Ignite Creation Date:
2024-05-06 @ 9:33 AM
Last Modification Date:
2024-10-26 @ 12:16 PM
Study NCT ID:
NCT03017820
Status:
RECRUITING
Last Update Posted:
2024-04-19
First Post:
2017-01-09
Brief Title:
VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma Acute Myeloid Leukemia or Lymphoma
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
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 HistiocyticDendritic Cell Neoplasms
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus carrying the human NIS and IFN beta genes VSV-hIFNbeta-sodium iodide symporter NIS with or without cyclophosphamide or ipilimumab and nivolumab or cemiplimab in treating patients with multiple myeloma acute myeloid leukemia AML or lymphoma that has come back or does not respond to treatment A virus called VSV-hIFNbeta-NIS which has been changed in a certain way may be able to kill cancer cells without damaging normal cells Cyclophosphamide is in a class of medications called alkylating agents It works by damaging the cells DNA and may kill cancer cells It may also lower the bodys immune response Immunotherapy with ipilmumab and nivolumab or cemiplimab may induce changes in bodys immune system and may interfere with the ability of tumor cells to grow and spread Giving VSV-hIFNbeta-NIS and ruxolitinib phosphate may work better at treating multiple myeloma acute myeloid leukemia and T-cell lymphoma
Detailed Description:
PRIMARY OBJECTIVE
I To determine the maximum tolerated dose MTD of 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 relapsedrefractory multiple myeloma acute myeloid leukemia T and B-cell lymphoma or histiocyticdendritic cell neoplasms in combination with ipilimumab and nivolumab in patients with multiple myeloma Group D and in combination with ipilimumab and cemiplimab in patients with T-cell lymphoma Group E
SECONDARY OBJECTIVES
I To determine the safety profile of VSV-hIFNbeta-NIS alone and in combination
II To estimate clinical response rate of VSV-hIFNbeta-NIS alone and in combination in patients with relapsedrefractory multiple myeloma acute myeloid leukemia T-cell and B-cell lymphoma or histiocyticdendritic cell neoplasms overall and by disease type
III To estimate progression-free and overall survival of VSV-hIFNbeta-NIS alone and in combination in patients with relapsedrefractory multiple myeloma acute myeloid leukemia T and B-cell lymphoma or histiocyticdendritic cell neoplasms overall and by disease type
CORRELATIVE OBJECTIVES
I 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-hIFNbeta-NIS using planar and single photon emission computed tomography SPECTcomputed tomography CT imaging
II To assess virus replication viremia viral shedding in urine and respiratory secretions and virus persistence after systemic administration of VSV-hIFNbeta-NIS
III To characterize the pharmacodynamics PD of VSV-IFNbeta-NIS by way of measuring serum interferon-beta and also vesicular stomatitis virus VSV-real time RT-polymerase chain reaction PCR of VSV-IFNbeta-NIS
IV Assess CD8 T cell both general and VSV-IFNbeta-NIS specific and natural killer NK cell responses
V Gene expression analysis pre- and post-virotherapy VI Assess presence of VSV in tumor and normal tissues subsequent to administration of intravenous IV VSV-IFNbeta-NIS
VII To identify the best dose of VSV-hIFNbeta-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-IFNbeta-NIS Patients are assigned to 1 of 3 groups
GROUP A Patients receive VSV-IFNbeta-NIS intravenously IV over 30 minutes on day 1 in the absence of disease progression or unacceptable toxicity
GROUP B NO LONGER ENROLLING Patients receive VSV-IFNbeta-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
GROUP C NO LONGER ENROLLING Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 ipilimumab IV over 30 minutes on day -3 and nivolumab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity
GROUP D Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 ipilimumab IV over 30 minutes on day -3 and cemiplimab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity
Patients undergo computed tomography CT scan position emission tomography PET scan throughout the study Patients may undergo tumor biopsy bone marrow biopsy and blood sample collection throughout the study
After completion of study treatment patients are followed up for 28 days and then every 3 months for up to 1 year or until progressive disease then every 6 months for 1 year
I To determine the maximum tolerated dose MTD of 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 relapsedrefractory multiple myeloma acute myeloid leukemia T and B-cell lymphoma or histiocyticdendritic cell neoplasms in combination with ipilimumab and nivolumab in patients with multiple myeloma Group D and in combination with ipilimumab and cemiplimab in patients with T-cell lymphoma Group E
SECONDARY OBJECTIVES
I To determine the safety profile of VSV-hIFNbeta-NIS alone and in combination
II To estimate clinical response rate of VSV-hIFNbeta-NIS alone and in combination in patients with relapsedrefractory multiple myeloma acute myeloid leukemia T-cell and B-cell lymphoma or histiocyticdendritic cell neoplasms overall and by disease type
III To estimate progression-free and overall survival of VSV-hIFNbeta-NIS alone and in combination in patients with relapsedrefractory multiple myeloma acute myeloid leukemia T and B-cell lymphoma or histiocyticdendritic cell neoplasms overall and by disease type
CORRELATIVE OBJECTIVES
I 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-hIFNbeta-NIS using planar and single photon emission computed tomography SPECTcomputed tomography CT imaging
II To assess virus replication viremia viral shedding in urine and respiratory secretions and virus persistence after systemic administration of VSV-hIFNbeta-NIS
III To characterize the pharmacodynamics PD of VSV-IFNbeta-NIS by way of measuring serum interferon-beta and also vesicular stomatitis virus VSV-real time RT-polymerase chain reaction PCR of VSV-IFNbeta-NIS
IV Assess CD8 T cell both general and VSV-IFNbeta-NIS specific and natural killer NK cell responses
V Gene expression analysis pre- and post-virotherapy VI Assess presence of VSV in tumor and normal tissues subsequent to administration of intravenous IV VSV-IFNbeta-NIS
VII To identify the best dose of VSV-hIFNbeta-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-IFNbeta-NIS Patients are assigned to 1 of 3 groups
GROUP A Patients receive VSV-IFNbeta-NIS intravenously IV over 30 minutes on day 1 in the absence of disease progression or unacceptable toxicity
GROUP B NO LONGER ENROLLING Patients receive VSV-IFNbeta-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
GROUP C NO LONGER ENROLLING Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 ipilimumab IV over 30 minutes on day -3 and nivolumab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity
GROUP D Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 ipilimumab IV over 30 minutes on day -3 and cemiplimab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity
Patients undergo computed tomography CT scan position emission tomography PET scan throughout the study Patients may undergo tumor biopsy bone marrow biopsy and blood sample collection throughout the study
After completion of study treatment patients are followed up for 28 days and then every 3 months for up to 1 year or until progressive disease then every 6 months for 1 year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01CA262613 | NIH | Mayo Clinic Institutional Review Board | httpsreporternihgovquickSearchR01CA262613 |
| NCI-2017-00049 | REGISTRY | None | None |
| MC1684 | OTHER | None | None |
| P30CA015083 | NIH | None | None |
| 16-005474 | OTHER | None | None |