A Phase II Study of Carfilzomib in Relapsed Waldenström's Macroglobulinemia (WM) IST-CAR-531

Inclusion Criteria

• •Biopsy proven WM with relapsed/refractory symptomatic disease are eligible for enrollment.
• •Bone marrow lymphoplasmacytosis with:
• •* \> 10% lymphoplasmacytic cells (measured within 28 days prior to registration OR
• •* Aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 28 days prior to registration).
• •* Measurable disease defined as a quantitative IgM monoclonal protein of \>500 mg/dL obtained within 28 days prior to registration
• •* CD20+ bone marrow or lymph node by immunohistochemistry or flow cytometry obtained within 28 days prior to registration
• •* Lymph node biopsy must be done \<28 days prior to registration if used as an eligibility criterion for study entry.
• •Symptomatic disease, as defined by the IWWM, includes the following criteria: Hemoglobin less than 10 g/dL, platelet count less than 100,000 uL, bulky adenopathy or organomegaly, symptomatic hyperviscosity syndrome, severe neuropathy, amyloidosis, cryoglobulinemia, cold agglutinin disease, or evidence of transformation high-grade non-Hodgkin's lymphoma.
• •Patients must not be receiving concurrent steroids \> 10 mg prednisone (or equivalent) per day.
• •Prior irradiation is allowed if \> 28 days prior to registration have elapsed since the date of last treatment.
• •Women must not be pregnant or breast-feeding due to the fact that the reproductive risk to humans taking carfilzomib is unknown. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• •Women of childbearing potential and sexually active males must use an accepted and effective method of contraception throughout the study and for 8 weeks after completion of the study.
• •Patients must be \> 18 years old.
• •Patients must have ECOG performance status of \< 2.
• •Patients may have received prior bortezomib therapy.
• •Adequate hepatic function, with serum ALT ≤ 3times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to randomization
• •Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to randomization
• •Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to randomization (subjects may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines)
• •Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if WM involvement in the bone marrow is \> 50%) within 14 days prior to randomization
• •Creatinine clearance (CrCl) ≥ 15 mL/minute within 7 days prior to randomization, either measured or calculated using a standard formula (e.g., Cockcroft and Gault)