Myelodysplastic SyndromesPhase 2NCT00262873
Bortezomib in Treating Patients With Myelodysplastic Syndromes
A Phase 2 study testing bortezomib in people with Myelodysplastic Syndromes, run by University of Rochester at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Oct 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
- Transfusion dependence is defined as requiring ≥ 2 units of packed RBCs within an 8-week period prior to study entry
- Hemoglobin < 11g/dL on 2 separate occasions 2 weeks apart
- No iron, cyanocobalamin (vitamin B_12), or folic acid deficiency or other causes of anemia
- Must have 1 of the following FAB subtypes:
- Refractory anemia
- Refractory anemia with ringed sideroblasts
- Refractory anemia with excess blasts
- Secondary MDS (if ≥ 3 years since active primary cancer)
- 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
- Karnofsky 50-100%
Life expectancy
- At least 6 months
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 2 mg/dL
- AST and ALT < 2 times upper limit of normal
Renal
- Creatinine clearance ≥ 30 mL/min
Cardiovascular
- No significant cardiovascular condition that would preclude study participation
- No uncontrolled hypertension
Pulmonary
- No significant pulmonary condition that would preclude study participation
Immunologic
- No serious concurrent infection
- Active infections must be adequately treated with antibiotics prior to study entry
- No hypersensitivity to bortezomib, boron, or mannitol
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for up to 4 weeks after completion of study treatment
- No peripheral neuropathy ≥ grade 2
- No uncontrolled seizure activity, as defined by no activity within the past year on stable anticonvulsant medications
- No other malignancy within the past 3 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
- No endocrine, neurologic, or other systemic disease that would preclude study entry
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior allogeneic bone marrow transplantation
- Concurrent transfusion support allowed
- Concurrent epoetin alfa or darbepoetin alfa allowed if initiated before start of study therapy, dose is stable for ≥ 4 weeks, and dose is stable during study participation
- No concurrent platelet growth factor support
- No concurrent thalidomide
Chemotherapy
- No concurrent chemotherapy
- No concurrent hydroxyurea
Endocrine therapy
- Concurrent corticosteroids for chronic autoimmune or inflammatory condition allowed if initiated before start of study therapy and maintained on a stable or decreasing dose
Other
- Recovered from all prior therapies
- At least 4 weeks since prior MDS therapy, except epoetin alfa, darbepoetin alfa, filgrastim (G-CSF), pegfilgrastim (G-CSF), or transfusion support
- At least 30 days since prior investigational agents
- No prior bortezomib
- No other concurrent investigational agents
- No other concurrent therapy for MDS
Trial locations and contacts
1 site in 1 country.
United States1 site
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: A Phase II Pilot Study of VELCADE in Patients With MDS
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.
Read the detailed description
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.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- bortezomib
- Keywords
- previously treated myelodysplastic syndromes, refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes
- Medical subject headings
- Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Anemia, Refractory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib | Experimental | Not described Receives: Drug: bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced an Adverse Event
Measured: For 21 days/course for up to 12 courses
Number of Participants Who Experienced Cytopenias
Measured: 21 Days/course for up to 12 courses
Secondary outcomes (6)
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.
Measured: day 14
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2005 (estimated)
- Study startMay 2005
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jane Liesveld, University of Rochester
- Investigators
- Jane L. Liesveld, MD, Study chair, James P. Wilmot Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00262873
- Sponsor's protocol ID
- CDR0000449689
- Other IDs
- URCC-U20403, MILLENNIUM-i34103-042
- Status last verified
- Apr 2016
- First submitted
- 6 Dec 2005
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21740082
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Pilot Study of VELCADE in Patients With MDS
- ClinicalTrials.gov ID
- NCT00262873
- Acronym / sponsor ID
- CDR0000449689
- Conditions
- Myelodysplastic Syndromes
- Keywords
- previously treated myelodysplastic syndromes, refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- May 2005
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 7 Dec 2005 (estimated)
- Results
- Posted 9 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib | Experimental | Drug: bortezomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bortezomib | Drug | Bortezomib |
Primary outcome
Number of Participants Who Experienced an Adverse Event
Time frame: For 21 days/course for up to 12 courses
Number of Participants Who Experienced Cytopenias
Time frame: 21 Days/course for up to 12 courses
6 secondary outcomes
Interleukin 6 Levels in Serum
Time frame: day 14
Vascular Endothelial Growth Factor (VEGF) Levels in Serum
Time frame: day 14
Average Percentage of Light Density Cells in Apoptosis
Time frame: day 14
Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow
Time frame: day 14
Average Number of Erthroid Burst Forming Units in Bone Marrow
Time frame: day 14
Average Number of Leukemia Forming Units in Bone Marrow
Time frame: day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21740082Liesveld 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane L. Liesveld, MD study chair
James P. Wilmot Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bortezomib in people with Myelodysplastic Syndromes, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced an Adverse Event (time frame: For 21 days/course for up to 12 courses). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00262873, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2016.