Clofarabine for Myelodysplastic Syndrome (MDS) Patients Who Failed Vidaza Treatment (tx)
Status:
Terminated
Trial end date:
2010-03-01
Target enrollment:
Participant gender:
Summary
The investigators hypothesize that, in addition to its apoptotic effect, clofarabine induces
DNA hypomethylation. If the investigators' hypothesis is correct, findings from the present
proposal will not only contribute to information relating to the mechanisms of action of
clofarabine but also provide the opportunity for combined epigenetic targeting of MDS using
clofarabine with either another hypomethylating agent or a histone deacetylase inhibitor.
Clofarabine has demonstrated anti-cancer activity through inhibition of DNA synthesis and
repair, induction of apoptosis, and possibly through other mechanisms. Numerous responses
have been observed after treatment with clofarabine in heavily pre-treated
relapsed/refractory patients with ALL, AML and high risk MDS.
In the present proposal, the investigators will study the clinical and laboratory effects of
2 different dosages of clofarabine in patients who have failed the hypomethylating agent,
5-azacytidine. This study will recruit patients who have received at least six cycles of
5-azacytidine without response or whose disease has progressed or relapsed while on
5-azacytidine. The first cohort of patients will receive clofarabine 10 mg/m2/day for five
days and the second cohort of patients 5 mg/m2/day for five days, both every four to six
weeks. The investigators will determine the frequency of response to the two dosages of
nucleoside analog in this group of patients. Measurement of responses will include
improvement in the peripheral blood count, reduction in the blood and platelet transfusion
need and eradication of cytogenetically abnormal clones. Successful completion of this study
will define the position of clofarabine in MDS in the era of epigenetic targeting.