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

NCT02514382 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: 16M-15-2NCI-2015-01069REO 019P30CA014089
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events assessed by CTCAE version 4.03

  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.

  Up to 30 days post-treatment

Secondary Outcomes (1)

• ORR

  Up to 3 years

Study Arms (1)

Treatment (dexamethasone, bortezomib, wild-type reovirus)

EXPERIMENTAL

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; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Wild-type Reovirus

Interventions

Bortezomib DRUG

Given SC or IV

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (dexamethasone, bortezomib, wild-type reovirus)

Dexamethasone DRUG

Given PO, IV, or IM

Also known as: 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

Treatment (dexamethasone, bortezomib, wild-type reovirus)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dexamethasone, bortezomib, wild-type reovirus)

Pharmacological Study OTHER

Correlative studies

Treatment (dexamethasone, bortezomib, wild-type reovirus)

Wild-type Reovirus BIOLOGICAL

Given IV

Also known as: Reolysin

Treatment (dexamethasone, bortezomib, wild-type reovirus)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Oncolytics Biotech: collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Related Publications (1)

• Nawrocki ST, Olea J, Villa Celi C, Dadrastoussi H, Wu K, Tsao-Wei D, Colombo A, Coffey M, Fernandez Hernandez E, Chen X, Nuovo GJ, Carew JS, Mohrbacher AF, Fields P, Kuhn P, Siddiqi I, Merchant A, Kelly KR. Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial. Clin Cancer Res. 2023 Dec 15;29(24):5087-5103. doi: 10.1158/1078-0432.CCR-23-0229.

  PMID: 37812476 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; reolysin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Kevin Kelly, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 3, 2015
• Study Start: August 21, 2015
• Primary Completion: April 19, 2022
• Study Completion: April 19, 2022
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

US (1)