Combination Chemotherapy in Treating Patients With Myelodysplastic Syndrome

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combining topotecan and cytarabine given with amifostine in treating patients who have myelodysplastic syndrome.

Detailed Description
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OBJECTIVES: Determine the toxic effects of amifostine, topotecan, and cytarabine in patients with poor risk myelodysplastic syndrome. Determine the hematologic response rate, cytogenetic response rate, and the rate of polyclonal hematopoiesis following this treatment regimen. Determine the duration of response and time to disease progression following this treatment regimen in these patients. OUTLINE: Patients receive topotecan by continuous IV over 24 hours plus cytarabine IV over 2 hours, on days 1-5. Patients receive amifostine IV over 15 minutes every other day for a maximum of 60 days. Patients may receive a second course of the same regimen 8 weeks after the first. Patients are followed at least monthly for 2 years, then every 3-6 months until death. PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study within 1 to 1.5 years.

Official Title
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Treatment of Poor Risk Myelodysplasia With the Combination of Amifostine, Topotecan and ARA-C: A Phase II Study

Conditions
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Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: amifostine trihydrate
* Drug: cytarabine
* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed poor risk myelodysplastic syndrome, including at least one of the following: Bilineage cytopenia Unfavorable cytogenetic abnormalities Refractory anemia with excess blasts and/or refractory anemia with excess blast in transformation (greater than 5% blast) At least 0.5 on the International Prognostic Score System No chronic myelomonocytic leukemia No hypocellular myelodysplastic syndrome (marrow cellularity less than 30%) PATIENT CHARACTERISTICS: Age: 16 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count less than 1,500/mm3 Platelet count less than 100,000/mm3 Hemoglobin less than 10 g/dL Hepatic: ALT less than 5 times upper limit of normal Renal: Creatinine no greater than 1.4 mg/dL Cardiovascular: No congestive heart failure Other: Not pregnant or nursing Fertile patients must use effective contraception Must have right atrial catheter inserted PRIOR CONCURRENT THERAPY: Biologic therapy: No prior blood or bone marrow transplantations Chemotherapy: No prior acute myeloid leukemia chemotherapy (except hydroxyurea or low dose cytarabine) No prior topotecan No prior amifostine Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: At least 24 hours since prior antihypertensive medication prior to amifostine

Ages Eligible for Study
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Minimum Age: 16 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: amifostine trihydrate|nan|
|Drug: cytarabine|nan|
|Drug: topotecan hydrochloride|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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secondary myelodysplastic syndromes, childhood myelodysplastic syndromes, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, de novo myelodysplastic syndromes