Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission
Condition: Adult Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: filgrastim; Anti-Thymocyte Globulin; busulfan; fludarabine phosphate; methotrexate; tacrolimus; Allogeneic Hematopoietic Stem Cell Transplantation
Intervention description: Given SC; Given IV; Given IV; Given IV; Given IV; Given PO or IV; Undergo allogeneic PBSC transplantation
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Fludarabine; Busulfan; Tacrolimus; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 121.0
Sex: All
Minimum age: 60 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: adult acute myeloid leukemia in remission; secondary acute myeloid leukemia; adult acute monocytic leukemia (M5b); adult acute erythroid leukemia (M6); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Summary:

      This phase II trial studies how well fludarabine and busulfan followed by a donor
      (allogeneic) stem cell transplant work in treating older patients with acute myeloid leukemia
      that is in first complete remission. Giving low doses of chemotherapy, such as fludarabine
      and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of
      cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells.
      It may also stops the patient's immune system from rejecting the donor's stem cells. When the
      healthy stem cells from a donor are infused into the patient they may help the patient's bone
      marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem
      cells may replace the patient's immune system and help destroy any remaining cancer cells.
      Sometimes the transplanted cells from a donor can make an immune response against the body's
      normal cells (called graft-versus-host disease). Giving tacrolimus, methotrexate, and rabbit
      antithymocyte globulin before or after the transplant may stop this from happening.
    

Eligibility criteria:

        Eligibility Criteria:

          -  Patients with acute myeloid leukemia (AML) (excluding French-American-British [FAB]
             classification system M3) who have achieved a first morphologic complete remission and
             who meet the criteria below; patients with preceding myelodysplastic syndrome (MDS) or
             treatment-related AML are eligible; patients with prior central nervous system (CNS)
             involvement are eligible as long as disease is in remission at transplant; patients
             with acute leukemia following blast transformation of prior chronic myeloid leukemia
             (CML) or other myeloproliferative disease are excluded

          -  Complete remission (CR) will be defined according to the revised recommendations of
             the International Working Group (24) as all of the following:

               -  Normal bone marrow morphology with < 5% blasts

               -  Absolute neutrophil count (ANC) > 1,000/uL, referring to the count needed to
                  confirm that the patient achieved a CR

               -  Platelet count > 100,000/uL

               -  No extramedullary leukemia

               -  No blasts in peripheral blood

          -  CR was achieved after one or two (but no more than two) cycles of induction
             chemotherapy with standard cytotoxic chemotherapy (e.g., cytarabine and an
             anthracycline) or after no more than four cycles of a hypomethylating agent containing
             regimen including either 5-azacytidine or decitabine

          -  Patients may have received as many as but no more than two cycles of consolidation
             therapy prior to transplant; any consolidation regimen that does not require
             transplant can be used; no more than 6 months can elapse from documentation of
             morphologic CR to transplant; the platelet count does not need to be > 100,000/uL
             after consolidation, as long as the bone marrow assessment prior to transplant does
             not show relapse

          -  Identification of hematopoietic cell donor

          -  >= 4 weeks since prior chemotherapy, radiation therapy, and surgery

          -  Performance status 0-2

          -  Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary
             disease

          -  Left ventricular ejection fraction (LVEF) by multi gated acquisition scan (MUGA) or
             echocardiogram (ECHO) >= 30%

          -  No uncontrolled diabetes mellitus or active serious infection requiring antibiotics

          -  No known hypersensitivity to E. coli-derived products

          -  No human immunodeficiency virus (HIV) infection

          -  Calculated creatinine clearance >= 40 cc/min

          -  Bilirubin < 2 mg/dL

             * If bilirubin is 2-3 mg/dL, but direct bilirubin is normal then patient will be
             considered eligible

          -  Aspartate aminotransferase (AST) < 3 x upper limit of normal

          -  DONOR: HLA-identical sibling (6/6); the donor must be determined to be an human
             leukocyte antigen (HLA)-identical sibling (6/6) by serologic typing for class (A, B)
             and low resolution molecular typing for class II (DRB1)

          -  DONOR: Matched unrelated donor (10/10); high resolution molecular typing at the
             following loci is required: HLA-A, -B, -C, -DRB1, and -DQB1

          -  DONOR: the donor must be healthy and must be an acceptable donor as per institutional
             standards for stem cell donation

          -  DONOR: the donor must have no significant cardiopulmonary, renal, endocrine, or
             hepatic disease

          -  DONOR: there is no donor age restriction if the donor is a matched sibling

          -  DONOR: syngeneic donors are not eligible