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Wild-Type Reovirus, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

This study is currently recruiting participants.
Verified April 2017 by University of Southern California
Sponsor:
ClinicalTrials.gov Identifier:
NCT02514382
First Posted: August 3, 2015
Last Update Posted: April 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
Oncolytics Biotech
Information provided by (Responsible Party):
University of Southern California
  Purpose
This phase Ib trial studies the safety and best dose of wild-type reovirus in combination with bortezomib and dexamethasone and to see how well they work in treating patients with multiple myeloma that has returned (relapsed) or does not respond to treatment (refractory). A virus, called wild-type reovirus, may be able to infect cancer cells and slow the cancer growth and kill cancer cells. Bortezomib and dexamethasone may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving wild-type reovirus together with bortezomib and dexamethasone may be a better treatment for multiple myeloma.

Condition Intervention Phase
Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma Drug: Bortezomib Drug: Dexamethasone Other: Laboratory Biomarker Analysis Other: Pharmacological Study Biological: Wild-type Reovirus Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of REOLYSIN® (Reovirus Serotype 3 - Dearing Strain) Combined With Standard Doses of Bortezomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Incidence of adverse events assessed by CTCAE version 4.03 [ Time Frame: Up to 30 days post-treatment ]
    The safety of the bortezomib, dexamethasone, and wild-type reovirus combination will be assessed by the evaluation of the type, frequency, and severity of adverse events.


Secondary Outcome Measures:
  • ORR [ Time Frame: Up to 3 years ]
    Will determine ORR (CR + PR) in the Phase 1b part to the combination at escalating doses.


Estimated Enrollment: 18
Actual Study Start Date: August 21, 2015
Estimated Study Completion Date: August 21, 2019
Estimated Primary Completion Date: August 21, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dexamethasone, bortezomib, wild-type reovirus)
Patients receive dexamethasone PO, IV, or IM and bortezomib SC (preferably) or IV over 3-5 seconds on days 1, 8, and 15. Patients also receive wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Bortezomib
Given SC or IV
Other Names:
  • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  • LDP 341
  • MLN341
  • PS-341
  • PS341
  • Velcade
Drug: Dexamethasone
Given PO, IV, or IM
Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • Visumetazone
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Biological: Wild-type Reovirus
Given IV
Other Name: Reolysin

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) with the maximum REOLYSIN (wild-type reovirus) dose limited to 4.5 x 10^10 tissue culture infection dose (TCID)50 and the safety profile of REOLYSIN in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (MM). (Phase 1b) II. To further explore the safety and tolerability of the combination and to determine the overall response rate (ORR) (complete response [CR] + partial response [PR]) to REOLYSIN in combination with bortezomib and dexamethasone in patients with relapsed or refractory MM. (Phase 1b Dose Expansion)

SECONDARY OBJECTIVES:

I. To determine ORR in the Phase 1b part to the combination at escalating doses.

II. To determine the progression-free survival (PFS) of patients with relapsed or refractory MM treated with REOLYSIN in combination with bortezomib and dexamethasone.

III. To evaluate the effect of REOLYSIN in combination with bortezomib and dexamethasone treatments on overall survival (OS).

IV. To conduct pharmacodynamic studies as described.

OUTLINE: This is a phase Ib, dose-escalation study of wild-type reovirus followed by a phase Ib expansion trial.

Patients receive dexamethasone orally (PO), intravenously (IV), or intramuscularly (IM) and bortezomib subcutaneously (SC) (preferably) or IV over 3-5 seconds on days 1, 8, and 15. Patients also receive wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month and then every 3 months thereafter.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have relapsed or refractory MM after at least one line of therapy
  • Have a confirmed diagnosis of MM with measurable disease, as defined by the presence of monoclonal immunoglobulin protein in serum electrophoreses of at least 0.5 g/dL for immunoglobulin G (IgG) or 0.25 g/dL for IgA, or measurable light chain in serum (100 mg/L) or urinary excretion of at least 200 mg monoclonal light chain per 24 hours
  • Have NO continuing acute toxic effects (except alopecia) of any prior chemotherapy, radiotherapy or surgical procedures; all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) grade =< 1; surgery (except minor procedures such as biopsies, IV line placement, etc.) must have occurred at least 28 days prior to study enrollment
  • Have received NO anti-cancer therapy within 28 days prior to receiving study drug
  • Have received NO radiotherapy within 14 days prior to receiving study drug
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance score =< 2
  • Have a life expectancy of at least 3 months
  • Absolute neutrophil count (ANC) >= 1 x 10^9 (International System [SI] units 10^9/L) (with or without filgrastim [G-CSF])
  • Platelets >= 50 x10^9 (SI units 10^9/L)
  • Serum creatinine =< 2 x upper limit of normal (ULN)
  • Bilirubin =< 1.5 x ULN
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (=< 5 x ULN if patients have liver involvement with MM)
  • Proteinuria < grade 2
  • Have a negative pregnancy test if a female with childbearing potential
  • Have signed an informed consent indicating that the patient is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, possible alternative therapies, potential benefits, side effects, risks, and discomforts
  • Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests

Exclusion Criteria:

  • Have a history of or current evidence of intracranial disease; patients with brain metastases must be excluded from this clinical trial
  • Be on immunosuppressive therapy or have human immunodeficiency virus (HIV) infection or active hepatitis B or C
  • Be a pregnant or breast-feeding woman; female patients of childbearing potential must agree to use effective contraception, must be surgically sterile, or must be postmenopausal; male patients must agree to use effective contraception or be surgically sterile; barrier methods are a recommended form of contraception
  • Have clinically significant cardiac disease (New York Heart Association, class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction 1 year prior to study entry, or a known history of grade 2 or higher compromised left ventricular ejection fraction
  • Have dementia or altered mental status that would prohibit informed consent
  • Have any other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the principal investigator, would make the patient inappropriate for this study
  • Have a history of allergic (anaphylactic) sensitivity to bortezomib, boron or mannitol
  • Have grade 2 or greater neuropathy at the time of screening
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02514382


Contacts
Contact: Sondra Ortiz, RN 323-865-0451 Sondra.ortiz@med.usc.edu
Contact: Christine Duran 323-865-0371 Christine.Duran@med.usc.edu

Locations
United States, California
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Sondra R. Ortiz, RN    323-865-0451    Sondra.ortiz@med.usc.edu   
Principal Investigator: Kevin R. Kelly, MD         
Sponsors and Collaborators
University of Southern California
National Cancer Institute (NCI)
Oncolytics Biotech
Investigators
Principal Investigator: Kevin Kelly, MD University of Southern California
  More Information

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT02514382     History of Changes
Other Study ID Numbers: 16M-15-2
NCI-2015-01069 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
REO 019
16M-15-2 ( Other Identifier: USC / Norris Comprehensive Cancer Center )
P30CA014089 ( U.S. NIH Grant/Contract )
First Submitted: July 30, 2015
First Posted: August 3, 2015
Last Update Posted: April 11, 2017
Last Verified: April 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Dexamethasone acetate
Dexamethasone
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors