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Azacitidine Plus Amifostine in Treating Patients With Myelodysplastic Syndrome

Primary Purpose

Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
amifostine trihydrate
azacitidine
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring refractory anemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes

Eligibility Criteria

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

DISEASE CHARACTERISTICS: Cytologically confirmed myelodysplastic syndrome (MDS) Intermediate 1, 2, or high risk disease OR Low risk disease with one of the following: Symptomatic anemia requiring transfusion for at least 3 months prior to study Symptomatic thrombocytopenia requiring platelet transfusion Platelet count less than 50,000/mm3 Absolute neutrophil count less than 1,000/mm3 with an infection Stable disease for 1 month with no progression to acute myeloid leukemia Declined or not eligible for allogeneic bone marrow transplant (alloBMT) No prior treatment of MDS with chemotherapy or alloBMT No prior leukemia or more than 30% myeloblasts in the bone marrow PATIENT CHARACTERISTICS: Age: Over 18 Performance status: 0-2 Life expectancy: Greater than 4 months Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 1.5 times normal (unless due to hemolysis or ineffective erythropoiesis) AST and ALT less than 2 times normal Renal: Creatinine less than 1.5 times normal Cardiovascular: No uncontrolled or severe congestive heart failure Pulmonary: Serum CO2 greater than 18 mmHg Other: No uncorrected folate or vitamin B12 deficiency HIV negative No other medical or psychiatric illness that would preclude study At least 3 years since prior nonleukemic malignancy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 1 month since prior interferon, interleukin-3, or interleukin-11 At least 1 month since prior epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF) No concurrent hematologic growth factors Chemotherapy: See Disease Characteristics Prior chemotherapy for nonleukemic malignancy allowed No prior azacitidine Endocrine therapy: At least 1 month since prior corticosteroids or danazol No concurrent steroids Radiotherapy: Prior radiotherapy for nonleukemic malignancy allowed Surgery: Not specified Other: No prior antithymocyte globulin or cyclosporine No prior amifostine

Sites / Locations

  • University of Michigan Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
May 2, 2000
Last Updated
December 19, 2012
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005598
Brief Title
Azacitidine Plus Amifostine in Treating Patients With Myelodysplastic Syndrome
Official Title
A Phase II Trial of 5-Azacytidine (NSC #102816) and Ethyol (Amifostine) in the Treatment of Adults With Myelodysplastic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
October 2000 (undefined)
Primary Completion Date
December 2001 (Actual)
Study Completion Date
March 2002 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

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. Amifostine may improve blood counts in patients with myelodysplastic syndrome. Combining azacitidine with amifostine may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of azacitidine plus amifostine in treating patients who have myelodysplastic syndrome.
Detailed Description
OBJECTIVES: I. Determine the response rate to azacitidine plus amifostine in patients with myelodysplastic syndromes. II. Evaluate the toxicity of this treatment regimen in these patients. III. Assess the rate of progression to acute myeloid leukemia and overall survival in these patients treated with this regimen. IV. Evaluate the relationship between response status and cytogenetics, FAB class, ras mutations, and the presence of nonclonal hematopoiesis with this treatment regimen in these patients. V. Assess the effect of this treatment regimen on the number of bone marrow hematopoietic progenitor cells in these patients. VI. Evaluate neutrophil adhesion and chemotaxis in these patients before and after this treatment regimen. OUTLINE: Patients receive amifostine IV over 1-3 minutes on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 plus azacitidine subcutaneously on days 1-7. Treatment repeats every 28 days for 4 courses. Patients who achieve complete remission receive an additional 3 courses, and patients who achieve hematologic improvement or partial remission continue treatment until disease progression or unacceptable toxicity. Patients are followed until death. PROJECTED ACCRUAL: A total of 17-32 patients will be accrued for this study within approximately 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
refractory anemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
amifostine trihydrate
Intervention Type
Drug
Intervention Name(s)
azacitidine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Cytologically confirmed myelodysplastic syndrome (MDS) Intermediate 1, 2, or high risk disease OR Low risk disease with one of the following: Symptomatic anemia requiring transfusion for at least 3 months prior to study Symptomatic thrombocytopenia requiring platelet transfusion Platelet count less than 50,000/mm3 Absolute neutrophil count less than 1,000/mm3 with an infection Stable disease for 1 month with no progression to acute myeloid leukemia Declined or not eligible for allogeneic bone marrow transplant (alloBMT) No prior treatment of MDS with chemotherapy or alloBMT No prior leukemia or more than 30% myeloblasts in the bone marrow PATIENT CHARACTERISTICS: Age: Over 18 Performance status: 0-2 Life expectancy: Greater than 4 months Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 1.5 times normal (unless due to hemolysis or ineffective erythropoiesis) AST and ALT less than 2 times normal Renal: Creatinine less than 1.5 times normal Cardiovascular: No uncontrolled or severe congestive heart failure Pulmonary: Serum CO2 greater than 18 mmHg Other: No uncorrected folate or vitamin B12 deficiency HIV negative No other medical or psychiatric illness that would preclude study At least 3 years since prior nonleukemic malignancy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 1 month since prior interferon, interleukin-3, or interleukin-11 At least 1 month since prior epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF) No concurrent hematologic growth factors Chemotherapy: See Disease Characteristics Prior chemotherapy for nonleukemic malignancy allowed No prior azacitidine Endocrine therapy: At least 1 month since prior corticosteroids or danazol No concurrent steroids Radiotherapy: Prior radiotherapy for nonleukemic malignancy allowed Surgery: Not specified Other: No prior antithymocyte globulin or cyclosporine No prior amifostine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harry P. Erba, MD, PhD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0752
Country
United States

12. IPD Sharing Statement

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Azacitidine Plus Amifostine in Treating Patients With Myelodysplastic Syndrome

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