Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

PRIMARY OBJECTIVES: I. To evaluate the effect of clofarabine induction and consolidation therapy on overall survival in comparison with standard therapy (daunorubicin \[daunorubicin hydrochloride\] \& cytarabine) in newly-diagnosed acute myeloid leukemia (AML) patients age \>= 60 years. SECONDARY OBJECTIVES: I. To evaluate complete remission (CR) rates, duration of remission, and toxicity/treatment-related mortality of clofarabine in comparison with standard therapy (daunorubicin \& cytarabine) in newly-diagnosed AML patients age \>= 60 years. II. To evaluate the feasibility of consolidation with reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-identical donors in patients who achieve a response to induction therapy, including the incidence of successful engraftment, acute and chronic graft-versus-host disease, transplant-related mortality, and its impact on overall survival in comparison to patients receiving chemotherapy. III. To evaluate the duration of remission and disease-free survival of patients in complete remission following completion of consolidation therapy who are subsequently randomized to receive scheduled low-dose decitabine maintenance in comparison with observation. IV. To perform expression and methylation profiling on all patients receiving decitabine and to correlate their integrated epigenetic signatures with response to decitabine. V. To examine the epigenetic profiles of remission marrow in patients randomized to observation vs. decitabine to determine whether epigenetic signature of apparently morphologically normal bone marrow is predictive of relapse or response to decitabine maintenance. VI. To explore the possible association of response to clofarabine with ABC-transporter P-glycoprotein (Pgp). VII. To assess the intensity of expression of CXC chemokine receptor type 4 (CXCR4) on diagnostic leukemia cells and to correlate this parameter with other established prognostic factors. VIII. To assess the entire spectrum of somatic mutations and affected pathways at diagnosis of AML and elucidate the association between gene mutation and outcome. IX. To examine the impact of smoking, obesity, regular acetaminophen use, regular aspirin use, benzene exposure, living in a rural/farm environment and some other underlying exposures and lifestyle factors associated with AML development on overall survival (OS). X. To investigate potential correlative results between array comparative genomic hybridization (CGH) findings and acute myeloid leukemia patient characteristics. TERTIARY OBJECTIVES: I. To compare health-related quality of life (QOL) (physical, functional, leukemia-specific well-being) and fatigue in elderly AML patients receiving standard induction therapy with those receiving clofarabine. II. To measure the change in health-related QOL that occurs over time (within treatment groups). III. To comprehensively assess patient function at the time of study enrollment. IV. To determine if components of a comprehensive geriatric assessment or QOL scales predict ability to complete AML treatment. V. To describe the impact of transplant on QOL in AML patients above age 60. OUTLINE: INDUCTION THERAPY: Patients are randomized to 1 of 2 treatment arms. ARM A (STANDARD THERAPY): Patients receive daunorubicin hydrochloride at 60 mg/m\^2 intravenously (IV) over 10-15 minutes on days 1-3 and cytarabine at 100 mg/m\^2 IV continuously on days 1-7. Patients with residual disease or those who do not achieve an aplastic bone marrow on day 12-14 (i.e., \< 5% blasts and \< 20% cellularity or markedly/moderately hypocellular) may receive a second course of induction therapy beginning no sooner than day 14. ARM B: Patients receive clofarabine at 30 mg/m\^2 IV over 1 hour on days 1-5. Patients with residual disease or those who do not achieve an aplastic bone marrow on day 12-14 (i.e., \< 5% blasts and \< 20% cellularity or markedly/moderately hypocellular) may receive a second course of induction therapy beginning no sooner than day 21 and no later than day 56. Patients who achieve a complete remission (CR) or CR with incomplete marrow recovery (CRi) after induction therapy proceed to consolidation therapy (Arms C and D). Patients who are 60-69 years of age who achieve a "morphologic leukemia-free state" after induction therapy and who have an HLA-identical donor proceed to allogeneic stem cell transplantation. CONSOLIDATION THERAPY: Beginning within 60 days after documentation of CR or CRi, patients receive consolidation therapy in the same arm they were randomized to for induction therapy. ARM C (STANDARD THERAPY): Patients receive cytarabine at 1500 mg/m\^2 IV over 1 hour once or twice daily on days 1-6. Treatment repeats every 4-6 weeks for 2 courses. ARM D: Patients receive clofarabine at 20 mg/m\^2 IV over 1 hour on days 1-5. Treatment repeats every 4-6 weeks for 2 courses. Patients who remain in CR after completion of consolidation therapy are randomized to one of the two maintenance therapy arms (Arms E and F). MAINTENANCE THERAPY: Beginning within 60 days after completion of consolidation therapy, patients receive maintenance therapy and are randomized to 1 of 2 arms. Patients not eligible for randomization to decitabine maintenance after recovery from consolidation will be followed according to Arm E. ARM E: Patients undergo observation monthly for 12 months. ARM F: Patients receive decitabine at 20 mg/m\^2 IV over 1 hour on days 1-3. Treatment repeats every 4 weeks for 12 months the absence of unacceptable toxicity. ALLOGENEIC STEM CELL TRANSPLANTATION WITH REDUCED-INTENSITY CONDITIONING REGIMEN (Arm G): Patients begin reduced-intensity conditioning 30-90 days after the initiation of induction therapy. CONDITIONING REGIMEN: Patients receive fludarabine phosphate at 30 mg/m\^2 IV over 30 minutes on days -7 to -3, busulfan at 0.8 mg/kg IV over 2 hours every 6 hours on days -4 and -3 (for a total of 8 doses), and anti-thymocyte globulin at 2.5 mg/kg/day IV over 4-6 hours on days -4 to -2. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. After completion of study treatment, patients are followed up every 3 months for 4 years, every 6 months for 1 year, and then annually thereafter.