Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

• Overall survival time [ Time Frame: Time from study entry to the date of death due to any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
  Methods of Kaplan and Meier will also be used to evaluate survival distributions between the two treatment arms. Median and year-based survival estimates will be calculated along with corresponding 95% confidence intervals. In addition, use of Cox proportional hazards models to evaluate differences in OS between the treatment arms with stratification on age group as well as adjustment for other potential factors of interest.
  
  

• Complete remission rate (CR and CRi) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  Defined as the number of patients who achieve a CR divided by the total number of evaluable patients. Will also calculate corresponding 95% binomial confidence intervals for these estimates. Complete remission rates will also be compared between arms using Mantel-Haenszel chi-square tests stratified on age group.
  
  
• Disease-free survival [ Time Frame: Time from documentation of complete remission to the time of relapse and/or death, assessed up to 10 years ] [ Designated as safety issue: No ]
  Logrank statistics and Kaplan-Meier plots will be used to estimate and compare the DFS distributions between the two treatment arms. The methods of Kaplan and Meier will be used to calculate median DFS and corresponding 95% confidence intervals.
  
  
• Progression-free survival [ Time Frame: Time from study entry to the time of documented progression of disease, assessed up to 10 years ] [ Designated as safety issue: No ]
  Kaplan-Meier plots will be used to estimate the survival curves. Stratified log-rank tests will be employed to compare each of these time to event endpoints across treatment regimens.
  
  
• Frequency and severity of adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
  Defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns for each of the treatment arms.
  
  

PRIMARY OBJECTIVE:

I. To determine if treatment of older acute myeloid leukemia (AML) patients with decitabine and bortezomib significantly improves the overall survival times of older AML patients compared with decitabine alone.

SECONDARY OBJECTIVES:

I. To determine the rate of complete remission (CR and CR + CRi) for each of the 2 treatment regimens in the proposal.

II. To determine the overall survival, progression-free survival, disease-free survival and for each of the treatment regimens on this study.

III. To determine whether ongoing treatment with these regimens prolongs overall survival even in the absence of complete remission.

IV. To describe the frequency and severity of adverse events, as well as the tolerability of each of these regimens in patients treated on this study.

V. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, molecular genetics, WBC count, blood and bone marrow blast count, age, performance status and comprehensive geriatric assessment on clinical outcomes.

OUTLINE: This is a multicenter study. Patients are stratified according to age (60-69 years vs >= 70 years). Patients are randomized to 1 of 2 treatment arms.

ARM I:

REMISSION INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour once daily (QD) on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II:

REMISSION INDUCTION THERAPY: Patients receive decitabine IV over 1 hour QD on days 2-11 and bortezomib subcutaneously (SC) on days 1, 4, 8, and 12. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then once a year for 6 years.