phase 2 study of carfilzomib in relapsed multiple myeloma

Conditions: Multiple Myeloma

Summary: to evaluate the best overall response rate, safety and tolerability of carfilzomib in patients with relapsed or refractory multiple myeloma.

two groups of patients with multiple myeloma were initially studied: bortezomib-naïve and bortezomib-treated. following amendment 2, only bortezomib-naïve patients were enrolled. study results were reported in 2 parts, depending on whether a patient received prior bortezomib.

Eligibility criteria:
inclusion criteria: disease related * multiple myeloma * subjects must have measurable disease, defined as one or more of the following: * serum m-protein ≥ 1 g/dl * urine m-protein ≥ 200 mg/24 hours * subjects must have been responsive (i.e., achieve a minimal response \[mr\] or better) to standard, first line therapy * relapsed and/or refractory or progressive disease after at least one, but no more than three, prior therapeutic treatments or regimens for multiple myeloma. refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy. induction therapy and stem cell transplant will be considered as one regimen demographic * males and females ≥18 years of age * life expectancy of more than three months * eastern cooperative oncology group (ecog) performance status of 0-2 laboratory * adequate hepatic function, with bilirubin \< 2.0 times the upper limit of normal, and aspartate aminotransferase (ast) and alanine aminotransferase (alt) of \< 3.0 times the upper limit of normal * uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing * total white blood cell (wbc) count ≥ 2,000/mm³, absolute neutrophil count \> 1,000/mm³, hemoglobin ≥ 8.0 g/dl, and platelet count \> 50,000/mm³ * subjects should be platelet transfusion independent * screening absolute neutrophil count (anc) should be independent of granulocyte colony stimulating factor (g-csf) or granulocyte macrophage colony stimulating factor (gm-csf) support for ≥ 1 week and of pegylated g-csf for ≥ 2 weeks * subjects may receive red blood cell (rbc) transfusion or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines * calculated or measured creatinine clearance of ≥ 30 ml/minute, calculated using the formula of cockcroft and gault \[(140 - age) x mass (kg) / (72 x creatinine mg/dl)\]. multiply result by 0.85 if female. * serum creatinine ≤ 2 mg/dl ethical / other * written informed consent in accordance with federal, local, and institutional guidelines * female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. post menopausal females (\> 45 years old and without menses for \> 1 year) and surgically sterilized females are exempt from a pregnancy test. male subjects must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential. * subjects must be able to receive outpatient treatment and laboratory monitoring at the institute that administers agent. exclusion criteria: disease related * multiple myeloma immunoglobulin m (igm) * subjects previously treated with any proteasome inhibitor (for part 2 proteasome inhibitor - naïve only, criteria added at amendment 2) * subjects must not be primary refractory to standard first-line therapy * subjects with non-secretory multiple myeloma, defined as \< 1 g/dl m-protein in serum, \< 200 mg/24 hour m-protein in urine * subjects with disease measurable only by serum free light chain (sflc) analysis * glucocorticoid therapy (prednisone \>10 mg/day orally or equivalent) within the last three weeks * poems syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) * plasma cell leukemia * chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy, within the three weeks prior to first dose * radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose * participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to first dose, whichever time is greater * prior treatment with carfilzomib concurrent conditions * major surgery within three weeks before day 1 * congestive heart failure (new york heart association class iii to iv), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months * acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose * known or suspected human immunodeficiency (hiv) infection or subjects who are hiv seropositive * active hepatitis a, b, or c infection * non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer \< gleason grade 6 with stable prostate-specific antigen (psa) * subjects with treatment related myelodysplastic syndrome * significant neuropathy (grade 3, 4 or grade 2 with pain) at the time of study initiation * subjects with known contraindication to receiving allopurinol * subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment * subjects with known or suspected amyloidosis subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis * any clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent ethical / other * female subjects who are pregnant or lactating * serious psychiatric or medical conditions that could interfere with treatment