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.

Condition	Treatment or Intervention	Phase
de novo myelodysplastic syndromes refractory anemia with excess blasts in transformation refractory anemia with excess blasts secondary myelodysplastic syndromes	Procedure: supportive care  Procedure: chemotherapy  Behavior: supportive care/therapy  Drug: chemoprotection  Drug: amifostine  Drug: cytarabine  Drug: topotecan	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the toxic effects of amifostine, topotecan, and cytarabine in patients with poor risk myelodysplastic syndrome. II. Determine the hematologic response rate, cytogenetic response rate, and the rate of polyclonal hematopoiesis following this treatment regimen. III. Determine the duration of response and time to disease progression following this treatment regimen in these patients.

PROTOCOL 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.

Ages Eligible for Study:  16 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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%)

--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

--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

California
      Cancer Center and Beckman Research Institute, City of Hope, Duarte,  California,  91010-3000,  United States

Study chairs or principal investigators

Henry C. Fung,  Study Chair,  ALZA   

Study ID Numbers:  CDR0000066982; CHNMC-IRB-98056; NCI-V99-1533; ALZA-CHNMC-IRB-98056
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003827
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08