Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Amifostine Plus Topotecan in Treating Patients With Myelodysplastic Syndrome

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Supportive care, Treatment Closed 18 and over Pharmaceutical / Industry UARIZ-HSC-97148 ALZA-97-017-ii, NCI-V98-1454, NCT00003415

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.

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

Expected Enrollment

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

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.

List AF, Talley M, Obregon Y, et al.: Combined treatment with amifostine and topotecan: high remitting potential in advanced myelodysplastic syndrome (MDS). [Abstract] Proceedings of the American Society of Clinical Oncology 19: A103, 28a, 2000.

Trial Contact Information

Trial Lead Organizations

Arizona Cancer Center at University of Arizona Health Sciences Center

Alan List, MD, Protocol chair(Contact information may not be current)		Ph: 520-626-6044; 800-622-2673

Registry Information
Official Title		Phase I/II Study of Combined Treatment With Amifostine (Ethyol) and Topotecan (Hycamtin MS) in Patients With Myelodysplastic Syndrome
Trial Start Date		1998-09-23
Registered in ClinicalTrials.gov		NCT00003415
Date Submitted to PDQ		1998-07-08
Information Last Verified		2000-07-01

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