A Phase 2 Trial of Filanesib in Relapsed/Refractory Multiple Myeloma (AfFIRM)

The AfFIRM Study is a Phase 2 study during which patients with advanced multiple myeloma will receive single-agent investigational study drug filanesib (ARRY-520). Patients will be followed to determine the effectiveness of filanesib in treating myeloma. Approximately 160 patients from North America and Europe will be enrolled in this study.

Eligible patients will have received at least two prior lines of therapy; have received prior bortezomib and lenalidomide; and have disease refractory to carfilzomib and/or pomalidomide.

Study Overview

• Status: Completed
• Conditions: Advanced Multiple Myeloma
• Intervention / Treatment: Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous; Drug: Filanesib, KSP (Eg5) inhibitor; intravenous

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Institut Jules Bordet
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Tom Baker Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • QEII Health Sciences Center
  • Quebec
    • Montreal, Quebec, Canada
      • Jewish General Hospital
• France
  • Bierre-Benite Cedex, France
    • Centre Hospitalier Lyon-Sud
  • Lille Cedex, France
    • Hôpital Claude Huriez
  • Marseille Cedex 9, France
    • Institut Paoli Calmettes
  • Nantes Cedex, France
    • CHU Hôtel Dieu
  • Nimes Cedex 9, France
    • G.H.U Caremeau
  • Toulouse, France
    • Institut Universitaire de Cancer
  • Tours Cedex, France
    • CHU tours-Hopital Bretonneau
  • Vandoeuvre les Nancy, France
    • CHU de Nancy - Hopital de Brabois
• Germany
  • Dresden, Germany
    • TU Dresden Medizinische Fakultat, Medizinische Klinik und Poliklinik I
  • Hamburg, Germany
    • Asklepios Kliniken Hamburg GmbH
  • Heidelberg, Germany
    • University Hospital Heidelberg
  • Leipzig, Germany
    • University Hospital Leipzig
  • Tubingen, Germany
    • University of Tubingen
  • Wurzburg, Germany
    • Julius Maximilians Universitat Wurzburg
• Greece
  • Athens, Greece
    • General Hospital of Athens "Evangelismos"
  • Athens, Greece
    • University of Athens School of Medicine
• Spain
  • Badalona, Spain
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital Clinic de Barcelona
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain
    • Hospital Universitario La Fe
  • Zaragoza, Spain
    • Hospital Quiron de Zaragoza
• United Kingdom
  • London, United Kingdom
    • Kings College Hospital NHS Foundation Trust
  • London, United Kingdom
    • Barts Health NHS Trust
  • Southhampton, United Kingdom
    • Southhampton General Hospital
  • Surrey, United Kingdom
    • The Royal Marsden NHS Foundation Trust
  • Wolverhampton, United Kingdom
    • New Cross Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Uab Comprehensive Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • San Francisco, California, United States, 94143
      • University of California, San Francisco Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University, Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center and Medical Pavilion
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center For Cancer And Blood Disorders
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University in St. Louis
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Nebraska Hematology Oncology, P.C.
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10065
      • NY Presbyterian - Weill Cornell Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Washington
    • Spokane Valley, Washington, United States, 99216
      • Cancer Care Northwest

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:

• Patients with confirmed multiple myeloma whose treatment history must include all of the following:

  1. Received at least 2 prior lines of therapy (induction therapy and stem cell transplant ± maintenance are to be considered a single line of therapy).
  2. Received at least 2 cycles of a bortezomib-containing regimen and 2 cycles of a lenalidomide-containing regimen, unless intolerant to these agents (defined as requiring discontinuation due to toxicity).
  3. Disease refractory to a carfilzomib-containing regimen and/or a pomalidomide containing regimen. Refractory is defined as either failure to achieve a minimal response (MR) or better while on therapy, or development of progressive disease (PD) while on therapy or within 60 days from last dose of therapy.

• Measurable multiple myeloma disease, defined as meeting at least one of the following criteria within 14 days prior to first dose of study drug:

  1. A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ≥ 1.0 g/dL.
  2. Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ≥ 200 mg/24 hours.
  3. Involved serum free light chain (FLC) level ≥ 10 mg/dL, provided the serum FLC ratio is abnormal.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to first dose of study drug.
• Adequate hematology, hepatic and renal function laboratory values within 14 days prior to first dose of study drug.
• Additional criteria exist.

Key Exclusion Criteria:

• Prior treatment with filanesib (ARRY-520) 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).
• Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to first dose of study drug.
• 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 drug. 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.
• Use of an investigational agent that is not expected to be cleared by the time of first dose of study drug or that has been demonstrated to have prolonged side effects. Patients must have recovered from all side effects to a Grade 0 or 1 (except alopecia and neuropathy).
• Any severe concurrent disease or condition (including severe graft-versus-host disease, requirement for dialysis, symptomatic congestive heart failure [New York Heart Association Class III or IV], unstable angina pectoris, cardiac arrhythmia) which, 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Filanesib	Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous; standard of care; Drug: Filanesib, KSP (Eg5) inhibitor; intravenous; multiple dose, single schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
In patients with low Baseline alpha 1-acid glycoprotein (AAG), assess the efficacy of the study drug in terms of objective response rate.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
In patients with high Baseline AAG, assess the efficacy of the study drug in terms of objective response rate.	up to 2 years
In all patients, assess the efficacy of the study drug in terms of duration of response.	up to 2 years
In all patients, assess the efficacy of the study drug in terms of progression-free survival.	up to 2 years
In all patients, assess the efficacy of study drug in terms of overall survival.	up to 2 years
In all patients, assess the safety of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.	up to 2 years
In a subset of all patients, characterize the pharmacokinetics (PK) of the study drug in terms of plasma concentration-time profiles.	6 months
In a subset of all patients, assess the correlation between study drug exposure and changes in corrected QT interval (QTc) in terms of changes in QTc versus time-matched study drug plasma concentrations.	6 months

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): September 5, 2017

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (Estimate): March 20, 2014

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 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; Antineoplastic Agents; Immunologic Factors; Antimitotic Agents; Mitosis Modulators; Adjuvants, Immunologic; Lenograstim; Filanesib
• Other Study ID Numbers: ARRAY-520-215; 2014-001051-23 (EudraCT Number); C4371002 (Other Identifier: Pfizer)

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.