Busulfan and Cyclophosphamide Followed by Bone Marrow Transplantation in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of busulfan and cyclophosphamide followed by bone marrow transplantation in treating patients who have acute myelogenous leukemia or myelodysplastic syndrome.

Detailed Description
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OBJECTIVES: Determine the remission duration, disease-free survival, and overall survival of patients with acute myelogenous leukemia in remission or early relapse or myelodysplastic syndrome treated with high-dose busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation. OUTLINE: Patients receive oral high-dose busulfan every 6 hours for 14-16 doses on days -9 to -6, followed by high-dose cyclophosphamide IV over 1 hour on days -5 to -2. Allogeneic bone marrow is infused on day 0. Patients who have already had 1 transplant receive high-dose cyclophosphamide IV on days -6 and -5, total body irradiation twice a day on days -4 to -1, and allogeneic bone marrow infusion on day 0. All patients receive prophylaxis for graft versus host disease. Patients are followed every 6 months for at least 2 years. PROJECTED ACCRUAL: A total of 25-40 patients will be accrued for this study.

Official Title
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Phase II Study of High-Dose Busulfan and Cyclophosphamide Followed by Allogeneic Bone Marrow Transplantation for Patients With Acute Myelogenous Leukemia

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

Intervention / Treatment
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* Drug: busulfan
* Drug: cyclophosphamide
* Procedure: allogeneic bone marrow transplantation
* Procedure: bone marrow ablation with stem cell support
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Morphologically proven (from bone marrow aspirate smears or touch preps of marrow biopsy) acute myelogenous leukemia or myelodysplastic syndrome of 1 of the following subtypes: Acute myeloblastic leukemia (M1, M2) Acute promyelocytic leukemia (M3) Acute myelomonocytic leukemia (M4) Acute monocytic leukemia (M5) Acute erythroleukemia (M6) Acute megakaryocytic leukemia (M7) Refractory anemia Refractory anemia with excess blasts Refractory anemia with excess blasts in transformation Refractory anemia with ringed sideroblasts Chronic myelomonocytic leukemia In remission or in early relapse as defined by less than 20% blast cells in the marrow or overt active acute myeloid leukemia Suitable marrow donor, defined as a sibling donor matched at the HLA-A, HLA-B, and HLA-D/DR locus nonreactive in bidirectional mixed lymphocyte culture or a donor who is mismatched at 1 antigen loci Active CNS disease allowed PATIENT CHARACTERISTICS: Age: 16 to physiologic 60 Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 3 times upper limit of normal (ULN) unless due to Gilbert's disease SGOT no greater than 3 times ULN Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: Cardiac ejection fraction normal Pulmonary: FEV_1 at least 50% of predicted DLCO at least 50% of predicted Other: HIV negative No evidence of persistent infection No concurrent organ damage or medical problems that would preclude study therapy PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No concurrent antibiotics

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: busulfan|nan|
|Drug: cyclophosphamide|nan|
|Procedure: allogeneic bone marrow transplantation|nan|
|Procedure: bone marrow ablation with stem cell support|nan|
|Radiation: 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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recurrent adult acute myeloid leukemia, adult acute myeloid leukemia in remission, adult acute erythroid leukemia (M6), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute promyelocytic leukemia (M3), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute megakaryoblastic leukemia (M7), refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, adult acute monocytic leukemia (M5b), previously treated myelodysplastic syndromes, myelodysplastic/myeloproliferative disease, unclassifiable, atypical chronic myeloid leukemia, 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, adult acute myeloid leukemia with t(15;17)(q22;q12), childhood myelodysplastic syndromes