Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies

INCLUSION CRITERIA: Phase 1b * Histologically confirmed diagnosis of a hematologic malignancy, excluding patients with acute leukemia or MDS. * Relapsed after standard therapy for their malignancy and considered to be an appropriate candidate for a Phase 1 clinical study by their treating physician. Phase 2 * Multiple myeloma with measurable disease * Waldenström macroglobulinemia with symptomatic relapse * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. Ethical/Other * Patients must sign a written informed consent form in accordance with federal, local, and institutional guidelines. * Female patients of childbearing potential must have a negative serum or urine pregnancy test and agree to use effective contraception. Male patients must use an effective barrier method of contraception. EXCLUSION CRITERIA: * Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy intended to treat underlying malignancy, within 3 weeks prior to first dose or 6 weeks for antibody therapy. * Radiation therapy within 3 weeks prior to first dose. Radioimmunotherapy within 8 weeks prior to first dose. Localized radiation therapy within 1 week prior to first dose. * Immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required). * Prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-vs-host disease (GvHD; as defined in Filipovich 2005). * Evidence of central nervous system (CNS) lymphoma. * Prior treatment with carfilzomib unless in the phase 2. * Major surgery within 3 weeks prior to first dose. * Symptomatic Congestive heart failure, ischemia, conduction abnormalities, or myocardial infarction within 6 months. * Acute active infection requiring systemic antibiotics, antivirals, or antifungals. * Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive. * Active hepatitis A, B, or C infection. * Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose. * Patients with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis. * History of previous clinically significant GI bleed in the last 6 months prior to first dose. * Female patients who are pregnant or lactating.