Amifostine in Treating Young Patients With Newly Diagnosed De Novo Myelodysplastic Syndromes

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as amifostine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well amifostine works in treating young patients with newly diagnosed de novo myelodysplastic syndromes.

Detailed Description
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OBJECTIVES: Primary Determine the hematologic effects of amifostine, in terms of, complete and partial response, in pediatric patients with newly diagnosed de novo myelodysplastic syndromes (MDS). Determine the safety and efficacy of this drug in these patients. Secondary Determine the efficacy of this drug in preventing conversion of MDS to acute myeloid leukemia (AML) in terms of the proportion of patients who remain free of AML at the completion of study treatment. Determine the duration of progression-free remission from MDS conversion to AML in patients treated with this drug. Determine the effect of karyotypic abnormalities on survival and the duration from diagnosis of MDS until conversion to AML in patients treated with this drug. Determine the effect of bone marrow blast count on survival and the duration from diagnosis of MDS until conversion to AML in patients treated with this drug. Determine the effect of the number of cytopenias on survival in patients treated with this drug. Correlate the duration of time from diagnosis of MDS until conversion to AML with survival in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive amifostine IV over 1-3 minutes on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Treatment repeats every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease who are planning to undergo matched donor bone marrow or cord blood transplantation continue therapy until transplantation. Patients with stable or responding disease who are not undergoing transplantation may receive up to 4 additional courses of amifostine in the absence of disease progression or unacceptable toxicity. Following completion of therapy with amifostine, patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 10-20 patients will be accrued for this study within 5-10 months.

Official Title
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A Phase II Study Of Amifostine In Children With Myelodysplastic Syndrome

Conditions
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Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Drug: amifostine trihydrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of myelodysplastic syndromes (MDS) One of the following subtypes: Refractory anemia (RA) RA with ringed sideroblasts RA with excess blasts Refractory cytopenia with multilineage dysplasia (RCMD) RCMD and ringed sideroblasts MDS, unclassified MDS associated with isolated del 5(q) De novo disease No treatment-induced MDS No juvenile myelomonocytic leukemia No Down syndrome, Fanconi's anemia, or other inherited forms of hypoplastic bone marrow failure PATIENT CHARACTERISTICS: Age 1 to 21 at original diagnosis Performance status Karnofsky 50-100% (patients > 16 years of age) Lansky 50-100% (patients 1 to 16 years of age) Life expectancy At least 8 weeks Hematopoietic See Disease Characteristics Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT < 2.5 times ULN Renal Radioisotope glomerular filtration rate ≥ 60 mL/min OR Creatinine clearance > 60 mL/min (based on Schwartz formula) Calcium normal Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Serum electrolytes normal Phosphorus normal Magnesium normal Glucose normal No other concurrent malignancy PRIOR CONCURRENT THERAPY: Biologic therapy More than 8 weeks since prior growth factors No concurrent growth factors No concurrent hematopoietic stem cell transplantation No concurrent immunomodulating agents Chemotherapy No prior amifostine No other concurrent anticancer chemotherapy Endocrine therapy No concurrent daily steroid therapy Radiotherapy Not specified Surgery Not specified Other No prior therapy for MDS

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 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: amifostine trihydrate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological effects (complete and partial response) |  |  | 
| Safety and efficacy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy |  |  | 
| Duration of progression-free remission |  |  | 
| Effect of karyotypic abnormalities on survival |  |  | 
| Effect of the number of cytopenias on survival |  |  | 
| Correlation of the duration of time from diagnosis of myelodysplastic syndromes until conversion to acute myeloid leukemia |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory anemia with excess blasts, refractory anemia, refractory anemia with ringed sideroblasts, de novo myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, refractory cytopenia with multilineage dysplasia