Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia
RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with vorinostat works in treating patients with high-risk myelodysplastic syndrome or acute myelogenous leukemia.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Velcade Plus Vorinostat in the Treatment of High Risk MDS and Relapsed/Refractory AML|
- Number of Patients by Best Clinical Response [ Time Frame: At Completion of Course 3 (Day 63) ] [ Designated as safety issue: No ]Assessed by the International Working Group response criteria: Categories include Complete Remission (CR), Partial Remission (PR), Marrow CR, Hematologic Improvement (HI), Stable Disease, Cytogenic Response and Disease Progression. clinical response = CR+PR+HI. Thus, all patients who complete at least 1 full cycle of therapy will be considered evaluable for response.
- Analysis of Natural Killer (NK) Cell Activating and Inhibitory Receptor Alterations, NK Cell Receptor Ligand Alterations, HLA Class I Expression on Target Cells (Myeloid Blasts), and NK-mediated Cell Killing [ Time Frame: Pre-Study and After 3 Cycles ] [ Designated as safety issue: No ]
- Correlation of the Above Changes With Response [ Time Frame: Pre-Study and After 3 Cycles ] [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Experimental: Velcade + Vorinostat
This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles.
1.3mg/m^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
Other Name: VelcadeDrug: vorinostat
400 mg orally (po) every day on days 1-14 of a 21 day cycle
Other Name: suberoylanilide hydroxamic acid (SAHA)
- To determine the clinical response to bortezomib and vorinostat in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia, as defined by the International Working Group response criteria.
- To characterize the quantitative and qualitative toxicities of this regimen in these patients.
- To assess the effect of this regimen on natural killer (NK) cell function, in terms of activating and inhibitory receptor alterations, target cell ligand and HLA class I modulation, and NK-mediated cell killing.
- To correlate the above changes with clinical response.
OUTLINE: Patients receive bortezomib subcutaneously (SQ) on days 1, 4, 8, and 11 and oral vorinostat once daily on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response, partial response, or hematologic improvement may receive 3 additional courses of therapy (for a maximum of 6 courses).
Bone marrow and peripheral blood samples are collected at baseline and at the completion of 3 courses of therapy for analysis of target cells (myeloid blasts) (i.e., HLA class I receptor analysis and natural killer [NK] cell receptor ligand analysis) and analysis of activating NK cell receptor alterations and NK-mediated cell killing.
After completion of study treatment, patients are followed periodically for up to 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00818649
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Erica Warlick, MD||Masonic Cancer Center, University of Minnesota|