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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Multiple Myeloma
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Genesis Cancer Center
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare
  • Florida
    • Fort Myers, Florida, United States, 33905
      • Florida Cancer Specialists
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Crescent City Research Consortium
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Forrest General Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care - Blue Ash
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Knight Cancer Institute at Oregon Health & Science University
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Health Care System
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • Simmons Cancer Center - UT Southwestern Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • WVU - Mary Babb Randolph Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Carfilzomib + Filanesib; 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.	Drug: Carfilzomib, proteasome inhibitor; intravenous; multiple dose, single schedule; Drug: Filanesib, KSP(Eg5) inhibitor; intravenous; multiple dose, single schedule; Drug: Dexamethasone, steroid; oral or intravenous; as indicated, per the carfilzomib prescribing information; Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous; standard of care
EXPERIMENTAL: Carfilzomib; Single agent arm. Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information.	Drug: Carfilzomib, proteasome inhibitor; intravenous; multiple dose, single schedule; Drug: Dexamethasone, steroid; oral or intravenous; as indicated, per the carfilzomib prescribing information

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess the efficacy of both carfilzomib + study drug and single-agent carfilzomib 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
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
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

Other Outcome Measures

Outcome Measure	Time Frame
Evaluate patient serum levels of alpha 1-acid glycoprotein (AAG) at Baseline and during the treatment period.	18 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Clinical Trial Pfizer CT.gov Call Center, Pfizer

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): May 1, 2016

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 14, 2013
• First Posted (ESTIMATE): November 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Adjuvants, Immunologic; Dexamethasone; Lenograstim; Proteasome Inhibitors; Filanesib
• Other Study ID Numbers: ARRAY-520-216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.