Phase 1b/2 Study of Carfilzomib in Relapsed Solid Tumors, Multiple Myeloma, or Lymphoma

Inclusion Criteria

Disease related

Phase 1 Subjects (Bolus and Infusion):

Solid Tumor:

• Histologically confirmed advanced solid tumor
• 1 to 3 prior treatment regimens
• At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional computed tomography (CT) scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per Response Evaluation Criteria in Solid Tumors [RECIST] criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Medical Monitor

Multiple Myeloma (MM):

• Relapsed and/or refractory multiple myeloma following 2 or more prior treatment regimens.
• Measurable disease as indicated by one or more of the following:
• Serum M-protein ≥ 1 g/dL
• Urine M-protein ≥ 200 mg/24 hr
• Serum Free Light Chain: Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal

Lymphoma:

• Histologically or cytologically confirmed lymphoma.
• Patients must have had an initial diagnosis of indolent non-Hodgkin lymphoma (NHL) (including follicular, small lymphocytic, lymphoplasmacytoid, and marginal zone lymphoma), indolent disease that transformed to a more aggressive subtype, as previously described or patients may have mantle cell lymphoma.
• Patients are required to have received prior rituximab (alone or combined with other treatment) and are considered refractory to (defined as no response, or progression within 6 months of completing therapy) or intolerant of continued rituximab.
• Patients may have received up to a maximum of four prior unique chemotherapy regimens, including if not contra-indicated autologous stem-cell transplantation (ASCT).
• For patients to enroll in the expanded dose group for lymphoma, patients must have measurable disease

Phase 2 Bolus Subjects:

-Histologically confirmed advanced solid tumor diagnosis and:

• Non-small cell lung cancer (NSCLC): Failed at least 1 prior platinum-based chemotherapy regimen but not more than 3 prior therapies for metastatic disease
• Small cell lung cancer (SCLC): Failed 1 to 3 prior chemotherapy regimens
• Ovarian: Failed at least 1 prior platinum-based chemotherapy regimen but not more than 4 therapies for metastatic disease
• Renal: Failed at least 2 prior chemotherapy regimens for metastatic disease
• Other solid tumor types: Failed at least 1 prior chemotherapy regimen for metastatic or relapsed disease and for which standard of care therapy is no longer effective or does not exist
• At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional CT scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per RECIST criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Medical Monitor

Demographic

• Males and females ≥ 18 years of age
• Life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

Laboratory

• Adequate hepatic function, with bilirubin 1.5 times the upper limit of normal (ULN), and alanine aminotransferase (ALT) 3 times ULN
• Absolute neutrophil count (ANC) > 1000/mm³, hemoglobin ≥ 8 gm/dL for solid tumors or 7.0 gm/dL for MM, and platelet count ≥ 100,000/mm³ for solid tumors or ≥ 30,000/mm³ for MM.
• Subjects should not have received platelet transfusions for at least 1 week prior to screening
• Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for ≥ 2 weeks
• Subjects may receive red blood cell (RBC) transfusions or receive supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines
• Calculated or measured creatinine clearance (CrCl) of ≥ 20 mL/minute calculated using the