Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

Inclusion criteria

• Participants must meet all of the following inclusion criteria to be eligible to enroll in this study.
• Patients meeting the criteria for symptomatic multiple myeloma that has relapsed or is refractory to at least 2 prior lines of therapy.
• Previous therapy with bortezomib.
• Previous therapy with thalidomide or lenalidomide.
• Patients must have measurable disease and therefore must have at least one of the following:

Serum M-protein ≥1 gm/dL (≥10 gm/L) Urine M-protein ≥200 mg/24 hr Serum FLC assay: involved FLC ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to enrollment
• Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to enrollment Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (participants may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines)
• Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if thought to be secondary to myeloma involvement of the bone marrow ) within 14 days prior to enrollment (platelet transfusions are allowed)
• Creatinine clearance (CrCl) ≥ 15 mL/minute within 14 days prior to enrollment, either estimated or calculated using a standard formula (eg, Cockcroft and Gault)
• Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.
• Male participants must agree to practice contraception.

Exclusion criteria

• Prior treatment with carfilzomib.
• Known CNS involvement with myeloma
• Pregnant or lactating females
• Major surgery within 21 days prior to registration.
• Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 7 days prior to enrollment
• Known human immunodeficiency virus infection
• Active hepatitis B or C infection
• Unstable angina or myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
• Concurrent malignancies, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
• Significant neuropathy (Grades 3-4, ) within 14 days prior to enrollment
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
• Contraindication to any of the required concomitant drugs or supportive treatments, including options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
• Concurrent therapy with any other anticancer therapeutic with activity against multiple myeloma
• Concurrent therapy with investigative agents (e.g., antibiotics or antiemetics)