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A Vaccine (VSV-IFNβ-NIS) in Combination with Cemiplimab and Ipilimumab for the Treatment of Recurrent Peripheral T-cell Lymphoma
Trial Status: active
This phase I trial studies the side effects and best dose of a vaccine (VSV-IFNβ-NIS) in combination with cemiplimab and ipilimumab in treating patients with peripheral T-cell lymphoma that has come back after a period of improvement. 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. Immunotherapy with monoclonal antibodies, such as cemiplimab and ipilimumab, 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 in combination with cemiplimab and ipilimumab may be safe and effective in treating patients with recurrent peripheral T-cell lymphoma.
Inclusion Criteria
Age ≥ 18 years
Relapsed or refractory disease as follows:
* Group E only: Relapsed peripheral T-cell lymphoma (PTCL) of the following histologies: peripheral T-cell lymphoma-not otherwise specified (NOS) (PTCL-NOS); anaplastic large cell (ALCL), and mycosis fungoides (MF)
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/prothrombin time (INR/PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy, then INR or aPTT is within target range of therapy (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 T-cell lymphoma (TCL)/B-cell lymphoma (BCL) only:
* The following laboratory values obtained ≤ 14 days prior to registration
** Absolute neutrophil count (ANC) ≥ 1,000/µL
** Platelets (PLT) ≥ 100,000/µL
** Hemoglobin ≥ 8.0 g/dl
* Measurable disease by CT or magnetic resonance imaging (MRI): Must have at least one lesion that has a single diameter of ≥ 1.5 cm or tumor cells in the blood > 5 x 10^9/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
Exclusion Criteria
Availability of and patient acceptance of curative therapy
Uncontrolled infection
Active tuberculosis or hepatitis, or chronic hepatitis
Any of the following prior therapies:
* Chemotherapy (immunomodulatory imide drug [IMIDs], alkylating agents, proteosome inhibitors) ≤ 2 weeks prior to registration
* Immunotherapy (monoclonal antibodies) ≤ 4 weeks prior to registration
* Experimental agent in case of acute myeloid leukemia (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)
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 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 the genotoxic, mutagenic, and teratogenic effects of which 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
Additional exclusion for Group E (combination with ipilimumab and nivolumab or cemiplimab) ONLY:
* Diagnosis of AML
* Diagnosis of angioimmunoblastic T-cell lymphoma (AITL)
* Hypersensitivity to ipilimumab or its excipients
Additional locations may be listed on ClinicalTrials.gov for NCT06508463.
Locations matching your search criteria
United States
Arizona
Scottsdale
Mayo Clinic in Arizona
Status: Active
Contact: Javier L. Munoz
Phone: 480-301-8000
Minnesota
Rochester
Mayo Clinic in Rochester
Status: Active
Contact: Nabila Nora Bennani
Phone: 507-284-2511
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) of recombinant vesicular stomatitis virus-expressing human interferon beta and sodium-iodide symporter (VSV-hIFNβ-NIS) in combination with ipilimumab and cemiplimab in patients with T-cell lymphoma (Group E).
SECONDARY OBJECTIVES:
I. 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.
OUTLINE:
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 orally (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, as well as biopsy, and blood, buccal cell, and urine sample collection throughout the study. Patients also undergo echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) during screening.
After completion of VSV-hIFNβ-NIS, patients are followed up on days 8, 10, 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.
