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
概览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 127
- 试验地点
- 4
- 主要终点
- Incidence of adverse events of grade 3 or higher
概览
简要总结
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.
详细描述
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 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 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.
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-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.
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-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: 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, 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: 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Bone Marrow Biopsy (Procedure)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Biospecimen Collection (Procedure)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Biopsy Procedure (Procedure)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Positron Emission Tomography (Procedure)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Computed Tomography (Procedure)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Biospecimen Collection (Procedure)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Biological)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Single Photon Emission Computed Tomography (Procedure)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Bone Marrow Aspiration (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Biopsy Procedure (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Biospecimen Collection (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Bone Marrow Biopsy (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Computed Tomography (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Positron Emission Tomography (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Biological)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Single Photon Emission Computed Tomography (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Multigated Acquisition Scan (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Echocardiography Test (Procedure)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Bone Marrow Aspiration (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Biopsy Procedure (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Biospecimen Collection (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Bone Marrow Biopsy (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Computed Tomography (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Positron Emission Tomography (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Biological)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Single Photon Emission Computed Tomography (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Bone Marrow Aspiration (Procedure)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Biopsy Procedure (Procedure)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Bone Marrow Biopsy (Procedure)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Computed Tomography (Procedure)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Positron Emission Tomography (Procedure)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Biological)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Single Photon Emission Computed Tomography (Procedure)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: ipilimumab (Biological)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Bone Marrow Aspiration (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Biopsy Procedure (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Biospecimen Collection (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Bone Marrow Biopsy (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Computed Tomography (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Positron Emission Tomography (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Biological)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: ipilimumab (Biological)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Multigated Acquisition Scan (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Echocardiography Test (Procedure)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Bone Marrow Aspiration (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Biopsy Procedure (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Biospecimen Collection (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Bone Marrow Biopsy (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Computed Tomography (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Positron Emission Tomography (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Biological)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Multigated Acquisition Scan (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Echocardiography Test (Procedure)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Bone Marrow Aspiration (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Biopsy Procedure (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Biospecimen Collection (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Bone Marrow Biopsy (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Computed Tomography (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Positron Emission Tomography (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter (Biological)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Multigated Acquisition Scan (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Echocardiography Test (Procedure)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Bone Marrow Aspiration (Procedure)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Cyclophosphamide (Drug)
Group C (VSV-hIFNbeta-NIS, ruxolitinib, cyclophosphamide)
** Group C no longer enrolling **
干预措施: Ruxolitinib (Drug)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Nivolumab (Biological)
Group D (VSV-IFNbeta-NIS, rruxolitinib, nivolumab, ipilimumab) - MM only
** Group D no longer enrolling **
干预措施: Ruxolitinib (Drug)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Cemiplimab (Biological)
Group E (VSV-IFNbeta-NIS, ruxolitinib, cemiplimab, ipilimumab - PTCL only
PTCL 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.
干预措施: Ruxolitinib (Drug)
Group G (VSV-IFNbeta-NIS, ruxolitinib) - PTCL Expansion Cohort
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.
干预措施: Ruxolitinib (Drug)
Group A (VSV-hIFNbeta-NIS, ruxolitinib)
** Group A no longer enrolling **
干预措施: Ruxolitinib (Drug)
Group B (VSV-hIFNbeta-NIS, ruxolitinib)
** Group B no longer enrolling **
干预措施: Ruxolitinib (Drug)
Group F (VSV-IFNbeta-NIS, ruxolitinib) - BCL Expansion Cohort
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.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Incidence of adverse events of grade 3 or higher
时间窗: 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.
次要结局
- Overall survival(From registration to death due to any cause, assessed up to 2 years)
- Progression-free survival(From registration to disease progression or death due to any cause, assessed up to 2 years)
- Clinical response(Up to 2 years)