Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Study of Haploidentical Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With High-Risk Acute Myeloid Leukemia in First Remission

Conditions
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Adult Acute Erythroid Leukemia, Adult Acute Monoblastic and Acute Monocytic Leukemia, Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: anti-thymocyte globulin
* Drug: fludarabine phosphate
* Drug: thiotepa
* Procedure: biological therapy
* Procedure: bone marrow ablation with stem cell support
* Procedure: chemotherapy
* Procedure: non-specific immune-modulator therapy
* Procedure: peripheral blood stem cell transplantation
* Procedure: radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: anti-thymocyte globulin|nan|
|Drug: fludarabine phosphate|nan|
|Drug: thiotepa|nan|
|Procedure: biological therapy|nan|
|Procedure: bone marrow ablation with stem cell support|nan|
|Procedure: chemotherapy|nan|
|Procedure: non-specific immune-modulator therapy|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Procedure: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult erythroleukemia (M6a), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myelomonocytic leukemia (M4)