Study of Carfilzomib in Combination w/Dexamethasone in Patients w/Newly Diagnosed Multiple Myeloma

Inclusion Criteria:

- Subjects must have newly diagnosed multiple myeloma immunoglobulin G (IgG),
immunoglobulin A (IgA), immunoglobulin E (IgE) or immunoglobulin D (IgD) by the
International Myeloma Foundation (IMF) 2003 Diagnostic Criteria

- Subjects must be treatment naïve.

- Patient must not have been previously treated with any prior systemic therapy for the
treatment of multiple myeloma.

- Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does
not disqualify the patient (the dose should not exceed the equivalent of 160 mg of
dexamethasone in a 2 week period).

- Patients treated with local radiotherapy with or without concomitant exposure to
steroids, for pain control or management of cord/nerve root compression, are eligible.

- One week must have lapsed since last date of radiotherapy, which is recommended to be
a limited field.

- Patients who require concurrent radiotherapy should have entry to the protocol
deferred until the radiotherapy is completed and one week have passed since the last
date of therapy.

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

- All necessary baseline studies for determining eligibility must be obtained within 21
days prior to enrollment.

- Age 18 years at the time of signing Informed Consent.

- Life expectancy of more than three months.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 or Karnofsky
performance status of ≥ 60.

- Subject must be able to adhere to the study visit schedule and other protocol
requirements.

- 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 three months following the last dose if sexually active with a female of
child-bearing potential.

- Subjects must be able to receive outpatient treatment and laboratory monitoring at the
institute that administers agent.

Exclusion Criteria:

- Patient has > Grade 2 peripheral neuropathy on clinical examination within 14 days
before enrollment.

- Renal insufficiency as measured by calculated creatinine clearance < 15 mL/min by
Cockroft-Gault formula.

- Subjects with evidence of mucosal or internal bleeding and/or platelet refractory
(i.e., unable to maintain a platelet count 50,000 cells/mm³).

- Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm³. Growth factors may
not be used to meet ANC eligibility criteria.

- Total bilirubin > 2.0 mg/dL or bilirubin ≥ 2 x upper limit of normal (ULN).

- Subjects with a hemoglobin < 8.0 g/dL (Transfusion are permitted).

- Alanine aminotransferase (ALT) (SGPT) > 2.5 x ULN.

- Aspartate aminotransferase (AST) ≥ 2.5 x ULN.

- Major surgery within three weeks of starting study drug (Cycle 1 Day 1).

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities. Prior to study entry, any ECG
abnormality at screening has to be documented by the investigator as not medically
relevant.

- Clinically relevant active infection requiring either oral or intravenous antibiotics
or antifungal agents.

- Serious co-morbid medical conditions such as chronic obstructive or chronic
restrictive pulmonary disease, and cirrhosis.

- Any condition, including laboratory abnormalities, that in the opinion of the
Investigator places the subject at unacceptable risk if he/she were to participate in
the study.

- Prior malignancy (within the last 3 years) except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ
prostate cancer or if the expected survival from other malignancy is less than 90% at
5 years.

- Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 despite medical treatment).

- Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).

- Known HIV infection.

- Known active hepatitis B or C viral infection.

- Plasma cell leukemia.

- Glucocorticoid therapy (prednisone > 20 mg/day or equivalent) within the last three
weeks.

- Any prior treatment for multiple myeloma with standard regimens or investigative
regimens.

- Subjects with treatment related myelodysplastic syndrome.

- Subjects in whom the required program of oral and intravenous fluid hydration is
contraindicated, e.g., due to pre-existing significant pulmonary, cardiac or renal
impairment.

- Subjects with known primary amyloidosis.

- Female subject is pregnant or breast-feeding.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.