A Vaccine (VSV-hIFNβ-NIS) With or Without Cyclophosphamide and Combinations of Ipilimumab, Nivolumab, and Cemiplimab in Treating Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma

Summary

This phase I trial studies the best dose and side effects of the VSV-hIFNβ-NIS vaccine with or without cyclophosphamide and combinations of ipilimumab, nivolumab, and cemiplimab in treating patients with multiple myeloma, acute myeloid leukemia or lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). VSV-IFNβ-NIS is a modified version of the vesicular stomatitis virus (also called VSV). This virus can cause infection and when it does it typically infects pigs, cattle, or horses but not humans. The VSV used in this study has been altered by having two extra genes (pieces of DNA) added. The first gene makes a protein called NIS that is inserted into the VSV. NIS is normally found in the thyroid gland (a small gland in the neck) and helps the body concentrate iodine. Having this additional gene will make it possible to track where the virus goes in the body (which organs). The second addition is a gene for human interferon beta (β) or hIFNβ. Interferon is a natural anti-viral protein, intended to protect normal healthy cells from becoming infected with the virus. VSV is very sensitive to the effect of interferon. Many tumor cells have lost the capacity to either produce or respond to interferon. Thus, interferon production by tumor cells infected with VSV-IFNβ-NIS will protect normal cells but not the tumor cells. The VSV with these two extra pieces is referred to as VSV-IFNβ-NIS. 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 monoclonal antibodies, such as ipilimumab, nivolumab, and cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving VSV-IFNβ-NIS with or without cyclophosphamide and combinations of ipilimumab, nivolumab, and cemiplimab may be safe and effective in treating patients with recurrent peripheral T-cell lymphoma.

Conditions

• B-Cell Non-Hodgkin Lymphoma
• Histiocytic and Dendritic Cell Neoplasm
• Myelodysplastic Syndrome
• Previously Treated Myelodysplastic Syndrome
• 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

Interventions

PROCEDURE

Biopsy Procedure

Undergo tumor or lymph node biopsy

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

PROCEDURE

Computed Tomography

Undergo SPECT/CT

DRUG

Cyclophosphamide

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET scan

BIOLOGICAL

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

Given IV

PROCEDURE

Single Photon Emission Computed Tomography

Undergo SPECT/CT

BIOLOGICAL

Cemiplimab

Given IV

DRUG

Ruxolitinib

Given PO

BIOLOGICAL

ipilimumab

Given IV

BIOLOGICAL

Nivolumab

Given IV

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA scan

PROCEDURE

Echocardiography Test

Undergo echocardiography

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Mayo Clinic

  lead OTHER

Principal Investigators

• Nora Bennani, M.D. · Mayo Clinic in Rochester

• Joselle Cook, M.B.B.S. · Mayo Clinic in Rochester

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-04-04

Primary Completion

2028-12-31

Completion

2032-04-01

FDA Drug

Yes

Countries

• United States

Study Locations