Azacytidine and Bortezomib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes
Recruitment status was: Recruiting
RATIONALE: Drugs used in chemotherapy, such as azacytidine work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. Giving azacytidine together with bortezomib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when giving together with azacytidine in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Phase I Study of Vidaza and Velcade (Bortezomib) in Acute Myeloid Leukemia|
- Maximum tolerated dose of bortezomib in combination with azacytidine [ Designated as safety issue: Yes ]
- Overall response rate [ Designated as safety issue: No ]
- Rate of complete remission [ Designated as safety issue: No ]
- Biological activity of azacytidine and bortezomib as demethylating agents [ Designated as safety issue: No ]
- Correlation of intracellular concentration of azacytidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response [ Designated as safety issue: No ]
- Biologic role of microRNAs in determining clinical response to study drugs [ Designated as safety issue: No ]
- Achievement of other pharmacodynamic endpoints [ Designated as safety issue: No ]
|Study Start Date:||April 2008|
|Estimated Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
- To determine the maximum tolerated dose (MTD) bortezomib in combination with Azacytidine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
- To define the specific toxicities and the dose limiting toxicity (DLT) of Azacytidine plus bortezomib combination.
- To determine the overall response rate (ORR).
- To determine the rate of complete remission (CR) of Azacytidine plus bortezomib in relapsed/refractory AML and MDS.
- To correlate the biological activity of Azacytidine as demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation) with clinical endpoints and plasma pharmacokinetics of azacytidine.
- To characterize the biological activity of bortezomib as a potential demethylating agent.
- To correlate intracellular concentration of azacytidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response.
- To explore the biologic role of microRNAs in determining clinical response to the azacytidine plus bortezomib combination and achievement of the other pharmacodynamic endpoints.
OUTLINE: This is a dose-escalation study of bortezomib.
Patients receive azacytidine IV over 30 minutes on days 1-7 and bortezomib IV on days 2 and 5 or on days 2, 5, and 9 or on days 2, 5, 9, and 12. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib and tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
After completion of study treatment, patients are followed for at least 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00624936
|United States, Ohio|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210-1240|
|Principal Investigator:||William G. Blum, MD||Ohio State University Comprehensive Cancer Center|
|Principal Investigator:||Guido Marcucci, MD||Ohio State University Comprehensive Cancer Center|