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Amifostine Plus Topotecan in Treating Patients With Myelodysplastic Syndrome

Primary Purpose

Leukemia, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
amifostine trihydrate
topotecan hydrochloride
Sponsored by
University of Arizona
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arizona Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
January 30, 2013
Sponsor
University of Arizona
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1. Study Identification

Unique Protocol Identification Number
NCT00003415
Brief Title
Amifostine Plus Topotecan in Treating Patients With Myelodysplastic Syndrome
Official Title
Phase I/II Study of Combined Treatment With Amifostine (Ethyol) and Topotecan (Hycamtin MS) in Patients With Myelodysplastic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
July 2000
Overall Recruitment Status
Completed
Study Start Date
September 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
November 2002 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Arizona

4. Oversight

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes
Keywords
refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
amifostine trihydrate
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan F. List, MD
Organizational Affiliation
University of Arizona
Official's Role
Study Chair
Facility Information:
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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.
Results Reference
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Amifostine Plus Topotecan in Treating Patients With Myelodysplastic Syndrome

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