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
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation; Anti-Thymocyte Globulin; Azacitidine; Busulfan; Fludarabine Phosphate; Laboratory Biomarker Analysis; Methotrexate; Pharmacological Study; Tacrolimus
Intervention description: 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
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Azacitidine; Fludarabine; Busulfan; Tacrolimus; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meets one of the following sets of criteria:

               -  Myelodysplastic syndromes (MDS):

                    -  Disease with high-risk features (found either at diagnosis or before
                       initiation of cytotoxic therapy), defined as one of the following:

                         -  International prognostic scoring system (IPSS) risk >= intermediate-2

                         -  Refractory anemia with excess blasts by French-American-British (FAB)
                            classification

                         -  High-risk cytogenetics (either complex or -7)

                    -  Less than 10% bone marrow blasts as determined by bone marrow biopsy within
                       the past 4 weeks (reduction in marrow blast percentage may be achieved with
                       chemotherapy or other therapy)

                    -  Less than 75 years old

               -  Acute myeloid leukemia (AML):

                    -  No FAB M3

                    -  No acute leukemia following blast transformation of prior chronic
                       myelogenous leukemia or other myeloproliferative disease

                    -  Patients with preceding MDS or treatment-related AML are eligible

                    -  Prior central nervous system (CNS) involvement is allowed provided the
                       disease is in remission at transplantation

                    -  Morphologic complete remission (leukemia-free state) is defined as meeting
                       all of the following criteria:

                         -  Bone marrow blasts < 5% (as determined by bone marrow within the past 4
                            weeks), but without requirement for normal peripheral blood counts

                         -  No extramedullary leukemia

                         -  No blasts in peripheral blood

                    -  Achieved complete remission (CR) after no more than 2 courses of induction
                       chemotherapy

                         -  Patients treated with azacitidine or decitabine who achieve a
                            leukemia-free state are eligible (may have required up to 4 courses of
                            therapy to reach this status)

                    -  Age 60 to 74 years

          -  Donors must meet the following criteria:

               -  One of the following:

                    -  HLA-identical sibling (6/6) by serologic typing for class (A, B) and
                       low-resolution molecular typing for class II (DRB1)

                    -  Matched unrelated donor (8/8) by high-resolution molecular typing at HLA-A,
                       -B, -C, and DRB1

               -  No syngeneic donors

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Calculated creatinine clearance ≥ 40 mL/min

          -  Bilirubin < 2 mg/dL OR bilirubin 2-3 mg/dL provided direct bilirubin is normal

          -  Aspartate aminotransferase (AST) < 3 times upper limit of normal

          -  Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% with no symptomatic
             pulmonary disease

          -  Left ventricle ejection fraction (LVEF) >= 30% by echocardiogram (ECHO) or multigated
             acquisition (MUGA)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No uncontrolled diabetes mellitus or active serious infections

          -  No known hypersensitivity to E. coli-derived products, azacitidine, or mannitol

          -  No human immunodeficiency virus (HIV) infection or active hepatitis B or C

          -  Prior azacitidine or decitabine allowed

               -  No patients who progressed from MDS to AML during treatment with azacitidine or
                  decitabine

          -  At least 4 weeks since prior deoxyribonucleic acid (DNA)-hypomethylating chemotherapy,
             radiotherapy, and/or surgery

          -  No more than 2 courses of consolidation therapy before transplantation (for patients
             with AML)

               -  Any consolidation regimen that does not require transplantation can be used

               -  No more than 6 months from documentation of morphologic CR to transplantation