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Trial record 1 of 1 for:    NCT03017820
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VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03017820
Recruitment Status : Suspended (Cohort A temporarily closed per study design)
First Posted : January 11, 2017
Last Update Posted : November 2, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

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]) 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.

Condition or disease Intervention/treatment Phase
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 Biological: Biological Therapy Procedure: Computed Tomography Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Single Photon Emission Computed Tomography Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 4, 2017
Estimated Primary Completion Date : January 15, 2021
Estimated Study Completion Date : January 15, 2021


Arm Intervention/treatment
Experimental: Treatment (VSV-IFNbeta-NIS)
Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, and then undergo SPECT/CT 3-5 days later.
Biological: Biological Therapy
Given VSV-hIFNbeta-NIS IV
Other Names:
  • Biological Response Modifier Therapy
  • Biological Response Modifiers Therapy
  • Biologics Therapies
  • Biotherapy
  • BRM therapy

Procedure: Computed Tomography
Undergo SPECT/CT
Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT SCAN
  • tomography

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Procedure: Single Photon Emission Computed Tomography
Undergo SPECT/CT
Other Names:
  • Medical Imaging, Single Photon Emission Computed Tomography
  • Single Photon Emission Tomography
  • single-photon emission computed tomography
  • SPECT
  • SPECT imaging
  • SPECT SCAN
  • SPET
  • tomography, emission computed, single photon
  • Tomography, Emission-Computed, Single-Photon




Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Clinical response [ Time Frame: Up to 1 year ]
    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.

  2. Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 1 year ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).

  3. Progression-free survival [ Time Frame: From registration to disease progression or death due to any cause, assessed up to 1 year ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).


Other Outcome Measures:
  1. Biodistribution and kinetics of virus spread assessed by SPECT/CT imaging [ Time Frame: Up to 1 year ]
    Descriptive statistics and scatterplots will form the basis of presentation of these variables. Correlations between the laboratory values and other outcome measures will be carried out by standard parametric and non-parametric tests (e.g., Pearson's and Spearman's rho). Will be correlated with tumor distribution.

  2. NIS gene expression in tumor samples assessed by SPECT/CT imaging [ Time Frame: Up to 1 year ]
    Descriptive statistics and scatterplots will form the basis of presentation of these variables. Correlations between the laboratory values and other outcome measures will be carried out by standard parametric and non-parametric tests (e.g., Pearson's and Spearman's rho). Will be correlated with tumor distribution.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03017820


Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Martha Lacy Mayo Clinic

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT03017820     History of Changes
Other Study ID Numbers: MC1684
NCI-2017-00049 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1684 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: January 11, 2017    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Mycoses
Mycosis Fungoides
Lymphoma, T-Cell, Cutaneous
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases