Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II clinical trial is studying how well giving busulfan, fludarabine phosphate, and
      anti-thymocyte globulin followed by donor stem cell transplant and azacitidine works in
      treating patients with high-risk myelodysplastic syndrome and older patients with acute
      myeloid leukemia. Giving low doses of chemotherapy, such as busulfan and fludarabine
      phosphate, before a donor stem cell transplant helps stop the growth of cancer cells. It also
      stops the patient's immune system from rejecting the donor's stem cells. The donated stem
      cells may replace the patient's immune cells and help destroy any remaining cancer cells
      (graft-vs-tumor effect). Sometimes the transplanted cells from a donor can also make an
      immune response against the body's normal cells. Giving anti-thymocyte globulin before
      transplant and giving azacitidine, tacrolimus, and methotrexate after the transplant may stop
      this from happening.
    

Detailed description: 
      PRIMARY OBJECTIVE:

      I. To determine if this treatment can improve 2-year progression-free survival (PFS) in
      patients with high risk myelodysplastic syndrome (MDS) and in patients with acute myeloid
      leukemia (AML) >= 60 yrs age

      SECONDARY OBJECTIVES:

      I. To determine the safety and feasibility of using post-transplantation azacitidine.

      II. To determine the ability to use pharmacokinetic-directed busulfan to achieve area under
      the curve (AUC) within 20% of target AUC in > 80% of patients.

      III. To determine the rate of grade II-IV and III-IV acute graft-vs-host disease (GVHD).

      IV. To determine the incidence of extensive chronic GVHD. V. To determine treatment-related
      mortality at 100 days and at 1 year. VI. To determine 5-year overall survival.

      OUTLINE:

      REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV)
      over 30 minutes on days -7 to -3, busulfan IV over 45 minutes on days -6 to -3, and
      anti-thymocyte globulin IV over 4-10 hours on days -6 to -5 (matched sibling donor [MSD]) or
      -6 to -4 (matched unrelated donor [MUD]).

      TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0
      or on days 0-1.

      GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV on days -2
      to 90 with taper on days 150-180. Patients also receive methotrexate IV on days 1, 3, 6
      (MSD), and 11 (MUD).

      CONSOLIDATION: Beginning on day 42, patients receive azacitidine subcutaneously (SC) or IV on
      days 1-5.

      Treatment repeats every 4 weeks for 6 courses. Blood and bone marrow samples may be collected
      periodically for correlative and pharmacokinetic studies.

      After completion of study treatment, patients are followed up every 6 months for 5 years.
    

Intervention name(s): Allogeneic Hematopoietic Stem Cell Transplantation; Anti-Thymocyte Globulin; Azacitidine; Busulfan; Fludarabine Phosphate; Laboratory Biomarker Analysis; Methotrexate; Pharmacological Study; Tacrolimus
Intervention type(s): Procedure; Biological; Drug; Drug; Drug; Other; Drug; Other; Drug
Intervention description(s): Undergo allogeneic hematopoietic stem cell transplantation; Given IV; Given SC or IV; Given IV; Given IV; Correlative studies; Given IV; Correlative studies; Given PO or IV
Other intervention name(s): Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Antithymocyte Globulin; Antithymocyte Serum; ATG; ATS; 5 AZC; 5-AC; 5-Azacytidine; 5-AZC; Azacytidine; Azacytidine, 5-; Ladakamycin; Mylosar; Onureg; U-18496; Vidaza; 1, 4-Bis[methanesulfonoxy]butane; BUS; Bussulfam; Busulfanum; Busulfex; Busulphan; CB 2041; CB-2041; Glyzophrol; GT 41; GT-41; Joacamine; Methanesulfonic Acid Tetramethylene Ester; Methanesulfonic acid, tetramethylene ester; Mielucin; Misulban; Misulfan; Mitosan; Myeleukon; Myeloleukon; Myelosan; Mylecytan; Myleran; Sulfabutin; Tetramethylene Bis(methanesulfonate); Tetramethylene bis[methanesulfonate]; WR-19508; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; FK 506; Fujimycin; Hecoria; Prograf; Protopic
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Azacitidine; Fludarabine; Busulfan; Tacrolimus; Antilymphocyte Serum
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment