Vorinostat and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma
About this trial
This is an interventional treatment trial for Refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria: Histologically and clinically confirmed multiple myeloma Relapsed or refractory disease after prior chemotherapy or transplantation* Measurable disease, defined by quantitative immunoglobulin levels in serum and/or urine and bone marrow plasmacytosis Non-secretory disease allowed provided MRI or positron emission tomography or CT scan can accurately measure at least one plasmacytoma lesion No known CNS involvement Life expectancy > 3 months ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% Absolute neutrophil count ≥ 1,000/mm³ (unless myelosuppression is secondary to bone marrow plasmacytosis [> 80% involvement]) Platelet count ≥ 50,000/mm³ (unless myelosuppression is secondary to bone marrow plasmacytosis [> 80% involvement]) Bilirubin ≤ 2 times upper limit of normal (ULN) AST and ALT ≤ 2 times ULN Creatinine < 2 mg/dL OR creatinine clearance > 40 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to swallow pills Patients with a history of seizures are eligible provided seizures are under adequate control with non-enzyme inducing anticonvulsant medication No history of allergic reactions attributed to study agents No sensory or motor neuropathy ≥ grade II No uncontrolled current illness including, but not limited to, the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situation that would limit study compliance No grade 3 QT prolongation (i.e., > 500 msec) at baseline See Disease Characteristics Prior bortezomib allowed At least 2 weeks since prior therapy for multiple myeloma Concurrent growth factors (filgrastim [G-CSF] and epoetin alfa) to sustain peripheral blood counts (during the first course of therapy only) allowed Concurrent steroid therapy (≤ 20 mg of prednisone) for patients requiring chronic use for disorders other than myeloma allowed No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational or commercial agents or therapies for this malignancy
Sites / Locations
- University of Maryland Greenebaum Cancer Center
Arms of the Study
Arm 1
Experimental
Treatment (vorinostat, bortezomib)
Patients receive bortezomib IV on days 1, 4, 8, and 11 followed by oral SAHA twice daily on days 4-11. Beginning in course 3, some patients may receive low-dose oral dexamethasone on days 4-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional cohort of 10 patients receive treatment at the MTD. Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and biomarker correlative studies.