Myelodysplastic SyndromePhase 2NCT00939159
Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
A Phase 2 study testing LBH589 in people with Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if LBH589 can help to control lower-risk (low or intermediate-1 risk) MDS. The safety of this drug will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- LBH589
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Jun 2013
- 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
- Patients with intermediate-1 risk MDS or transfusion dependent low risk MDS by the IPSS classification. Patient must have one or more cytopenia as defined by IPSS (Cytopenias are defined as an absolute neutrophil count < 1800 K/uL; or hemoglobin < 10 g/dl or platelets < 10^5 K/uL).
- Signed informed consent indicating that patients are aware of the investigational nature of this study prior to participation in the study and any related procedures being performed.
- Age >/= 18 years old
- Prior therapy with growth factor support, lenalidomide, 5-azacytidine, decitabine or other investigational agents is allowed if last dose was given more than 14 days prior to first dose of LBH 589.
- Previously untreated patients are eligible for this study.
- Patients must meet the following laboratory criteria: AST/SGOT and ALT/SGPT </= 2.5 x upper limit of normal (ULN) or </= 5.0 x ULN if the transaminase elevation is due to leukemic involvement; Serum bilirubin </= 1.5 x ULN; Serum creatinine </= 1.5 x ULN or 24-hour creatinine clearance >/= 50 ml/min; Serum potassium >/= lower limit of normal (LLN); Serum phosphorous >/= LLN; Serum total calcium (corrected for serum albumin) or serum ionized calcium >/= LLN; Serum magnesium >/= LLN; TSH and free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement)
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- Baseline MUGA or ECHO must demonstrate LVEF >/= the lower limit of the institutional normal of 50%.
- ECOG Performance Status of </= 2
- Women of childbearing potential (WOCBP) defined as not post-menopausal for 12 months or no previous surgical sterilization must have a negative serum pregnancy test within 72 hours of the first administration of oral LBH589.
- Male patients who agree to use a condom during sexual contact with a female of child bearing potential.
- Patients with a heart rate >/= 50 beats per minute with or without a pacemaker.
Who cannot join
- Prior treatment with an HDAC inhibitor for MDS or any other malignancy.
- Patients currently treated with valproic acid for neurological or other conditions who can not be changed to another therapy.
- Impaired cardiac function including any one of the following: Screening ECG with QTc > 450 msec confirmed by central laboratory prior to enrollment in study; Pts with congenital long QT syndrome; History of sustained ventricular tachycardia; History of ventricular fibrillation or torsades de pointes; Pts with myocardial infarction or unstable angina within 6 mo. of study entry; Congestive heart failure; Right bundle branch block with left anterior hemiblock (bifascicular block)
- Concomitant use of drugs with a risk of causing torsades de pointes. A wash-out period of at least 72 hours is required. Patients using medications that have a relative risk of prolonging the QT interval or inducing torsades de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug.
- Concomitant use of CYP3A4 inhibitors. A wash-out period of at least 72 hours is required.
- Patients with unresolved diarrhea greater than CTCAE grade 1
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- Patients who have undergone major surgery less than 4 weeks prior to screening visit or who have not recovered from side effects of such therapy.
- Patients who have received chemotherapy, any investigational drug or undergone major surgery within 3 weeks prior to starting study drug or who have not recovered from side effects of such therapy (CTCAE Grade 1), with the exception of nitrosoureas, which should be discontinued at least six weeks before enrollment.
- Concomitant use of any anti-cancer therapy or radiation therapy.
- Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
- Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C.
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
- Female patients who are pregnant or breastfeeding.
- Uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen.
- Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
- Peripheral neuropathy greater than CTCAE grade 2
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome
The goal of this clinical research study is to learn if LBH589 can help to control lower-risk (low or intermediate-1 risk) MDS. The safety of this drug will also be studied.
Read the detailed description
Study Drug:
LBH589 is a drug that may slow down the growth of cancer cells or kill cancer cells by blocking certain enzymes (proteins produced by cells).
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take LBH589 capsules by mouth 3 times a week for 3 weeks (for example on Days 1, 3, 5, 8, 10,12, 15, 17, and 19) then 1 week of rest of each 28-day study "cycle."
You should take LBH589 at the same time each morning. Each dose of LBH589 should be taken with 1 cup (8 ounces) of water.
You should swallow the capsules whole and not chew them. You must not eat grapefruit and Seville (sour) oranges or drink their juices during your entire participation on the study.
If you vomit while taking LBH589, then you should wait until your next scheduled dose to take another capsule. If you forget to take your capsules in the morning, you can take them up to 12 hours after the usual time you take it. After 12 hours, do not take LBH589 that day. Instead, wait until your next scheduled dose. Do not make up missed doses.
Call your study doctor or study staff as soon as possible if you have any unusual symptoms. Do not wait until your next visit to tell your doctor about your symptoms. If you have side effects at your assigned dose level, then your dose may be lowered. You may also have to stop taking LBH589 for a short period, and the side effect(s) will be watched by your doctor until they resolve.
Take the drug just as the doctor tells you. Do not miss any capsules. You will be asked to return all study drug in the bottles provided, whether your take all the capsules or not. Empty bottles should also be brought back to the clinic. Capsules should not be transferred between bottles at any time.
At each visit, you must tell the study staff about any other drugs you are taking during the study. This includes prescription drugs, over-the-counter drugs, and vitamins. Your study doctor will tell you if you need to stop taking any of these drugs.
Study Visits:
At least every week during Cycle 1 and every cycle after that, you will have the following tests and procedures performed:
- Blood (about 1 tablespoon) will be drawn for routine tests
- You will have a physical exam, including measurement of your vital signs.
On Day 21 (+/- 7 days) of Cycle 1, you will have a bone marrow biopsy/aspirate to check the status of the disease.
On Days 1 and 5 of Cycle 1, and Days 5 and 22 of Cycles 2 and beyond, you will have ECGs. If your doctor thinks it is necessary, you may have ECGs more often.
On Day 1 of Cycle 2 and beyond you will have EKG prior to taking the study medication.
Length of Study:
You may continue taking the study drug for up to 24 months. You will be taken off study if intolerable side effects occur or the disease gets worse.
End of Study Visit:
When you stop taking LBH589, you will have the following tests and procedures performed:
- Blood (about 1 tablespoon) will be drawn for routine tests
- You will have a bone marrow aspiration and biopsy to check the status of the disease.
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- You will have an ECG.
This is an investigational study. LBH589 is not FDA approved or commercially available. At this time, LBH589 is only being used for research.
Up to 40 participants will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- LBH589
- Keywords
- Low or Intermediate-1 Risk Myelodysplastic Syndrome, MDS, Cancer, LBH589
- Medical subject headings
- Myelodysplastic Syndromes, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LBH589Drug
20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| LBH589 | Experimental | LBH589 20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle. Receives: Drug: LBH589 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate Based on the Hematologic Improvement
Overall response rate defined by International Working Group (IWG) response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks: Erythroid response (pretreatment, <11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,<100x10^9/L): If starting with >20x10^9/L platelets:
absolute increase 30x10^9/L, Increase from baseline <20 x10^9/L to >20x10^9/L and by =/> 100%; Neutrophil response (pretreatment, <1.0x10^9/L): =/> 100% increase \& absolute increase >0.5x10^9/L; Progression or relapse after HI: At least 1 of the following: =/>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence .
Measured: Assessment with 28-day cycle until response, then every 3 cycles as needed, for up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2009 (estimated)
- Study startAug 2009
- Primary completionJun 2013
- Study completionJun 2013
Why it stopped: Low Accrual
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 SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, MD, Study chair, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00939159
- Sponsor's protocol ID
- 2007-0713
- Status last verified
- Jul 2018
- First submitted
- 10 Jul 2009
- Last updated
- 23 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Dimicoli S, Jabbour E, Borthakur G, Kadia T, Estrov Z, Yang H, Kelly M, Pierce S, Kantarjian H, Garcia-Manero G. Phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in patients with low or intermediate-1 risk myelodysplastic syndrome. Am J Hematol. 2012 Jan;87(1):127-9. doi: 10.1002/ajh.22198. Epub 2011 Nov 10.
PubMed 22072492
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00939159
- Acronym / sponsor ID
- 2007-0713
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Low or Intermediate-1 Risk Myelodysplastic Syndrome, MDS, Cancer, LBH589
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 17 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Aug 2009
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 14 Jul 2009 (estimated)
- Results
- Posted 18 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if LBH589 can help to control lower-risk (low or intermediate-1 risk) MDS. The safety of this drug will also be studied.
Detailed description
Study Drug:
LBH589 is a drug that may slow down the growth of cancer cells or kill cancer cells by blocking certain enzymes (proteins produced by cells).
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take LBH589 capsules by mouth 3 times a week for 3 weeks (for example on Days 1, 3, 5, 8, 10,12, 15, 17, and 19) then 1 week of rest of each 28-day study "cycle."
You should take LBH589 at the same time each morning. Each dose of LBH589 should be taken with 1 cup (8 ounces) of water.
You should swallow the capsules whole and not chew them. You must not eat grapefruit and Seville (sour) oranges or drink their juices during your entire participation on the study.
If you vomit while taking LBH589, then you should wait until your next scheduled dose to take another capsule. If you forget to take your capsules in the morning, you can take them up to 12 hours after the usual time you take it. After 12 hours, do not take LBH589 that day. Instead, wait until your next scheduled dose. Do not make up missed doses.
Call your study doctor or study staff as soon as possible if you have any unusual symptoms. Do not wait until your next visit to tell your doctor about your symptoms. If you have side effects at your assigned dose level, then your dose may be lowered. You may also have to stop taking LBH589 for a short period, and the side effect(s) will be watched by your doctor until they resolve.
Take the drug just as the doctor tells you. Do not miss any capsules. You will be asked to return all study drug in the bottles provided, whether your take all the capsules or not. Empty bottles should also be brought back to the clinic. Capsules should not be transferred between bottles at any time.
At each visit, you must tell the study staff about any other drugs you are taking during the study. This includes prescription drugs, over-the-counter drugs, and vitamins. Your study doctor will tell you if you need to stop taking any of these drugs.
Study Visits:
At least every week during Cycle 1 and every cycle after that, you will have the following tests and procedures performed:
- Blood (about 1 tablespoon) will be drawn for routine tests
- You will have a physical exam, including measurement of your vital signs.
On Day 21 (+/- 7 days) of Cycle 1, you will have a bone marrow biopsy/aspirate to check the status of the disease.
On Days 1 and 5 of Cycle 1, and Days 5 and 22 of Cycles 2 and beyond, you will have ECGs. If your doctor thinks it is necessary, you may have ECGs more often.
On Day 1 of Cycle 2 and beyond you will have EKG prior to taking the study medication.
Length of Study:
You may continue taking the study drug for up to 24 months. You will be taken off study if intolerable side effects occur or the disease gets worse.
End of Study Visit:
When you stop taking LBH589, you will have the following tests and procedures performed:
- Blood (about 1 tablespoon) will be drawn for routine tests
- You will have a bone marrow aspiration and biopsy to check the status of the disease.
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- You will have an ECG.
This is an investigational study. LBH589 is not FDA approved or commercially available. At this time, LBH589 is only being used for research.
Up to 40 participants will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LBH589 | Experimental | Drug: LBH589LBH589 20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with intermediate-1 risk MDS or transfusion dependent low risk MDS by the IPSS classification. Patient must have one or more cytopenia as defined by IPSS (Cytopenias are defined as an absolute neutrophil count < 1800 K/uL; or hemoglobin < 10 g/dl or platelets < 10^5 K/uL).
- Signed informed consent indicating that patients are aware of the investigational nature of this study prior to participation in the study and any related procedures being performed.
- Age >/= 18 years old
- Prior therapy with growth factor support, lenalidomide, 5-azacytidine, decitabine or other investigational agents is allowed if last dose was given more than 14 days prior to first dose of LBH 589.
- Previously untreated patients are eligible for this study.
Key exclusion criteria (16 listed)
- Prior treatment with an HDAC inhibitor for MDS or any other malignancy.
- Patients currently treated with valproic acid for neurological or other conditions who can not be changed to another therapy.
- Impaired cardiac function including any one of the following: Screening ECG with QTc > 450 msec confirmed by central laboratory prior to enrollment in study; Pts with congenital long QT syndrome; History of sustained ventricular tachycardia; History of ventricular fibrillation or torsades de pointes; Pts with myocardial infarction or unstable angina within 6 mo. of study entry; Congestive heart failure; Right bundle branch block with left anterior hemiblock (bifascicular block)
- Concomitant use of drugs with a risk of causing torsades de pointes. A wash-out period of at least 72 hours is required. Patients using medications that have a relative risk of prolonging the QT interval or inducing torsades de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug.
- Concomitant use of CYP3A4 inhibitors. A wash-out period of at least 72 hours is required.
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 |
|---|---|---|
| LBH58920 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle. | Drug | LBH589 |
Primary outcome
Overall Response Rate Based on the Hematologic Improvement
Time frame: Assessment with 28-day cycle until response, then every 3 cycles as needed, for up to 24 months
Overall response rate defined by International Working Group (IWG) response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks: Erythroid response (pretreatment, <11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,<100x10^9/L): If starting with >20x10^9/L platelets: absolute increase 30x10^9/L, Increase from baseline <20 x10^9/L to >20x10^9/L and by =/> 100%; Neutrophil response (pretreatment, <1.0x10^9/L): =/> 100% increase \& absolute increase >0.5x10^9/L; Progression or relapse after HI: At least 1 of the following: =/>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence .
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22072492Dimicoli S, Jabbour E, Borthakur G, Kadia T, Estrov Z, Yang H, Kelly M, Pierce S, Kantarjian H, Garcia-Manero G. Phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in patients with low or intermediate-1 risk myelodysplastic syndrome. Am J Hematol. 2012 Jan;87(1):127-9. doi: 10.1002/ajh.22198. Epub 2011 Nov 10.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
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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.
Guillermo Garcia-Manero, MD study chair
UT MD Anderson 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 LBH589 in people with Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center 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 11 inclusion and 16 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: stopped early, as of the sponsor's last update on 23 Aug 2018. 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 18 Jun 2015). 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?
Overall Response Rate Based on the Hematologic Improvement (time frame: Assessment with 28-day cycle until response, then every 3 cycles as needed, for up to 24 months). 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 NCT00939159, 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 23 Aug 2018.