Clinical Trials

Inclusion

• ANC ≥ 1500/uL
• AST ≤ 2.5 x ULN
• Creatinine ≤ 1.5 x ULN
• Creatinine clearance as calculated by the method of Cockroft and Gault ≥ 30 mL/minute
• Patients with relapsed or refractory multiple myeloma requiring treatment
• Patients who have received prior bortezomib therapy will be allowed on trial as long as they did not progress during bortezomib or ≤ 60 days of therapy discontinuation
• Negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential (WOCBP) only (a WOCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months)
• Willingness to return to enrolling institution for follow-up
• Life expectancy ≥ 12 weeks
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
• Male subject agrees to use an acceptable method for contraception for the duration of the study
• Patients have a baseline LVEF ≥ 45% at baseline
• Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• PLT ≥ 100,000/uL
• Total bilirubin ≤1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN, the direct bilirubin must be &le 2.0 mg/dL
• Measurable disease of multiple myeloma as defined by at least ONE of the following:
• Serum monoclonal protein ≥ 1.0 g/dL, ≥ 200 mg of monoclonal protein in the urine on 24 hour electrophoresis, serum immunoglobulin free light chain &ge 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio, monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease), or measurable plasmacytoma
• ECOG Performance Status (PS) 0, 1, or 2
• Hgb ≥ 9 g/dl

Exclusion

• Major surgery, open biopsy (excluding bone marrow) or significant traumatic injury &le 4 weeks prior to registration
• Melphalan or other myelosuppressive agents including lenalidomide and non-myelosuppressive agents such as thalidomide or high dose corticosteroids &le 2 weeks prior to registration
• Concurrent use of corticosteroids, but patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
• Uncontrolled infection
• Pregnant women or women of reproductive ability who are unwilling to use effective contraception
• Nursing women
• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
• Other co-morbidity or psychiatric illness which would interfere with patient's ability to participate in this trial
• Recent history of myocardial infarction in the six months prior to registration
• Uncontrolled angina or electrocardiographic evidence of acute ischemia
• Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of active conduction system abnormalities
• Cardiac amyloidosis with hypotension (systolic BP less than 100mmHg)
• MGUS or smoldering myeloma
• Serious non-healing wound, or ulcer
• Known hypersensitivity to Bortezomib, boron or mannitol
• Patient has &ge Grade 2 peripheral neuropathy within 14 days before enrollment
• Patient has received other investigational drugs with 14 days before enrollment
• Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
• Infection requiring systemic antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection
• Inability to swallow orally administered medication
• Prior allogeneic bone marrow or organ transplantation
• Patients who are currently receiving digoxin, cyclosporine, tacrolimus or sirolimus
• Severe cardiac comorbidity
• Known positive for HIV or active infectious hepatitis, type A, B or C