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Recurrent Plasma Cell MyelomaPhase 1/2NCT00450814

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

A Phase 1/2 study testing Cyclophosphamide, Laboratory Biomarker Analysis and Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Laboratory Biomarker Analysis and Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited States
Study dates
30 Nov 2006to 20 Nov 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase I/II Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, With or Without Cyclophosphamide, in Patients With Recurrent or Refractory Multiple Myeloma

This phase I/II trial studies the side effects and best dose of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients with multiple myeloma that has come back (recurrent) or has not responded to previous treatment (refractory). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vaccine therapy together with cyclophosphamide may be a better treatment for multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Cyclophosphamide, Laboratory Biomarker Analysis, Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter, Pharmacological Study
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide SymporterBiological

    Also called MV-NIS

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT00450814
Study groupRoleWhat they receive
Stage 1 (MV-NIS alone)ExperimentalPatients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011)
Receives: Other: Laboratory Biomarker Analysis; Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter; Other: Pharmacological Study
Stage 2 (MV-NIS and cyclophosphamide)ExperimentalPatients 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)
Receives: Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

    Measured: 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

    Measured: Up to 1 year

Secondary outcomes (9)

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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.

    Measured: 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.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2007 (estimated)
  2. Study start30 Nov 2006
  3. Primary completion10 Jul 2018
  4. Study completion20 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00450814
Sponsor's protocol ID
MC038C
Other IDs
NCI-2009-01194, MC038C, P30CA015083, R01CA125614, R01CA168719
Status last verified
Jan 2019
First submitted
20 Mar 2007
Last updated
16 Dec 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Laboratory Biomarker Analysis and Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) (time frame: 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00450814.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2019.

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