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Myelodysplastic Syndromes

Anemia, Refractory, with Excess of Blasts

Anemia, Refractory

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Myelodysplastic Syndrome With Excess Blasts

Sideroblastic Anemia Pyridoxine-refractory Autosomal Recessive

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All Drugs and Chemicals

Bortezomib

bortezomib

Jane L. Liesveld, MD

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with myelodysplastic syndromes.

OBJECTIVES:

Primary

* Determine the efficacy of bortezomib, in terms of reduced cytopenia, in patients with myelodysplastic syndromes.
* Determine the safety and toxic effects of this drug in these patients.

Secondary

* Determine changes in marrow blast percentage or karyotypic profile in patients treated with this drug.

OUTLINE: This is an open-label study.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Bortezomib in Treating Patients With Myelodysplastic Syndromes

A Phase II Pilot Study of VELCADE in Patients With MDS

interleukin-6 levels were measured by enzyme-linked immunosorbant assay ELISA in serum from participants exposed to bortezomib.

Levels were measured at Day 0 and Day 14 of cycle 1 of the clinical trial.

VEGF levels were measured by ELISA (R\&DSystems) in serum from participants exposed to bortezomib. Levels were measured at Day 0 and Day 14 of cycle 1 of the clinical trial.

The CD34+ fraction of light density marrow obtained from patients at baseline and while receiving bortezomib were assessed through measurement of Annexin V (assay obtained form R\&D Systems) and by flow cytometry analysis.

Colony forming unit-granulocyte-macrophage (CFU-GM) progenitors, erythroid burst forming units (BFU-E), and leukemia colony forming units (CFU-L) were measured at day 0 and day 14 of cycle 1. Five × 10(4) light density cell for granulocyte-macrophage colony forming unit (CFU-GM) or erythroid burst forming unit (BFU-E) assays were plated in 0.9% methylcellulose, 30% FCS, 2 mmol/L L-glutamine, 10-4 mol/L β-mercaptoethanol, and 1% BSA with 3U/ml human erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, and 50 ng/ml stem cell factor (SCF) (c-kit ligand). For leukemia colony forming units (CFU-Ls), the plating mixture was comparable with the exception that the cytokines utilized were 4 U/ml erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, 100 ng/ml c-kit ligand, and 100 ng/ml Flt3 ligand. The methylcellulose mixture and associated reagents were purchased from Stem Cell Technologies (Vancouver, BC). Colonies were scored at Day 14 and were defined as \> 20 grouped cells.

University of Rochester

attending physician

Bortezomib was given at a dose of 1.3 mg per meter squared on day 1, 4, 8, and 11 on a 21 day cycle. Up to 12 cycles were allowed. Response assessments were made after the 3rd, 6th and 12 cycles of therapy.

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

All study visits were completed and the trial concluded normally for the limited number of enrolled participants; therefore, the study was considered to have been completed. However, the study is under-powered.

Jane Liesveld, M.D.

Number of Participants Who Experienced an Adverse Event

Number of Participants Who Experienced Cytopenias

pre bortezomib

post bortezomib

data was only available on 5 participants

Interleukin 6 Levels in Serum

Vascular Endothelial Growth Factor (VEGF) Levels in Serum

marrow samples were not available on all participants at baseline

Average Percentage of Light Density Cells in Apoptosis

baseline marrow samples were available only 5 participants

Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow

analysis was performed on only four participants

Average Number of Erthroid Burst Forming Units in Bone Marrow

baseline bone marrow was only available on 5 participants

Spots Global Cancer Trial Database for Bortezomib in Treating Patients With Myelodysplastic Syndromes

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