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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00450814
First received: March 20, 2007
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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 or does not respond to treatment. 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 safe treatment for multiple myeloma.


Condition Intervention Phase
Refractory Multiple Myeloma
Drug: cyclophosphamide
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • MTD of oncolytic measles virus encoding thyroidal sodium iodide symporter when administered with or without cyclophosphamide (Phase I) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Defined as the highest safely-tolerated dose level where at most 1 out of six patients experiences dose-limiting toxicity (DLT) or no DLT observed out of 3 patients at the maximum dose level, provided no DLT is observed at any of the previous dose levels.

  • Proportion of confirmed response, defined as a partial response (PR) or better (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Confirmed response will be evaluated using all cycles.

  • Proportion of successes (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Ninety-five percent confidence intervals for the true success proportion will be calculated according to the method of Duffy and Santner.


Secondary Outcome Measures:
  • Incidence of toxicity incidents as 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 ] [ Designated as safety issue: Yes ]
  • Number of clinical responses (Phase I) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The number of responses (complete response [CR], very good partial response [VGPR], partial response [PR], or minimal response [MR]) will be summarized by simple descriptive summary statistics across all patients in each group as well as by dose level.

  • Tolerability of this regimen (Phase I) [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Tolerability will be explored in an ancillary manner through time-related variables including time until any treatment related toxicity, time until treatment related grade 3+ toxicity and time until hematologic nadirs (white blood cells [WBC], ANC, platelets). 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 logrank testing involving one covariate at a time.

  • Overall survival (Phase II) [ Time Frame: Time from registration to death due to any cause, assessed up to 1 year ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.

  • Time to progression (Phase II) [ Time Frame: Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year ] [ Designated as safety issue: No ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.

  • Progression-free rate (Phase II) [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • Progression-free rate (Phase II) [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events, graded according to the NCI CTCAE v3.0 (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.


Other Outcome Measures:
  • In vivo oncolytic measles virus encoding thyroidal sodium iodide symporter biodistribution and kinetics of virus spread and elimination as assessed by whole body gamma camera and single-photon emission computed tomography (SPECT)/CT imaging [ Time Frame: Up to 15 days after oncolytic measles virus encoding thyroidal sodium iodide symporter infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: January 2007
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 (MV-NIS alone)
Patients receive MV-NIS IV over 1 hour on day 1. (closed to accrual on 12/17/2009 and reopened 10/13/2011).
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Given IV
Other Name: MV-NIS
Other: laboratory biomarker analysis
Correlative studies
Experimental: Part 2 (MV-NIS and cyclophosphamide)
Patients receive cyclophosphamide IV over 30 minutes 2 days before MV-NIS IV is administered over 1 hour on day 1.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Given IV
Other Name: MV-NIS
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of measles virus encoding the human 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. (Phase II)

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 alone 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 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-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.

Part 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.

Part 2 (MV-NIS AND CYCLOPHOSPHAMIDE): Patients receive cyclophosphamide IV over 30 minutes 2 days before MV-NIS IV is administered over 1 hour on day 1.

After completion of study treatment, patients are followed up every 3 months for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed or refractory myeloma that with evidence of progression on an IMiD, a proteasome inhibitor, and an alkylator.

NOTE: Progression within 1 year post-high-dose chemotherapy with autologous stem cell support would qualify as alkylator refractory

  • 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 virus titers (measles neutralizing antibody) < 0.5

Exclusion Criteria:

  • Availability of known standard therapy that is definitely capable of extending life expectancy (patients who are on maintenance therapy with bisphosphonates are not excluded)
  • Uncontrolled infection
  • Active tuberculosis
  • Chemotherapy =< 3 weeks prior to study registration
  • Immunotherapy =< 4 weeks prior to study registration
  • Biologic therapy =< 4 weeks prior to study registration
  • New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT])
  • 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
  • Allergy to iodine (this does not include reactions to intravenous contrast materials)
  • 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
  • Prior allogeneic hematopoietic stem cell transplantation
  • Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450814

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Angela Dispenzieri         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Angela Dispenzieri Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00450814     History of Changes
Other Study ID Numbers: MC038C, NCI-2009-01194, Mod06-005263-65, MC038C, R01CA125614, P30CA015083, R01CA168719
Study First Received: March 20, 2007
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 19, 2014