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Sponsors and Collaborators: |
M.D. Anderson Cancer Center Genzyme |
Information provided by: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT00065143 |
The goal of this clinical research study is to learn if clofarabine, when given in combination with ara-C (cytarabine), can help to improve the disease's response to therapy and to increase the duration of response in patients who are 50 years or older with leukemia. The safety of this combination treatment will also be studied.
Condition | Intervention | Phase |
Leukemia, Myeloid Myelodysplastic Syndromes |
Drug: clofarabine Drug: Ara-C |
Phase II |
MedlinePlus related topics: | Cancer Leukemia, Adult Acute Leukemia, Adult Chronic |
ChemIDplus related topics: | Cytarabine Cytarabine hydrochloride Clofarabine |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study |
Official Title: | A Phase II Study of Clofarabine in Combination With Cytarabine (Ara-C) in Patients >/= 50 Years With Newly Diagnosed and Previously Untreated Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) (>/= 10% Bone Marrow Blasts) |
Estimated Enrollment: | 60 |
Study Start Date: | June 2003 |
The treatment of acute myeloid leukemia (AML) in older patients has not improved significantly in recent years when compared with the considerable progress that has been made in younger patients. Hence, new drugs and approaches are needed in this poor-prognosis group of patients with AML.
Nucleoside analogs are among the most active antileukemic agents available. Clofarabine was synthesized as a rational extension of the experience with other deoxyadenosine analogs. Clofarabine is converted to the monophosphate form by the enzyme deoxycytidine kinase which represents the major metabolite of clofarabine. Phosphorylation of clofarabine is substantially more efficient than that of other nucleosides such as fludarabine and so is intracellular retention of the triphosphate form of clofarabine. Mechanisms of action include inhibition of DNA synthesis, inhibition of DNA polymerases, and potent inhibition of ribonucleotide reductase (RNR) resulting in depletion of normal nucleotides and increased DNA uptake of the analog. Single agent clofarabine has shown activity in phase I studies in AML and ALL. As a potent inhibitor of RNR, however, clofarabine is ideal to be incorporated into biochemical modulation strategies such as have been tested and validated with fludarabine and ara-C in AML. By combining clofarabine with ara-C, inhibition of RNR by clofarabine will result in a drop of deoxynucleotides causing a decrease in the feedback inhibition of deoxycytidine kinase which is the rate-limiting step in the synthesis of ara-CTP leading to increased retention of ara-CTP. Therefore, the activity of clofarabine and ara-C in leukemic cells would be complemented by a biochemical synergism between these agents that should result in better clinical efficacy. We have established the safety of the combination in salvage patients with acute leukemias.
Ages Eligible for Study: | 50 Years to 74 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Texas | |||||
The University of Texas M.D. Anderson Cancer Center | |||||
Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center |
Genzyme |
Principal Investigator: | Stefan Faderl, MD | M.D. Anderson Cancer Center |
Website for The University of Texas M.D. Anderson Cancer Center 
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Study ID Numbers: | ID03-0139 |
First Received: | July 17, 2003 |
Last Updated: | October 17, 2006 |
ClinicalTrials.gov Identifier: | NCT00065143 |
Health Authority: | United States: Food and Drug Administration |
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