Study closed to enrollment

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.
• Female patients who are pregnant or lactating.
• History of clincially significant GI bleeds in the last 6 months prior to first dose.