Phase I/II Pilot Study of Therapy with Azacytidine to Induce Differentiation in Patients with Myelodysplastic Syndromes
Basic Trial Information
|Phase II, Phase I||Treatment||Closed||over 15||NCI||CLB-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.
See General Eligibility Criteria
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.
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.
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.
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
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.