Decitabine, Bortezomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients with Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Female patients who: * Are postmenopausal for at least 1 year before the Screening visit, OR * Are surgically sterile OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception at the same time from the time of signing the informed consent through 30 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse
• Male patients, even if surgically sterilized (i.e., status post vasectomy), who: must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse
• Adults with acute myeloid leukemia (AML), excluding the M3 subtype (acute promyelocytic leukemia), that are not likely to respond to conventional therapy, including: * Relapsed or refractory AML after one to four prior induction regimens (not counting consolidation therapies while in complete response [CR], and not counting autologous transplant while in CR), * Newly diagnosed AML patient’s age not fit for standard therapy
• Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as Fms-like tyrosine kinase 3 [FLT-3] status) will be obtained as per standard practice
• Performance status of 60% or greater by the Karnofsky scale
• A minimum of 2 weeks (or five half-lives) must have elapsed since the completion of prior anti-AML chemotherapy; hydroxyurea for control of blasts is not counted as chemotherapy, and may be given prior to and during cycle 1 of induction to control the white blood cell count
• Patients may have had autologous transplant; they must be at least 100 days post transplant, and have had recovery of their counts with absolute neutrophil count (ANC) > 1000 and platelets greater than 100 K at some point post-transplant, and be without active cytomegalovirus (CMV) or fungal disease
• There are no minimum hematological parameter requirements prior to the first two cycles, as patients with AML and myelodysplastic syndrome (MDS) are understood to have low ANC and platelet counts when the disease is active
• Patients must have a serum bilirubin =< 1.5 mg/dl
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 times the institutional upper limits of normal (unless due to Gilbert’s syndrome)

Exclusion Criteria

• There is no specific platelet and absolute neutrophil count that will exclude patients from this study given the natural history of AML
• Patient has >= grade 2 peripheral neuropathy
• Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant; a left ventricular ejection fraction (LVEF) must be > 50
• Patient has hypersensitivity to VELCADE (bortezomib), boron, or mannitol
• Female subject is pregnant or lactating; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for postmenopausal or surgically sterilized women
• Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on day 1 before first dose of study drug, if applicable
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• 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
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial
• Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy
• Patients with active/uncontrolled central nervous system (CNS) leukemia
• Patients eligible, at the time of starting treatment, for curative therapeutic approaches (such as allogeneic transplant) are not eligible for the trial; however, patients who achieve CR or partial response (PR) as a result of therapy on this trial may proceed to allogeneic transplant
• Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study other than hydroxyurea for control of counts
• Human immunodeficiency virus (HIV)-positive