Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission

PRIMARY OBJECTIVES:

I. Determine if allogeneic transplantation from a matched sibling or unrelated donor using a
non-myeloablative preparative regimen results in a 2-year disease-free survival (DFS) that is
better than historical results using standard chemotherapy.

SECONDARY OBJECTIVES:

I. Determine 2-year actuarial risks of transplant-related mortality, acute and chronic
graft-versus-host (GVHD) disease and relapse among patients with acute myeloid leukemia (AML)
in first complete remission (CR1) following a non-myeloablative preparative regimen.

II. To examine recovery of T and B cell number and function following non-myeloablative stem
cell transplant.

III. To examine the time course of T, B and myeloid progenitor chimerism following this
preparative regimen.

IV. To characterize the pharmacokinetics of intravenous busulfan used in a non-myeloablative
preparation regimen in AML patients age >= 60 years.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine intravenously (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.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV
twice daily (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 PERIPHERAL BLOOD STEM CELL TRASNPLANTATION (PBSC): Patients undergo allogeneic
PBSC transplant on day 0. Patients then receive filgrastim subcutaneously (SC) daily
beginning on day 12 and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then every 6 months
for 3 years.

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