The purpose of this study is to test the safety and tolerability of carfilzomib at different dose levels on hematological cancers such as multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's disease, or Waldenstrom's macroglobulinemia. Carfilzomib is a proteasome inhibitor, an enzyme responsible for degrading a wide variety of cellular proteins.

Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutional guidelines

2. Males and females ≥18 years of age

3. Histologically confirmed diagnosis of one of the hematologic malignancies below:

   • Multiple myeloma (MM)
   • Non-Hodgkin's lymphoma (NHL)
   • Waldenström's Macroglobulinemia (WM)
   • Hodgkin's disease (HD)

4. Subjects who are refractory or relapsed following at least two prior therapies

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

6. Adequate cardiovascular function without symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months

7. 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

8. Total white blood cell (WBC) count ≥ 2,000/mm³, absolute neutrophil count (ANC) ≥ 1000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³

   • Screening 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 receiving supportive care including erythropoietin, darbepoetin and/or bisphosphonates can continue to do so, but must be transfusion independent; subjects receiving erythropoietic support must remain on the same dose for the first 28 days of study participation

9. An estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault

10. Serum creatinine ≤ 2.0 mg/dL

11. Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing

12. Female subjects of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test. Male subjects must use an effective barrier method of contraception throughout the study and for three months following the last dose if sexually active with a female of child-bearing potential.

Exclusion Criteria:

1. Female subjects who are pregnant or lactating
2. Subjects who are transfusion dependent
3. Subjects with NHL or HL who have received steroid therapy in the previous seven days
4. Subjects with MM or Waldenström's Macroglobulinemia who have received steroid therapy in the previous three weeks, except for MM subjects in the Carfilzomib + DEX Expansion Cohort, where previous treatment with dexamethasone will be allowed. The dose and schedule of administration of dexamethasone will be adjusted to that used in the protocol
5. Radiation, chemotherapy, or immunotherapy in the previous four weeks, or subjects who, in the judgment of the Investigator, have not recovered from the effects of previous therapy
6. For the Dose Escalation period, subjects who have received prior radioimmunotherapy with anti-cluster of differentiation (CD)20 monoclonal antibodies such as Bexxar® or Zevalin®; subjects treated with these products will be allowed in the Dose Expansion period
7. Subjects who have received allogeneic stem cell transplant therapy
8. Subjects with NHL or HL who have received autologous stem cell transplant therapy and have relapsed within 100 days of therapy
9. Rituxan therapy within three months before Day 1 unless there is evidence of disease progression
10. Major surgery within three weeks before Day 1
11. Congestive heart failure (CHF) (New York Heart Association class III to IV)
12. Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
13. Subjects who are known or suspected of having human immunodeficiency virus (HIV) infection or who are HIV seropositive
14. Active hepatitis A, B, or C infection; or positive for Hepatitis C ribonucleic acid (RNA) or hepatitis B antigen
15. 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 with stable prostate specific antigen (PSA) levels for three years
16. Subjects with treatment-related myelodysplastic disorder
17. Subjects with known brain metastasis (active central nervous system [CNS] disease only)
18. Serious psychiatric or medical conditions that could interfere with treatment
19. Participation in an investigational therapeutic study within one month prior to Day 1
20. Significant neurotoxicity (Grade 2 or higher with pain) at the time of study initiation
21. Concurrent therapy with approved or investigative anticancer therapeutics
22. Subjects with previous hypersensitivity to bortezomib injection
23. Subjects with contraindications to receiving allopurinol
24. 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
25. Subjects with known or suspected amyloidosis
26. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis