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 March 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00450814
First received: March 20, 2007
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

RATIONALE: 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 or by stopping them from dividing. Giving vaccine therapy together with cyclophosphamide may be an effective treatment for multiple myeloma.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy when given with or without cyclophosphamide in treating patients with recurrent or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: MV-NIS
Drug: cyclophosphamide
Other: I-123 prior MV-NIS
Other: I-123 post MV-NIS
Drug: Liothyronine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase I 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:
  • Toxicity [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Hematologic response (complete response, very good partial response, minimal response) [ Designated as safety issue: No ]
  • Viral replication and shedding [ Designated as safety issue: No ]
  • Biodistribution and kinetics of viral spread and NIS gene expression [ Designated as safety issue: No ]
  • Tolerability [ Designated as safety issue: Yes ]

Estimated Enrollment: 54
Study Start Date: May 2007
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MV-NIS without cyclophosphamide
Determine in a sequential manner the MTD of MV-NIS when administered without cyclophosphamide.
Biological: MV-NIS
Dose escalation theme. Start at 10^7 TCID50 increase by a factor of 3 to a final dose of 81x10^7 TCID50.
Other Name: oncolytic measles virus encoding thyroidal sodium iodide symporter
Other: I-123 prior MV-NIS
5 mCi Oral Any time pre-MV-NIS (for baseline I-123 scan)
Other: I-123 post MV-NIS
5 mCi Oral at Days 3, 8, and 15 (two additional doses may be given for imaging based on imaging results)
Other Name: 5 mCi Oral at Days 3, 8, and 15 (two additional doses may be given for imaging based on imaging results)
Drug: Liothyronine
0.025 mg - 1 oral tablet three times daily. Starting 4 days prior to MV-NIS administration through day of last 123I scan (no longer than Day 29)
Other Name: Cytomel
Experimental: MV-NIS + Cyclophosphamide
Determine in a sequential manner the MTD of MV-NIS when administered with cyclophosphamide.
Biological: MV-NIS
Dose escalation theme. Start at 10^7 TCID50 increase by a factor of 3 to a final dose of 81x10^7 TCID50.
Other Name: oncolytic measles virus encoding thyroidal sodium iodide symporter
Drug: cyclophosphamide
10mg/kg
Other: I-123 prior MV-NIS
5 mCi Oral Any time pre-MV-NIS (for baseline I-123 scan)
Other: I-123 post MV-NIS
5 mCi Oral at Days 3, 8, and 15 (two additional doses may be given for imaging based on imaging results)
Other Name: 5 mCi Oral at Days 3, 8, and 15 (two additional doses may be given for imaging based on imaging results)
Drug: Liothyronine
0.025 mg - 1 oral tablet three times daily. Starting 4 days prior to MV-NIS administration through day of last 123I scan (no longer than Day 29)
Other Name: Cytomel

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and toxicity of Edmonston vaccine strain oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma.
  • Determine the maximum tolerated dose of MV-NIS when administered with or without cyclophosphamide in these patients.

Secondary

  • Determine the time course of viral gene expression and viral elimination, and the biodistribution of virally infected cells at various time points after treatment with these regimens using iodine I 123 gamma camera imaging.
  • Assess viral replication, viremia, viral shedding in urine and respiratory secretions, and viral persistence after treatment with these regimens.
  • Monitor humoral responses to MV-NIS in these patients.
  • Explore the antimyeloma 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.

OUTLINE: This is a dose-escalation study of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS). Patients are stratified according to receipt of cyclophosphamide during study treatment (yes vs no). Patients are initially accrued to part 1. Once the maximum tolerated dose (MTD) of MV-NIS alone is determined, subsequent patients are accrued to part 2.

  • Part 1 (MV-NIS alone [closed to accrual as of 12/17/09]): Patients receive MV-NIS IV over 30 minutes on day 1.

Cohorts of 3-6 patients receive escalating doses of MV-NIS until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

  • Part 2 (MV-NIS and cyclophosphamide): Patients receive cyclophosphamide IV over 30 minutes on day -1 and MV-NIS IV over 30 minutes on day 1.

Cohorts of 3-6 patients receive escalating doses of MV-NIS* in combination with cyclophosphamide until the MTD is determined. The MTD of MV-NIS is defined as in part 1.

NOTE: *Starting dose of MV-NIS is the MTD determined in part 1.

Blood and bone marrow samples are obtained for research studies, including flow cytometry, at baseline and at week 6. Serial measurements of viral RNA in mononuclear cells are conducted in samples of blood, saliva, and urine on days 3, 8, and 15 and are tested for viral replication by quantitative reverse transcriptase-polymerase chain reaction. Measles virus-specific immunity is evaluated at baseline and on day 42.

After the completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of recurrent or refractory multiple myeloma

    • Previously treated with ≥ 2 nonoverlapping chemotherapeutic combinations

      • Thalidomide and corticosteroids are considered chemotherapy
    • No known standard therapy that is definitely capable of extending life expectancy exists

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.5 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 2 times ULN
  • Creatinine < 2 times ULN
  • INR ≤ 1.4 times ULN
  • Thyroid-stimulating hormone 0.3-5.0 mlU/L
  • Free thyroxine 0.8-1.87 ng/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
  • No uncontrolled infection
  • No active tuberculosis
  • No clinically significant cardiac condition or illness, including any of the following:

    • New York Heart Association class III-IV congestive heart failure
    • Known symptomatic coronary artery disease
    • Symptoms of coronary artery disease on systems review
    • Cardiac arrhythmia (atrial fibrillation or supraventricular tachycardia)
  • No active CNS disorder or seizure disorder
  • No HIV positivity
  • No allergy to iodine (not including reactions to IV contrast materials)
  • No exposure to household individuals ≤ 15 months of age or to any household individual with known immunodeficiency

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior allogeneic hematopoietic stem cell transplantation
  • No prior exposure to heat-inactivated measles virus vaccine
  • More than 3 weeks since prior and no other concurrent chemotherapy
  • More than 4 weeks since prior and no other concurrent immunotherapy
  • More than 4 weeks since prior biologic therapy
  • No concurrent radiotherapy
  • No other concurrent ancillary investigational therapy, including drugs, biologicals, or gene therapy, for therapeutic intent or symptomatic control
  • Concurrent bisphosphonates as maintenance therapy allowed
  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: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Angela Dispenzieri, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Angela Dispenzieri, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Angela Dispenzieri, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00450814     History of Changes
Other Study ID Numbers: MC038C, P30CA015083, MC038C, 06-005263, NCI-2009-01194
Study First Received: March 20, 2007
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
refractory multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
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 August 19, 2014