A Study of Filanesib (ARRY-520) and Carfilzomib in Patients With Advanced Multiple Myeloma

Phase 2

Completed

Conditions: Advanced Multiple Myeloma

Interventions: Drug: Carfilzomib, proteasome inhibitor; intravenous
Drug: Filanesib, KSP(Eg5) inhibitor; intravenous
Drug: Dexamethasone, steroid; oral or intravenous
Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous

Registration Number: NCT01989325

Lead Sponsor: Pfizer

Brief Summary: This is a Phase 2 study during which patients with advanced multiple myeloma will receive either carfilzomib alone (single-agent) or carfilzomib in combination with investigational study drug filanesib (ARRY-520). Patients will be followed to determine the effectiveness of both single-agent carfilzomib and carfilzomib + filanesib in treating myeloma. Patients will be allowed to crossover from single-agent carfilzomib to carfilzomib + filanesib if disease progression occurs. Approximately 75 patients from the US will be enrolled in this study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 77

Inclusion Criteria

Confirmed multiple myeloma with measurable disease.
Disease refractory to last myeloma regimen.
Patients must have received at least 2 prior treatment regimens, including bortezomib and an IMiD (e.g., lenalidomide, thalidomide, pomalidomide). Induction therapy and stem cell transplant ± maintenance are to be considered as a single regimen.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to first dose of study treatment.
Adequate hematology, liver and renal function laboratory values within 14 days prior to first dose of study treatment.
Additional criteria exist.

Key

Exclusion Criteria

Prior treatment with carfilzomib, filanesib, or any other KSP inhibitor.
Past or current plasma cell leukemia.
Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
Ongoing Grade 3 or Grade 4 peripheral neuropathy, or Grade 2 peripheral neuropathy with pain despite appropriate interventions, within 28 days prior to first dose of study treatment.
Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to first dose of study treatment.
Concomitant malignancies or previous malignancies (other than multiple myeloma) with less than a 2-year disease-free interval at the time of first dose of study treatment. Patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or Stage 1 prostate cancer are eligible irrespective of the time of diagnosis.
Known pulmonary hypertension of any severity.
Concurrent cardiac disease that, in the judgment of the Investigator, would make the patient inappropriate for study participation.
Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C.
Acute active infection requiring treatment.
Additional criteria exist.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carfilzomib + Filanesib	Filanesib, KSP(Eg5) inhibitor; intravenous	Single agent + Carfilzomib arm. Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information. Filgrastim to be administered per the approved product prescribing information and institutional guidelines.
Carfilzomib + Filanesib	Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous	Single agent + Carfilzomib arm. Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information. Filgrastim to be administered per the approved product prescribing information and institutional guidelines.
Carfilzomib	Carfilzomib, proteasome inhibitor; intravenous	Single agent arm. Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information.
Carfilzomib	Dexamethasone, steroid; oral or intravenous	Single agent arm. Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information.
Carfilzomib + Filanesib	Carfilzomib, proteasome inhibitor; intravenous	Single agent + Carfilzomib arm. Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information. Filgrastim to be administered per the approved product prescribing information and institutional guidelines.
Carfilzomib + Filanesib	Dexamethasone, steroid; oral or intravenous	Single agent + Carfilzomib arm. Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information. Filgrastim to be administered per the approved product prescribing information and institutional guidelines.

Primary Outcome Measures

Name	Time	Method
Assess the efficacy of both carfilzomib + study drug and single-agent carfilzomib in terms of progression-free survival.	18 months

Secondary Outcome Measures

Name	Time	Method
Assess the efficacy of both carfilzomib + study drug and single-agent carfilzomib in terms of objective response rate.	18 months
Characterize the pharmacokinetics (PK) of study drug, carfilzomib and a carfilzomib metabolite in patients treated with carfilzomib + study drug in terms of plasma concentration-time profiles and model-based PK parameters.	6 months
Following crossover from single-agent carfilzomib, assess the efficacy of carfilzomib + study drug in terms of objective response rate.	18 months
Assess the safety of both carfilzomib + study drug and single-agent carfilzomib in terms of adverse events, clinical laboratory tests and electrocardiograms.	18 months
Following crossover from single-agent carfilzomib, assess the safety of carfilzomib + study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.	18 months

Trial Locations

Locations (22): Genesis Cancer Center
🇺🇸
Hot Springs, Arkansas, United States
Prairie Lakes Health Care System
🇺🇸
Watertown, South Dakota, United States
Memorial Sloan Kettering
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New York, New York, United States
Crescent City Research Consortium
🇺🇸
Marrero, Louisiana, United States
St. Joseph Heritage Healthcare
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Santa Rosa, California, United States
UCLA
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Los Angeles, California, United States
Florida Cancer Specialists
🇺🇸
Fort Myers, Florida, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸
Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Karmanos Cancer Institute
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Detroit, Michigan, United States
Forrest General Cancer Center
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Hattiesburg, Mississippi, United States
Nebraska Cancer Specialists
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Omaha, Nebraska, United States
Oncology Hematology Care - Blue Ash
🇺🇸
Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
Knight Cancer Institute at Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Simmons Cancer Center - UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Virginia Cancer Specialists
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Fairfax, Virginia, United States
WVU - Mary Babb Randolph Cancer Center
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Morgantown, West Virginia, United States
Medical College of Wisconsin Cancer Center
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Milwaukee, Wisconsin, United States
Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States