B-Cell Non-Hodgkin LymphomaPhase 1NCT03017820
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
A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Bone Marrow Biopsy in people with B-Cell Non-Hodgkin Lymphoma and Histiocytic and Dendritic Cell Neoplasm, run by Mayo Clinic at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-Cell Non-Hodgkin Lymphoma, Histiocytic and Dendritic Cell Neoplasm, Myelodysplastic Syndrome
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Bone Marrow Biopsy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Apr 2017to 1 Apr 2032
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years
- Relapsed or refractory disease as follows:
- 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
- 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)
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- Group F only: Expansion Cohort for B-cell lymphoma (other than Burkitt's lymphoma) with low tumor burden
- Group G only: Expansion Cohort for peripheral T cell lymphoma (PTCL) with low tumor burden
- 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 MULTIPLE MYELOMA ONLY: Measurable disease of multiple myeloma as defined by at least ONE of the following:
- Serum monoclonal protein >= 1.0 g/dL by protein electrophoresis
- >= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
- Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- FOR MULTIPLE MYELOMA ONLY: Absolute neutrophil count (ANC) >= 1000/uL (obtained =< 14 days prior to registration)
- FOR MULTIPLE MYELOMA ONLY: Platelet (PLT) >= 100,000/uL (obtained =< 14 days prior to registration)
- FOR MULTIPLE MYELOMA ONLY: Hemoglobin >= 8.5 g/dl (obtained =< 14 days prior to registration)
- FOR AML ONLY: No ANC restriction (obtained =< 14 days prior to registration)
- FOR AML ONLY: PLT >= 10,000/uL (transfusion to get platelets >= 10,000 is allowed) (obtained =< 14 days prior to registration)
- FOR AML ONLY: Hemoglobin >= 7.5 g/dl (obtained =< 14 days prior to registration)
- FOR AML ONLY: Absence of uncompensated disseminated intravascular coagulation (DIC- as diagnosed by standard International Society on Thrombosis and Hemostasis [ISTH] criteria)
- FOR TCL/BCL ONLY: ANC >= 1,000/uL (obtained =< 14 days prior to registration)
- FOR TCL/BCL ONLY: PLT >= 100,000/uL (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
- FOR HCN ONLY: ANC >= 1,000/uL obtained =< 15 days prior to registration
- FOR HCN ONLY: PLT >= 100,000/uL obtained =< 15 days prior to registration
- FOR HCN ONLY: Hemoglobin >= 8.0 g/dl obtained =< 15 days prior to registration
- FOR HCN ONLY: Measurable disease by CT or MRI: Must have at least one lesion that has a single diameter of >= 1.5 cm or tumor cells in the blood >5 x10^9/L. NOTE: Skin lesions can be used if the area is >= 1.5 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
Who cannot join
- 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
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- Experimental agent in case of 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 AML, the concurrent use of hydroxyurea to help control proliferative counts is allowed throughout the treatment protocol;
- NOTE: in TCL, patients may use topical emollients or corticosteroids, acetic acid soaks, etc. to control pruritus 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
- AML ONLY: Current disseminated intravascular coagulopathy (DIC)
- ADDITIONAL EXCLUSION CRITERIA FOR GROUP A (LOW TUMOR BURDEN) ONLY:
- Diagnosis of AML
- Multiple myeloma only: > 25% plasma cells or plasmacytoma > 5cm in largest diameter
- Lymphoma or HCN only: Any mass >5cm
- Diagnosis of Burkitt's lymphoma
- ADDITIONAL EXCLUSION CRITERIA FOR GROUP B (HIGH TUMOR BURDEN) ONLY:
- Diagnosis of AML
- Diagnosis of Burkitt's lymphoma
- ADDITIONAL EXCLUSION CRITERIA FOR GROUP C (COMBINATION WITH CYCLOPHOSPHAMIDE) ONLY:
- Diagnosis of AML
- Diagnosis of Burkitt's lymphoma
- ADDITIONAL EXCLUSION CRITERIA FOR GROUP E (COMBINATION WITH CEMIPLIMAB) ONLY:
- Diagnosis of AML
- Diagnosis of AITL
- ADDITIONAL EXCLUSION CRITERIA FOR GROUP F (BCL EXPANSION COHORT) ONLY:
- Diagnosis of Burkitt's lymphoma
- ADDITIONAL EXCLUSION CRITERIA FOR GROUP G (PTCL EXPANSION COHORT) ONLY:
- Diagnosis of cutaneous TCL
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Nora Bennani, M.D.
- Recruiting
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Nathan L. Punwani, M.D.
About this study
Official title: MC1684 Phase I Trial of Systemic Administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon, in Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, Lymphomas, or Histiocytic/Dendritic Cell Neoplasms
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the maximum tolerated dose (MTD) of recombinant vesicular stomatitis virus-expressing human interferon beta and sodium-iodide symporter (VSV-hIFNβ-NIS) in different treatment regimens (alone [Group A, F, G] in combination with ruxolitinib [Group B] and in combination with cyclophosphamide [Group C]) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms; in combination with ipilimumab and nivolumab in patients with multiple myeloma [Group D] and in combination with cemiplimab in patients with T-cell lymphoma [Group E].
SECONDARY OBJECTIVES:
- To determine the safety profile of VSV-hIFNβ-NIS (alone and in combination). II. To estimate clinical response rate of VSV-hIFNβ-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms overall and by disease type.
III. To estimate progression-free and overall survival of VSV-hIFNβ-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms overall and by disease type.
CORRELATIVE OBJECTIVES:
- To determine the time course of viral gene expression and virus elimination, and the biodistribution of virally infected cells at various times points after infection with VSV-hIFNβ-NIS using planar and single photon emission computed tomography (SPECT)/computed tomography (CT) or fluorine F 18 tetrafluoroborate (TFB)-positron emission tomography (PET) imaging.
II. To assess virus replication, viremia, viral shedding in urine and respiratory secretions, and virus persistence after systemic administration of VSV-hIFNβ-NIS.
III. To characterize the pharmacodynamics (PD) of VSV-IFNβ-NIS by way of measuring serum interferon-β and also vesicular stomatitis virus (VSV)-real time (RT)-polymerase chain reaction (PCR) of VSV-IFNβ-NIS.
IV. Assess CD8+ T cell (both general and VSV-IFNβ-NIS specific) and natural killer (NK) cell responses.
- Gene expression analysis pre- and post-virotherapy. VI. Assess presence of VSV in tumor and normal tissues subsequent to administration of intravenous (IV) VSV-IFNβ-NIS.
VII. To identify the best dose of VSV-hIFNβ-NIS in the regimen being evaluated based on activity observed in the correlative measures described above in those dose levels identified as tolerable.
OUTLINE: This is a dose escalation study of VSV-hIFNβ-NIS followed by a dose-expansion study. Patients are assigned to 1 of 7 groups.
GROUP A (CLOSED 7/30/2025): Patients receive VSV-hIFNβ-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 may also receive optional TFB IV and undergo optional PET scan, as well as optional biopsy of imaging positive area on study.
GROUP B (CLOSED 4/20/2026): Patients receive ruxolitinib PO on days -1 to 9 and VSV-hIFNβ-NIS IV over 30 minutes on day 1 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 multigated acquisition (MUGA) scan during screening as well as optional biopsy of imaging positive area on study.
GROUP C (CLOSED 7/30/2025): Patients receive ruxolitinib PO on days -1 to 9, VSV-hIFNβ-NIS IV over 30 minutes on day 1, and cyclophosphamide IV over 2 hours on day 2 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 may also receive optional TFB IV and undergo optional PET scan, as well as optional biopsy of imaging positive area on study.
GROUP D (CLOSED 7/30/2025): Patients receive nivolumab IV over 30 minutes on day -3, ipilimumab IV over 30 minutes on day -3, VSV-hIFNβ-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 may also receive optional TFB IV and undergo optional PET scan, as well as optional biopsy of imaging positive area on study.
GROUP E: Patients receive cemiplimab 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 F: Patients receive VSV-hIFNβ-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 G: Patients receive VSV-hIFNβ-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.
After completion of VSV-hIFNβ-NIS, patients are followed up on days 15 and 29, at 6 weeks, and then every 3 months until 1 year or until disease progression, whichever is longer, followed by every 6 months until a total of 2 years after registration.
- Conditions
- B-Cell Non-Hodgkin Lymphoma, Histiocytic and Dendritic Cell Neoplasm, Myelodysplastic Syndrome, Previously Treated Myelodysplastic Syndrome, Recurrent Adult Acute Myeloid Leukemia, Recurrent Anaplastic Large Cell Lymphoma
- Being tested
- Biopsy Procedure, Biospecimen Collection, Bone Marrow Biopsy, Computed Tomography, Cyclophosphamide
- Medical subject headings
- Lymphoma, B-Cell, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Mycosis Fungoides, Multiple Myeloma, Lymphoma, T-Cell, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, Bx
Undergo tumor or lymph node biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone marrow biopsy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo SPECT/CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET scan
Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide SymporterBiological
Also called Oncolytic VSV-hIFNbeta-NIS, Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter, Voyager-V1, VSV-expressing hIFNb and NIS
Given IV
Single Photon Emission Computed TomographyProcedure or surgery
Also called Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography
Undergo SPECT/CT
CemiplimabBiological
Also called 1801342-60-8, Cemiplimab RWLC, Cemiplimab-rwlc, Immunoglobulin G4
Given IV
RuxolitinibDrug
Also called (3R)-3-cyclopentyl-3-(4-(7h-pyrrolo(2,3-d)pyrimidin-4-yl)pyrazol-1-yl)propanenitrile, 941678-49-5, INCB 018424, INCB-018424
Given PO
NivolumabBiological
Also called 946414-94-4, ABP 206, BCD-263, BMS 936558
Given IV
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA scan
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo echocardiography
Bone Marrow AspirationProcedure or surgery
Also called bone marrow aspiratio
Undergo bone marrow aspiration
| Study group | Role | What they receive |
|---|---|---|
| Group A (VSV-hIFNbeta-NIS, ruxolitinib) | Experimental | Group A no longer enrolling Closed with Amendment 10, 9/18/2025. Receives: Procedure: Biopsy Procedure; 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; Drug: Ruxolitinib; Procedure: Bone Marrow Aspiration |
| Group B (VSV-hIFNbeta-NIS, ruxolitinib) | Experimental | Group B no longer enrolling Closed with Amendment 11, 5/21/2026 Receives: Procedure: Biopsy Procedure; 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; Drug: Ruxolitinib; Procedure: Echocardiography Test; Procedure: Bone Marrow Aspiration |
| Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide) | Experimental | Group C no longer enrolling Closed with Amendment 10, 9/18/2025. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Positron Emission Tomography; Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter; Procedure: Single Photon Emission Computed Tomography; Drug: Ruxolitinib; Procedure: Bone Marrow Aspiration |
| Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only | Experimental | Group D no longer enrolling Closed with Amendment 10, 9/18/2025. Receives: Procedure: Biopsy Procedure; 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; Drug: Ruxolitinib; Biological: Nivolumab; Procedure: Multigated Acquisition Scan; Procedure: Bone Marrow Aspiration |
| Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only | Experimental | PTCL patients receive cemiplimab IV over 30 minutes on day -3 and VSV-hIFNβ-NIS IV over 30-60 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients may receive ruxolitinib PO on days 2-6 for symptom management. 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. Receives: Procedure: Biopsy Procedure; 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; Drug: Ruxolitinib; Procedure: Multigated Acquisition Scan; Procedure: Echocardiography Test; Procedure: Bone Marrow Aspiration |
| Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort | Experimental | 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. Receives: Procedure: Biopsy Procedure; 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; Drug: Ruxolitinib; Procedure: Multigated Acquisition Scan; Procedure: Echocardiography Test; Procedure: Bone Marrow Aspiration |
| Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort | Experimental | 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. Receives: Procedure: Biopsy Procedure; 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; Drug: Ruxolitinib; Procedure: Multigated Acquisition Scan; Procedure: Echocardiography Test; Procedure: Bone Marrow Aspiration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Secondary outcomes (3)
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.
Measured: Up to 2 years
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).
Measured: From registration to disease progression or death due to any cause, assessed up to 2 years
Overall survival
The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).
Measured: From registration to death due to any cause, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2017 (estimated)
- Study start4 Apr 2017
- Primary completion31 Dec 2028 (estimated)
- Study completion1 Apr 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for B-Cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Nora Bennani, M.D., Principal investigator, Mayo Clinic in RochesterJoselle Cook, M.B.B.S., Principal investigator, Mayo Clinic in Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03017820
- Sponsor's protocol ID
- MC1684
- Other IDs
- R01CA262613, P50CA186781, 16-005474
- Status last verified
- Jun 2026
- First submitted
- 9 Jan 2017
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cook J, Peng KW, Witzig TE, Broski SM, Villasboas JC, Paludo J, Patnaik M, Rajkumar V, Dispenzieri A, Leung N, Buadi F, Bennani N, Ansell SM, Zhang L, Packiriswamy N, Balakrishnan B, Brunton B, Giers M, Ginos B, Dueck AC, Geyer S, Gertz MA, Warsame R, Go RS, Hayman SR, Dingli D, Kumar S, Bergsagel L, Munoz JL, Gonsalves W, Kourelis T, Muchtar E, Kapoor P, Kyle RA, Lin Y, Siddiqui M, Fonder A, Hobbs M, Hwa L, Naik S, Russell SJ, Lacy MQ. Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. Blood Adv. 2022 Jun 14;6(11):3268-3279. doi: 10.1182/bloodadvances.2021006631.
PubMed 35175355Macapagal SC, Bennani NN. Nodal peripheral T-cell lymphoma: Chemotherapy-free management, are we there yet? Blood Rev. 2023 Jul;60:101071. doi: 10.1016/j.blre.2023.101071. Epub 2023 Mar 3.
PubMed 36898933
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MC1684 Phase I Trial of Systemic Administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon, in Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, Lymphomas, or Histiocytic/Dendritic Cell Neoplasms
- ClinicalTrials.gov ID
- NCT03017820
- Acronym / sponsor ID
- MC1684
- Conditions
- B-Cell Non-Hodgkin Lymphoma, Histiocytic and Dendritic Cell Neoplasm, Myelodysplastic Syndrome, Previously Treated Myelodysplastic Syndrome, Recurrent Adult Acute Myeloid Leukemia, Recurrent Anaplastic Large Cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 99 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 4 Apr 2017 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 1 Apr 2032 (estimated)
- First posted
- 11 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To determine the maximum tolerated dose (MTD) of recombinant vesicular stomatitis virus-expressing human interferon beta and sodium-iodide symporter (VSV-hIFNβ-NIS) in different treatment regimens (alone [Group A, F, G] in combination with ruxolitinib [Group B] and in combination with cyclophosphamide [Group C]) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms; in combination with ipilimumab and nivolumab in patients with multiple myeloma [Group D] and in combination with cemiplimab in patients with T-cell lymphoma [Group E].
SECONDARY OBJECTIVES:
- To determine the safety profile of VSV-hIFNβ-NIS (alone and in combination). II. To estimate clinical response rate of VSV-hIFNβ-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms overall and by disease type.
III. To estimate progression-free and overall survival of VSV-hIFNβ-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms overall and by disease type.
CORRELATIVE OBJECTIVES:
- To determine the time course of viral gene expression and virus elimination, and the biodistribution of virally infected cells at various times points after infection with VSV-hIFNβ-NIS using planar and single photon emission computed tomography (SPECT)/computed tomography (CT) or fluorine F 18 tetrafluoroborate (TFB)-positron emission tomography (PET) imaging.
II. To assess virus replication, viremia, viral shedding in urine and respiratory secretions, and virus persistence after systemic administration of VSV-hIFNβ-NIS.
III. To characterize the pharmacodynamics (PD) of VSV-IFNβ-NIS by way of measuring serum interferon-β and also vesicular stomatitis virus (VSV)-real time (RT)-polymerase chain reaction (PCR) of VSV-IFNβ-NIS.
IV. Assess CD8+ T cell (both general and VSV-IFNβ-NIS specific) and natural killer (NK) cell responses.
- Gene expression analysis pre- and post-virotherapy. VI. Assess presence of VSV in tumor and normal tissues subsequent to administration of intravenous (IV) VSV-IFNβ-NIS.
VII. To identify the best dose of VSV-hIFNβ-NIS in the regimen being evaluated based on activity observed in the correlative measures described above in those dose levels identified as tolerable.
OUTLINE: This is a dose escalation study of VSV-hIFNβ-NIS followed by a dose-expansion study. Patients are assigned to 1 of 7 groups.
GROUP A (CLOSED 7/30/2025): Patients receive VSV-hIFNβ-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 may also receive optional TFB IV and undergo optional PET scan, as well as optional biopsy of imaging positive area on study.
GROUP B (CLOSED 4/20/2026): Patients receive ruxolitinib PO on days -1 to 9 and VSV-hIFNβ-NIS IV over 30 minutes on day 1 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 multigated acquisition (MUGA) scan during screening as well as optional biopsy of imaging positive area on study.
GROUP C (CLOSED 7/30/2025): Patients receive ruxolitinib PO on days -1 to 9, VSV-hIFNβ-NIS IV over 30 minutes on day 1, and cyclophosphamide IV over 2 hours on day 2 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 may also receive optional TFB IV and undergo optional PET scan, as well as optional biopsy of imaging positive area on study.
GROUP D (CLOSED 7/30/2025): Patients receive nivolumab IV over 30 minutes on day -3, ipilimumab IV over 30 minutes on day -3, VSV-hIFNβ-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 may also receive optional TFB IV and undergo optional PET scan, as well as optional biopsy of imaging positive area on study.
GROUP E: Patients receive cemiplimab 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 F: Patients receive VSV-hIFNβ-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 G: Patients receive VSV-hIFNβ-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.
After completion of VSV-hIFNβ-NIS, patients are followed up on days 15 and 29, at 6 weeks, and then every 3 months until 1 year or until disease progression, whichever is longer, followed by every 6 months until a total of 2 years after registration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Group A (VSV-hIFNbeta-NIS, ruxolitinib) | Experimental | Procedure: Biopsy Procedure, 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, Drug: Ruxolitinib, Procedure: Bone Marrow AspirationGroup A no longer enrolling Closed with Amendment 10, 9/18/2025. |
| Group B (VSV-hIFNbeta-NIS, ruxolitinib) | Experimental | Procedure: Biopsy Procedure, 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, Drug: Ruxolitinib, Procedure: Echocardiography Test, Procedure: Bone Marrow AspirationGroup B no longer enrolling Closed with Amendment 11, 5/21/2026 |
| Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Bone Marrow Biopsy, Procedure: Computed Tomography, Drug: Cyclophosphamide, Procedure: Positron Emission Tomography, Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter, Procedure: Single Photon Emission Computed Tomography, Drug: Ruxolitinib, Procedure: Bone Marrow AspirationGroup C no longer enrolling Closed with Amendment 10, 9/18/2025. |
| Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only | Experimental | Procedure: Biopsy Procedure, 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, Drug: Ruxolitinib, Biological: Nivolumab, Procedure: Multigated Acquisition Scan, Procedure: Bone Marrow AspirationGroup D no longer enrolling Closed with Amendment 10, 9/18/2025. |
| Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only | Experimental | Procedure: Biopsy Procedure, 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, Drug: Ruxolitinib, Procedure: Multigated Acquisition Scan, Procedure: Echocardiography Test, Procedure: Bone Marrow AspirationPTCL patients receive cemiplimab IV over 30 minutes on day -3 and VSV-hIFNβ-NIS IV over 30-60 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients may receive ruxolitinib PO on days 2-6 for symptom management. 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 F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort | Experimental | Procedure: Biopsy Procedure, 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, Drug: Ruxolitinib, Procedure: Multigated Acquisition Scan, Procedure: Echocardiography Test, Procedure: Bone Marrow AspirationBCL 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 G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort | Experimental | Procedure: Biopsy Procedure, 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, Drug: Ruxolitinib, Procedure: Multigated Acquisition Scan, Procedure: Echocardiography Test, Procedure: Bone Marrow AspirationPTCL 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- Age >= 18 years
- Relapsed or refractory disease as follows:
- 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)
Key exclusion criteria (36 listed)
- Availability of and patient acceptance of curative therapy
- Uncontrolled infection
- Active tuberculosis or hepatitis, or chronic hepatitis
- Any of the following prior therapies:
- 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])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BxUndergo tumor or lymph node biopsy | Procedure or surgery | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| Bone Marrow BiopsyAlso: Biopsy of Bone Marrow, Biopsy, Bone MarrowUndergo bone marrow biopsy | Procedure or surgery | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo SPECT/CT | Procedure or surgery | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide) |
| Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET scan | Procedure or surgery | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide SymporterAlso: Oncolytic VSV-hIFNbeta-NIS, Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter, Voyager-V1, VSV-expressing hIFNb and NISGiven IV | Biological | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| Single Photon Emission Computed TomographyAlso: Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomographyUndergo SPECT/CT | Procedure or surgery | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| CemiplimabAlso: 1801342-60-8, Cemiplimab RWLC, Cemiplimab-rwlc, Immunoglobulin G4Given IV | Biological | Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only |
| RuxolitinibAlso: (3R)-3-cyclopentyl-3-(4-(7h-pyrrolo(2,3-d)pyrimidin-4-yl)pyrazol-1-yl)propanenitrile, 941678-49-5, INCB 018424, INCB-018424Given PO | Drug | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| NivolumabAlso: 946414-94-4, ABP 206, BCD-263, BMS 936558Given IV | Biological | Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only |
| Multigated Acquisition ScanAlso: Blood Pool Scan, Equilibrium, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool ScanUndergo MUGA scan | Procedure or surgery | Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| Echocardiography TestAlso: EC, EchocardiographyUndergo echocardiography | Procedure or surgery | Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
| Bone Marrow AspirationAlso: bone marrow aspiratioUndergo bone marrow aspiration | Procedure or surgery | Group A (VSV-hIFNbeta-NIS, ruxolitinib), Group B (VSV-hIFNbeta-NIS, ruxolitinib), Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide), Group D (VSV-IFNbeta-NIS, ruxolitinib, nivolumab, ipilimumab) - MM only, Group E (VSV-IFNbeta-NIS, cemiplimab, ruxolitinib - PTCL only, Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort, Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort |
Primary outcome
Incidence of adverse events of grade 3 or higher
Time frame: Up to 2 years
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.
3 secondary outcomes
Clinical response
Time frame: Up to 2 years
Progression-free survival
Time frame: From registration to disease progression or death due to any cause, assessed up to 2 years
Overall survival
Time frame: From registration to death due to any cause, assessed up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Results publication: PubMed 35175355Cook J, Peng KW, Witzig TE, Broski SM, Villasboas JC, Paludo J, Patnaik M, Rajkumar V, Dispenzieri A, Leung N, Buadi F, Bennani N, Ansell SM, Zhang L, Packiriswamy N, Balakrishnan B, Brunton B, Giers M, Ginos B, Dueck AC, Geyer S, Gertz MA, Warsame R, Go RS, Hayman SR, Dingli D, Kumar S, Bergsagel L, Munoz JL, Gonsalves W, Kourelis T, Muchtar E, Kapoor P, Kyle RA, Lin Y, Siddiqui M, Fonder A, Hobbs M, Hwa L, Naik S, Russell SJ, Lacy MQ. Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. Blood Adv. 2022 Jun 14;6(11):3268-3279. doi: 10.1182/bloodadvances.2021006631.
- Derived from this study: PubMed 36898933Macapagal SC, Bennani NN. Nodal peripheral T-cell lymphoma: Chemotherapy-free management, are we there yet? Blood Rev. 2023 Jul;60:101071. doi: 10.1016/j.blre.2023.101071. Epub 2023 Mar 3.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nora Bennani, M.D. principal investigator
Mayo Clinic in Rochester
Joselle Cook, M.B.B.S. principal investigator
Mayo Clinic in Rochester
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Bone Marrow Biopsy in people with B-Cell Non-Hodgkin Lymphoma and Histiocytic and Dendritic Cell Neoplasm, run by Mayo Clinic at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Referral Office (855-776-0015, mayocliniccancerstudies@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events of grade 3 or higher (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03017820, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.