Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Infections

Immune System Diseases

Heart and Blood Diseases

Mouth and Tooth Diseases

Rare Diseases

Syndrome

Recurrence

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Mycoses

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Mycosis Fungoides

Lymphoma, T-Cell, Cutaneous

Multiple Myeloma

Neoplasms, Plasma Cell

Stomatitis

Virus Diseases

Lymphoma, B-Cell

Immunoblastic Lymphadenopathy

Vesicular Stomatitis

Lymphoma, Large-Cell, Anaplastic

Lymphoma, Non-Hodgkin

Lymphadenopathy

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Disease Attributes

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Bone Marrow Diseases

Precancerous Conditions

Bacterial Infections

Communicable Diseases

Bacterial Infections and Mycoses

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

B-cell Lymphoma

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

Acute Graft Versus Host Disease

Angioimmunoblastic T-cell Lymphoma

Angioimmunoblastic Lymphadenopathy With Dysproteinemia

Anaplastic Large Cell Lymphoma

Dendritic Cell Tumor

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Micronutrients

Nivolumab

Antibodies

Cyclophosphamide

Cemiplimab

Ipilimumab

Immunoglobulins

Immunoglobulin G

Interferons

Immunoglobulins, Intravenous

Iodine

Interferon-beta

Cadexomer iodine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antiviral Agents

Antineoplastic Agents, Immunological

Anti-Infective Agents, Local

Trace Elements

Patients receive VSV-IFNbeta-NIS intravenously (IV) while on study. Patients undergo SPECT, CT scan, PET scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

Multiple myeloma patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, ipilimumab IV over 30 minutes on day -3 and cemiplimab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity. Patients undergo SPECT, CT scan, PET scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

PTCL patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, ipilimumab IV over 30 minutes on day -3 and cemiplimab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity. Patients undergo SPECT, CT scan, PET scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

BCL patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients undergo SPECT, CT scan, PET scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

PTCL patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients undergo SPECT, CT scan, PET scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

Biopsy

Biospecimen Collection

Bone Marrow Biopsy

Computed Tomography

Positron Emission Tomography

Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter

Single Photon Emission Computed Tomography

Clinical Trials Referral Office

Javier L. Munoz, M.D.

Nora Bennani, M.D.

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 \[NIS\]) with or without cyclophosphamide or ipilimumab and nivolumab or cemiplimab in treating patients with multiple myeloma, acute myeloid leukemia (AML) or 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. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Immunotherapy with ipilmumab and nivolumab or cemiplimab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving VSV-hIFNbeta-NIS and ruxolitinib phosphate may work better at treating multiple myeloma, acute myeloid leukemia and T-cell lymphoma.

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) of VSV-hIFNβ-NIS in different treatment regimens (alone \[Group A, F, G\] in combination with ruxolitinib \[Group B\] and in combination with cyclophosphamide \[Group C\]) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms; in combination with ipilimumab and nivolumab in patients with multiple myeloma \[Group D\] and in combination with ipilimumab and cemiplimab in patients with T-cell lymphoma \[Group E\].

SECONDARY OBJECTIVES:

I. To determine the safety profile of VSV-hIFNbeta-NIS (alone and in combination).

II. To estimate clinical response rate of VSV-hIFNbeta-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T-cell and B-cell lymphoma or histiocytic/dendritic cell neoplasms overall and by disease type.

III. To estimate progression-free and overall survival of VSV-hIFNbeta-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms overall and by disease type.

CORRELATIVE 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- and post-virotherapy. VI. Assess presence of VSV in tumor and normal tissues subsequent to administration of intravenous (IV) VSV-IFNbeta-NIS.

VII. To identify the best dose of VSV-hIFNbeta-NIS in the regimen being evaluated based on activity observed in the correlative measures described above in those dose levels identified as tolerable.

OUTLINE: This is a dose escalation study of VSV-IFNbeta-NIS. Patients are assigned to 1 of 3 groups.

GROUP A: Patients receive VSV-IFNbeta-NIS intravenously (IV) over 30 minutes on day 1 in the absence of disease progression or unacceptable toxicity.

GROUP B: \*\*NO LONGER ENROLLING\*\* Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and cyclophosphamide IV over 2 hours on day 2 in the absence of disease progression or unacceptable toxicity.

GROUP C: \*\*NO LONGER ENROLLING\*\* Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, ipilimumab IV over 30 minutes on day -3 and nivolumab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity.

GROUP D: Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, ipilimumab IV over 30 minutes on day -3 and cemiplimab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity.

Patients undergo computed tomography (CT) scan, position emission tomography (PET) scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

After completion of study treatment, patients are followed up for 28 days, and then every 3 months for up to 1 year or until progressive disease, then every 6 months for 1 year.

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma

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, Lymphomas, or Histiocytic/Dendritic Cell Neoplasms

Assessed by single photon emission computed tomography (SPECT)/computed tomography (CT) imaging. 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.

Assessed by the Common Terminology Criteria for Adverse Events version 4.0. 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.

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 acute myeloid leukemia \[AML\]; CR or PR for T-cell lymphoma \[TCL\]) will be summarized by simple descriptive summary statistics.

The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).

National Cancer Institute (NCI)

Mayo Clinic

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma	NCT03017820	B-Cell Non-Hodg... Histiocytic and... Myelodysplastic... Previously Trea... Recurrent Adult... Recurrent Anapl... Recurrent Angio... Recurrent Mycos... Recurrent Plasm... Recurrent Prima... Recurrent T-Cel... Refractory Acut... Refractory Anap... Refractory Angi... Refractory Myco... Refractory Peri... Refractory Plas... Refractory Prim... Refractory T-Ce...	Biopsy Biospecimen Col... Bone Marrow Bio... Computed Tomogr... Cyclophosphamid... Positron Emissi... Recombinant Ves... Single Photon E... Cemiplimab	18 Years -	Mayo Clinic
VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma	NCT03017820	B-Cell Non-Hodg... Histiocytic and... Myelodysplastic... Previously Trea... Recurrent Adult... Recurrent Anapl... Recurrent Angio... Recurrent Mycos... Recurrent Plasm... Recurrent Prima... Recurrent T-Cel... Refractory Acut... Refractory Anap... Refractory Angi... Refractory Myco... Refractory Peri... Refractory Plas... Refractory Prim... Refractory T-Ce...	Biopsy Biospecimen Col... Bone Marrow Bio... Computed Tomogr... Cyclophosphamid... Positron Emissi... Recombinant Ves... Single Photon E... Cemiplimab	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for histiocytic and dendritic cell neoplasm