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
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
4 other identifiers
interventional
127
1 country
2
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2017
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 9, 2017
CompletedFirst Posted
Study publicly available on registry
January 11, 2017
CompletedStudy Start
First participant enrolled
April 4, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2032
April 13, 2026
April 1, 2026
11.8 years
January 9, 2017
April 7, 2026
Conditions
Outcome Measures
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.
Up to 2 years
Secondary Outcomes (3)
Clinical response
Up to 2 years
Progression-free survival
From registration to disease progression or death due to any cause, assessed up to 2 years
Overall survival
From registration to death due to any cause, assessed up to 2 years
Other Outcomes (2)
Biodistribution and kinetics of virus spread
Up to 2 years
NIS gene expression in tumor samples
Up to 2 years
Study Arms (7)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
EXPERIMENTAL\*\* Group A no longer enrolling \*\*
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
EXPERIMENTAL\*\* Group B no longer enrolling \*\*
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
EXPERIMENTAL\*\* Group C no longer enrolling \*\*
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
EXPERIMENTAL\*\* Group D no longer enrolling \*\*
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
EXPERIMENTALPTCL 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 F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
EXPERIMENTALBCL 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
EXPERIMENTALPTCL 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.
Interventions
Undergo tumor or lymph node biopsy
Given IV
Undergo PET scan
Undergo SPECT/CT
Given IV
Undergo echocardiography
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo SPECT/CT
Given IV
Given IV
Given PO
Given IV
Undergo MUGA scan
Undergo bone marrow aspiration
Eligibility Criteria
You may qualify if:
- 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)
- 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:
- +24 more criteria
You may not qualify if:
- 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
- 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 pruritis 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
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Publications (2)
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.
PMID: 35175355RESULTMacapagal 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.
PMID: 36898933DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nora Bennani, M.D.
Mayo Clinic in Rochester
- PRINCIPAL INVESTIGATOR
Joselle Cook, M.B.B.S.
Mayo Clinic in Rochester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 9, 2017
First Posted
January 11, 2017
Study Start
April 4, 2017
Primary Completion (Estimated)
December 31, 2028
Study Completion (Estimated)
April 1, 2032
Last Updated
April 13, 2026
Record last verified: 2026-04