Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT00818649|
Recruitment Status : Terminated (Met protocol stop rule [i.e., extreme toxicity])
First Posted : January 8, 2009
Results First Posted : February 25, 2013
Last Update Posted : December 28, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myelodysplastic Syndrome||Drug: bortezomib Drug: vorinostat||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Velcade Plus Vorinostat in the Treatment of High Risk MDS and Relapsed/Refractory AML|
|Study Start Date :||January 2009|
|Actual Primary Completion Date :||May 2012|
|Actual Study Completion Date :||May 2012|
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: Velcade
400 mg orally (po) every day on days 1-14 of a 21 day cycle
Other Name: suberoylanilide hydroxamic acid (SAHA)
- Number of Patients by Best Clinical Response [ Time Frame: At Completion of Course 3 (Day 63) ]Assessed by the International Working Group response criteria: Complete Remission - <5% myeloblasts with normal maturation of all cell lines; Partial Remission - bone marrow blasts decreased by > 50% over pre-treatment but still >5%; and Hematologic Improvement - hemoglobin increase by > 1.5g/dl or decreased transfusions by at least 4/8 week period, platelet absolute increase of >30 X 10^9/L for those starting at >20 X 10^9/L . For those < 20 X 10^9 /L at baseline increase by 100%.
- Correlative Laboratory Studies [ Time Frame: Pre-Study and After 3 Cycles ]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
- Correlation of Cell Alterations With Clinical Response [ Time Frame: Pre-Study and After 3 Cycles ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|