Health TrialsbyHealthPanel

A Vaccine (VSV-hIFNβ-NIS) With or Without Cyclophosphamide and Combinations of Ipilimumab, Nivolumab, and Cemiplimab in Treating Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma

ConditionsB-Cell Non-Hodgkin LymphomaHistiocytic and Dendritic Cell NeoplasmMyelodysplastic SyndromePreviously Treated Myelodysplastic SyndromeRecurrent Adult Acute Myeloid LeukemiaRecurrent Anaplastic Large Cell LymphomaRecurrent Angioimmunoblastic T-Cell LymphomaRecurrent Mycosis FungoidesRecurrent Plasma Cell MyelomaRecurrent Primary Cutaneous T-Cell Non-Hodgkin LymphomaRecurrent T-Cell Non-Hodgkin LymphomaRefractory Acute Myeloid LeukemiaRefractory Anaplastic Large Cell LymphomaRefractory Angioimmunoblastic T-Cell LymphomaRefractory Mycosis FungoidesRefractory Peripheral T-Cell Lymphoma, Not Otherwise SpecifiedRefractory Plasma Cell MyelomaRefractory Primary Cutaneous T-Cell Non-Hodgkin LymphomaRefractory T-Cell Non-Hodgkin Lymphoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

About this trial

This phase I trial studies the best dose and side effects of the VSV-hIFNβ-NIS vaccine with or without cyclophosphamide and combinations of ipilimumab, nivolumab, and cemiplimab in treating patients with multiple myeloma, acute myeloid leukemia or lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). VSV-IFNβ-NIS is a modified version of the vesicular stomatitis virus (also called VSV). This virus can cause infection and when it does it typically infects pigs, cattle, or horses but not humans. The VSV used in this study has been altered by having two extra genes (pieces of DNA) added. The first gene makes a protein called NIS that is inserted into the VSV. NIS is normally found in the thyroid gland (a small gland in the neck) and helps the body concentrate iodine. Having this additional gene will make it possible to track where the virus goes in the body (which organs). The second addition is a gene for human interferon beta (β) or hIFNβ. Interferon is a natural anti-viral protein, intended to protect normal healthy cells from becoming infected with the virus. VSV is very sensitive to the effect of interferon. Many tumor cells have lost the capacity to either produce or respond to interferon. Thus, interferon production by tumor cells infected with VSV-IFNβ-NIS will protect normal cells but not the tumor cells. The VSV with these two extra pieces is referred to as VSV-IFNβ-NIS. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Immunotherapy with monoclonal antibodies, such as ipilimumab, nivolumab, and cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving VSV-IFNβ-NIS with or without cyclophosphamide and combinations of ipilimumab, nivolumab, and cemiplimab may be safe and effective in treating patients with recurrent peripheral T-cell lymphoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age >= 18 years

Groups A, B, C or D: Multiple myeloma (MM) previously treated with an immunomodulatory imide drug (IMID), a proteosome inhibitor, and an alkylating agent

All Groups except D: Relapsed peripheral T-cell lymphoma (PTCL) of the following histologies: peripheral T-cell lymphoma-NOS (PTCL-NOS); angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell (ALCL), and mycosis fungoides (MF). Patients should have failed standard therapy and in the case of PTCL-NOS, AITL, and ALCL either have failed or be ineligible for high-dose therapy with autologous stem cell transplant

Group B and C only: B-cell lymphoma (other than Burkitt's lymphoma), or histiocytic/dendritic cell neoplasms (HCN) at any stage

Disqualifiers

Availability of and patient acceptance of curative therapy

Uncontrolled infection

Active tuberculosis or hepatitis, or chronic hepatitis

Chemotherapy (IMIDs, alkylating agents, proteosome inhibitors) =< 2 weeks prior to registration

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tumor or lymph node biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Computed Tomography

    Procedure/Surgery

    Undergo SPECT/CT

  • Cyclophosphamide

    Drug

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET scan

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

    Biological/Vaccine

    Given IV

  • Single Photon Emission Computed Tomography

    Procedure/Surgery

    Undergo SPECT/CT

  • Cemiplimab

    Biological/Vaccine

    Given IV

  • Ruxolitinib

    Drug

    Given PO

  • Nivolumab

    Biological/Vaccine

    Given IV

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA scan

  • Echocardiography Test

    Procedure/Surgery

    Undergo echocardiography

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

Treatment groups

99 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: Group A (VSV-hIFNbeta-NIS, ruxolitinib)Experimental treatment 9 interventions
Group B: Group B (VSV-hIFNbeta-NIS, ruxolitinib)Experimental treatment 10 interventions
Group C: Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)Experimental treatment 10 interventions
Group D: Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM onlyExperimental treatment 11 interventions
Group E: Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL onlyExperimental treatment 12 interventions
Group F: Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion CohortExperimental treatment 11 interventions
Group G: Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion CohortExperimental treatment 11 interventions

Trial outcomes

Primary outcomes

1

Incidence of adverse events of grade 3 or higher

Assessed by the Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns (by cohort and overall). Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The rate of grade 3 or higher non-hematologic adverse events, and the rate of grade 4 or higher adverse event (hematologic and non-hematologic) will be computed each with a 95% exact binomial confidence.

Time frame
Up to 2 years

Secondary outcomes

1

Clinical response

The number of responses (complete response \[CR\], very good partial response, partial response \[PR\], or minimal response for multiple myeloma; CR, CR with incomplete recovery, cytogenetic complete response, PR for acute myeloid leukemia \[AML\]; CR or PR for T-cell lymphoma \[TCL\]) will be summarized by simple descriptive summary statistics.

Time frame
Up to 2 years
2

Progression-free survival

The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).

Time frame
From registration to disease progression or death due to any cause, assessed up to 2 years
3

Overall survival

The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).

Time frame
From registration to death due to any cause, assessed up to 2 years

Other outcomes

1

Biodistribution and kinetics of virus spread

Assessed by single photon emission computed tomography (SPECT)/computed tomography (CT) imaging. Descriptive statistics and scatterplots will form the basis of presentation of these variables. Correlations between the laboratory values and other outcome measures will be carried out by standard parametric and non-parametric tests (e.g., Pearson's and Spearman's rho). Will be correlated with tumor distribution.

Time frame
Up to 2 years
2

NIS gene expression in tumor samples

Assessed by single photon emission computed tomography (SPECT)/computed tomography (CT) imaging. Descriptive statistics and scatterplots will form the basis of presentation of these variables. Correlations between the laboratory values and other outcome measures will be carried out by standard parametric and non-parametric tests (e.g., Pearson's and Spearman's rho). Will be correlated with tumor distribution.

Time frame
Up to 2 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
Apply now