Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation

Exclusion Criteria

• •Diagnosis other than acute myelogenous leukemia, myeloproliferative disorder, or myelodysplastic syndrome
• •Chemotherapy or radiotherapy within 14 days of initiating treatment in this study with the exception of lenalidomide, decitabine, azacitidine, imatinib mesylate, dasatinib, nilotinib hydrochloride and hydroxyurea
• •Prior dose-intense therapy requiring HSC support within 56 days of initiating treatment in this study
• •Uncontrolled bacterial, viral, fungal or parasitic infections
• •Uncontrolled CNS metastases
• •Known amyloid deposition in heart
• •Organ dysfunction
• •* LVEF \<40% or cardiac failure not responsive to therapy
• •* FVC, FEV1, or DLCO \<50% of predicted and/or receiving supplementary continuous oxygen
• •* Evidence of hepatic synthetic dysfunction, or total bilirubin \>2x or AST \>3x ULN
• •* Measured creatinine clearance \<20 ml/min
• •* Karnofsky score \<70%
• •Life expectancy limited by another co-morbid illness
• •Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
• •Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• •Documented hypersensitivity to fludarabine or melphalan or to bortezomib, boron or mannitol or any components of the formulation
• •Patients unable or unwilling to provide consent
• •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
• •Patient has received other investigational drugs with 14 days before enrollment
• •Serious medical or psychiatric illness likely to interfere with participation in this clinical study