Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
This study has been terminated.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: July 10, 2009
Last updated: June 3, 2015
Last verified: June 2015
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.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase II Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome
Primary Outcome Measures:
- Overall Response Rate Based on the Hematologic Improvement [ Time Frame: Assessment with 28-day cycle until response, then every 3 cycles as needed ] [ Designated as safety issue: No ]
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 .
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||June 2013 (Final data collection date for primary outcome measure)
LBH589 20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle.
20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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)
- 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.
- 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
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00939159
|UT MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
||Guillermo Garcia-Manero, MD
||UT MD Anderson Cancer Center
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||July 10, 2009
|Results First Received:
||June 3, 2015
||June 3, 2015
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Low or Intermediate-1 Risk Myelodysplastic Syndrome
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on November 24, 2015
Bone Marrow Diseases
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action