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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-01194 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| MC038C | Other Identifier | Mayo Clinic | |
| P30CA015083 | U.S. NIH Grant/Contract | View source | |
| R01CA125614 | U.S. NIH Grant/Contract | View source | |
| R01CA168719 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stage 1 (MV-NIS alone) | Experimental | Patients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011) |
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| Stage 2 (MV-NIS and cyclophosphamide) | Experimental | 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | Given IV |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 weeks |
| 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. | 6 weeks |
| 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 | Up to 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Angela Dispenzieri | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
Phase I: INITIALLY CLOSED ON 12/17/2009 AND STAGE 2 BEGUN; HOWEVER, DUE TO NEW MANUFACTURING CAPABILITIES, STAGE 1 RE-OPENED ON October 13, 2011, FOR DOSE LEVELS 5 AND 6. Phase II: Accrual to Cohort A closed due to failed interim analysis. Cohort B closed due to lack of accrual.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 1 | Patients receive 1x10^6 MV-NIS (TCID50) IV over 1 hour on day 1. |
| FG001 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 2 | Patients receive 1x10^7 MV-NIS (TCID50) IV over 1 hour on day 1. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 20, 2017 |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
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| Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter | Biological | Given IV |
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| Pharmacological Study | Other | Correlative studies |
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| 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. | Up to 1 year |
| 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 from registration to death due to any cause, assessed up to 1 year |
| 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 from registration to the earliest date with documentation of disease progression, assessed up to 1 year |
| 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 | At 1 year |
| 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 | At 2 years |
| 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 | Up to 5 years |
| 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 from registration to the earliest of progressive disease, alternative treatment for myeloma, or death due to any cause, assessed up to 1 year |
| 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. | Up to 1 year |
| Up to 1 year |
| 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. | Up to 1 year |
| 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. | Up to 1 year |
| 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). | Up to 6 weeks |
| 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). | Up to 6 weeks |
| 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. | Up to 6 weeks |
| 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). | Up to 6 weeks |
| 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). | Up to 6 weeks |
| FG002 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 3 | Patients receive 1x10^8 MV-NIS (TCID50) IV over 1 hour on day 1. |
| FG003 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 4 | Patients receive 1x10^9 MV-NIS (TCID50) IV over 1 hour on day 1. |
| FG004 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 5 | Patients receive 1x10^10 MV-NIS (TCID50) IV over 1 hour on day 1. |
| FG005 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 6 | Patients receive 1x10^11 MV-NIS (TCID50) IV over 1 hour on day 1. |
| FG006 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then (Stage 1 MTD/100=10^7) MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) |
| FG007 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then 3 x 10^7 MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) |
| FG008 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then 9 x 10^7 MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) |
| FG009 | Phase II (Acetaminophen + Benadryl + MV-NIS) Cohort A | Cohort A patients (relapsed or refractory multiple myeloma who have exhausted all therapeutic options) receive 650 mg Acetaminophen and 50 mg Benadryl orally 30 minutes prior to MV-NIS then receive MV-NIS IV over 1 hour on day 1. |
| FG010 | Phase II (Acetaminophen + Benadryl + MV-NIS) Cohort B | Cohort B patients (relapsing from VGPR or CR and have not > received myeloma directed therapy for at least 12 weeks) receive 650 mg Acetaminophen and 50 mg Benadryl orally 30 minutes prior to MV-NIS then receive MV-NIS IV over 1 hour on day 1. |
| COMPLETED |
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| NOT COMPLETED |
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Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 1 | Patients receive 1x10^6 MV-NIS (TCID50) IV over 1 hour on day 1. |
| BG001 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 2 | Patients receive 1x10^7 MV-NIS (TCID50) IV over 1 hour on day 1. |
| BG002 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 3 | Patients receive 1x10^8 MV-NIS (TCID50) IV over 1 hour on day 1. |
| BG003 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 4 | Patients receive 1x10^9 MV-NIS (TCID50) IV over 1 hour on day 1. |
| BG004 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 5 | Patients receive 1x10^10 MV-NIS (TCID50) IV over 1 hour on day 1. |
| BG005 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 6 | Patients receive 1x10^11 MV-NIS (TCID50) IV over 1 hour on day 1. |
| BG006 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then (Stage 1 MTD/100=10^7) MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) |
| BG007 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then 3 x 10^7 MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) |
| BG008 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then 9 x 10^7 MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) |
| BG009 | Phase II (Acetaminophen + Benadryl + MV-NIS) | Patients receive 650 mg Acetaminophen and 50 mg Benadryl orally 30 minutes prior to MV-NIS then receive MV-NIS IV over 1 hour on day 1. |
| BG010 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| ECOG Performance Status | Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | Only phase I patients who completed the study are included in this analysis. | Posted | Count of Participants | Participants | 6 weeks |
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| Primary | 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. | Only phase I stage 1 patients who completed the study are included in this analysis. Dose levels 1-6 of Phase I Stage 1 patients were combined in this analysis to determine the MTD as defined above. | Posted | Number | Dose Level | 6 weeks |
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| Primary | 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 | Only phase II patients who completed the study are included in this analysis. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B. | Posted | Number | proportion of patients | Up to 1 year |
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| Secondary | 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. | Per protocol, Phase I specified secondary endpoint is evaluated for each STAGE independently; thus, the stage 1 dose level groups were combined and the stage 2 dose level groups were combined for this analysis PER PROTOCOL. | Posted | Number | percentage of patients | Up to 1 year |
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| Secondary | 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. | Per protocol, Phase I specified secondary endpoint is evaluated for each STAGE independently; thus, the stage 1 dose level groups were combined and the stage 2 dose level groups were combined for this analysis PER PROTOCOL. | Posted | Count of Participants | Participants | Up to 1 year |
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| Secondary | 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. | Only phase II patients who completed the study are included in this analysis. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B. | Posted | Median | 95% Confidence Interval | months | Time from registration to death due to any cause, assessed up to 1 year |
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| Secondary | 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. | Phase II specified secondary endpoint will only include Phase II patients. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating in Cohort B early and to get the overall TTP for Phase II patients. | Posted | Median | 95% Confidence Interval | months | Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year |
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| Secondary | 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 | Phase II specified secondary endpoint will only include Phase II patients. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B. | Posted | Number | percentage of patients | At 1 year |
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| Secondary | 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 | Phase II specified secondary endpoint will only include Phase II patients. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B. | Posted | Number | percentage of patients | At 2 years |
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| Secondary | 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 | Phase II specified secondary endpoint will only include Phase II patients. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating in Cohort B early and to get the overall PFS for Phase II patients. | Posted | Median | 95% Confidence Interval | months | Up to 5 years |
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| Secondary | 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. | Phase II specified secondary endpoint will only include Phase II patients. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B. | Posted | Median | 95% Confidence Interval | months | Time from registration to the earliest of progressive disease, alternative treatment for myeloma, or death due to any cause, assessed up to 1 year |
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| Secondary | 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. | Only phase II patients who completed the study are included in this analysis. Phase II Cohort A and Phase II Cohort B were combined for this analysis due to accrual terminating early in Cohort B and to obtain the overall toxicity rate among Phase II patients. | Posted | Number | percentage of patients | Up to 1 year |
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| Other Pre-specified | 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. | Not Posted | Up to 1 year | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | Not Posted | Up to 1 year | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | Not Posted | Up to 1 year | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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). | Not Posted | Up to 6 weeks | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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). | Not Posted | Up to 6 weeks | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | Not Posted | Up to 6 weeks | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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). | Not Posted | Up to 6 weeks | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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). | Not Posted | Up to 6 weeks | Participants |
Up to 1 year
Only patients who received at least 1 cycle of treatment and submitted AE data are summarized below. Each CTCAE term is a specific event used for medical documentation & is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any serious or non-serious events considered related to the primary event; collectively, these events are referred to as Expedited AEs, & appear in the SAE table. Phase II Cohort A and B combined as they received the same treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 1 | Patients receive 1x10^6 MV-NIS (TCID50) IV over 1 hour on day 1. | 2 | 3 | 2 | 3 | 3 | 3 |
| EG001 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 2 | Patients receive 1x10^7 MV-NIS (TCID50) IV over 1 hour on day 1. | 2 | 3 | 0 | 3 | 3 | 3 |
| EG002 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 3 | Patients receive 1x10^8 MV-NIS (TCID50) IV over 1 hour on day 1. | 2 | 3 | 0 | 3 | 3 | 3 |
| EG003 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 4 | Patients receive 1x10^9 MV-NIS (TCID50) IV over 1 hour on day 1. | 2 | 4 | 1 | 4 | 3 | 4 |
| EG004 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 5 | Patients receive 1x10^10 MV-NIS (TCID50) IV over 1 hour on day 1. | 3 | 4 | 1 | 4 | 4 | 4 |
| EG005 | Phase I: Stage 1 (MV-NIS Alone) Dose Level 6 | Patients receive 1x10^11 MV-NIS (TCID50) IV over 1 hour on day 1. | 5 | 7 | 1 | 7 | 7 | 7 |
| EG006 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then (Stage 1 MTD/100=10^7) MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) | 2 | 3 | 0 | 3 | 3 | 3 |
| EG007 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then 3 x 10^7 MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) | 3 | 3 | 0 | 3 | 3 | 3 |
| EG008 | Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3 | Patients receive 10 mg/kg cyclophosphamide IV over 30 minutes and then 9 x 10^7 MV-NIS (TCID50) IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11) | 1 | 2 | 0 | 2 | 2 | 2 |
| EG009 | Phase II (Acetaminophen + Benadryl + MV-NIS) | Patients receive 650 mg Acetaminophen and 50 mg Benadryl orally 30 minutes prior to MV-NIS then receive MV-NIS IV over 1 hour on day 1. | 6 | 15 | 1 | 15 | 15 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin decreased | Blood and lymphatic system disorders | MedDRA 9 | Systematic Assessment |
| |
| Restrictive cardiomyopathy | Cardiac disorders | MedDRA 9 | Systematic Assessment |
| |
| Duodenal hemorrhage | Gastrointestinal disorders | MedDRA 9 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 9 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 9 | Systematic Assessment |
| |
| Fever | General disorders | MedDRA 9 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 9 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 9 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 9 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 9 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 9 | Systematic Assessment |
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| Hemoglobin decreased | Blood and lymphatic system disorders | MedDRA 9 | Systematic Assessment |
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| Left ventricular failure | Cardiac disorders | MedDRA 9 | Systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | MedDRA 9 | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA 9 | Systematic Assessment |
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| Photophobia | Eye disorders | MedDRA 9 | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA 9 | Systematic Assessment |
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| Ear, nose and throat examination abnormal | Gastrointestinal disorders | MedDRA 9 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 9 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 9 | Systematic Assessment |
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| Chills | General disorders | MedDRA 9 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 9 | Systematic Assessment |
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| Fever | General disorders | MedDRA 9 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 9 | Systematic Assessment |
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| Pain | General disorders | MedDRA 9 | Systematic Assessment |
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| Cytokine release syndrome | Immune system disorders | MedDRA 9 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA 9 | Systematic Assessment |
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| Peripheral nerve infection | Infections and infestations | MedDRA 9 | Systematic Assessment |
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| Phlebitis infective | Infections and infestations | MedDRA 9 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 9 | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA 9 | Systematic Assessment |
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| Upper respiratory infection | Infections and infestations | MedDRA 9 | Systematic Assessment |
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| Fracture | Injury, poisoning and procedural complications | MedDRA 9 | Systematic Assessment |
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| Activated partial thromboplastin time prolonged | Investigations | MedDRA 9 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 9 | Systematic Assessment |
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| CD4 lymphocytes decreased | Investigations | MedDRA 9 | Systematic Assessment |
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| Creatinine increased | Investigations | MedDRA 9 | Systematic Assessment |
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| Electrocardiogram QTc interval prolonged | Investigations | MedDRA 9 | Systematic Assessment |
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| Leukocyte count decreased | Investigations | MedDRA 9 | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA 9 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 9 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 9 | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Hypercalcemia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Hyperuricemia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | MedDRA 9 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 9 | Systematic Assessment |
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| Joint pain | Musculoskeletal and connective tissue disorders | MedDRA 9 | Systematic Assessment |
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| Treatment related secondary malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 9 | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | MedDRA 9 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 9 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 9 | Systematic Assessment |
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| Taste alteration | Nervous system disorders | MedDRA 9 | Systematic Assessment |
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| Confusion | Psychiatric disorders | MedDRA 9 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 9 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA 9 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 9 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 9 | Systematic Assessment |
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| Rash desquamating | Skin and subcutaneous tissue disorders | MedDRA 9 | Systematic Assessment |
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| Hemorrhage | Vascular disorders | MedDRA 9 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 9 | Systematic Assessment |
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| Thrombosis | Vascular disorders | MedDRA 9 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Angela Dispenzieri, M.D., Morie A. Gertz, M.D. | Mayo Clinic | (507) 284-2511 | Dispenzieri.Angela@mayo.edu, Gertz.Morie@mayo.edu |
| Jul 15, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
Not provided
Not provided
| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| 1 |
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| 2 |
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