Ignite Creation Date:
2024-05-05 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00065143
Status:
COMPLETED
Last Update Posted:
2018-11-07
First Post:
2003-07-17
Brief Title:
Clofarabine Plus Cytarabine in Patients With Previously Untreated Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2018-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 diseases 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
Detailed Description:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None