An Open-label, Single-arm, Phase 2 Study of Carfilzomib in Patients With Relapsed and Refractory Multiple Myeloma

Inclusion Criteria:

- Disease Related

- Multiple myeloma

- Subjects must have measurable disease defined as one of the following:

- Serum M-protein ≥ 1 g/dL

- Urine M-protein ≥ 200 mg/24 hours

- Subjects must have been responsive (i.e., achieved an MR or better) to
first-line, standard of care therapy

- Refractory to the most recently received therapy. Refractory disease is defined
as ≤ 25% response or progression during therapy or within 60 days after
completion of therapy.

- Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction
therapy and stem cell transplant will be considered as one regimen

- Subjects must have received prior treatment with bortezomib, and either
thalidomide or lenalidomide

- Subjects must have received an alkylating agent either alone or in combination
wiht other myeloma treatments (history of stem cell transplant is acceptable)

- Subjects must have received an anthracycline either alone or in combination with
other myeloma treatments, unless not clinically indicated

- Demographic

- Males and females > 18 years of age

- Life expectancy of more than three months

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

- Laboratory

- Adequate hepatic function, with bilirubin less than 2.0 times the upper limit of
normal, and AST and ALT of less than 3.0 times the upper limit of normal

- Absolute neutrophil count > 1,000/mm3, hemoglobin > 8.0 g/dL, and platelet count
> 50,000/mm3

- Subjects should be platelet transfusion independent

- Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and
of pegylated G-CSF for ≥ 2 weeks

- Subjects may receive red blood cell (RBC) or platelet transfusions or receive
supportive care such as erythropoietin and darbepoetin in accordance with
institutional guidelines

- Calculated and measured creatinine clearance of ≥ 30 mL/minute, calculated using
the formula of Cockcroft and Gault [(140 - Age) X Mass (kg) / (72 X Creatinine
mg/dL)]. Multiply result by 0.85 if female.

- Ethical / Other

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

- Female subjects of child-bearing potential must have a negative serum pregnancy
test within seven days of the first dose and agree to use dual methods of
contraception during and for 3 months following last dose of drug. Post
menopausal females (> 45 years old and without menses for > 1 year) and
surgically sterilized females are exempt from a pregnancy test. Male subjects
must use an effective barrier method of contraception during study and for 3
months following the last dose if sexually active with a female of child-bearing
potential.

Exclusion Criteria:

- Disease Related

- Multiple Myeloma IgM

- Subjects who failed to achieve at least a confirmed MR(≥ 25% reduction in
M-protein for ≥ 6 weeks)

- Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in
serum and < 200 mg/24 hr M-protein in urine

- Subjects with disease measurable only by serum free light chain (SFLC) analysis

- Glucocorticoid therapy (prednisone > 10 mg/day orally or equivalent) within the
last three weeks

- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal
protein, and skin changes)

- Plasma cell leukemia

- Chemotherapy with approved or investigative anticancer therapeutics including
steroid therapy within the three weeks prior to first dose

- Radiation therapy or immunotherapy in the previous four weeks; localized
radiation therapy within 1 week prior to first dose

- Participation in an investigational therapeutic study within three weeks or
within five drug half-lives (t1/2) prior to Day 1, whichever time is greater

- Prior treatment with carfilzomib

- Concurrent Conditions

- Major surgery within three weeks before Day 1

- Congestive heart failure (New York Heart Association class III to IV),
symptomatic ischemia, conduction abnormalities uncontrolled by conventional
intervention, or myocardial infarction in the previous six months

- Acute active infection requiring systemic antibiotics, antivirals or
antifungals within 2 weeks prior to first dose

- Known or suspected HIV infection or subjects who are HIV seropositive

- Active hepatitis A,B,or C infection

- 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
- Subjects with treatment related myelodysplastic syndrome

- Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study
initiation

- 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

- Subjects with known or suspected amyloidosis

- Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis

- Any clinically significant medical disease or condition that, in the
Investigator's opinion, may interfere with protocol adherence or a subject's
ability to give informed consent

- Ethical / Other

- Female subjects who are pregnant or lactating

- Serious psychiatric or medical conditions that could interfere with treatment