Trial Outcomes & Findings for Bortezomib in Treating Patients With Myelodysplastic Syndromes (NCT NCT00262873)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

For 21 days/course for up to 12 courses

Results posted on

2016-05-09

Participant Flow

23 patients were screened for the study.

15 patients did not meet study eligibility criteria.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	8
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	5

Baseline Characteristics

Bortezomib in Treating Patients With Myelodysplastic Syndromes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib n=8 Participants 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 <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=93 Participants
Age, Categorical >=65 years	5 Participants n=93 Participants
Age, Continuous	69 years n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants
Region of Enrollment United States	8 participants n=93 Participants

PRIMARY outcome

Timeframe: For 21 days/course for up to 12 courses

Population: patients enrolled to receive study drug

Outcome measures

Outcome measures
Measure	Bortezomib n=8 Participants 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.
Number of Participants Who Experienced an Adverse Event	6 participants

PRIMARY outcome

Timeframe: 21 Days/course for up to 12 courses

Population: This data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: day 14

Population: data was only available on 5 participants

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.

Outcome measures

Outcome measures
Measure	Bortezomib n=5 Participants 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.
Interleukin 6 Levels in Serum post bortezomib	8.6 pg/ml Standard Deviation 3.3
Interleukin 6 Levels in Serum pre bortezomib	6.8 pg/ml Standard Deviation 1.7

SECONDARY outcome

Timeframe: day 14

Population: data was only available on 5 participants

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.

Outcome measures

Outcome measures
Measure	Bortezomib n=5 Participants 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.
Vascular Endothelial Growth Factor (VEGF) Levels in Serum pre bortezomib	402 pg/ml Standard Deviation 105
Vascular Endothelial Growth Factor (VEGF) Levels in Serum post bortezomib	254 pg/ml Standard Deviation 69

SECONDARY outcome

Timeframe: day 14

Population: marrow samples were not available on all participants at baseline

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.

Outcome measures

Outcome measures
Measure	Bortezomib n=5 Participants 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.
Average Percentage of Light Density Cells in Apoptosis pre bortezomib	6.68 percentage of apoptotic cells Standard Deviation 2.67
Average Percentage of Light Density Cells in Apoptosis post bortezomib	11.37 percentage of apoptotic cells Standard Deviation 3.73

SECONDARY outcome

Timeframe: day 14

Population: baseline marrow samples were available only 5 participants

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.

Outcome measures

Outcome measures
Measure	Bortezomib n=5 Participants 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.
Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow pre bortezomib	16.1 number of colonies per 50000 cell plated Standard Deviation 12.8
Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow post bortezomib	28.6 number of colonies per 50000 cell plated Standard Deviation 25.8

SECONDARY outcome

Timeframe: day 14

Population: analysis was performed on only four participants

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.

Outcome measures

Outcome measures
Measure	Bortezomib n=4 Participants 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.
Average Number of Erthroid Burst Forming Units in Bone Marrow pre bortezomib	14.75 number of colonies per 50000 cell plated Standard Deviation 14.98
Average Number of Erthroid Burst Forming Units in Bone Marrow post bortezomib	14.75 number of colonies per 50000 cell plated Standard Deviation 25.51

SECONDARY outcome

Timeframe: day 14

Population: baseline bone marrow was only available on 5 participants

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.

Outcome measures

Outcome measures
Measure	Bortezomib n=5 Participants 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.
Average Number of Leukemia Forming Units in Bone Marrow pre bortezomib	27.65 number of colonies per 50000 cell plated Standard Deviation 25.15
Average Number of Leukemia Forming Units in Bone Marrow post bortezomib	54.28 number of colonies per 50000 cell plated Standard Deviation 59.16

Adverse Events

Bortezomib

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bortezomib n=8 participants at risk 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.
Respiratory, thoracic and mediastinal disorders pneumonia	12.5% 1/8 • Number of events 1 • 4 years
Gastrointestinal disorders constipation	12.5% 1/8 • Number of events 1 • 4 years

Other adverse events

Other adverse events
Measure	Bortezomib n=8 participants at risk 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.
Cardiac disorders Hypotension	12.5% 1/8 • Number of events 1 • 4 years
Nervous system disorders Neuropathy	37.5% 3/8 • Number of events 3 • 4 years
Gastrointestinal disorders Constipation	50.0% 4/8 • Number of events 4 • 4 years
Infections and infestations Fever	12.5% 1/8 • Number of events 1 • 4 years
Blood and lymphatic system disorders Low Platelets	12.5% 1/8 • Number of events 1 • 4 years

Additional Information

Jane Liesveld, M.D.

University of Rochester

Phone: 585-275-4099

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place