de Novo Myelodysplastic SyndromesPhase 2NCT00357162
Belinostat in Treating Patients With Myelodysplastic Syndromes
A Phase 2 study testing belinostat in people with de Novo Myelodysplastic Syndromes and Previously Treated Myelodysplastic Syndromes, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well belinostat works in treating patients with myelodysplastic syndromes. Belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes
- What is being tested?
- belinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Dec 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
Who may be able to join
- Histologically confirmed myelodysplastic syndromes (MDS)
- De novo or secondary MDS
- Patients with < 5 % bone marrow blasts must meet ≥ 1 of the following criteria:
- Symptomatic anemia with either hemoglobin < 10.0 g/dL or required RBC transfusions within the past 3 months
- Thrombocytopenia with ≥ 2 platelet counts < 50,000/mm³ or significant hemorrhage requiring platelet transfusions
- Neutropenia with ≥ 2 absolute neutrophil counts < 1,000/mm³
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- No acute myeloid leukemia (≥ 20% bone marrow blasts)
- ECOG performance status 0-2
- Life expectancy > 12 weeks
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ≤ 2 times ULN
- Creatinine ≤ 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101
- No HIV positivity
- QTc interval ≤ 500 msec
- No long QT syndrome
- No significant cardiovascular disease, including any of the following:
- Unstable angina pectoris
- Uncontrolled hypertension
- Congestive heart failure related to primary cardiac disease
- Condition requiring anti-arrhythmic therapy
- Ischemic or severe valvular heart disease
- Myocardial infarction within the past 6 months
- No other uncontrolled serious medical condition (e.g., cardiac arrhythmias or diabetes)
- Recovered from prior therapy
- No more than 2 prior therapies for MDS
- Prior hematopoietic growth factors, androgens, and other supportive care agents allowed and are not considered in the prior therapy total
- No prior allogeneic stem cell transplantation
- More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- No prior histone deacetylase (HDAC) inhibitors for treatment of MDS
- More than 2 weeks since prior valproic acid or other HDAC inhibitors
- No other concurrent investigational agents
- No concurrent medication that may cause torsades depointes, including any of the following:
- Disopyramide
- Dofetilide
- Ibutilide
- Procainamide
- Quinidine
- Sotalol
- Bepridil
- Methadone
- Amiodarone hydrochloride
- Arsenic trioxide
- Cisapride
- Calcium-channel blockers (e.g., lidoflazine)
- Anti-infective agents (i.e., clarithromycin, erythromycin, halofantrine, pentamidine, or sparfloxacin)
- Domperidone or droperidol
- Antipsychotic agents (i.e., chlorpromazine, haloperidol, mesoridazine, thioridazine, or pimozide)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome
This phase II trial is studying how well belinostat works in treating patients with myelodysplastic syndromes. Belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.
Read the detailed description
OBJECTIVES:
- Establish the efficacy and safety of PXD101 (belinostat) in patients with myelodysplastic syndromes that progressed after or is ineligible for azacitidine treatment.
II. Assess the biological activity of PXD101 in these patients via assays of histone acetylation, gene expression profiling, and DNA methylation.
OUTLINE: This is a multicenter study.
Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response, partial response, or hematologic improvement after 4 courses receive 4 additional courses of therapy. After completion of study treatment, patients are followed every 3-6 months for up to 3 years.
- Conditions
- de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes
- Being tested
- belinostat
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
belinostatDrug
Also called PXD101
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Patients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: belinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart
Complete Response (CR)
A CR is defined as a participant with bone marrow showing less than 5% myeloblasts with no evidence of dysplasia and with adequate peripheral blood counts for at least 2 months (hemoglobin > 11 g/dl, neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3) and with no blasts in the peripheral.
Partial Response (PR)
All the CR criteria except bone marrow blasts decreased by ≥ 50% over pretreatment, or a less advanced WHO classification than pretreatment.
Hematologic Improvement (HI)
A 2g/dl increase in hemoglobin for participants with <11g/dl hemoglobin at pretreatment, or an increase of >30,000/mm^3 platelets for participants with <100,000/mm^3 at pretreatment, or a 100% increase in neutrophil counts for participants with <1500/mm^3 at pretreatment
Measured: 12 weeks
Secondary outcomes (4)
Time to Progression
Estimated using the method of Kaplan-Meier.
Measured: Time from registration to the date of progression or last follow-up, assessed up to 3 years
Overall Survival
Estimated using the method of Kaplan-Meier.
Measured: From date of registration to the date of last follow-up or death due to any cause, assessed up to 3 years
Duration of Response
Estimated using the method of Kaplan-Meier.
Measured: From the date of documented response until the date of progression or last follow-up, assessed up to 3 years
Toxicity of Belinostat in Patients With Myelodysplastic Syndrome
Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Reporting events deemed at least possibly related to study treatment.
Measured: Prior to each course (every 21 days), and every 3 months for up to 3 years after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2006 (estimated)
- Study startMay 2006
- Primary completionDec 2010
- Study completionDec 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.
- Other trials for de Novo Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Amanda Cashen, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00357162
- Sponsor's protocol ID
- NCI-2009-00143
- Other IDs
- NCI-2009-00143, MAYO-MC0581, NCI-7258, CDR0000489197, MC0581, 7258, P30CA015083, N01CM62205
- Status last verified
- Dec 2011
- First submitted
- 26 Jul 2006
- Last updated
- 20 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00357162
- Acronym / sponsor ID
- NCI-2009-00143
- Conditions
- de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 27 Jul 2006 (estimated)
- Results
- Posted 20 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well belinostat works in treating patients with myelodysplastic syndromes. Belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.
Detailed description
OBJECTIVES:
- Establish the efficacy and safety of PXD101 (belinostat) in patients with myelodysplastic syndromes that progressed after or is ineligible for azacitidine treatment.
II. Assess the biological activity of PXD101 in these patients via assays of histone acetylation, gene expression profiling, and DNA methylation.
OUTLINE: This is a multicenter study.
Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response, partial response, or hematologic improvement after 4 courses receive 4 additional courses of therapy. After completion of study treatment, patients are followed every 3-6 months for up to 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Drug: belinostatPatients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (51 listed)
- Histologically confirmed myelodysplastic syndromes (MDS)
- Patients with < 5 % bone marrow blasts must meet ≥ 1 of the following criteria:
- No acute myeloid leukemia (≥ 20% bone marrow blasts)
- ECOG performance status 0-2
- Life expectancy > 12 weeks
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| belinostatAlso: PXD101Given IV | Drug | Treatment (enzyme inhibitor therapy) |
Primary outcome
Number of Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart
Time frame: 12 weeks
Complete Response (CR) A CR is defined as a participant with bone marrow showing less than 5% myeloblasts with no evidence of dysplasia and with adequate peripheral blood counts for at least 2 months (hemoglobin > 11 g/dl, neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3) and with no blasts in the peripheral. Partial Response (PR) All the CR criteria except bone marrow blasts decreased by ≥ 50% over pretreatment, or a less advanced WHO classification than pretreatment. Hematologic Improvement (HI) A 2g/dl increase in hemoglobin for participants with <11g/dl hemoglobin at pretreatment, or an increase of >30,000/mm^3 platelets for participants with <100,000/mm^3 at pretreatment, or a 100% increase in neutrophil counts for participants with <1500/mm^3 at pretreatment
4 secondary outcomes
Time to Progression
Time frame: Time from registration to the date of progression or last follow-up, assessed up to 3 years
Overall Survival
Time frame: From date of registration to the date of last follow-up or death due to any cause, assessed up to 3 years
Duration of Response
Time frame: From the date of documented response until the date of progression or last follow-up, assessed up to 3 years
Toxicity of Belinostat in Patients With Myelodysplastic Syndrome
Time frame: Prior to each course (every 21 days), and every 3 months for up to 3 years after completion of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
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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.
Amanda Cashen principal investigator
Mayo Clinic
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 belinostat in people with de Novo Myelodysplastic Syndromes and Previously Treated Myelodysplastic Syndromes, run by National Cancer Institute (NCI) 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?
The sponsor lists 51 inclusion and 0 exclusion criteria. 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 20 May 2014. 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 20 Mar 2013). 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 Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 May 2014.