Clinical Trials /

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

NCT03017820

Description:

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]) in treating patients with multiple myeloma, acute myeloid leukemia, or T-cell 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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Anaplastic Large Cell Lymphoma
  • Multiple Myeloma
  • Mycosis Fungoides
  • Peripheral T-Cell Lymphoma, NOS
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • T-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Suspended

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma
  • 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, and T-Cell Neoplasms

Clinical Trial IDs

  • ORG STUDY ID: MC1684
  • SECONDARY ID: NCI-2017-00049
  • SECONDARY ID: MC1684
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03017820

Conditions

  • Previously Treated Myelodysplastic Syndrome
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Anaplastic Large Cell Lymphoma
  • Recurrent Angioimmunoblastic T-cell Lymphoma
  • Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma
  • Recurrent Mycosis Fungoides
  • Recurrent Plasma Cell Myeloma
  • Recurrent T-Cell Non-Hodgkin Lymphoma
  • Refractory Anaplastic Large Cell Lymphoma
  • Refractory Angioimmunoblastic T-cell Lymphoma
  • Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma
  • Refractory Mycosis Fungoides
  • Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • Refractory Plasma Cell Myeloma
  • Refractory T-Cell Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Biological TherapyBiological Response Modifier Therapy, Biological Response Modifiers Therapy, Biologics Therapies, Biotherapy, BRM therapyTreatment (VSV-IFNbeta-NIS)

Purpose

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]) in treating patients with multiple myeloma, acute myeloid leukemia, or T-cell 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of VSV-hIFNbeta-NIS in patients with
      relapsed/refractory multiple myeloma, acute myeloid leukemia, or T-cell lymphoma.

      SECONDARY OBJECTIVES:

      I. To determine the safety profile of VSV-hIFNbeta-NIS. II. To estimate clinical response
      rate in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, or T-cell
      lymphoma overall and by disease type.

      III. To estimate progression-free and overall survival in patients with relapsed/refractory
      multiple myeloma, acute myeloid leukemia, or T-cell lymphoma overall and by disease type.

      TERTIARY 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 (SPECT)/computed
      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.

      OUTLINE: This is a dose escalation study.

      Patients receive VSV-IFNbeta-NIS intravenously (IV) over 30 minutes on day 1, and then
      undergo SPECT/CT 3-5 days later.

      After completion of study treatment, patients are followed up for 28 days, and then every 3
      months for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (VSV-IFNbeta-NIS)ExperimentalPatients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, and then undergo SPECT/CT 3-5 days later.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Relapsed or refractory:
    
                   -  Multiple myeloma (MM) previously treated with an immunomodulatory drug (IMID), a
                      proteosome inhibitor and an alkylating agent; OR
    
                   -  Oligoblastic acute myeloid leukemia (AML) (=< 30% blasts), excluding acute
                      promyelocytic leukemia (PML-RARA rearranged- AML-M3); either primary refractory
                      or relapsed/refractory disease after at least two front line chemotherapy
                      regimens (note: induction and consolidation chemotherapy is considered one line
                      of therapy, additionally allogeneic stem cell transplant after induction/
                      consolidation is not considered an additional line of therapy); diagnosis based
                      on 2008 World Health Organization (WHO) criteria; OR
    
                   -  Relapsed T-cell lymphoma (TCL) or the following types: peripheral T-cell
                      lymphoma-NOS (PTCL-NOS); angioimmunoblastic T-cell lymphoma (AITL), anaplastic
                      large cell (ALCL), and cutaneous TCL (CTCL) of 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
    
              -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2 times upper
                 limit of normal (ULN)
    
              -  Creatinine =< 2.0 mg/dL
    
              -  Direct bilirubin =< 1.5 x ULN
    
              -  International normalized ratio (INR)/prothrombin time (PT) and activated partial
                 thromboplastin time (aPTT) =< 1.5 x ULN
    
              -  If baseline liver disease, Child Pugh score not exceeding class A
    
              -  Negative pregnancy test for persons of child-bearing potential
    
              -  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
    
              -  FOR MULTIPLE MYELOMA ONLY: Platelet (PLT) >= 100,000/uL
    
              -  FOR MULTIPLE MYELOMA ONLY: Hemoglobin >= 8.5 g/dl
    
              -  FOR AML ONLY: No ANC restriction
    
              -  FOR AML ONLY: PLT >= 10,000/uL (transfusion to get platelets >= 10,000 is allowed)
    
              -  FOR AML ONLY: Hemoglobin >= 7.5 g/dl
    
              -  FOR AML ONLY: Absence of uncompensated disseminated intravascular coagulation (DIC- as
                 diagnosed by standard International Society on Thrombosis and Hemostasis [ISTH]
                 criteria)
    
              -  FOR TCL ONLY: ANC >= 1,000/uL
    
              -  FOR TCL ONLY: PLT >= 100,000/uL
    
              -  FOR TCL ONLY: Hemoglobin >= 8.5 g/dl
    
              -  FOR TCL 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 x10^9/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
    
              -  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 in Rochester, Minnesota 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 history of hepatitis B or C, 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
    
                   -  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
    
              -  Acute promyelocytic leukemia (AML - M3)
    
              -  Prior allogeneic bone marrow transplant
    
              -  Multiple myeloma only: >= 15% plasmas cells or plasmacytoma > 5 cm in largest diameter
    
              -  TCL only: Any mass >= 5 cm
    
              -  AML only: current disseminated intravascular coagulopathy (DIC)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of adverse events of grade 3 or higher assessed by the Common Terminology Criteria for Adverse Events version 4.0
    Time Frame:Up to 1 year
    Safety Issue:
    Description: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.

    Secondary Outcome Measures

    Measure:Clinical response
    Time Frame:Up to 1 year
    Safety Issue:
    Description: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 AML; CR or PR for TCL) will be summarized by simple descriptive summary statistics.
    Measure:Overall survival
    Time Frame:From registration to death due to any cause, assessed up to 1 year
    Safety Issue:
    Description:The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).
    Measure:Progression-free survival
    Time Frame:From registration to disease progression or death due to any cause, assessed up to 1 year
    Safety Issue:
    Description:The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Suspended
    Lead Sponsor:Mayo Clinic

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