Intravenous Vesicular Stomatitis Virus in Patients With Peripheral T-cell Lymphoma

MC1684 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

This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus (VSV) carrying the human (h) sodium iodide symporter (NIS) and Interferon (IFN) beta (β) genes (VSV-hIFNβ-NIS) in combination with cemiplimab in patients with T-cell lymphoma. A virus, called VSV-hIFNβ-NIS, which has been changed in a certain way, may be able to kill cancer cells without damaging normal cells. Immunotherapy with ipilmumab and cemiplimab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Study Overview

• Status: Recruiting
• Conditions: Mycosis Fungoides; Anaplastic Large Cell Lymphoma; Peripheral T Cell Lymphoma; Relapsed Peripheral T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Relapsed Anaplastic Large Cell Lymphoma; Relapsed Mycosis Fungoides
• Intervention / Treatment: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography; Biological: Cemiplimab; Procedure: Computed Tomography; Procedure: Single Photon Emission Computed Tomography; Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter; Procedure: Bone Marrow Biopsy

Detailed Description

PRIMARY OBJECTIVE: To determine the maximum tolerated dose (MTD) of VSV-hIFNβ-NIS in combination with cemiplimab in patients with T-cell lymphoma [Group E].

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.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic in Arizona
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Nathan Punwani, M.D.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Nora Bennani, M.D.
      • Principal Investigator: Kah Whye Peng, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years

• Relapsed or refractory:

  • Group E only: Relapsed peripheral T-cell lymphoma (PTCL) of the following histologies: peripheral T-cell lymphoma-NOS (PTCL-NOS); anaplastic large cell (ALCL), and mycosis fungoides (MF)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2 times upper limit of normal (ULN) (obtained =< 15 days prior to registration)
• Creatinine =< 2.0 mg/dL (obtained =< 15 days prior to registration)
• Direct bilirubin =< 1.5 x ULN (obtained =< 15 days prior to registration)
• International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (obtained =< 15 days prior to registration)
• If baseline liver disease, Child Pugh score not exceeding class A (obtained =< 15 days prior to registration)
• Negative pregnancy test for persons of child-bearing potential (obtained =< 15 days prior to registration)
• FOR T-Cell Lymphoma (TCL)/B-Cell Lymphoma (BCL) ONLY: Absolute Neutrophil Count (ANC) >= 1,000/microliter (μL) (obtained =< 14 days prior to registration)
• FOR TCL/BCL ONLY: Platelets >= 100,000/μL (obtained =< 14 days prior to registration)
• FOR TCL/BCL ONLY: Hemoglobin >= 8.5 g/dl (obtained =< 14 days prior to registration)
• FOR TCL/BCL ONLY: Measurable disease by CT or magnetic resonance imaging (MRI): must have at least one lesion that has a single diameter of > 2 cm or tumor cells in the blood > 5 x 10^9/L; NOTE: skin lesions can be used if the area is > 2 cm in at least one diameter and photographed with a ruler and the images are available in the medical record
• Absence of active central nervous system (CNS) involvement; NOTE: pre-enrollment lumbar puncture not mandatory
• Ability to provide written informed consent
• Willingness to return to Mayo Clinic for follow-up
• Life expectancy >= 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Willing to provide mandatory biological specimens for research purposes

Exclusion Criteria:

• Availability of and patient acceptance of curative therapy
• Uncontrolled infection
• Active tuberculosis or hepatitis, or chronic hepatitis

• Any of the following prior therapies:

  • Chemotherapy (IMIDs, alkylating agents, proteosome inhibitors) =< 2 weeks prior to registration
  • Immunotherapy (monoclonal antibodies) =< 4 weeks prior to registration
  • Experimental agent in case of Acute Myeloid Leukemia (AML) or TCL within 4 half-lives of the last dose of the agent
• New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias [atrial fibrillation or supraventricular tachycardia (SVT)]
• Active CNS disorder or seizure disorder or known CNS disease or neurologic symptomatology; in case of AML active CNS involvement as detected by lumbar puncture or neuro-imaging (only to be done if clinically indicated)
• Human immunodeficiency virus (HIV) positive test result or other immunodeficiency or immunosuppression

• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-Food and Drug Administration [FDA] approved indication and in the context of a research investigation);

  • NOTE: in TCL, patients may use topical emollients or corticosteroids, acetic acid soaks, etc. to control pruritis and prevent infection; no topical chemotherapy is allowed (no topical nitrogen mustard)

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

  • Pregnant women or women of reproductive ability who are unwilling to use effective contraception
  • Nursing women
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment

• ADDITIONAL EXCLUSION CRITERIA FOR GROUP E (COMBINATION WITH IPILIMUMAB AND CEMIPLIMAB) ONLY:

  • Diagnosis of AML
  • Diagnosis of Angioimmunoblastic T-cell Lymphoma (AITL)
  • Hypersensitivity to ipilimumab or its excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group E (VSV-IFNβ-NIS, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only; PTCL patients receive VSV-IFNβ-NIS IV over 30 minutes on day 1 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.	Procedure: Biopsy; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Biological: Cemiplimab; Given IV; Other Names: REGN2810; Cemiplimab RWLC; Cemiplimab-rwlc; Libtayo; Immunoglobulin G4; 1801342-60-8; Anti-(Human Programmed Cell Death Protein 1) (Human Monoclonal REGN2810 Heavy Chain); Disulfide with Human Monoclonal REGN2810 kappa-chain; Procedure: Computed Tomography; Undergo SPECT/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Single Photon Emission Computed Tomography; Undergo SPECT/CT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter; Given IV; Other Names: Voyager-V1; Oncolytic VSV-hIFNbeta-NIS; Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter; VSV-expressing hIFNb and NIS; VSV-hIFNb-NIS; VSV-hIFNbeta-NIS; VV1; VSV-hIFNβ-NIS; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow
Experimental: Group E (VSV-IFNβ-NIS, cemiplimab) - PTCL Expansion Cohort; PTCL patients receive VSV-IFNβ-NIS IV over 30 minutes on day 1 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.	Procedure: Biopsy; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Biological: Cemiplimab; Given IV; Other Names: REGN2810; Cemiplimab RWLC; Cemiplimab-rwlc; Libtayo; Immunoglobulin G4; 1801342-60-8; Anti-(Human Programmed Cell Death Protein 1) (Human Monoclonal REGN2810 Heavy Chain); Disulfide with Human Monoclonal REGN2810 kappa-chain; Procedure: Computed Tomography; Undergo SPECT/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Single Photon Emission Computed Tomography; Undergo SPECT/CT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter; Given IV; Other Names: Voyager-V1; Oncolytic VSV-hIFNbeta-NIS; Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter; VSV-expressing hIFNb and NIS; VSV-hIFNb-NIS; VSV-hIFNbeta-NIS; VV1; VSV-hIFNβ-NIS; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events of grade 3 or higher	Assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Response to treatment will be recorded as stringent Complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), Minimal Response (MR), stable disease (SD), and progressive disease (PD).	Up to 2 years
Progression-free survival (PFS)	PFS is defined as the time from study enrollment to disease progression or death due to any cause.	Up to 2 years
Overall survival (OS)	OS is defined as the time from study enrollment to death due to any cause.	Up to 2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kah Whye Peng, PhD, Mayo Clinic in Rochester; Principal Investigator: Nora Bennani, MD, Mayo Clinic in Rochester

Publications and helpful links

General Publications

• Cook J, Peng KW, Witzig TE, Broski SM, Villasboas JC, Paludo J, Patnaik M, Rajkumar V, Dispenzieri A, Leung N, Buadi F, Bennani N, Ansell SM, Zhang L, Packiriswamy N, Balakrishnan B, Brunton B, Giers M, Ginos B, Dueck AC, Geyer S, Gertz MA, Warsame R, Go RS, Hayman SR, Dingli D, Kumar S, Bergsagel L, Munoz JL, Gonsalves W, Kourelis T, Muchtar E, Kapoor P, Kyle RA, Lin Y, Siddiqui M, Fonder A, Hobbs M, Hwa L, Naik S, Russell SJ, Lacy MQ. Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. Blood Adv. 2022 Jun 14;6(11):3268-3279. doi: 10.1182/bloodadvances.2021006631.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: July 12, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell, Cutaneous; Hemic and Lymphatic Diseases; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Large-Cell, Anaplastic; Mycosis Fungoides; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Physical Phenomena; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Elementary Particles; Light; Optical Phenomena; Radiation, Nonionizing; Immunoglobulin G; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Disulfides; X-Rays; Photons; cemiplimab; sodium-iodide symporter
• Other Study ID Numbers: MC1684 Arm E; R01CA262613 (U.S. NIH Grant/Contract: NIH); 16-005474 (Other Identifier: Mayo Clinic Institutional Review Board); P50CA186781 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No