Clinical trial NCT01029054 (phase 1/phase 2, status: completed)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: carfilzomib, lenalidomide plus dexamethasone, carfilzomib, lenalidomide plus dexamethasone
SMILES: NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O, NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O
Eligibility criteria:

        Inclusion Criteria

          1. Newly diagnosed, histologically confirmed, previously untreated Stage I, II, or III
             multiple myeloma requiring systemic chemotherapy

          2. Diagnosis of symptomatic multiple myeloma per IMWG uniform criteria within the past 90
             days

          3. Measurable disease, per IMWG (International Myeloma Working Group) criteria (>= one of
             the following) within the past 4 weeks:

               -  Monoclonal protein >= 0.5 g/dL by serum protein electrophoresis

               -  Monoclonal light chain >= 200 mg by 24-hour urine protein electrophoresis

               -  If serum protein electrophoresis is felt to be unreliable for routine M-protein
                  measurement, then quantitative immunoglobulin levels are acceptable

          4. Life expectancy > 3 months

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

          6. Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST (Aspartate
             Aminotransferase) and ALT (Alanine Transaminase) < 2.5 x ULN

          7. Absolute neutrophil count (ANC) >=1.0 x 109/L, hemoglobin >= 8 g/dL, platelet count >=
             75 x 109/L

          8. Calculated creatinine clearance (by Cockroft-Gault) >= 60 ml/min

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

         10. Subjects must agree to adhere to all study requirements, including birth control
             measures and pregnancy testing, visit schedule, outpatient treatment, required
             concomitant medications, and laboratory monitoring.

         11. Must be able to take either 81 mg or 325 mg aspirin daily as prophylactic
             anticoagulation.

        Exclusion Criteria

          1. Non-secretory or hyposecretory multiple myeloma, defined as <0.5 g/dL M-protein in
             serum, <200 mg/24 hr urine M-protein, or disease only measured by serum free light
             chain

          2. POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin
             Changes) syndrome

          3. Plasma cell leukemia

          4. Waldenström's macroglobulinemia or IgM myeloma

          5. Radiotherapy to multiple sites or immunotherapy within 2 weeks before start of
             protocol treatment (localized radiotherapy to a single site at least 1 week before
             start is permissible)

          6. Patient must not have been previously treated with any prior systemic therapy for the
             treatment of multiple myeloma

               -  Prior treatment of hypercalcemia or spinal cord compression or aggressively
                  progressing myeloma with corticosteroids does not disqualify the patient (the
                  dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week
                  period)

               -  Bisphosphonates are permitted

          7. Participation in an investigational therapeutic study within 3 weeks or within 5 drug
             halflives (t1/2) prior to first dose, whichever time is greater

          8. Pregnant or lactating females

          9. History of allergy to mannitol

         10. Major surgery within 3 weeks prior to first dose

         11. Myocardial infarction within 3 months prior to enrollment, NYHA (New York Heart
             Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities

         12. Uncontrolled hypertension or diabetes

         13. Acute active infection requiring systemic antibiotics, antivirals, or antifungals
             within two weeks prior to first dose

         14. Known or suspected HIV infection, known HIV seropositivity

         15. Active hepatitis infection

         16. Non-hematologic malignancy within the past 3 years except a) adequately treated basal
             cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or
             prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or
             cancer considered cured by surgical resection alone

         17. Any 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

         18. Significant neuropathy (Grade >2) at the time of the first dose and/or within 14 days
             before enrollment

         19. Contraindication to any of the required concomitant drugs

         20. Subjects in whom the required program of PO and IV fluid hydration is contraindicated

         21. Subjects with known or suspected amyloidosis of any organ

         22. Subjects with pleural effusions requiring thoracentesis or ascites requiring
             paracentesis