Advanced Multiple Myeloma
Conditions
Brief summary
This is a Phase 2 study during which patients with advanced multiple myeloma will receive either carfilzomib alone (single-agent) or carfilzomib in combination with investigational study drug filanesib (ARRY-520). Patients will be followed to determine the effectiveness of both single-agent carfilzomib and carfilzomib + filanesib in treating myeloma. Patients will be allowed to crossover from single-agent carfilzomib to carfilzomib + filanesib if disease progression occurs. Approximately 75 patients from the US will be enrolled in this study.
Interventions
DRUGCarfilzomib, proteasome inhibitor; intravenous
multiple dose, single schedule
DRUGFilanesib, KSP(Eg5) inhibitor; intravenous
multiple dose, single schedule
DRUGDexamethasone, steroid; oral or intravenous
as indicated, per the carfilzomib prescribing information
standard of care
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Confirmed multiple myeloma with measurable disease. * Disease refractory to last myeloma regimen. * Patients must have received at least 2 prior treatment regimens, including bortezomib and an IMiD (e.g., lenalidomide, thalidomide, pomalidomide). Induction therapy and stem cell transplant ± maintenance are to be considered as a single regimen. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to first dose of study treatment. * Adequate hematology, liver and renal function laboratory values within 14 days prior to first dose of study treatment. * Additional criteria exist. Key
Exclusion criteria
* Prior treatment with carfilzomib, filanesib, 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). * Ongoing Grade 3 or Grade 4 peripheral neuropathy, or Grade 2 peripheral neuropathy with pain despite appropriate interventions, within 28 days prior to first dose of study treatment. * Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to first dose of study treatment. * 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 treatment. 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. * Known pulmonary hypertension of any severity. * Concurrent cardiac disease that, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assess the efficacy of both carfilzomib + study drug and single-agent carfilzomib in terms of progression-free survival. | 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Assess the efficacy of both carfilzomib + study drug and single-agent carfilzomib in terms of objective response rate. | 18 months |
| Assess the safety of both carfilzomib + study drug and single-agent carfilzomib in terms of adverse events, clinical laboratory tests and electrocardiograms. | 18 months |
| Following crossover from single-agent carfilzomib, assess the efficacy of carfilzomib + study drug in terms of objective response rate. | 18 months |
| Following crossover from single-agent carfilzomib, assess the safety of carfilzomib + study drug in terms of adverse events, clinical laboratory tests and electrocardiograms. | 18 months |
| Characterize the pharmacokinetics (PK) of study drug, carfilzomib and a carfilzomib metabolite in patients treated with carfilzomib + study drug in terms of plasma concentration-time profiles and model-based PK parameters. | 6 months |
Other
| Measure | Time frame |
|---|---|
| Evaluate patient serum levels of alpha 1-acid glycoprotein (AAG) at Baseline and during the treatment period. | 18 months |
Countries
United States
Outcome results
None listed