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

Alternate Title

Azacitidine Plus Amifostine in Treating Patients With Myelodysplastic Syndrome

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Supportive care, Treatment	Completed	Over 18	NCI	CCUM-9906 NCI-T99-0069, NCT00005598, T99-0069

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.

Entry 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

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

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

Expected Enrollment

A total of 17-32 patients will be accrued for this study within approximately 
2 years.

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.

Trial Contact Information

Trial Lead Organizations

University of Michigan Comprehensive Cancer Center

Harry Erba, MD, PhD, Protocol chair		Ph: 734-647-8921; 800-865-1125

Registry Information
Official Title		A Phase II Trial of 5-Azacytidine (NSC #102816) and Ethyol (Amifostine) in the Treatment of Adults with Myelodysplastic Syndromes
Trial Start Date		2000-10-23
Registered in ClinicalTrials.gov		NCT00005598
Date Submitted to PDQ		2000-03-01
Information Last Verified		2002-06-01
NCI Grant/Contract Number		CA46592

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