Modified Virus Therapy for Cancer

Recruiting at 1 trial location

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy, Immunotherapy, Experimental agents

Disqualifiers: Uncontrolled infection, Active tuberculosis, Hepatitis, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had chemotherapy within 2 weeks or immunotherapy within 4 weeks before joining. It's best to discuss your specific medications with the trial team.

What data supports the idea that Modified Virus Therapy for Cancer is an effective treatment?

The available research shows that Modified Virus Therapy for Cancer, specifically using the vesicular stomatitis virus expressing interferon-beta (VSV-IFNβ), has demonstrated effectiveness in treating various cancers. In studies, this treatment has shown the ability to kill cancer cells while sparing normal cells. For example, in a study involving patients with T-cell lymphoma, some patients experienced significant tumor reduction, with one patient achieving complete remission lasting over 20 months. Additionally, in preclinical models, VSV-IFNβ was effective against non-small cell lung cancer and prostate cancer, reducing tumor growth and promoting strong immune responses against the tumors. These findings suggest that this treatment can effectively target and destroy cancer cells while also boosting the body's immune response to fight the cancer. ^{1 2 3 4 5}

What safety data is available for Modified Virus Therapy for Cancer?

The safety data for Modified Virus Therapy, specifically using recombinant vesicular stomatitis virus expressing human interferon-beta (VSV-hIFNβ), includes several preclinical and clinical studies. Preclinical studies in rodents and nonhuman primates showed that VSV-hIFNβ can be administered safely at certain doses, with some transient changes in liver enzymes and platelet counts in rats, but no neurological signs or significant abnormalities in rhesus macaques. In a phase 1 clinical trial involving patients with relapsed/refractory hematologic malignancies, VSV-IFNβ-NIS was administered at various dose levels without dose-limiting toxicities, and some patients experienced partial or complete responses. These studies suggest that VSV-hIFNβ has a favorable safety profile, with manageable side effects and potential therapeutic benefits. ^{2 3 5 6 7}

Is the treatment VSV-hIFNβ-NIS a promising cancer treatment?

Yes, VSV-hIFNβ-NIS is a promising cancer treatment because it can specifically target and kill cancer cells while sparing normal cells. It also helps the immune system fight tumors, making it a potential new tool for treating cancer. ^{2 3 4 8 9}

Research Team

Joselle Cook, M.B.B.S.

Principal Investigator

Mayo Clinic in Rochester

Nora Bennani, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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.

Inclusion Criteria

I am 18 years old or older.

My PTCL has returned after standard treatment failed.

My blood cancer can be measured by tests.

Exclusion Criteria

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

I am willing and able to undergo treatment aimed at curing my disease.

Pregnancy, breastfeeding, or inadequate contraception

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive VSV-hIFNβ-NIS with or without additional drugs such as cyclophosphamide, ipilimumab, nivolumab, or cemiplimab, depending on the group assignment

1-2 weeks

Multiple visits (in-person) for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Follow-up visits on days 15 and 29, at 6 weeks, then every 3 months until 1 year, followed by every 6 months until 2 years

Long-term follow-up

Participants are monitored for long-term safety and survival outcomes

Up to 2 years

Treatment Details

Interventions

• Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Virus Therapy)
• Ruxolitinib Phosphate (JAK Inhibitor)

Trial Overview 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.

Participant Groups

Group I: Group G (VSV-IFNbeta-NIS alone) - PTCL Expansion Cohort Experimental Treatment 8 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 Cohort Experimental Treatment 8 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) only Experimental Treatment 9 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) only Experimental Treatment 9 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 Treatment 8 Interventions

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

Group VI: Group B (VSV-IFNbeta-NIS, ruxolitinib, cyclophosphamide) Experimental Treatment 9 Interventions

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

Group VII: Group A (VSV-IFNbeta-NIS) Experimental Treatment 8 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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The combination of vesicular stomatitis virus expressing IFNβ (VSV-IFNβ) and radiotherapy (RT) significantly enhances tumor killing in prostate cancer models, leading to increased infection and replication of the virus in tumor cells.

This combination therapy not only induces direct tumor cell death but also stimulates a robust antitumor immune response, evidenced by increased CD8+ and CD4+ T-cell numbers and complete resistance to tumor rechallenge in treated mice, suggesting a promising approach for high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Attenuates Prostate Tumor Antiviral Responses to Vesicular Stomatitis Virus Containing IFNβ, Resulting in Pronounced Antitumor Systemic Immune Responses. Udayakumar, TS., Betancourt, DM., Ahmad, A., et al.[2021]

VSV-IFN-β, a recombinant virus expressing interferon-β, showed significant antitumor activity in preclinical studies with syngeneic squamous cell carcinoma models, demonstrating both safety and efficacy in immunocompetent rats.

The treatment did not cause acute organ toxicity or death, and both intratumoral and intravenous administration of VSV-IFN-β led to tumor growth delay and improved survival, supporting its potential for clinical testing in human head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical safety and activity of recombinant VSV-IFN-β in an immunocompetent model of squamous cell carcinoma of the head and neck. Kurisetty, VV., Heiber, J., Myers, R., et al.[2021]

Genetically engineered vesicular stomatitis virus (VSV-IFNbeta) can selectively target and kill cancer cells while sparing normal cells, due to its ability to exploit defects in the interferon (IFN) response in transformed cells.

VSV-IFNbeta not only shows reduced growth in normal cells due to the production of recombinant IFN-beta, but also retains strong oncolytic activity against metastatic lung cancer in mice, generating effective antitumor immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of recombinant vesicular stomatitis viruses that exploit defects in host defense to augment specific oncolytic activity. Obuchi, M., Fernandez, M., Barber, GN.[2020]

VSV-IFNβ shows strong antitumor activity against non-small cell lung cancer (NSCLC) in preclinical models, significantly reducing tumor growth and improving survival rates in mouse models, with a cure rate of 30% in treated mice.

The treatment with VSV-IFNβ not only directly attacks tumor cells but also enhances the immune response by decreasing regulatory T cells and increasing CD8+ T cells, suggesting it promotes systemic antitumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer. Patel, MR., Jacobson, BA., Ji, Y., et al.[2021]

In a phase 1 clinical trial involving 15 patients with relapsed/refractory hematologic malignancies, the intravenous administration of VSV-IFNβ-NIS showed no dose-limiting toxicities and resulted in significant responses in 3 out of 7 patients with T-cell lymphoma, including one complete response lasting 20 months.

The efficacy of VSV-IFNβ-NIS appears to stem from both direct destruction of tumor cells and enhanced immune responses, as indicated by robust viral replication and increased tumor-reactive T-cells in the responding patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. Cook, J., Peng, KW., Witzig, TE., et al.[2022]

Vesicular stomatitis virus encoding interferon β (VSV-IFNβ) shows promising efficacy in preclinical cancer models, with 37 out of 42 experiments reporting positive outcomes across various administration routes.

Despite the encouraging results, further research is needed to confirm the safety and efficacy of VSV-IFNβ before it can be translated into clinical trials, as some studies did report negative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical efficacy of oncolytic VSV-IFNβ in treating cancer: A systematic review. Moglan, AM., Albaradie, OA., Alsayegh, FF., et al.[2023]

In toxicology studies involving rats and rhesus macaques, the oncolytic vesicular stomatitis virus expressing human interferon-beta (VSV-hIFNbeta) showed no significant adverse effects at a safe starting dose of 7.59 x 10^9 TCID(50) in rats, with temporary increases in liver enzymes that normalized by day 4.

Rhesus macaques tolerated doses of VSV-hIFNbeta up to 10^10 TCID(50) without neurological signs or abnormalities, indicating a favorable safety profile, which supports cautious dose escalation in upcoming clinical trials for patients with hepatocellular carcinoma (HCC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety studies on intrahepatic or intratumoral injection of oncolytic vesicular stomatitis virus expressing interferon-beta in rodents and nonhuman primates. Jenks, N., Myers, R., Greiner, SM., et al.[2021]

Mutant strains of vesicular stomatitis virus (VSV) have been developed that cannot counteract the body's natural interferon-beta (IFN-beta) signaling, making them more effective at targeting tumor cells with weak antiviral defenses.

These VSV mutants show promise as a potential systemic treatment for distal and metastatic cancers, suggesting a new avenue for oncolytic virus therapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vesicular stomatitis virus: an exciting new therapeutic oncolytic virus candidate for cancer or just another chapter from Field's Virology? Giedlin, MA., Cook, DN., Dubensky, TW.[2019]

In a study using transgenic mice with chronic hepatitis B virus (HBV) infection, a recombinant vesicular stomatitis virus (VSV) expressing the HBV middle surface envelope glycoprotein (MS) successfully generated specific CD8 T cell and antibody responses against HBV.

These results suggest that VSV could be a promising therapeutic vaccine platform for treating chronic HBV infections, particularly in cases with low HBV antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A vesicular stomatitis virus-based therapeutic vaccine generates a functional CD8 T cell response to hepatitis B virus in transgenic mice. Cobleigh, MA., Wei, X., Robek, MD.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Radiation Attenuates Prostate Tumor Antiviral Responses to Vesicular Stomatitis Virus Containing IFNβ, Resulting in Pronounced Antitumor Systemic Immune Responses. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Preclinical safety and activity of recombinant VSV-IFN-β in an immunocompetent model of squamous cell carcinoma of the head and neck. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Development of recombinant vesicular stomatitis viruses that exploit defects in host defense to augment specific oncolytic activity. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Preclinical efficacy of oncolytic VSV-IFNβ in treating cancer: A systematic review. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Safety studies on intrahepatic or intratumoral injection of oncolytic vesicular stomatitis virus expressing interferon-beta in rodents and nonhuman primates. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Vesicular stomatitis virus: an exciting new therapeutic oncolytic virus candidate for cancer or just another chapter from Field's Virology? [2019]

9. United States pubmed.ncbi.nlm.nih.gov

A vesicular stomatitis virus-based therapeutic vaccine generates a functional CD8 T cell response to hepatitis B virus in transgenic mice. [2021]