CClinicalTrials.gg
Sign In
CompletedNCT00450814Updated Dec 16, 2019Results posted

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

A Phase 1/2 interventional study of Cyclophosphamide and Laboratory Biomarker Analysis in Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-12-16.

Sponsored by Mayo Clinic · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Registered 3 months after the study started (first participant enrolled Nov 2006, registered Mar 2007).
Phase
Phase 1/2
Study type
Interventional
Enrollment
48
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 48 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.

Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
48 participants (actual)

Study arms

  • 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)

    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)

    Drug: Cyclophosphamide · Other: Laboratory Biomarker Analysis · Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter · Other: Pharmacological Study

Interventions

  • DrugCyclophosphamide

    Given IV

    Also known as: (-)-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

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • BiologicalOncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter

    Given IV

    Also known as: MV-NIS

  • OtherPharmacological Study

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)

    The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of patients reporting a dose-limiting event are reported.

    Time frame: 6 weeks

  2. Maximum Tolerated Dose (MTD) (Phase I)

    The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The MTD is reported below.

    Time frame: 6 weeks

  3. Proportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II)

    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. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Time frame: Up to 1 year

Secondary outcomes

  1. Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase I)

    The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below by stage for Phase I patients.

    Time frame: Up to 1 year

  2. Number of Patients With Clinical Responses (Phase I)

    The number of patients with clinical responses (CR, VGPR, PR, or minimal response \[MR\]) will be summarized by stage.

    Time frame: Up to 1 year

  3. Overall Survival (Phase II)

    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.

    Time frame: Time from registration to death due to any cause, assessed up to 1 year

  4. Time to Progression (TTP) (Phase II)

    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 frame: Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year

  5. Progression-free Survival (Phase II)

    1-year progression-free survival (PFS1). Evidence of local recurrence, distant metastasis, or death from any cause within 1 year counted as events in the time-to-event Kaplan-Meier analysis of progression-free survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Time frame: At 1 year

  6. Progression-free Survival (Phase II)

    2-year progression-free survival (PFS2). Evidence of local recurrence, distant metastasis, or death from any cause within 2 years counted as events in the time-to-event Kaplan-Meier analysis of progression-free survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Time frame: At 2 years

  7. Progression-free Survival (Phase II)

    Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Time frame: Up to 5 years

  8. Failure-free Survival (Phase II)

    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.

    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

  9. Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase II)

    The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below for Phase II patients.

    Time frame: Up to 1 year

Other outcomes

  1. Time Until Any Treatment Related Toxicity (Phase I)

    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 frame: Up to 1 year

  2. Time Until Hematologic Nadirs (White Blood Cells, ANC, Platelets) (Phase I)

    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 frame: Up to 1 year

  3. Time Until Treatment Related Grade 3+ Toxicity (Phase I)

    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.

    Time frame: Up to 1 year

  4. Biodistribution and Kinetics of Virus Spread

    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).

    Time frame: Up to 6 weeks

  5. NIS Gene Expression in Vivo

    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).

    Time frame: Up to 6 weeks

  6. Radiation Dose

    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.

    Time frame: Up to 6 weeks

  7. Viral Replication

    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).

    Time frame: Up to 6 weeks

  8. Viral Shedding

    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).

    Time frame: Up to 6 weeks

07

Results

Posted Dec 16, 2019

Participant flow

Participant flow — Overall Study
MilestonePhase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3Phase II (Acetaminophen + Benadryl + MV-NIS) Cohort APhase II (Acetaminophen + Benadryl + MV-NIS) Cohort B
Started333447332124
Completed333336332114
Not completed00011100010
Withdrew: Failed to complete the initial therapy00011100000
Withdrew: Patient withdrawal prior to treatment00000000010

Outcome measures

PrimaryNumber of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)

The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of patients reporting a dose-limiting event are reported.

Time frame:
6 weeks
Reported as:
Count of participants · Participants
Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)
ParticipantsPhase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3
Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)000001000
PrimaryMaximum Tolerated Dose (MTD) (Phase I)

The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The MTD is reported below.

Time frame:
6 weeks
Reported as:
Number · Dose Level
Maximum Tolerated Dose (MTD) (Phase I)
Dose LevelPhase I (Stage 1)
Maximum Tolerated Dose (MTD) (Phase I)6
PrimaryProportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II)

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. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Time frame:
Up to 1 year
Reported as:
Number · proportion of patients
Proportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II)
proportion of patientsPhase II (Acetaminophen + Benadryl + MV-NIS)
Proportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II)0
SecondaryOverall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase I)

The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below by stage for Phase I patients.

Time frame:
Up to 1 year
Reported as:
Number · percentage of patients
Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase I)
percentage of patientsPhase I: Stage 1 (MV-NIS Alone)Phase I: Stage 2 (MV-NIS and Cyclophosphamide)
Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase I)3825
SecondaryNumber of Patients With Clinical Responses (Phase I)

The number of patients with clinical responses (CR, VGPR, PR, or minimal response \[MR\]) will be summarized by stage.

Time frame:
Up to 1 year
Reported as:
Count of participants · Participants
Number of Patients With Clinical Responses (Phase I)
ParticipantsPhase I: Stage 1 (MV-NIS Alone)Phase I: Stage 2 (MV-NIS and Cyclophosphamide)
Number of Patients With Clinical Responses (Phase I)10
SecondaryOverall Survival (Phase II)

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.

Time frame:
Time from registration to death due to any cause, assessed up to 1 year
Reported as:
Median · months
Overall Survival (Phase II)
monthsPhase II (Acetaminophen + Benadryl + MV-NIS)
Overall Survival (Phase II)12.0 (5.6 to NA)
SecondaryTime to Progression (TTP) (Phase II)

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 frame:
Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year
Reported as:
Median · months
Time to Progression (TTP) (Phase II)
monthsPhase II (Acetaminophen + Benadryl + MV-NIS)
Time to Progression (TTP) (Phase II)1.48 (1.35 to 240)
SecondaryProgression-free Survival (Phase II)

1-year progression-free survival (PFS1). Evidence of local recurrence, distant metastasis, or death from any cause within 1 year counted as events in the time-to-event Kaplan-Meier analysis of progression-free survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time frame:
At 1 year
Reported as:
Number · percentage of patients
Progression-free Survival (Phase II)
percentage of patientsPhase II (Acetaminophen + Benadryl + MV-NIS)
Progression-free Survival (Phase II)6.7
SecondaryProgression-free Survival (Phase II)

2-year progression-free survival (PFS2). Evidence of local recurrence, distant metastasis, or death from any cause within 2 years counted as events in the time-to-event Kaplan-Meier analysis of progression-free survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time frame:
At 2 years
Reported as:
Number · percentage of patients
Progression-free Survival (Phase II)
percentage of patientsPhase II (Acetaminophen + Benadryl + MV-NIS)
Progression-free Survival (Phase II)6.7
SecondaryProgression-free Survival (Phase II)

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time frame:
Up to 5 years
Reported as:
Median · months
Progression-free Survival (Phase II)
monthsPhase II (Acetaminophen + Benadryl + MV-NIS)
Progression-free Survival (Phase II)1.48 (1.35 to 2.40)
SecondaryFailure-free Survival (Phase II)

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.

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
Reported as:
Median · months
Failure-free Survival (Phase II)
monthsPhase II (Acetaminophen + Benadryl + MV-NIS)
Failure-free Survival (Phase II)1.4783 (1.2155 to 2.3982)
SecondaryOverall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase II)

The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below for Phase II patients.

Time frame:
Up to 1 year
Reported as:
Number · percentage of patients
Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase II)
percentage of patientsPhase II (Acetaminophen + Benadryl + MV-NIS)
Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase II)73.3
Other pre-specifiedTime Until Any Treatment Related Toxicity (Phase I)

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 frame:
Up to 1 year

Results for this outcome have not been posted.

Other pre-specifiedTime Until Hematologic Nadirs (White Blood Cells, ANC, Platelets) (Phase I)

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 frame:
Up to 1 year

Results for this outcome have not been posted.

Other pre-specifiedTime Until Treatment Related Grade 3+ Toxicity (Phase I)

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.

Time frame:
Up to 1 year

Results for this outcome have not been posted.

Other pre-specifiedBiodistribution and Kinetics of Virus Spread

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).

Time frame:
Up to 6 weeks

Results for this outcome have not been posted.

Other pre-specifiedNIS Gene Expression in Vivo

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).

Time frame:
Up to 6 weeks

Results for this outcome have not been posted.

Other pre-specifiedRadiation Dose

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.

Time frame:
Up to 6 weeks

Results for this outcome have not been posted.

Other pre-specifiedViral Replication

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).

Time frame:
Up to 6 weeks

Results for this outcome have not been posted.

Other pre-specifiedViral Shedding

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).

Time frame:
Up to 6 weeks

Results for this outcome have not been posted.

Adverse events

Collected over Up to 1 year. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Phase I: Stage 1 (MV-NIS Alone) Dose Level 12/3 (66.7%)2/3 (66.7%)3/3 (100%)
Phase I: Stage 1 (MV-NIS Alone) Dose Level 22/3 (66.7%)0/3 (0%)3/3 (100%)
Phase I: Stage 1 (MV-NIS Alone) Dose Level 32/3 (66.7%)0/3 (0%)3/3 (100%)
Phase I: Stage 1 (MV-NIS Alone) Dose Level 42/4 (50%)1/4 (25%)3/4 (75%)
Phase I: Stage 1 (MV-NIS Alone) Dose Level 53/4 (75%)1/4 (25%)4/4 (100%)
Phase I: Stage 1 (MV-NIS Alone) Dose Level 65/7 (71.4%)1/7 (14.3%)7/7 (100%)
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 12/3 (66.7%)0/3 (0%)3/3 (100%)
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 23/3 (100%)0/3 (0%)3/3 (100%)
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 31/2 (50%)0/2 (0%)2/2 (100%)
Phase II (Acetaminophen + Benadryl + MV-NIS)6/15 (40%)1/15 (6.7%)15/15 (100%)
Most frequent serious events
Most frequent serious events
EventPhase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3Phase II (Acetaminophen + Benadryl + MV-NIS)
Duodenal hemorrhageGastrointestinal disorders1/30/30/30/40/40/70/30/30/20/15
NauseaGastrointestinal disorders1/30/30/30/40/40/70/30/30/20/15
VomitingGastrointestinal disorders1/30/30/30/40/40/70/30/30/20/15
FeverGeneral disorders1/30/30/30/40/40/70/30/30/20/15
DehydrationMetabolism and nutrition disorders1/30/30/30/40/40/70/30/30/20/15
Restrictive cardiomyopathyCardiac disorders0/30/30/30/41/40/70/30/30/20/15
Platelet count decreasedInvestigations0/30/30/30/41/40/70/30/30/20/15
PneumonitisRespiratory, thoracic and mediastinal disorders0/30/30/31/40/40/70/30/30/20/15
Neutrophil count decreasedInvestigations0/30/30/30/40/41/70/30/30/20/15
Hemoglobin decreasedBlood and lymphatic system disorders0/30/30/30/40/40/70/30/30/21/15
Most frequent other events
Showing 10 of 58
Most frequent other events
EventPhase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3Phase II (Acetaminophen + Benadryl + MV-NIS)
Hemoglobin decreasedBlood and lymphatic system disorders3/33/33/33/44/47/73/33/32/215/15
NauseaGastrointestinal disorders1/32/32/31/43/45/72/33/32/212/15
VomitingGastrointestinal disorders0/33/30/30/43/42/70/31/30/28/15
Creatinine increasedInvestigations3/32/31/32/43/41/72/31/31/27/15
Leukocyte count decreasedInvestigations2/33/33/33/43/47/72/33/32/211/15
Lymphocyte count decreasedInvestigations0/30/30/30/41/40/73/32/32/25/15
Neutrophil count decreasedInvestigations2/33/33/31/43/46/73/32/32/29/15
Platelet count decreasedInvestigations3/33/33/31/44/47/73/33/32/213/15
CoughRespiratory, thoracic and mediastinal disorders3/30/31/31/42/43/71/32/32/210/15
FeverGeneral disorders1/30/30/31/42/46/71/30/31/213/15

Baseline characteristics

Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B.

Age, Continuous
Age, Continuous(years)Phase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3Phase II (Acetaminophen + Benadryl + MV-NIS)Total
Median64 (59 to 66)66 (57 to 68)51 (43 to 74)65 (63 to 82)63 (56 to 65)59 (49 to 65)62 (49 to 81)60 (59 to 65)65 (59 to 71)59 (40 to 72)60 (40 to 82)
Sex: Female, Male
Sex: Female, Male(Participants)Phase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3Phase II (Acetaminophen + Benadryl + MV-NIS)Total
Female121215110418
Male2121212221126
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Phase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3Phase II (Acetaminophen + Benadryl + MV-NIS)Total
American Indian or Alaska Native00000000000
Asian00000000000
Native Hawaiian or Other Pacific Islander00000000000
Black or African American00000000011
White3333363321342
More than one race00000000000
Unknown or Not Reported00000000011
ECOG Performance Status
ECOG Performance Status(Participants)Phase I: Stage 1 (MV-NIS Alone) Dose Level 1Phase I: Stage 1 (MV-NIS Alone) Dose Level 2Phase I: Stage 1 (MV-NIS Alone) Dose Level 3Phase I: Stage 1 (MV-NIS Alone) Dose Level 4Phase I: Stage 1 (MV-NIS Alone) Dose Level 5Phase I: Stage 1 (MV-NIS Alone) Dose Level 6Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3Phase II (Acetaminophen + Benadryl + MV-NIS)Total
0001035221923
1211301011515
212100010016
08

Study locations

1 site
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 20, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 16, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00450814
Lead sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Mar 22, 2007
Start date
Nov 30, 2006
Primary completion
Jul 10, 2018
Completion
Nov 20, 2019
Results posted
Dec 16, 2019
Last update
Dec 16, 2019

Study contacts

Angela Dispenzieri
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Multiple Myeloma→

Other studies from this sponsor

Mayo Clinic

Start the discussion