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

• Status: Completed
• Trial end date: 2016-06-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antilymphocyte Serum; Busulfan; Fludarabine; Fludarabine phosphate; Lenograstim; Methotrexate; Tacrolimus; Vidarabine

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