A Safety Study of Carfilzomib, Cyclophosphamide & Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma

This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated
dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex)
prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant
eligible multiple myeloma. The study will also explore the efficacy of Car-Cy-Dex including
overall response after induction therapy, overall response at 3 and 6 months post ASCT, and
time to progression, progression free survival, and time to next therapy if it occurs within
6 months post ASCT.

Inclusion Criteria:

- Cytopathologically or histologically confirmed diagnosis of MM

- Measurable disease, as indicated by one or more of the following:

- Serum M-protein ≥ 1.0 g/dL

- Urine Bence Jones protein ≥ 200 mg/24 hr

- Elevated Free Light Chain as per the International Myeloma Working Group (IMWG)
criteria

- Males and females ≥ 18 years of age

- Life expectancy of more than 5 months

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

- Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN),
and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.5 times
ULN

- Serum Creatinine Clearance(CrCl) ≥ 30 mL/min, either measured or calculated using a
standard formula (e.g. Cockcroft and Gault)

- Additional Laboratory Requirements

- Absolute neutrophil count (ANC) ≥1.0 x 109/L

- Hemoglobin ≥8 g/dL [transfusion permitted]

- Platelet count ≥50.0 x 109/L

- 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 at least 2 weeks

- Patients may receive RBC or platelet transfusions, if clinically indicated, in
accordance with institutional guidelines

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

- Patients must agree to practice contraception

- Male patients must agree not to donate semen or sperm.

Exclusion Criteria:

- Patients with non-secretory or hyposecretory MM

- Prior treatment for MM (prior radiation therapy or dexamethasone up to 160 mg for
spinal cord compression is allowed. Other limited field radiation involving ≤ 1/3 of
the pelvic area is also allowed)

- Plasma cell leukemia

- Pregnant or lactating females

- Major surgery within 21 days prior to first dose

- Congestive heart failure (CHF) (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 14 days prior to first dose

- Patients receiving active treatment or intervention for any other malignancy or
patients who, at the Investigator's discretion, may require active treatment or
intervention for any other malignancy within 8 months of starting study treatment.

- Serious psychiatric or medical conditions that could interfere with treatment

- Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the
first dose and/or within 14 days before study treatment

- Contraindication to any of the required concomitant drugs, including antiviral (e.g.
Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in
a dose equivalent to dexamethasone ≥ 1.5 mg/day or prednisone ≥ 10 mg/day. (Steroid
use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.)

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

- Patients with primary systemic amyloidosis.