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

Myelodysplastic Syndrome Clinical Trial

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, Lymphomas, or Histiocytic/Dendritic Cell Neoplasms

Status Recruiting

Clinical Trial 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]) 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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• B-Cell Non-Hodgkin Lymphoma
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Multiple Myeloma
• Mycoses
• Mycosis Fungoides
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Neoplasms
• Neoplasms, Plasma Cell
• Preleukemia
• Previously Treated Myelodysplastic Syndrome
• Recurrence
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Anaplastic Large Cell Lymphoma
• Recurrent Angioimmunoblastic T-Cell Lymphoma
• Recurrent Mycosis Fungoides
• Recurrent Plasma Cell Myeloma
• Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
• Recurrent T-Cell Non-Hodgkin Lymphoma
• Refractory Acute Myeloid Leukemia
• Refractory Anaplastic Large Cell Lymphoma
• Refractory Angioimmunoblastic T-Cell Lymphoma
• Refractory Mycosis Fungoides
• Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified
• Refractory Plasma Cell Myeloma
• Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
• Refractory T-Cell Non-Hodgkin Lymphoma
• Syndrome

• NCT number: NCT03017820
• Study type: Interventional
• Source: Mayo Clinic
• Status: Recruiting
• Phase: Phase 1
• Start date: April 4, 2017
• Completion date: April 1, 2032