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| ID | Type | Description | Link |
|---|---|---|---|
| URCC-U20403 | |||
| MILLENNIUM-i34103-042 |
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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
Secondary
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bortezomib | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bortezomib | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event | For 21 days/course for up to 12 courses | |
| Number of Participants Who Experienced Cytopenias | 21 Days/course for up to 12 courses |
| Measure | Description | Time Frame |
|---|---|---|
| Interleukin 6 Levels in Serum | 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. | day 14 |
| Vascular Endothelial Growth Factor (VEGF) Levels in Serum |
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DISEASE CHARACTERISTICS:
Diagnosis of myelodysplastic syndromes (MDS)
Requires treatment or transfusion support for MDS, as indicated by 1 of the following:
Demonstrates transfusion or epoetin alfa dependence
Hemoglobin < 11g/dL on 2 separate occasions 2 weeks apart
Must have 1 of the following FAB subtypes:
No chronic myelomonocytic leukemia
Not refractory to platelet transfusion support (i.e., inability to maintain platelet count > 20,000/mm^3 with transfusion)
No current acute myelogenous leukemia (e.g., > 30% blasts)
PATIENT CHARACTERISTICS:
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
Immunologic
No serious concurrent infection
No hypersensitivity to bortezomib, boron, or mannitol
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Other
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| Name | Affiliation | Role |
|---|---|---|
| Jane L. Liesveld, MD | James P. Wilmot Cancer Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21740082 | Result | Liesveld JL, Rosell KE, Bechelli J, Lu C, Messina P, Mulford D, Ifthikharuddin JJ, Jordan CT, Phillips Ii GL. Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines. Cancer Invest. 2011 Aug;29(7):439-50. doi: 10.3109/07357907.2011.590567. |
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15 patients did not meet study eligibility criteria.
23 patients were screened for the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Bortezomib | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Bortezomib | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Experienced an Adverse Event | patients enrolled to receive study drug | Posted | Number | participants | For 21 days/course for up to 12 courses |
|
|
4 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bortezomib | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jane Liesveld, M.D. | University of Rochester | 585-275-4099 | Jane_Liesveld@urmc.rochester.edu |
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| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| D000753 | Anemia, Refractory |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000740 | Anemia |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
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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. |
| day 14 |
| Average Percentage of Light Density Cells in Apoptosis | 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. | day 14 |
| Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow | 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. | day 14 |
| Average Number of Erthroid Burst Forming Units in Bone Marrow | 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. | day 14 |
| Average Number of Leukemia Forming Units in Bone Marrow | 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. | day 14 |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Primary | Number of Participants Who Experienced Cytopenias | This data was not collected. | Posted | 21 Days/course for up to 12 courses |
|
|
| Secondary | Interleukin 6 Levels in Serum | 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. | data was only available on 5 participants | Posted | Mean | Standard Deviation | pg/ml | day 14 |
|
|
|
|
| Secondary | Vascular Endothelial Growth Factor (VEGF) Levels in Serum | 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. | data was only available on 5 participants | Posted | Mean | Standard Deviation | pg/ml | day 14 |
|
|
|
|
| Secondary | Average Percentage of Light Density Cells in Apoptosis | 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. | marrow samples were not available on all participants at baseline | Posted | Mean | Standard Deviation | percentage of apoptotic cells | day 14 |
|
|
|
|
| Secondary | Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow | 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. | baseline marrow samples were available only 5 participants | Posted | Mean | Standard Deviation | number of colonies per 50000 cell plated | day 14 |
|
|
|
| Secondary | Average Number of Erthroid Burst Forming Units in Bone Marrow | 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. | analysis was performed on only four participants | Posted | Mean | Standard Deviation | number of colonies per 50000 cell plated | day 14 |
|
|
|
| Secondary | Average Number of Leukemia Forming Units in Bone Marrow | 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. | baseline bone marrow was only available on 5 participants | Posted | Mean | Standard Deviation | number of colonies per 50000 cell plated | day 14 |
|
|
|
| 2 |
| 8 |
| 5 |
| 8 |
| constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Low Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D001896 |
| Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |