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

Phase 2

Completed

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

• Registration Number: NCT02092922
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-03-19
• Study First Submitted QC: 2014-03-19
• Study First Posted: 2014-03-20
• Study Start: 2014-05
• Primary Completion: 2016-07
• Disposition First Submitted: 2017-08-07
• Disposition First Submitted QC: 2017-08-07
• Disposition First Posted: 2017-08-08
• Study Completion: 2017-09-05
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-13
• Last Update Posted: 2020-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 154

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Filanesib	Filanesib, KSP (Eg5) inhibitor; intravenous	-
Filanesib	Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 patients with high Baseline AAG, assess the efficacy of the study drug in terms of objective response rate.	up to 2 years
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

Trial Locations

Locations (60)

Emory University, Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of California, San Francisco Medical Center; 🇺🇸 San Francisco, California, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

UAB Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Center for Cancer and Blood Disorders; 🇺🇸 Bethesda, Maryland, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Yale Comprehensive Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Mount Sinai Medical Center; 🇺🇸 New York, New York, United States

University of Kansas Cancer Center and Medical Pavilion; 🇺🇸 Westwood, Kansas, United States

City of Hope; 🇺🇸 Duarte, California, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Duke Cancer Center; 🇺🇸 Durham, North Carolina, United States

Institut Jules Bordet; 🇧🇪 Bruxelles, Belgium

University of Athens School of Medicine; 🇬🇷 Athens, Greece

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Centre Hospitalier Lyon-Sud; 🇫🇷 Bierre-Benite Cedex, France

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Universitaire Ziekenhuizen Leuven; 🇧🇪 Leuven, Belgium

The Royal Marsden NHS Foundation Trust; 🇬🇧 Surrey, United Kingdom

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

G.H.U Caremeau; 🇫🇷 Nimes Cedex 9, France

Institut Universitaire de Cancer; 🇫🇷 Toulouse, France

CHU Hotel Dieu; 🇫🇷 Nantes Cedex, France

Barts Health NHS Trust; 🇬🇧 London, United Kingdom

University Hospital Heidelberg; 🇩🇪 Heidelberg, Germany

General Hospital of Athens "Evangelismos"; 🇬🇷 Athens, Greece

Kings College Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

Southhampton General Hospital; 🇬🇧 Southhampton, United Kingdom

Julius Maximilians Universitat Wurzburg; 🇩🇪 Wurzburg, Germany

New Cross Hospital; 🇬🇧 Wolverhampton, United Kingdom

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario La Fe; 🇪🇸 Valencia, Spain

Hospital Quiron de Zaragoza; 🇪🇸 Zaragoza, Spain

NY Presbyterian - Weill Cornell Medical Center; 🇺🇸 New York, New York, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Washington University in St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Nebraska Hematology Oncology, P.C.; 🇺🇸 Lincoln, Nebraska, United States

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

Hopital Claude Huriez; 🇫🇷 Lille Cedex, France

CHU de Nancy - Hopital de Brabois; 🇫🇷 Vandoeuvre les Nancy, France

Asklepios Kliniken Hamburg GmbH; 🇩🇪 Hamburg, Germany

TU Dresden Medizinische Fakultat, Medizinische Klinik und Poliklinik I; 🇩🇪 Dresden, Germany

University of Tubingen; 🇩🇪 Tubingen, Germany

University Hospital Leipzig; 🇩🇪 Leipzig, Germany

CHU tours-Hopital Bretonneau; 🇫🇷 Tours Cedex, France

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Cancer Care Northwest; 🇺🇸 Spokane Valley, Washington, United States

Institut Paoli Calmettes; 🇫🇷 Marseille Cedex 9, France

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

QEII Health Sciences Center; 🇨🇦 Halifax, Nova Scotia, Canada