Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission
Adult Acute Myeloid Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
About this trial
This is an interventional treatment trial for Adult Acute Myeloid Leukemia in Remission focused on measuring 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
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
Sites / Locations
- UCSF Helen Diller Family Comprehensive Cancer Center
- Tunnell Cancer Center at Beebe Medical Center
- CCOP - Christiana Care Health Services
- Greenebaum Cancer Center at University of Maryland Medical Center
- Union Hospital of Cecil County
- Massachusetts General Hospital
- Dana-Farber/Brigham and Women's Cancer Center
- Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
- Beth Israel Deaconess Medical Center
- Masonic Cancer Center at University of Minnesota
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
- Cancer Institute of New Jersey at Cooper - Voorhees
- Roswell Park Cancer Institute
- Monter Cancer Center of the North Shore-LIJ Health System
- CCOP - North Shore University Hospital
- Don Monti Comprehensive Cancer Center at North Shore University Hospital
- Long Island Jewish Medical Center
- New York Weill Cornell Cancer Center at Cornell University
- Mount Sinai Medical Center
- Wake Forest University Comprehensive Cancer Center
- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Arms of the Study
Arm 1
Experimental
Treatment (fludarabine, busulfan, allogeneic PBSC)
PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover.