| Exclusion Criteria: | 1) A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >/= 5 years.
2) A history of allogeneic stem-cell transplantation
3) Primary central nervous system (CNS) tumors including primary CNS lymphoma
4) Central nervous system involvement by lymphoma
5) Myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association >class II), unstable angina, or unstable cardiac arrhythmia requiring medication
6) Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS intervals
7) Congenital long QT syndrome
8) Patients with a QTc interval > 470 msec
9) Vorinostat cohorts only: History of significant GI surgery or disease, which would impair intestinal absorption
10) Vorinostat cohorts only: Active peptic ulcer disease
11) Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia
12) Recent infection requiring systemic anti-infective treatment that was completed </= 14 days before enrollment/randomization (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection)
13) Subject known to have tested positive for human immunodeficiency virus (HIV)
14) Subject known to have tested positive for hepatitis C virus or acute or chronic hepatitis B infection
15) Any co-morbid medical condition that would increase the risk of toxicity in the opinion of Investigator or Sponsor
16) Treatment with anti-cancer therapy (chemotherapy, molecular targeted therapy, retinoid therapy, or hormonal therapy) within 28 days prior to study day 1 (6 weeks for nitrosoureas and mitomycin C).
17) Antibody therapy for the treatment of underlying malignancy within 28 days prior to study Day 1, with the exception of bevacizumab and other monoclonal antibodies with a half-life of greater than 10 days, which must be discontinued at least 8 weeks prior to study Day 1. Radioimmunoconjugates must be discontinued at least 10 weeks prior to study Day 1.
18) Prior exposure to AMG 655 or other investigational TRAIL receptor agonists is not permitted
19) Prior treatment with bortezomib or vorinostat is not permitted for subjects enrolling in the bortezomib and vorinostat cohorts, respectively
20) Part 1 only: Concomitant anticoagulant use other than for prophylaxis against central venous catheter thrombosis is not permitted
21) Part 1 only: Concomitant therapy with erythropoietin within 14 days of enrollment
22) Part 1 only: Concomitant therapy with granulocyte-colony stimulating factor (GCSF) or granulocyte-macrophage colony-stimulating factor (GMCSF) within 28 days of enrollment
23) Vorinostat cohort only: Concomitant therapy with anti-arrhythmic medicines or other medicinal products that lead to QT prolongation is not permitted
24) Vorinostat cohort only: Concomitant therapy with a histone deacetylase (HDAC) inhibitor (eg, valproic acid)
25) Therapeutic or palliative radiation therapy within 2 weeks before enrollment
26) Concurrent immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc. or chronic administration of > 5 mg/day of prednisone) within 28 days of day 1
27) Bortezomib cohorts only: Use of the following medications (prescription or nonprescription) or herbal supplements: CYP enzyme inhibitors (eg, ketoconazole, itraconazole, fluconazole, erythromycin, and clarithromycin) within 14 days or 5 half-lives (whichever is longer) before the first dose of investigational agent; CYP enzyme inducers (eg, rifampin, rifabutin, phenobarbital, phenytoin, and carbamazepine) and St. John's Wort) within 28 days or 5 half-lives (whichever is longer) before the first dose of investigational agent.
28) Vorinostat cohorts only: Consumption of grapefruit or grapefruit-containing products within 7 days before the first dose of investigational agent
29) Subject is not able to tolerate intravenous drug infusions
30) Known allergy to the excipients or investigational product
31) Bortezomib cohorts only: Known allergy to mannitol or boron
32) Prior participation in clinical trials (with investigational device or agent) within 28 days before the first dose of AMG 655
33) Major surgery within 28 days before the first dose of AMG 655
34) Subject of child-bearing potential is pregnant or nursing
35) Subject has previously enrolled in this study
36) Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
37) Subject will not be available for follow up assessments
38) Subject is unwilling to comply with the study requirements |