Study to Evaluate Safety Tolerability & Efficacy of Kyprolis (Carfilzomib) in Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• Documented RRMM after last treatment. Refractory is defined as meeting 1 or more of the following: Nonresponsive to most recent therapy (stable disease [SD] or progressive disease [PD]) while on treatment, or Disease progression within 60 days of discontinuation from the most recent therapy.
• Eligible to receive Kyprolis per the locally approved label.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate hepatic function within 28 days prior to enrollment: bilirubin 2.0 x 10^9/L circulating plasma cells by standard differentials).
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Myelodysplastic síndrome.
• Primary amyloidosis (subjects with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met).
• History of other malignancy within the past 5 years, with the following exception[s]: Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated cervical carcinoma in situ without evidence of disease. Adequately treated breast ductal carcinoma in situ without evidence of disease. Prostatic intraepithelial neoplasia without evidence of prostate cáncer. Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
• Known immediate or delayed hypersensitivity reaction to Captisol (a cyclodextrin derivative used to solubilize Kyprolis).
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs.
• Intolerance to hydration.
• Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant echocardiogram (ECHO) abnormalities, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to enrollment.
• Infiltrative pulmonary disease and/or known pulmonary hypertension.
• Active infection within 14 days prior to enrollment requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents. Such infections must be fully resolved prior to initiating study treatment.
• Pleural effusions requiring thoracentesis within 14 days prior to enrollment.
• Ascites requiring paracentesis within 14 days prior to enrollment.
• Uncontrolled hypertension, defined as an average systolic blood pressure > 159 mmHg or diastolic > 99 mm/Hg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology [ESH/ESC] 2013 guidelines.
• Active hepatitis B virus (HBV) infection. Subjects with positive hepatitis B surface antigen (HBsAg) or core antibody (anti-HBc) that achieve sustained virologic response with antiviral therapy directed at hepatitis B are allowed. Subjects with known history or resolved infection (negative for HBsAg but positive for antibodies to surface antigen, and/or core antigen) must be screened with HBV DNA levels. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (hepatitis B surface antibody [anti-HBs] positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA.
• Known human immunodeficiency virus (HIV) infection, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response following antiviral therapy are allowed).
• Ongoing graft-versus-host disease.
• Subjects with grade 3 or worse neuropathy within 14 days prior to enrollment.
• Antitumor therapy (eg, chemotherapy, immunotherapy, antibody therapy) or investigational agent within 28 days before enrollment or not recovered from any acute toxicity.
• Subjects on immunosuppressive therapy for graft versus host disease, even if it has resolved.
• Glucocorticoid therapy within 14 days before first dose