Vaccine Therapy With or Without Cyclophosphamide in Treating Patients With Recurrent or Refractory Multiple Myeloma - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00450814

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 I

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:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Measles Multiple Myeloma

Drug Information available for: Cyclophosphamide Liothyronine sodium Triiodothyronine Sodium iodide

U.S. FDA Resources

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 Study Completion Date:	June 2012
Estimated Primary Completion Date:	June 2012 (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

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

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

National Cancer Institute (NCI)

Investigators

Study Chair:

Angela Dispenzieri, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Angela Dispenzieri, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00450814 History of Changes
Other Study ID Numbers:	CDR0000530389, P30CA015083, MC038C, 06-005263, NCI-2009-01194
Study First Received:	March 20, 2007
Last Updated:	May 10, 2011
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 February 12, 2012