Filgrastim in Treating Patients With Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma
Based on the pre-clinical data the investigators hypothesize that G-CSF treatment in patients with multiple myeloma will generate a 'hostile' bone marrow microenvironment for myeloma cells, depriving them of key support signals and rendering them more sensitive to chemotherapy. The investigators therefore propose to do an initial pilot study 1) to explore the safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with bortezomib-, carfilzomib-, or IMID-refractory myeloma and 2) to generate correlative data for a subsequent larger study looking at the combination.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma|
- Safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with refractory multiple myeloma. [ Time Frame: Up to 30 days after last treatment ] [ Designated as safety issue: Yes ]Number and grade of adverse events based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Effects of G-CSF on bone marrow and bone marrow cytokine and chemokine levels. Including: Quantification of marrow osteoblasts and CAR cells, measurement of SDF-1 (CXCL12), IL-6, BAFF, assessment of myeloma cell proliferation and survival in bone marrow [ Time Frame: 14 days after last drug treatment ] [ Designated as safety issue: No ]
- Response rate as defined by the International Myeloma Working Group (IMWG) criteria [ Time Frame: 14 days after last drug treatment ] [ Designated as safety issue: No ]
- Overall survival duration of patients treated on study [ Time Frame: 1 year ] [ Designated as safety issue: No ]Defined as the date of first dose of study drug to the date of death from any cause.
- Progression-free survival of patients treated on study [ Time Frame: 1 year ] [ Designated as safety issue: No ]Defined as the interval from the date of first treatment to date of first documentation of disease progression.
- Duration of response of patients treated on study [ Time Frame: 1 year ] [ Designated as safety issue: No ]Defined as the interval from the date of first documentation of response to the first documentation of disease progression.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||December 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
Other Names:Drug: Bortezomib
Other Name: Velcade®Drug: Carfilzomib
Other Name: Kyprolis®Drug: Dexamethasone Drug: Cyclophosphamide
Other Name: CytoxanDrug: Thalidomide
Other Name: ThalomidDrug: Lenalidomide
Other Name: RevlimidDrug: Pomalidomide
Other Name: Pomalyst
Please refer to this study by its ClinicalTrials.gov identifier: NCT01537861
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Ravi Vij, M.D.||Washington University School of Medicine|