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

Phase 1

Recruiting

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

• Registration Number: NCT06508463
• Lead Sponsor: Mayo Clinic

Brief Summary

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 ipilimumab and 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.

Detailed Description

PRIMARY OBJECTIVE: To determine the maximum tolerated dose (MTD) of VSV-hIFNβ-NIS in combination with ipilimumab and 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 Timeline

• Study Start: 2024-01-05
• Study First Submitted: 2024-07-12
• Study First Submitted QC: 2024-07-12
• Study First Posted: 2024-07-18
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-10
• Primary Completion: 2028-12-31
• Study Completion: 2032-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Cemiplimab	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Computed Tomography	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Biopsy	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Cemiplimab	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Bone Marrow Biopsy	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Biopsy	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Biospecimen Collection	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Positron Emission Tomography	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Single Photon Emission Computed Tomography	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) only	Ipilimumab	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Biospecimen Collection	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Bone Marrow Biopsy	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Computed Tomography	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Positron Emission Tomography	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Single Photon Emission Computed Tomography	PTCL patients receive VSV-IFNβ-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.
Group E (VSV-IFNβ-NIS, ipilimumab, cemiplimab) - PTCL Expansion Cohort	Ipilimumab	PTCL patients receive VSV-IFNβ-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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Clinical response	Up to 2 years	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).
Progression-free survival (PFS)	Up to 2 years	PFS is defined as the time from study enrollment to disease progression or death due to any cause.
Overall survival (OS)	Up to 2 years	OS is defined as the time from study enrollment to death due to any cause.

Trial Locations

Locations (2)

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States