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Phase I/II Study of Combined Treatment With Amifostine (Ethyol) and Topotecan (Hycamtin MS) in Patients With Myelodysplastic Syndrome

Phase 1/Phase 2
18 Years
Not Enrolling
Leukemia, Myelodysplastic Syndromes

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Trial Information

Phase I/II Study of Combined Treatment With Amifostine (Ethyol) and Topotecan (Hycamtin MS) in Patients With Myelodysplastic Syndrome

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.

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.

Inclusion 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

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

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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Alan F. List, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Arizona


United States: Federal Government

Study ID:




Start Date:

September 1998

Completion Date:

November 2002

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • refractory anemia with excess blasts
  • refractory anemia with excess blasts in transformation
  • chronic myelomonocytic leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia



Arizona Cancer Center Tucson, Arizona  85724