What side effects are associated with this type of intervention?

Treatments for T-Cell Lymphoma, particularly those involving engineered viruses like VSV-hIFNbeta-NIS, cyclophosphamide, and immunotherapies such as ipilimumab and nivolumab, have several known side effects. Engineered viruses can cause flu-like symptoms, fatigue, and injection site reactions. Cyclophosphamide often leads to nausea, vomiting, hair loss, and increased infection risk due to bone marrow suppression. Immunotherapies can result in immune-related adverse events, including skin reactions, colitis, hepatitis, endocrinopathies, and pneumonitis.

What prior FDA approvals exist?

The FDA has approved several treatments for T-Cell Lymphoma, including traditional chemotherapies, targeted therapies, and immunotherapies. Notably, treatments like brentuximab vedotin (an antibody-drug conjugate) and pralatrexate (a folate analog metabolic inhibitor) have been approved. While specific FDA approvals for treatments using engineered viruses like VSV-hIFNbeta-NIS are not detailed, the concept of using modified viruses for selective cancer cell killing is an emerging area of research, with ongoing trials exploring their efficacy and safety.

What other types of research exist?

Promising novel alternatives for T-Cell Lymphoma patients include: 1) Venetoclax plus obinutuzumab, which has shown improved progression-free survival and acceptable tolerability in clinical trials. 2) Ivosidenib, a mutant-IDH1 inhibitor, which has demonstrated efficacy in IDH1-mutant gliomas and is being explored for other cancers. 3) Dual mutant-IDH1/2 inhibitor vorasidenib, currently in phase III trials for IDH1/2-mutant gliomas, may offer potential benefits. These therapies represent cutting-edge approaches that could be considered in 2024.

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Virus Therapy

Modified Virus Therapy for Cancer

Phase 1

Recruiting

Led By Joselle Cook, M.B.B.S.

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 18 years

Relapsed peripheral T-cell lymphoma (PTCL) of specific histologies with failed standard therapy

Must not have

Uncontrolled infection, active tuberculosis, or hepatitis

Current disseminated intravascular coagulopathy (DIC)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a modified virus treatment for patients with certain types of cancer that have returned or don't respond to usual treatments. The virus aims to kill cancer cells without harming normal ones. It is combined with other drugs to improve its effectiveness.

Who is the study for?

This trial is for adults over 18 with relapsed or refractory multiple myeloma, acute myeloid leukemia, or lymphoma. Participants must have a life expectancy of at least 12 weeks and be able to perform daily activities with minimal assistance (ECOG PS 0-2). They should not have HIV, active hepatitis, certain heart/CNS disorders, uncontrolled infections, or be pregnant/nursing.

What is being tested?

The trial tests VSV-hIFNbeta-NIS virus therapy alone or combined with cyclophosphamide (a DNA-damaging agent), ipilimumab and nivolumab (immunotherapies) in patients whose cancer has returned or resisted treatment. It aims to find the best dose and assess side effects while trying to kill cancer cells without harming normal ones.

What are the potential side effects?

Potential side effects include immune system reactions due to the virus therapy and immunotherapy agents which may cause flu-like symptoms, fatigue, skin reactions; cyclophosphamide can lead to nausea and hair loss. The severity of these side effects will vary among individuals.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My PTCL has returned after standard treatment failed.

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My blood cancer can be measured by tests.

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My multiple myeloma has returned or didn't respond to treatment with IMID, a proteasome inhibitor, and an alkylating agent.

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I can take care of myself and am up and about more than half of my waking hours.

Select...

I have B-cell lymphoma (not Burkitt's) or HCN at any stage.

Select...

My brain and spinal cord are free from cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any ongoing infections, tuberculosis, or hepatitis.

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I have a condition that affects my blood's ability to clot.

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I do not have heart conditions, active brain disorders, HIV, or a weak immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events of grade 3 or higher

Secondary study objectives

Clinical response

Overall survival

Progression-free survival

Other study objectives

Biodistribution and kinetics of virus spread

NIS gene expression in tumor samples

Side effects data

From 2012 Phase 2 trial • 124 Patients • NCT01334918

15%

Flushing

13%

Headache

11%

Dyspnoea

Dizziness

Chest discomfort

Nausea

Angina pectoris

Gastritis

100%

80%

60%

40%

20%

Study treatment Arm

SPECT

MDCT

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

7Treatment groups

Experimental Treatment

Group I: Group G (VSV-IFNbeta-NIS alone) - PTCL Expansion CohortExperimental Treatment7 Interventions

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.

Group II: Group F (VSV-IFNbeta-NIS alone) - B-Cell Leukemia (BCL) Expansion CohortExperimental Treatment7 Interventions

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.

Group III: Group E (VSV-IFNbeta-NIS, ipilimumab, cemiplimab) - Peripheral T-cell lymphoma (PTCL) onlyExperimental Treatment8 Interventions

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.

Group IV: Group D (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab) - Multiple Myeloma (MM) onlyExperimental Treatment8 Interventions

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.

Group V: Group C (VSV-IFNbeta-NIS, ruxolitinib, nivolumab)Experimental Treatment7 Interventions

\*\* Group C no longer enrolling \*\*

Group VI: Group B (VSV-IFNbeta-NIS, ruxolitinib, cyclophosphamide)Experimental Treatment8 Interventions

\*\* Group B no longer enrolling \*\*

Group VII: Group A (VSV-IFNbeta-NIS)Experimental Treatment7 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1090

Biospecimen Collection

2004

Completed Phase 3

~2020

Bone Marrow Biopsy

2021

Completed Phase 3

~230

Computed Tomography

2017

Completed Phase 2

~2740

Cyclophosphamide

2010

Completed Phase 4

~2310

Positron Emission Tomography

2011

Completed Phase 2

~2200

Single Photon Emission Computed Tomography

2008

Completed Phase 4

~320

Cemiplimab

2015

Completed Phase 3

~1470

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for T-Cell Lymphoma include targeted therapies and immunotherapies. Targeted therapies, such as monoclonal antibodies, work by specifically binding to cancer cell antigens, leading to direct cancer cell killing or marking them for destruction by the immune system. Immunotherapies, including checkpoint inhibitors and engineered viruses like VSV-hIFNbeta-NIS, enhance the body's immune response against cancer cells. VSV-hIFNbeta-NIS, for example, selectively infects and kills cancer cells while sparing normal cells, and may also stimulate an immune response against the tumor. These mechanisms are crucial for T-Cell Lymphoma patients as they offer more precise and potentially less toxic treatment options compared to traditional chemotherapy.

Advances in Immunotherapies for Gliomas.Extracorporeal photochemoimmunotherapy in cutaneous T-cell lymphoma.