Clinical trial NCT01857115 (phase 1/phase 2, status: active, not recruiting)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: carfilzomib, cyclophosphamide, dexamethasone
SMILES: CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1, ClCCN(CCCl)P1(=O)NCCCO1, C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F
Eligibility criteria:

        Inclusion Criteria:

        Disease-related

          1. Patient is a newly diagnosed MM patient.

          2. Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell
             transplantation.

          3. Patient has measurable disease, defined as follows: any quantifiable serum monoclonal
             protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where
             applicable, urine light-chain excretion of > 200 mg/24 hours. For patients with oligo-
             or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as
             determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an
             abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of
             patients admitted to this study will be oligo- or non-secretory MM with free light
             chains only in order to maximize interpretation of benefit results.

             Demographic:

          4. Age ≥ 18 years.

          5. Life expectancy ≥ 3 months.

          6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix F).

             Laboratory:

          7. 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 randomization.

          8. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to randomization.

          9. Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).

         10. Alanine transaminase (ALT): ≤ 3 x the ULN.

         11. Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to randomization (subjects may be
             receiving red blood cell [RBC] transfusions in accordance with institutional
             guidelines).

         12. Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if myeloma involvement in the bone marrow is
             > 50%) within 14 days prior to randomization.

         13. Creatinine clearance (CrCl) ≥ 15 mL/minute within 7 days prior to randomization,
             either measured or calculated using a standard formula (eg, Cockcroft and Gault).

             Ethical/Other:

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

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

         16. Male subjects must agree to practice contraception.

        Exclusion Criteria:

        Disease-related:

          1. Previous treatment with anti-myeloma therapy (does not include radiotherapy,
             bisphosphonates, or a single short course of steroid; ≤ to the equivalent of
             dexamethasone 40 mg/day for 4 days)

          2. Patient with relapsed or refractory multiple myeloma.

          3. Patients with non-secretory MM unless serum free light chains are present and the
             ratio is abnormal.

             Concurrent Conditions:

          4. Pregnant or lactating females (Appendix I).

          5. Major surgery within 21 days prior to randomization.

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

          7. Known human immunodeficiency virus infection.

          8. Active hepatitis B or C infection.

          9. Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA
             Class III or IV heart failure, uncontrolled angina, history of severe coronary artery
             disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or
             electrocardiographic evidence of acute ischemia or Grade 3 conduction system
             abnormalities unless subject has a pacemaker.

         10. Uncontrolled hypertension, uncontrolled congestive heart failure (CHF) or uncontrolled
             diabetes within 14 days prior to randomization.

         11. Non-hematologic malignancy within the past 3 years with the exception of a) adequately
             treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)
             carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or
             less with stable prostate-specific antigen levels; or d) cancer considered cured by
             surgical resection or unlikely to impact survival during the duration of the study,
             such as localized transitional cell carcinoma of the bladder or benign tumors of the
             adrenal or pancreas.

         12. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
             randomization.

         13. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
             carfilzomib).

         14. 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.

         15. Subjects with pleural effusions requiring thoracentesis or ascites requiring
             paracentesis within 14 days prior to randomization.

         16. 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.