Modified Virus Therapy for Cancer

Recruiting at 1 trial location

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy, Immunotherapy, Experimental agents

Disqualifiers: Uncontrolled infection, Active tuberculosis, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 16

Duration: 1-2 weeks

127 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new virus-based treatment for certain cancers, such as multiple myeloma, acute myeloid leukemia, and lymphoma, when they return or stop responding to treatment. The modified virus, called Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter, targets and kills cancer cells while sparing healthy ones. Some participants will also receive additional drugs, like cyclophosphamide and immune-boosting antibodies, to determine if they enhance the treatment's effectiveness. This trial seeks individuals with relapsed or hard-to-treat forms of these cancers, especially if previous treatments have failed. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found the VSV-hIFNβ-NIS treatment to be safe for people, causing no serious side effects when administered directly into tumors or through the bloodstream. This research indicates that the treatment is well-tolerated.

Ruxolitinib, another treatment in the trial, has been used safely for over ten years in conditions like myelofibrosis, a bone marrow disorder. Studies have shown that most side effects are manageable and include minor infections or low blood cell counts.

Overall, existing evidence supports the safety of both VSV-hIFNβ-NIS and ruxolitinib in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard cancer treatments like chemotherapy and radiation, the modified virus therapy uses a recombinant vesicular stomatitis virus (VSV) that expresses human interferon beta and a sodium-iodide symporter. This approach is unique because VSV can selectively infect and destroy cancer cells while sparing healthy ones, which could potentially lead to fewer side effects. Additionally, the inclusion of human interferon beta enhances the immune system's ability to fight cancer, and the sodium-iodide symporter may allow for better imaging and tracking of the virus in the body. Researchers are excited about this combination because it offers a novel mechanism of action and could significantly improve targeting and effectiveness in cancer treatment.

What evidence suggests that this trial's treatments could be effective for cancer?

Research shows that the VSV-IFNβ-NIS vaccine uses a modified virus to attack cancer cells while leaving healthy cells unharmed. This virus includes interferon-beta, a protein that fights infections and protects normal cells from infection. Many cancer cells cannot defend against interferon, so they remain vulnerable to the virus. In this trial, some participants will receive VSV-IFNβ-NIS combined with ruxolitinib, which has shown promise in treating certain blood disorders by extending patient survival and reducing symptoms. Together, these treatments aim to destroy cancer cells while causing minimal harm to healthy cells. Early studies suggest these therapies could be effective for challenging cancers like multiple myeloma, acute myeloid leukemia, and lymphoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Joselle Cook, M.B.B.S.

Principal Investigator

Mayo Clinic in Rochester

Nora Bennani, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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

My PTCL has returned after standard treatment failed.

My blood cancer can be measured by tests.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

Group I: Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort Experimental Treatment 11 Interventions

PTCL patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and ruxolitinib PO on days 2-6 in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT during screening and as clinically indicated thereafter, bone marrow aspiration and biopsy, tumor or lymph node biopsy, and collection of blood, buccal cells, and urine throughout the study. Patients undergo echocardiography or MUGA scan during screening as well as optional biopsy of imaging positive area on study.

Group II: Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort Experimental Treatment 11 Interventions

BCL patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and ruxolitinib PO on days 2-6 in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT during screening and as clinically indicated thereafter, bone marrow aspiration and biopsy, tumor or lymph node biopsy, and collection of blood, buccal cells, and urine throughout the study. Patients undergo echocardiography or MUGA scan during screening as well as optional biopsy of imaging positive area on study.

Group III: Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only Experimental Treatment 13 Interventions

PTCL patients receive cemiplimab IV over 30 minutes on day -3, ipilimumab IV over 30 minutes on day -3, VSV-hIFNβ-NIS IV over 30-60 minutes on day 1, and ruxolitinib PO on days 2-6 in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT at baseline and then as clinically indicated, biopsy, and blood, buccal cell, and urine sample collection throughout the study. Patients undergo echocardiography or MUGA scan during screening as well as optional biopsy of imaging positive area on study.

Group IV: Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only Experimental Treatment 11 Interventions

\*\* Group D no longer enrolling \*\*

Group V: Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide) Experimental Treatment 10 Interventions

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

Group VI: Group B (VSV-hIFNbeta-NIS, ruxolitinib) Experimental Treatment 11 Interventions

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

Group VII: Group A (VSV-hIFNbeta-NIS, ruxolitinib) Experimental Treatment 9 Interventions

\*\* Group A no longer enrolling \*\*

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4380721/

Efficacy, safety, and survival with ruxolitinib in patients with ...

In this 3-year update of COMFORT-I, ruxolitinib treatment demonstrated durable efficacy at doses that were stable over the course of long-term follow-up.

2.

acsjournals.onlinelibrary.wiley.com

acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35489

Clinical outcomes of ruxolitinib treatment in 595 intermediate ...

Overall survival and event-free survival rates are significantly superior, whereas rate of ruxolitinib discontinuations is significantly ...

3.

novartis.com

novartis.com/news/media-releases/novartis-announces-data-showing-jakavi-ruxolitinib-more-effective-best-available-therapy-acute-graft-versus-host-disease

Novartis announces data showing Jakavi® (ruxolitinib) ...

Novartis announces data showing Jakavi® (ruxolitinib) more effective than best available therapy in acute graft-versus-host disease · Robert Zeiser, M.D., et al.

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1409002

Ruxolitinib versus Standard Therapy for the Treatment ...

A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); ...

5.

jhoonline.biomedcentral.com

jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01471-z

Ten years of treatment with ruxolitinib for myelofibrosis

Ruxolitinib has been shown to not only improve splenomegaly and the burdensome symptoms associated with MF but also to improve overall survival (OS).

6.

hcp.jakafi.com

hcp.jakafi.com/polycythemia-vera/safety

Safety Profile in Polycythemia Vera (PV)

Review the safety information of Jakafi treatment for polycythemia vera in adults who have had an inadequate response to or are intolerant of hydroxyurea ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10373260/

Ten years of treatment with ruxolitinib for myelofibrosis

This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent ...

8.

hcp.jakafi.com

hcp.jakafi.com/acute-graft-versus-host-disease/safety-adverse-events

Safety Profile of Jakafi in aGVHD

Safety results for Jakafi ® (ruxolitinib) in REACH1 · Nonhematologic Adverse Reactions Occurring in ≥15% of Patients · Selected Laboratory Abnormalities Worsening ...

9.

acsjournals.onlinelibrary.wiley.com

acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35661

Ten years of experience with ruxolitinib since approval for ...

In the ruxolitinib global safety database, NMSC incidence was 0.46 cases per 100 patient-years. No new findings were identified compared with ...

10.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2011/202192lbl.pdf

JAKAFI (Ruxolitinib) Label - accessdata.fda.gov

monitoring of safety and efficacy. Jakafi should be avoided in patients with hepatic impairment with platelet counts less than. 100 X 10. 9.