Phase I/II Pilot Study of Therapy with Azacytidine to Induce Differentiation in Patients with Myelodysplastic Syndromes

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase ITreatmentClosedover 15NCICLB-8421


I.  Test the effect of azacytidine (AZA), given in repeated continuous 
low-dose infusions, on the differentiation of myelodysplastic syndromes.

II.  Determine an appropriate dose and regimen of AZA as a feasibility pilot 
for eventual application.

III.  Determine those myelodysplastic syndromes that will respond optimally to 
differentiation treatment.

IV.  Determine whether AZA will affect the natural history and outcome of 
myelodysplastic syndromes.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients older than 15 years of age 
with an established diagnosis of myelodysplastic syndrome as confirmed by 
examination of peripheral blood and bone marrow samples and as defined 
according to the FAB classification.  Patients with the following two 
categories of disease are eligible:  refractory anemia with excess blasts 
(i.e., 5-20% myeloblasts in the bone marrow and less than 5% blasts in the 
peripheral blood, together with abnormalities in erythroid, megakaryocytic, 
and granulocytic maturation consistent with myelodysplasia); or refractory 
anemia with excess blasts in transformation (i.e., 21-30% myeloblasts in the 
marrow, or more than 5% blasts in the peripheral blood, or Auer rods in 
granulocytic precursors in the marrow or blood with less than 30% myeloblasts 
and promyelocytes in the marrow).  Patients may not have received prior 
cytotoxic therapy for their marrow disease; those who have received cytosine 
arabinoside in doses of no more than 20 mg/sqm/day for up to 30 days who do 
not have a hypoplastic bone marrow and who have recovered from that treatment 
are eligible.  Previous treatment for cancer with chemotherapy or radiotherapy 
is allowed, but there may have been no radiotherapy or chemotherapy within the 
6 months prior to entry.  A life expectancy of at least 2 months, a CALGB 
performance status of 3 or less, a creatinine of less than 2 mg/dl, SGOT and 
SGPT levels less than 150 IU, and a serum CO2 level of at least 19 mEq/liter 
are required.  The bilirubin level must be 1.5 mg/dl or less unless there is 
active hemolysis or the elevation is secondary to ineffective erythropoiesis.  
Patients with uncontrolled or severe congestive heart failure are ineligible, 
as are those with any serious medical or psychiatric illness that would 
prevent informed consent.  Pregnancy excludes.

Expected Enrollment

20 patients will be entered.  Accrual is expected to be completed within 12 
months.  Per November 1986 update, the accrual goal has been extended to a 
total of 45 patients because early results have been very promising (5 of the 
first 13 evaluable patients have shown partial response).


Nonrandomized study.

Single-Agent Chemotherapy.  Azacytidine, AZA, NSC-102816.

Published Results

Silverman LR, Davis RB, Holland JF, et al.: 5-Azacytidine (AZ) as a low dose continuous infusion is an effective therapy for patients with myelodysplastic syndromes (MDS). [Abstract] Proceedings of the American Society of Clinical Oncology 8: A-768, 198, 1989.

Related Publications

Silverman LR, McKenzie DR, Peterson BL, et al.: Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 24 (24): 3895-903, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

James Holland, MD, Protocol chair
Ph: 212-241-4495

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.