Wild-Type Reovirus in Combination With Carfilzomib and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT02101944 | Completed Phase 1 DMC

• 10 other identifiers: NCI-2014-00643OSU-1403114031NCI-96032014C00919603P30CA016058U01CA076576UM1CA186691UM1CA186712
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of wild-type reovirus when combined with carfilzomib and dexamethasone in treating patients with multiple myeloma that has come back following treatment (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as dexamethasone and carfilzomib, 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. A virus called wild-type reovirus may be able to kill cancer cells without damaging normal cells and seems to work best when given with chemotherapy. Giving wild-type reovirus with chemotherapy may be a more effective treatment than chemotherapy alone.

Conditions

Anemia; Recurrent Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• Number and severity of adverse events

  Based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events will be perceived causal relationship to the study therapy.

  Up to 4 weeks post treatment

• Maximum tolerated dose of combination carfilzomib and wild-type reovirus

  Assessed by CTCAE version 5.0. Maximum tolerated dose defined as the highest dose with fewer than 33% dose limiting toxicities observed in cycle 1 or 2 evaluated using CTCAE version 5.0. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

  Up to 28 days

• Number of patients who required dose modifications and/or dose delays in subsequent cycles

  Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

  Up to 4 weeks post treatment

• Proportion of patients who go off treatment due to adverse reactions of refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial

  Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

  Up to 4 weeks post treatment

Secondary Outcomes (7)

• Reoviral capsid protein production via immunohistochemical analysis

  Up to day 9 of cycle 1

• Presence and location of intracellular reoviral ribonucleic acid (RNA) assessed by in situ hybridization

  Up to day 9 of cycle 1

• Number and percentage of subjects experiencing objective response

  Up to 4 weeks post treatment

• Clinical benefit endpoint described as that portion of patients experiencing complete response, very good partial response, or partial response

  Up to 4 weeks post treatment

• Duration of response

  Duration from first observation of partial response to the time of disease progression, up to 4 weeks post treatment

Other Outcomes (1)

• Immunologic correlative markers

  Up to 2 years

Study Arms (1)

Treatment (dexamethasone, carfilzomib, Reolysin)

EXPERIMENTAL

Patients receive dexamethasone intravenously (IV), carfilzomib IV over 30 minutes, and Reolysin IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carfilzomib; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Biological: Pelareorep

Interventions

Carfilzomib DRUG

Given IV

Also known as: Carfilnat, CFZ, Kyprolis, PR-171

Treatment (dexamethasone, carfilzomib, Reolysin)

Dexamethasone DRUG

Given IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, 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, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (dexamethasone, carfilzomib, Reolysin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dexamethasone, carfilzomib, Reolysin)

Pelareorep BIOLOGICAL

Given IV

Also known as: PO BB0209, PO-BB0209, Reolysin, Reovirus Serotype 3, Wild-type Reovirus

Treatment (dexamethasone, carfilzomib, Reolysin)

Eligibility Criteria

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

You may qualify if:

• Patient must have relapsed or refractory myeloma that fits or did fit International Myeloma Working Group (IMWG) diagnostic criteria for symptomatic myeloma (although new or worsening end organ damage is not required to be eligible) as defined below:
• Presence of clonal bone marrow plasma cells
• Evidence of any end organ damage criteria listed below (at any time) attributed to the patient's myeloma:
• Hypercalcemia: serum calcium \> 11.5 mg/dL or
• Renal insufficiency: serum creatinine \> 2 mg/dL
• Anemia \> 2 g/dL below the lower limit of normal or a hemoglobin value \< 10 g/dL
• Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
• In the safety expansion 10 patient group but not during dose escalation, patients must have measurable disease defined as any of the following:
• Serum monoclonal protein \>= 500 mg/dL by protein electrophoresis
• \> 200 mg of monoclonal protein in the urine on screening 24-hour electrophoresis
• Serum immunoglobulin free light chain \>= 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Patients must have been previously treated with an immunomodulatory drug (IMiD) and proteasome inhibitor, must be refractory to carfilzomib defined as progression on or within 2 months of a carfilzomib-containing therapy, and must be progressing
• Prior autologous and/or allogeneic transplant is permitted although transplant must have occurred greater than 90 days prior to registration
• Both men and women of all races and ethnic groups are eligible for this study
• Prior radiation is permitted; however, at least 2 weeks must have elapsed since the completion of prior radiation therapy and patients must have recovered from all radiation-associated toxicities to no greater than grade 1 at the time of registration

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study; patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg by mouth daily or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment
• Patients who are receiving any other therapeutic investigational agents
• Patients previously treated on clinical trial with Reolysin
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to protocol treatment of the mother, breastfeeding should be discontinued
• Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to \< 1 year, or confound data interpretation
• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes (POEMS) syndrome
• Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Dona AA, Tandoh T, Nigam L, Singer M, Caserta E, Murtadha M, Zhu Y, Moloudizargari M, Sharma P, Napolitano O, Winchester J, Chowdhury A, Pozhitkov A, Sanchez JF, Vahed H, Marcucci G, Coffey M, Nuovo G, Sborov DW, Pichiorri F, Hofmeister CC. Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects. J Hematol Oncol. 2025 Jan 20;18(1):1. doi: 10.1186/s13045-024-01645-3.

  PMID: 39828738 DERIVED

MeSH Terms

Conditions

Anemia; Multiple Myeloma

Interventions

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

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Craig C Hofmeister

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: December 9, 2014
• Primary Completion: May 5, 2021
• Study Completion: May 7, 2024
• Last Updated: May 17, 2024

Record last verified: 2024-05

Locations

US (3)