Clinical trial NCT02092922: A Phase 2 Trial of Filanesib in Relapsed/Refractory Multiple Myeloma (AfFIRM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Multiple Myeloma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-03-20
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: In patients with low Baseline alpha 1-acid glycoprotein (AAG), assess the efficacy of the study drug in terms of objective response rate.
timeFrame: up to 2 years
Secondary outcomes:
measure: In patients with high Baseline AAG, assess the efficacy of the study drug in terms of objective response rate.
timeFrame: up to 2 years
measure: In all patients, assess the efficacy of the study drug in terms of duration of response.
timeFrame: up to 2 years
measure: In all patients, assess the efficacy of the study drug in terms of progression-free survival.
timeFrame: up to 2 years
measure: In all patients, assess the efficacy of study drug in terms of overall survival.
timeFrame: up to 2 years
measure: In all patients, assess the safety of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.
timeFrame: up to 2 years
measure: In a subset of all patients, characterize the pharmacokinetics (PK) of the study drug in terms of plasma concentration-time profiles.
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center
state: Connecticut
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center and Medical Pavilion
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Hematology Oncology, P.C.
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: NY Presbyterian - Weill Cornell Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Spokane Valley
country: United States
facility: Cancer Care Northwest
state: Washington
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Sciences Center
state: Nova Scotia
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Bierre-Benite Cedex
country: France
facility: Centre Hospitalier Lyon-Sud
city: Lille Cedex
country: France
facility: Hopital Claude Huriez
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Nantes Cedex
country: France
facility: CHU Hotel Dieu
city: Nimes Cedex 9
country: France
facility: G.H.U Caremeau
city: Toulouse
country: France
facility: Institut Universitaire de Cancer
city: Tours Cedex
country: France
facility: CHU tours-Hopital Bretonneau
city: Vandoeuvre les Nancy
country: France
facility: CHU de Nancy - Hopital de Brabois
city: Dresden
country: Germany
facility: TU Dresden Medizinische Fakultat, Medizinische Klinik und Poliklinik I
city: Hamburg
country: Germany
facility: Asklepios Kliniken Hamburg GmbH
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Tubingen
country: Germany
facility: University of Tubingen
city: Wurzburg
country: Germany
facility: Julius Maximilians Universitat Wurzburg
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos"
city: Athens
country: Greece
facility: University of Athens School of Medicine
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Quiron de Zaragoza
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust
city: Southhampton
country: United Kingdom
facility: Southhampton General Hospital
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: