Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and GVHD in Allo-HCT for Hematologic Malignancies

Inclusion Criteria: * Lymphoid or Myeloid malignancy requiring allogeneic hematopoietic cell transplantation * Pathology review by the study institution is required * Prior high-dose chemotherapy and autologous HCT(s) is (are) allowed * Disease status: Stable disease or better at the time of enrollment * Age: \>18 and \<70 years old at the time of transplant (\< 71 years at transplant admission) * Life expectancy ≥ 6 months after transplant * A 8/8 or 7/8 HLA-matched donor is available * Karnofsky Performance Status \>70% (A measure of quality of life that ranges from 0 to 100 where 100 equals perfect health and 0 is death.) * Adequate cardiac \[LVEF (Left Ventricular Ejection Fraction) \>0.4\], pulmonary \[FEV1 (Forced Expiratory Volume in 1 Second), FVC (Forced Vital Capacity), corrected DLCO (Diffusing Capacity) ≥ 50% predicted\], hepatic \[DB (Direct Bilirubin) \<1.5xULN, AST (Aspartate Aminotransferase) / ALT (Alanine transaminase) ≤3xULN\] and renal function \[GFR (Glomerular Filtration Rate) ≥ 60 mL/min/1.73 m2\] Exclusion Criteria: * Progressive disease * Active central nervous system involvement by malignancy * Non compliance to medications or medical instructions * Lack of appropriate caregivers * Life expectancy \<6 months * Pregnant or lactating females * Uncontrolled infection requiring active treatment (systemic antibiotics, anti-virals, or anti-fungals) within 14 days * HIV-1/HIV-2 or HTLV-1/HTLV-2 seropositivity * Active hepatitis A, B or C infection * Unstable angina or myocardial infarction within 6 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, uncontrolled or persistent atrial fibrillation/flutter, history of ventricular fibrillation, ventricular tachycardia/torsade de pointes, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker * History of pulmonary hypertension * Uncontrolled hypertension or uncontrolled diabetes mellitus * 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 (PSA) 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 * Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) * Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all available anti-microbial drugs or intolerance to IV hydration due to pre-existing pulmonary or cardiac impairment * Subjects with pleural effusion requiring thoracentesis or ascites requiring paracentesis within 14 days prior to admission * Uncontrolled psychiatric condition * Any other clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent