- To evaluate the efficacy of single agent dinaciclib in patients with relapsed or refractory multiple myeloma.
- To evaluate the toxicities associated with dinaciclib in these patients.
- To evaluate the response duration and progression-free survival among these patients.
- To study the effect of dinaciclib on myeloma cell proliferation and apoptotic rates.
- To assess the ability of dinaciclib to inhibit drug targets (cyclin-dependent kinases in the myeloma cell).
OUTLINE: This is a multicenter, dose escalation study.
Patients receive dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and bone marrow samples are collected periodically for correlative studies.
After completion of study treatment, patients are followed up for up to 3 years.
- Diagnosis of relapsed or refractory multiple myeloma
- Measurable disease as defined by ≥ 1 of the following:
- Serum monoclonal protein ≥ 1.0 g/dL
- More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
- Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Not a candidate for stem cell transplantation or has had stem cells collected previously
- ECOG performance status 0-2
- Life expectancy ≥ 3 months
- ANC ≥ 1,000/mm^3
- Platelet count ≥ 75,000/mm^3
- Hemoglobin ≥ 8 g/dL
- Total serum bilirubin normal
- AST/ALT ≤ 2.5 upper limit of normal
- Creatinine < 2.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Willing to provide blood and bone marrow samples for research
- No other active malignancy except for nonmelanoma skin cancer or in situ cervical or breast cancer
- No uncontrolled concurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Psychiatric illness or social situations that would limit compliance with study requirements
PRIOR CONCURRENT THERAPY:
- No more than 5 prior therapies for this disease (stem cell transplantation and preceding induction therapy will be considered as 1 therapy)
- More than 3 weeks since prior myelosuppressive therapy for myeloma AND recovered from acute reversible adverse events
- More than 2 weeks since prior non-myelosuppressive agents (e.g., thalidomide or high dose corticosteroids)
- No concurrent high dose corticosteroids
- Concurrent corticosteroids allowed provided patients are on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than amyloid (i.e., adrenal insufficiency, rheumatoid arthritis, etc.)
- No concurrent inhibitors or inducers of CYP3A4
- No concurrent grapefruit juice or St. John wort
- No other concurrent investigational agents
- Concurrent bisphosphonates allowed
Last updated: 03/26/2012