Amifostine Plus Topotecan in Treating Patients With Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003415
First received: November 1, 1999
Last updated: January 30, 2013
Last verified: July 2000
  Purpose

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 Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: amifostine trihydrate
Drug: topotecan hydrochloride
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Study of Combined Treatment With Amifostine (Ethyol) and Topotecan (Hycamtin MS) in Patients With Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 26
Study Start Date: September 1998
Study Completion Date: November 2002
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003415

Locations
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
Sponsors and Collaborators
University of Arizona
Investigators
Study Chair: Alan F. List, MD University of Arizona
  More Information

Additional Information:
Publications:
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.

ClinicalTrials.gov Identifier: NCT00003415     History of Changes
Other Study ID Numbers: CDR0000066429, UARIZ-HSC-97148, ALZA-97-017-ii, NCI-V98-1454
Study First Received: November 1, 1999
Last Updated: January 30, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Amifostine
Topotecan
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014