin Lymphoma||Biological: Biological Therapy Procedure: Computed Tomography Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Single Photon Emission Computed Tomography||Phase 1|
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.
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.
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- and post-virotherapy. VI. Assess presence of VSV in tumor and normal tissues subsequent to administration of intravenous (IV) VSV-IFNbeta-NIS.
OUTLINE: This is a dose escalation study.
Patients receive VSV-IFNbeta-NIS intravenously (IV) over 30 minutes on day 1, and then undergo SPECT/CT 3-5 days later.
After completion of study treatment, patients are followed up for 28 days, and then every 3 months for up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Myeloid Leukemia, and T-Cell Neoplasms|
|Actual Study Start Date :||April 4, 2017|
|Estimated Primary Completion Date :||January 15, 2021|
|Estimated Study Completion Date :||January 15, 2021|
Experimental: Treatment (VSV-IFNbeta-NIS)
Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, and then undergo SPECT/CT 3-5 days later.
Biological: Biological Therapy
Given VSV-hIFNbeta-NIS IV
Procedure: Computed Tomography
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Procedure: Single Photon Emission Computed Tomography
- 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.
- 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).
- Biodistribution and kinetics of virus spread assessed by SPECT/CT imaging [ Time Frame: Up to 1 year ]Descriptive statistics and scatterplots will form the basis of presentation of these variables. Correlations between the laboratory values and other outcome measures will be carried out by standard parametric and non-parametric tests (e.g., Pearson's and Spearman's rho). Will be correlated with tumor distribution.
- NIS gene expression in tumor samples assessed by SPECT/CT imaging [ Time Frame: Up to 1 year ]Descriptive statistics and scatterplots will form the basis of presentation of these variables. Correlations between the laboratory values and other outcome measures will be carried out by standard parametric and non-parametric tests (e.g., Pearson's and Spearman's rho). Will be correlated with tumor distribution.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03017820
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Martha Q. Lacy|
|Principal Investigator:||Martha Lacy||Mayo Clinic|