Carfilzomib With Bendamustine and Dexamethasone in Multiple Myeloma

Multiple myeloma (MM) is a malignant plasma cell disorder resulting in approximately 11,000
deaths in the United States each year. It is estimated that between 60,000-80,000 people are
currently under treatment for refractory or relapsed MM. Prognosis and survival have improved
over the last 20 years, but the disease is still universally fatal despite efforts to develop
new and more effective chemotherapeutic regimens. Therefore, new regimens need to be
developed for patients prior to peripheral blood stem cell transplant and for those unable to
tolerate the toxicity of transplant.

Inclusion Criteria:

1. Age ≥ 18 years.

2. Life expectancy ≥ 3 months.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

4. Adequate hepatic function.

5. Sufficient Absolute neutrophil count (ANC) within 14 days prior to randomization.

6. Sufficient Hemoglobin within 14 days prior to randomization (subjects may be receiving
red blood cell (RBC) transfusions in accordance with institutional guidelines).

7. Sufficient platelet count 14 days prior to randomization.

8. Creatinine Clearance ≥ 30 mL/minute within 7 days prior to randomization.

9. Left Ventricular Ejection Fraction ≥ 40%.

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

11. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and
to practice contraception.

12. Male subjects must agree to practice contraception.

13. Patients must have histologically or cytologically confirmed symptomatic multiple
myeloma (MM). Patients should not have previously been treated.

14. Prior kyphoplasty, vertebroplasty, local radiation therapy for symptomatic bone
lesions (e.g., uncontrolled pain or high risk of pathologic fracture) are permitted.

15. Patients are allowed up to two cycles of high dose steroids if needed for symptomatic
disease before study enrollment.

Exclusion Criteria:

1. Patients who have had chemotherapy for Multiple Myeloma. Exception: local radiation
therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of
pathologic fracture).

2. Patients currently receiving high dose systemic steroids for treatment of Multiple
Myeloma in excess of 320mg total dose of dexamethasone or equivalent, patients who
received an investigational agent within 5 half-lives of the agent.

3. Patients with non-measurable Multiple Myeloma or primary plasma cell leukemia.

4. Pregnant or lactating females.

5. Major surgery within 21 days prior to enrollment.

6. Acute active infection requiring treatment (systemic antibiotics, antivirals, or
antifungals) within 14 days prior to enrollment.

7. Known human immunodeficiency virus (HIV) infection.

8. Known active hepatitis B or C infection.

9. Unstable angina or myocardial infarction within 4 months prior to enrollment.

10. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.

11. Uncontrolled, non-hematologic malignancy requiring active treatment.

12. Patients with known brain metastases (treated or not) will be excluded from this
clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.

13. Significant neuropathy within 14 days prior to randomization.

14. Known history of allergy to Captisol, or to other agents in the study.

15. Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.

16. Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis within 14 days prior to enrollment.

17. Any other 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.