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

Study Overview
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Brief Summary
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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.

Conditions
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Advanced Multiple Myeloma

Intervention / Treatment
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* Drug: Filanesib, KSP (Eg5) inhibitor; intravenous
* Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients with confirmed multiple myeloma whose treatment history must include all of the following: Received at least 2 prior lines of therapy (induction therapy and stem cell transplant ± maintenance are to be considered a single line of therapy). 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). 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: A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ≥ 1.0 g/dL. Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ≥ 200 mg/24 hours. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |