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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 : Recruiting
First Posted : January 11, 2017
Last Update Posted : June 27, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE January 9, 2017
First Posted Date  ICMJE January 11, 2017
Last Update Posted Date June 27, 2019
Actual Study Start Date  ICMJE April 4, 2017
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03017820 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
  • 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.
  • 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).
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 9, 2017)
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Biological: Biological Therapy
  • Procedure: Computed Tomography
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Procedure: Single Photon Emission Computed Tomography
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 9, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 15, 2021
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03017820
Other Study ID Numbers  ICMJE MC1684
NCI-2017-00049 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1684 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Martha Lacy Mayo Clinic
PRS Account Mayo Clinic
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP