RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I/II trial to study the effectiveness of amifostine plus topotecan in treating patients with myelodysplastic syndrome.

Condition	Treatment or Intervention	Phase
Previously Treated Myelodysplastic Syndrome de novo myelodysplastic syndrome refractory anemia with excess blasts in transformation refractory anemia with excess blasts Chronic Myelomonocytic Leukemia	Drug: amifostine  Drug: topotecan	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the hematologic and cytogenetic response to treatment with amifostine plus topotecan in patients with myelodysplastic syndromes.

II. Evaluate the toxic effects of this treatment in these patients.

III. Evaluate the effects of this treatment on bone marrow recovery in these patients.

PROTOCOL OUTLINE: This is a dose escalation study of topotecan.

Patients receive amifostine IV followed by topotecan IV over 30 minutes on days 1-5 every 4-8 weeks for at least two courses. Patients who are responding after two courses of induction receive maintenance courses every 6-8 weeks for up to ten courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients are treated at each dose level of topotecan. The maximum tolerated dose is defined as the dose at which no more than 2 of 6 patients experience dose limiting toxicity.

PROJECTED ACCRUAL: A maximum of 26 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed myelodysplatic syndrome (MDS), diagnosed at least 3 months prior to study enrollment, with one of the following subtypes: Refractory anemia with excess blasts (RAEB); RAEB in transformation (RAEB-T); Chronic myelomonocytic leukemia (CMML); CMML with leukocytosis not controlled by hydroxyurea eligible in absence of neutropenia
• No treatment- or mutagen-related MDS
• One or more cytopenias required: Untransfused hemoglobin less than 10 g/dL and/or transfusion-dependent (requiring at least four units of red blood cells in prior 12 weeks); Platelet count no greater than 50,000/mm3 or absolute neutrophil count less than 1,000/mm3
• No myelosclerosis occupying more than 30% of marrow

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent hematopoietic stimulants
• Chemotherapy: See Disease Characteristics; At least 35 days since prior chemotherapy
• Endocrine therapy: No concurrent androgen therapy; No concurrent corticosteroids
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: At least 35 days since any previous therapy for MDS (other than transfusion); No participation in any other experimental clinical trial within 35 days of entry into current trial

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%
• Life expectancy: At least 3 months
• Hematopoietic: See Disease Characteristics; No hereditary hemolytic disorders; Transferrin saturation greater than 20%; Ferritin at least 50 ng/mL
• Hepatic: Bilirubin less than 3 mg/dL; AST/ALT and LDH less than 2 times upper limit of normal
• Renal: Creatinine less than 2 mg/dL
• Cardiovascular: No significant cardiovascular disorders (unrelated to MDS); No uncontrolled hypertension
• Pulmonary: No significant pulmonary disorders (unrelated to MDS)
• Neurologic: No significant neurologic disorders (unrelated to MDS); No history of epilepsy
• Metabolic: No significant endocrine disorders (unrelated to MDS)
• Other: Not pregnant or nursing; No significant gastrointestinal diseases (unrelated to MDS) or GI blood loss; No significant genitourinary system diseases (unrelated to MDS); No active infection requiring IV antibiotic therapy; No other serious illness or medical condition; Not HIV positive; Not hepatitis B surface antigen positive; No iron, vitamin B12, or folate deficiencies; No autoimmune disease; No prior or concurrent malignancy within 2 years except in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin

Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States

Study chairs or principal investigators

Alan Francis List,  Study Chair,  Arizona Cancer Center   

Study ID Numbers:  CDR0000066429; UARIZ-HSC-97148; NCI-V98-1454; ALZA-97-017-ii
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003415
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08