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

Advanced Multiple Myeloma Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02092922
• Other study ID #: ARRAY-520-215
• Secondary ID: 2014-001051-23C4
• Status: Completed
• Phase: Phase 2
• Start date: May 2014
• Est. completion date: September 5, 2017

Study information

• Verified date: October 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: September 5, 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Multiple Myeloma
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Filanesib, KSP (Eg5) inhibitor; intravenous
multiple dose, single schedule
• Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous
standard of care

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Greece,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	In patients with high Baseline AAG, assess the efficacy of the study drug in terms of objective response rate.		up to 2 years
Secondary	In all patients, assess the efficacy of the study drug in terms of duration of response.		up to 2 years
Secondary	In all patients, assess the efficacy of the study drug in terms of progression-free survival.		up to 2 years
Secondary	In all patients, assess the efficacy of study drug in terms of overall survival.		up to 2 years
Secondary	In all patients, assess the safety of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.		up to 2 years
Secondary	In a subset of all patients, characterize the pharmacokinetics (PK) of the study drug in terms of plasma concentration-time profiles.		6 months
Secondary	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