Carfilzomib Multiple Myeloma Expanded Access Protocol for Patients With Relapsed and Refractory Disease

Inclusion Criteria:

1. Histologically documented multiple myeloma
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) status 0-2.
4. Life expectancy ≥ 3 months.

5. Measurable disease, defined as one or more of the following:

   • Serum M-protein ≥ 1 g/dL.
   • Urine M-protein ≥ 200 mg/24 hours.
   • For Immunoglobulin A (IgA) patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA), ≥ 750 mg/dl (0.75 g/dl).

6. For oligosecretory or non-secretory MM, either of the following:

   • Measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (ie, magnetic resonance imaging [MRI], computed tomography [CT] scan).
   • Documented abnormal free light chain ratio (NV: 0.26 to 1.65) or a value beyond the laboratory calculation range.

7. Received and either refractory or relapsed or discontinued due to toxicity to at least 4 prior lines of therapy as described below:

   • an immunomodulatory agent (lenolidamide or thalidomide)
   • bortezomib
   • an alkylating agent (standard or high dose)
   • a corticosteroid
8. Currently has progressive disease.

9. Refractory multiple myeloma defined as meeting one or more of the following:

   • Nonresponsive to most recent therapy (eg, stable disease only, or progressive disease while on treatment).
   • Disease progression within 60 days of discontinuation of most recent therapy (most recent therapy must be within 60 days of Screening).
10. Left ventricular ejection fraction (LVEF) ≥ 40% within 30 days before Cycle 1 Day 1. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multi gated acquisition scan (MUGA) is acceptable if ECHO is not available.
11. Adequate hepatic function, defined as aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) < 3 times the upper limit of normal and serum bilirubin ≤ 2.5 mg/dl.
12. Absolute neutrophil count ≥ 1,000 (may be supported by growth factors) and platelet count ≥ 40,000 within 14 days before Cycle 1 Day 1 without transfusion.
13. Creatinine clearance (CrCl) ≥15 mL/minute (measured or calculated using the Cockcroft and Gault Formula) within 14 days before Cycle 1 Day 1. This criterion does not apply to patients on hemodialysis.
14. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before Cycle 1 Day 1 and must agree to use dual contraception methods for the duration of treatment and for 3 months following the last dose of treatment. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential during the treatment period and for 3 months following the last dose of treatment.
15. Written informed consent in accordance with federal, local, and institutional guidelines.

Exclusion Criteria:

1. Prior treatment with carfilzomib or enrollment in any other Phase 3 carfilzomib trial.
2. Known human immunodeficiency virus (HIV) seropositivity.
3. Active infection requiring systemic treatment with anti-biotics, anti-virals, or anti-fungals.
4. Known, active hepatitis A, B, or C viral infection.
5. Concomitant use of approved or investigational anti-cancer therapeutic agents, other than dexamethasone or palliative radiation therapy. Patients receiving radiation for pain control are eligible for enrollment in this study. No wash-out period is required for other anti-myeloma treatments received.
6. Concomitant use of other investigational agents (eg, anti-biotics or anti-emetics).
7. Pregnancy or breastfeeding.
8. History of plasma cell leukemia, defined as > 2.0 × 10ˆ9/L circulating plasma cells.
9. History of amyloidosis.
10. Known history of allergy to Captisol®.
11. Active congestive heart failure (New York Heart Association Class 3-4), symptomatic ischemia, conduction abnormalities uncontrolled by a conventional intervention, or a myocardial infarction within the past 4 months.
12. Intolerance to hydration due to pre-existing pulmonary, cardiac, or renal impairment. Patients on hemodialysis should be considered as meeting this criterion for entry.
13. Waldenström macroglobulemia or immunoglobulin M (IgM) myeloma.