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NCT00450814

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

Completed Phase 1, PHASE2 Results posted Last updated 16 December 2019
What this trial tests

Phase 1, PHASE2 trial testing Cyclophosphamide in Recurrent Plasma Cell Myeloma in 48 participants. Completed in 20 November 2019.

Timeline
30 November 2006
Primary endpoint
10 July 2018
20 November 2019

Quick facts

Lead sponsorMayo Clinic
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment48
Start date30 November 2006
Primary completion10 July 2018
Estimated completion20 November 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Mayo Clinic

Who can join

18 and older, any sex, with Recurrent Plasma Cell Myeloma or Refractory Plasma Cell Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Primary · 6 weeks

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.

GroupValue95% CI
Phase I: Stage 1 (MV-NIS Alone) Dose Level 10
Phase I: Stage 1 (MV-NIS Alone) Dose Level 20
Phase I: Stage 1 (MV-NIS Alone) Dose Level 30
Phase I: Stage 1 (MV-NIS Alone) Dose Level 40
Phase I: Stage 1 (MV-NIS Alone) Dose Level 50
Phase I: Stage 1 (MV-NIS Alone) Dose Level 61
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 10
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 20
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 30
Maximum Tolerated Dose (MTD) (Phase I) Primary · 6 weeks

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.

GroupValue95% CI
Phase I (Stage 1)6
Proportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II) Primary · Up to 1 year

Confirmed response will be evaluated using all cycles. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. 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

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)0
Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase I) Secondary · Up to 1 year

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.

GroupValue95% CI
Phase I: Stage 1 (MV-NIS Alone)38
Phase I: Stage 2 (MV-NIS and Cyclophosphamide)25
Number of Patients With Clinical Responses (Phase I) Secondary · Up to 1 year

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

GroupValue95% CI
Phase I: Stage 1 (MV-NIS Alone)1
Phase I: Stage 2 (MV-NIS and Cyclophosphamide)0
Overall Survival (Phase II) Secondary · Time from registration to death due to any cause, assessed up to 1 year

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.

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)12.05.6 – NA
Time to Progression (TTP) (Phase II) Secondary · Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year

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.

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)1.481.35 – 240
Progression-free Survival (Phase II) Secondary · At 1 year

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

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)6.7
Progression-free Survival (Phase II) Secondary · At 2 years

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

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)6.7
Progression-free Survival (Phase II) Secondary · Up to 5 years

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 appe

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)1.481.35 – 2.40
Failure-free Survival (Phase II) Secondary · Time from registration to the earliest of progressive disease, alternative treatment for myeloma, or death due to any cause, assessed up to 1 year

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.

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)1.47831.2155 – 2.3982
Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase II) Secondary · Up to 1 year

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.

GroupValue95% CI
Phase II (Acetaminophen + Benadryl + MV-NIS)73.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 1 year. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I: Stage 1 (MV-NIS Alone) Dose Level 1
Serious: 2/3 (67%)
Deaths: 2/3
Phase I: Stage 1 (MV-NIS Alone) Dose Level 2
Serious: 0/3 (0%)
Deaths: 2/3
Phase I: Stage 1 (MV-NIS Alone) Dose Level 3
Serious: 0/3 (0%)
Deaths: 2/3
Phase I: Stage 1 (MV-NIS Alone) Dose Level 4
Serious: 1/4 (25%)
Deaths: 2/4
Phase I: Stage 1 (MV-NIS Alone) Dose Level 5
Serious: 1/4 (25%)
Deaths: 3/4
Phase I: Stage 1 (MV-NIS Alone) Dose Level 6
Serious: 1/7 (14%)
Deaths: 5/7
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 1
Serious: 0/3 (0%)
Deaths: 2/3
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 2
Serious: 0/3 (0%)
Deaths: 3/3
Phase I: Stage 2 (MV-NIS and Cyclophosphamide) Dose Level 3
Serious: 0/2 (0%)
Deaths: 1/2
Phase II (Acetaminophen + Benadryl + MV-NIS)
Serious: 1/15 (7%)
Deaths: 6/15

Serious adverse events (10 terms)

ReactionSystemPhase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 2 (MV-NIS a…Phase I: Stage 2 (MV-NIS a…Phase I: Stage 2 (MV-NIS a…Phase II (Acetaminophen + …
Hemoglobin decreasedBlood and lymphatic system disorders
Restrictive cardiomyopathyCardiac disorders
Duodenal hemorrhageGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
FeverGeneral disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
DehydrationMetabolism and nutrition disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Other adverse events (58 terms — click to expand)

ReactionSystemPhase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 1 (MV-NIS A…Phase I: Stage 2 (MV-NIS a…Phase I: Stage 2 (MV-NIS a…Phase I: Stage 2 (MV-NIS a…Phase II (Acetaminophen + …
Hemoglobin decreasedBlood and lymphatic system disorders
FeverGeneral disorders
Platelet count decreasedInvestigations
NauseaGastrointestinal disorders
ChillsGeneral disorders
Leukocyte count decreasedInvestigations
DiarrheaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Neutrophil count decreasedInvestigations
VomitingGastrointestinal disorders
Creatinine increasedInvestigations
Lymphocyte count decreasedInvestigations
Upper respiratory infectionInfections and infestations
HeadacheNervous system disorders
Rash desquamatingSkin and subcutaneous tissue disorders
Cytokine release syndromeImmune system disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Disseminated intravascular coagulationBlood and lymphatic system disorders
CD4 lymphocytes decreasedInvestigations
EncephalopathyNervous system disorders
HypotensionVascular disorders
Febrile neutropeniaBlood and lymphatic system disorders
Left ventricular failureCardiac disorders
Sinus bradycardiaCardiac disorders
HypothyroidismEndocrine disorders
PhotophobiaEye disorders
Ear, nose and throat examination abnormalGastrointestinal disorders
FatigueGeneral disorders
Injection site reactionGeneral disorders
PainGeneral disorders
InfectionInfections and infestations
Peripheral nerve infectionInfections and infestations
Phlebitis infectiveInfections and infestations
SinusitisInfections and infestations
Skin infectionInfections and infestations
FractureInjury, poisoning and procedural complications
Activated partial thromboplastin time prolongedInvestigations
Aspartate aminotransferase increasedInvestigations
Electrocardiogram QTc interval prolongedInvestigations
AnorexiaMetabolism and nutrition disorders

Most-reported serious reactions: Hemoglobin decreased, Restrictive cardiomyopathy, Duodenal hemorrhage, Nausea, Vomiting, Fever, Neutrophil count decreased, Platelet count decreased.

Data from ClinicalTrials.gov NCT00450814 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The emerging field of oncolytic virus-based cancer immunotherapy.
    Ma R, Li Z, Chiocca EA, Caligiuri MA, et al · · 2023 · cited 220× · PMID 36402738 · DOI 10.1016/j.trecan.2022.10.003
  2. New viruses for cancer therapy: meeting clinical needs.
    Miest TS, Cattaneo R. · · 2014 · cited 176× · PMID 24292552 · DOI 10.1038/nrmicro3140
  3. Immunotherapy of multiple myeloma.
    Minnie SA, Hill GR. · · 2020 · cited 160× · PMID 32149732 · DOI 10.1172/jci129205
  4. Systemic delivery of oncolytic viruses: hopes and hurdles.
    Ferguson MS, Lemoine NR, Wang Y. · · 2012 · cited 160× · PMID 22400027 · DOI 10.1155/2012/805629
  5. Recent advances of oncolytic virus in cancer therapy.
    Mondal M, Guo J, He P, Zhou D. · · 2020 · cited 154× · PMID 32078405 · DOI 10.1080/21645515.2020.1723363
  6. Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma.
    Dispenzieri A, Tong C, LaPlant B, Lacy MQ, et al · · 2017 · cited 123× · PMID 28439108 · DOI 10.1038/leu.2017.120
  7. Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects.
    Msaouel P, Opyrchal M, Dispenzieri A, Peng KW, et al · · 2018 · cited 110× · PMID 28228086 · DOI 10.2174/1568009617666170222125035
  8. White paper on microbial anti-cancer therapy and prevention.
    Forbes NS, Coffin RS, Deng L, Evgin L, et al · · 2018 · cited 106× · PMID 30081947 · DOI 10.1186/s40425-018-0381-3

Verify or expand the search:

Other trials of Cyclophosphamide

Trials testing the same drug.

Other recruiting trials for Recurrent Plasma Cell Myeloma

Currently open trials in the same condition.

Other Mayo Clinic trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00450814.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing