Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission
Phase II Study of Haploidentical Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With High-Risk Acute Myeloid Leukemia in First Remission
RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with fludarabine, thiotepa, and antithymocyte globulin before transplant may stop this from happening. PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with acute myeloid leukemia in remission.
OBJECTIVES: Primary - Determine the safety and antileukemia activity of haploidentical allogeneic peripheral blood stem cell transplantation in patients with high-risk acute myeloid leukemia in first remission. Secondary - Determine the early treatment-related mortality (before day 100) of patients treated with this regimen. - Determine the incidence of acute graft-versus-host disease in patients treated with this regimen. - Determine the incidence of graft failure in patients treated with this regimen. - Correlate a mismatch in the expression of the natural killer cell inhibitory receptors CD158a and CD158b with engraftment and disease recurrence in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive a preparative regimen comprising total-body irradiation twice on day -8; fludarabine IV over 30 minutes on days -7 to -3; thiotepa IV over 2 hours twice on day -7; and antithymocyte globulin IV over 4-6 hours on days -5 to -2. Patients undergo haploidentical allogeneic peripheral blood stem cell transplantation on day 0. Patients are followed at day 100, at least monthly for 2 years, and then periodically for 3 years. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study within 2.2 years.
Adult Acute Erythroid Leukemia
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
DISEASE CHARACTERISTICS: - Morphologically confirmed acute myeloid leukemia of 1 of the following subtypes: - Acute myeloblastic leukemia (M0, M1, M2) - Acute myelomonocytic leukemia (M4) - Acute monocytic leukemia (M5) - Acute erythroleukemia (M6) - Acute megakaryocytic leukemia (M7) - Must have 1 of the following karyotypic abnormalities at the time of diagnosis: - Complex cytogenetic abnormalities (≥ 3 cytogenetic clones) - Abnormalities of chromosome 5 [-5 or del(5q)] - Abnormalities of the long (q) arm of chromosome 3, 9, 11, 20, or 21 - Abnormalities of the short (p) arm of chromosome 17, monosomy 7, t(9;22), or t(6;9) (8) - In morphologic first complete remission*, as evidenced by all of the following for ≥ 4 weeks before study entry: - Absolute neutrophil count > 1,000/mm^3 - Platelet count > 100,000/mm^3 - Leukemic blasts not present in the peripheral blood - Cellularity of bone marrow biopsy > 20% with maturation of all cell lines - Less than 5% blasts by bone marrow biopsy - No extramedullary leukemia, such as CNS or soft tissue involvement NOTE: *Reduced hemoglobin concentration or hematocrit has no bearing on remission status - Haploidentical (3/6 or 4/6 antigen matched [A, B, and DR]) family donor available PATIENT CHARACTERISTICS: Age - 18 to 59 Performance status - ECOG 0-2 Life expectancy - Not specified Hematopoietic - See Disease Characteristics Hepatic - Bilirubin ≤ 2.0 mg/dL - AST < 2 times upper limit of normal Renal - Creatinine ≤ 1.5 mg/dL Cardiovascular - Ejection fraction > 40% by MUGA or echocardiogram - None of the following within the past 3 months: - Myocardial infarction - Significant congestive heart failure - Significant cardiac arrhythmia Pulmonary - FEV_1 and DLCO > 50% of predicted Immunologic - HIV negative - No active or unresolved infection - No evidence of invasive fungal infection (e.g., positive blood or deep tissue cultures or stains) Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No organ damage - No other medical problem that would preclude study participation - No other currently active tumor that would likely interfere with study treatment or that would likely compromise the patient's morbidity or mortality PRIOR CONCURRENT THERAPY: Biologic therapy - No concurrent routine use of filgrastim (G-CSF) or sargramostim (GM-CSF) to accelerate hematopoietic recovery post-transplantation Chemotherapy - More than 4 weeks since prior chemotherapy Endocrine therapy - Not specified Radiotherapy - More than 4 weeks since prior radiotherapy Surgery - Not specified
18 Years - 59 Years
Accepts Healthy Volunteers
Mark R. Litzow, MD, ,
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Mark R. Litzow, MD, Study Chair, Mayo Clinic