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.


Eligibility Criteria:
Inclusion Criteria:

* Patient must have a confirmed diagnosis of multiple myeloma. The patient may be any stage of multiple myeloma. The patient may have received one or more lines of prior therapy (there is no limit to number of prior lines of therapy permissible).
* Patient must be ≥18 years of age
* Patient must be in active treatment with one of the following:

  * twice-weekly bortezomib (on Days 1, 4, 8, and 11 of a 21-day cycle) with or without dexamethasone
  * carfilzomib (on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle) with or without dexamethasone
  * an IMID with or without dexamethasone daily on Days 1 to 21.
  * Patients being treated with bortezomib or carfilzomb may also be receiving an IMID or PO cyclophosphamide with the regimen.
* Patient must have shown stable or progressive disease on the current bortezomib-, carfilzomib-, or IMID-containing regimen with a measurable monoclonal protein component in the serum (at least 0.5 g/dl on electrophoresis or 0.05 g/dl \[50mg/dl\] on serum-free-light-chain). Patients who had an initial response on the current bortezomib-, carfilzomib-, or IMID-containing regimen but now have stable (plateaued) disease are eligible.
* Patient must have an ECOG performance status of 0 - 2
* Patient must be receiving concurrent treatment with bisphosphonates, with one dose occurring within 30 days prior to first day (Day -3) of protocol treatment
* Patient must have acceptable hematologic parameters, defined as:

  * Absolute neutrophil count \> 1000 cells/mm3
  * Platelets ≥ 50,000 cells/mm3
  * Hemoglobin ≥ 8 g/dl
* Patient must have adequate liver function, defined as:

  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 x upper limit of normal
  * Total bilirubin \< 2 x upper limit of normal
* Patient must be able to understand and willing to sign a written informed consent document

Exclusion Criteria:

* Patient must not be receiving any agents with known or suspected anti-myeloma activity (other than bortezomib, carfilzomib, dexamethasone, an IMID or PO cyclophosphamide, and bisphosphonates with the current regimen)
* Patient must not be actively using myeloid growth factors
* Patient must not have had any prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years
* Patient must not have any uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure
* Patient must not have neuropathy ≥ grade 3 or painful neuropathy ≥ grade 2 (NCI CTCAE v 4.0)
* Patient must not have any known active infections requiring IV antibiotic, antiviral, or antifungal therapy
* Patient must not be pregnant or breastfeeding