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Trial record 2 of 3 for:    Edmonston Strain of Measles Virus,

Vaccine Therapy With or Without Cyclophosphamide in Treating Patients With Recurrent or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00450814
Recruitment Status : Recruiting
First Posted : March 22, 2007
Last Update Posted : January 27, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

March 20, 2007
March 22, 2007
January 27, 2017
January 2007
December 2017   (Final data collection date for primary outcome measure)
  • MTD of oncolytic measles virus encoding thyroidal sodium iodide symporter when administered with or without cyclophosphamide (Phase I) [ Time Frame: 6 weeks ]
    Defined as the highest safely-tolerated dose level where at most 1 out of six patients experiences dose-limiting toxicity (DLT) or no DLT observed out of 3 patients at the maximum dose level, provided no DLT is observed at any of the previous dose levels.
  • Proportion of confirmed response, defined as a partial response (PR) or better (Phase II) [ Time Frame: Up to 1 year ]
    Confirmed response will be evaluated using all cycles. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the method of Duffy and Santner.
  • Toxicity
  • Maximum tolerated dose
Complete list of historical versions of study NCT00450814 on ClinicalTrials.gov Archive Site
  • Failure-free survival (Phase II) [ Time Frame: Time from registration to the earliest of progressive disease, alternative treatment for myeloma, or death due to any cause, assessed up to 1 year ]
    The distribution of failure-free survival will be estimated using the method of Kaplan-Meier.
  • Incidence of adverse events, graded according to the NCI CTCAE v3.0 (Phase II) [ 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. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
  • Incidence of toxicity incidents as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0) (Phase I) [ Time Frame: Up to 1 year ]
    The number and severity of toxicity incidents will indicate the level of myeloma. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
  • Number of clinical responses (Phase I) [ Time Frame: Up to 1 year ]
    The number of responses (CR, VGPR, PR, or minimal response [MR]) will be summarized by simple descriptive summary statistics across all patients in each group as well as by dose level.
  • Overall survival (Phase II) [ Time Frame: Time 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.
  • Progression-free rate (Phase II) [ Time Frame: At 1 year ]
  • Progression-free rate (Phase II) [ Time Frame: At 2 years ]
  • Time to progression (Phase II) [ Time Frame: Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.
  • Time until any treatment related toxicity (Phase I) [ Time Frame: Up to 1 year ]
    Tolerability will be explored in an ancillary manner through time-related variables, including time until any treatment related toxicity. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals. The effect of dose and ancillary dichotomized covariates such as age will be explored using log-rank testing involving one covariate at a time.
  • Time until hematologic nadirs (white blood cells, ANC, platelets) (Phase I) [ Time Frame: Up to 1 year ]
    Tolerability will be explored in an ancillary manner through time-related variables, including time until hematologic nadirs. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals. The effect of dose and ancillary dichotomized covariates such as age will be explored using log-rank testing involving one covariate at a time.
  • Time until treatment related grade 3+ toxicity (Phase I) [ Time Frame: Up to 1 year ]
    Tolerability will be explored in an ancillary manner through time-related variables, including time until treatment related grade 3+ toxicity. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals. The effect of dose and ancillary dichotomized covariates such as age will be explored using log-rank testing involving one covariate at a time.
  • Hematologic response (complete response, very good partial response, minimal response)
  • Viral replication and shedding
  • Biodistribution and kinetics of viral spread and NIS gene expression
  • Tolerability
  • Biodistribution and kinetics of virus spread [ Time Frame: Up to 6 weeks ]
    Will be correlated with tumor distribution. 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).
  • NIS gene expression in vivo [ Time Frame: Up to 6 weeks ]
    Will be correlated with tumor distribution. 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).
  • Radiation dose [ Time Frame: Up to 6 weeks ]
    The radiation dose that could be delivered to the bone marrow as well as critical organs such as the liver, lungs and kidneys if iodine-131 were to be administered using MIRDOSE 3 program will be estimated. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data results across dose levels will be carried out only as a hypothesis generating exercise.
  • Viral replication [ Time Frame: Up to 6 weeks ]
    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).
  • Viral shedding [ Time Frame: Up to 6 weeks ]
    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).
Not Provided
 
Vaccine Therapy With or Without Cyclophosphamide in Treating Patients With Recurrent or Refractory Multiple Myeloma
Phase I/II Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, With or Without Cyclophosphamide, in Patients With Recurrent or Refractory Multiple Myeloma
This phase I/II trial studies the side effects and best dose of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients with multiple myeloma that has come back (recurrent) or has not responded to previous treatment (refractory). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vaccine therapy together with cyclophosphamide may be a better treatment for multiple myeloma.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the confirmed response rate of MV-NIS alone in patients with relapsed or refractory multiple myeloma who have exhausted all therapeutic options. (Phase II, Cohort A) III. To evaluate the confirmed response rate of MV-NIS alone in patients who are relapsing from very good partial response (VGPR) or complete response (CR) and have not received myeloma directed therapy for at least 12 weeks. (Phase II, Cohort B)

SECONDARY OBJECTIVES:

I. To determine the safety and toxicity of the intravenous administration of an Edmonston vaccine strain measles virus engineered to express the thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the confirmed response rate of MV-NIS in patients with relapsed or refractory multiple myeloma. (Phase I) III. To further evaluate the adverse event profile of MV-NIS in patients with relapsed or refractory multiple myeloma. (Phase II) IV. To evaluate overall survival, failure-free survival and progression-free survival. (Phase II)

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 MV-NIS (when administered with or without cyclophosphamide) using 99m-technetium (Tc) gamma camera imaging. (Phase I and II) II. To assess virus replication, viremia, viral shedding in urine and respiratory secretions, and virus persistence after systemic administration of MV-NIS (when administered with or without cyclophosphamide). (Phase I and II) III. To monitor humoral responses to the injected virus. (Phase I and II) IV. To explore the anti-myeloma efficacy (i.e. clinical response rate, time to progression, progression free survival, duration of response) of the virus using standard myeloma response criteria as well as immunoglobulin free light chain measurements. (Phase I and II)

OUTLINE: This is a phase I, dose-escalation study of MV-NIS followed by a phase II study. Patients are assigned to 1 of 2 treatment arms (Stage 1 or Stage 2) in phase I and assigned to Stage 1 in phase II.

STAGE 1 (MV-NIS ALONE, closed to accrual on 12/17/2009 and reopened 10/13/2011): Patients receive MV-NIS intravenously (IV) over 1 hour on day 1.

STAGE 2 (MV-NIS AND CYCLOPHOSPHAMIDE, temporarily closed to accrual on 10/13/11): Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later.

After completion of study treatment, patients are followed up at 6 weeks, 12 weeks, and then every 3 months for 1 year.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen
    • Claphene
    • CP monohydrate
    • CTX
    • CYCLO-cell
    • Cycloblastin
    • Cycloblastine
    • Cyclophospham
    • Cyclophosphamid monohydrate
    • Cyclophosphamidum
    • Cyclophosphan
    • Cyclophosphane
    • Cyclophosphanum
    • Cyclostin
    • Cyclostine
    • Cytophosphan
    • Cytophosphane
    • Cytoxan
    • Fosfaseron
    • Genoxal
    • Genuxal
    • Ledoxina
    • Mitoxan
    • Neosar
    • Revimmune
    • Syklofosfamid
    • WR- 138719
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    Given IV
    Other Name: MV-NIS
  • Other: Pharmacological Study
    Correlative studies
  • Experimental: Stage 1 (MV-NIS alone)
    Patients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011)
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    • Other: Pharmacological Study
  • Experimental: Stage 2 (MV-NIS and cyclophosphamide)
    Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11)
    Interventions:
    • Drug: Cyclophosphamide
    • Other: Laboratory Biomarker Analysis
    • Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    • Other: Pharmacological Study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
85
December 2017
December 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Myeloma relapsing from partial response or better

    • Patients relapsing > 18 months from transplant if not on maintenance, or
    • If off maintenance, discontinued at least 6 months ago, or
    • If relapsing on maintenance, at least 3 years from transplant, or
    • Off prior myeloma therapy at least 6 months ago
    • Sufficient tumor burden that is assessable for response

      • Serum M-spike >= 0.5 g/dL, or
      • If immunoglobulin A (IgA) myeloma, IgA > 1000 mg/dL, or
      • Difference between involved and uninvolved free light chain (dFLC) > 10 mg/dL, or
      • Urine M-spike >= 200 mg/24 hours, or
      • Bone marrow plasmacytosis >= 10%, or
      • Plasmacytoma >= 2 cm in diameter
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelets (PLT) >= 50,000/uL
  • Hemoglobin >= 8.5 g/dl
  • Aspartate aminotransferase (AST) =< 2 times upper limit of normal
  • Creatinine < 2 times upper limit of normal
  • Total bilirubin =< 1.5 x upper limit of normal
  • International normalized ratio (INR) =< 1.4 x ULN at the time of registration
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic Rochester for follow-up
  • Life expectancy >= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Willingness to provide all biological specimens as required by the protocol
  • Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only
  • Measles antibody titer on the BioRad Multiplex assay less than or equal to 1.0

Exclusion Criteria:

  • Uncontrolled infection
  • Active tuberculosis
  • Any myeloma directed therapy within 12 weeks of registration including plasmapheresis or transfusion
  • New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review
  • Active central nervous system (CNS) disorder or seizure disorder
  • Human immunodeficiency virus (HIV) positive test result
  • 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)
  • Previous exposure to heat inactivated measles virus vaccine (this vaccine was given to some individuals between the years of 1963-1967)
  • Any of the following:

    • 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
  • Evidence of chronic or acute graft versus host disease or on-going treatment for graft versus host disease from prior allogeneic stem cell transplantation
  • Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
United States
 
 
NCT00450814
MC038C
NCI-2009-01194 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC038C ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
R01CA125614 ( U.S. NIH Grant/Contract )
R01CA168719 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Angela Dispenzieri Mayo Clinic
Mayo Clinic
August 2016

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