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NCT00450814 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2019-12-16

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Maximum Tolerated Dose (MTD) (Phase I)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Number of Patients With Clinical Responses (Phase I)

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outcome · POSTED

Overall Survival (Phase II)

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outcome · POSTED

Time to Progression (TTP) (Phase II)

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outcome · POSTED

Progression-free Survival (Phase II)

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outcome · POSTED

Progression-free Survival (Phase II)

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outcome · POSTED

Progression-free Survival (Phase II)

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outcome · POSTED

Failure-free Survival (Phase II)

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outcome · POSTED

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

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outcome · NOT POSTED

Time Until Any Treatment Related Toxicity (Phase I)

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outcome · NOT POSTED

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

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outcome · NOT POSTED

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

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outcome · NOT POSTED

Biodistribution and Kinetics of Virus Spread

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outcome · NOT POSTED

NIS Gene Expression in Vivo

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outcome · NOT POSTED

Radiation Dose

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outcome · NOT POSTED

Viral Replication

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outcome · NOT POSTED

Viral Shedding

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011)
    intervention Names
    1. Other: Laboratory Biomarker Analysis
    2. Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    3. Other: Pharmacological Study
    label
    Stage 1 (MV-NIS alone)
    type
    EXPERIMENTAL
  2. description
    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)
    intervention Names
    1. Drug: Cyclophosphamide
    2. Other: Laboratory Biomarker Analysis
    3. Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    4. Other: Pharmacological Study
    label
    Stage 2 (MV-NIS and cyclophosphamide)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Stage 2 (MV-NIS and cyclophosphamide)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Carloxan
    4. Ciclofosfamida
    5. Ciclofosfamide
    6. Cicloxal
    7. Clafen
    8. Claphene
    9. CP monohydrate
    10. CTX
    11. CYCLO-cell
    12. Cycloblastin
    type
    DRUG
  2. arm Group Labels
    1. Stage 1 (MV-NIS alone)
    2. Stage 2 (MV-NIS and cyclophosphamide)
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  3. arm Group Labels
    1. Stage 1 (MV-NIS alone)
    2. Stage 2 (MV-NIS and cyclophosphamide)
    description
    Given IV
    name
    Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    other Names
    1. MV-NIS
    type
    BIOLOGICAL
  4. arm Group Labels
    1. Stage 1 (MV-NIS alone)
    2. Stage 2 (MV-NIS and cyclophosphamide)
    description
    Correlative studies
    name
    Pharmacological Study
    type
    OTHER
Study design
allocation
NON_RANDOMIZED
intervention Model
SEQUENTIAL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
48
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. description
    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.
    measure
    Time Until Any Treatment Related Toxicity (Phase I)
    time Frame
    Up to 1 year
  2. description
    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.
    measure
    Time Until Hematologic Nadirs (White Blood Cells, ANC, Platelets) (Phase I)
    time Frame
    Up to 1 year
  3. description
    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.
    measure
    Time Until Treatment Related Grade 3+ Toxicity (Phase I)
    time Frame
    Up to 1 year
  4. description
    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).
    measure
    Biodistribution and Kinetics of Virus Spread
    time Frame
    Up to 6 weeks
  5. description
    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).
    measure
    NIS Gene Expression in Vivo
    time Frame
    Up to 6 weeks
  6. description
    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.
    measure
    Radiation Dose
    time Frame
    Up to 6 weeks
  7. description
    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).
    measure
    Viral Replication
    time Frame
    Up to 6 weeks
  8. description
    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).
    measure
    Viral Shedding
    time Frame
    Up to 6 weeks
primary Outcomes
  1. description
    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.
    measure
    Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)
    time Frame
    6 weeks
  2. description
    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.
    measure
    Maximum Tolerated Dose (MTD) (Phase I)
    time Frame
    6 weeks
  3. description
    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
    measure
    Proportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II)
    time Frame
    Up to 1 year
secondary Outcomes
  1. description
    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.
    measure
    Overall Toxicity Rate, 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
  2. description
    The number of patients with clinical responses (CR, VGPR, PR, or minimal response \[MR\]) will be summarized by stage.
    measure
    Number of Patients With Clinical Responses (Phase I)
    time Frame
    Up to 1 year
  3. description
    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.
    measure
    Overall Survival (Phase II)
    time Frame
    Time from registration to death due to any cause, assessed up to 1 year
  4. description
    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.
    measure
    Time to Progression (TTP) (Phase II)
    time Frame
    Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year
  5. description
    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
    measure
    Progression-free Survival (Phase II)
    time Frame
    At 1 year
  6. description
    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
    measure
    Progression-free Survival (Phase II)
    time Frame
    At 2 years
  7. description
    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
    measure
    Progression-free Survival (Phase II)
    time Frame
    Up to 5 years
  8. description
    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.
    measure
    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
  9. description
    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.
    measure
    Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase II)
    time Frame
    Up to 1 year
Full study description
brief 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.
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.
Source references
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice