Trial record 14 of 138 for:    lbh-589

Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00939159
Recruitment Status : Terminated (Low Accrual)
First Posted : July 14, 2009
Results First Posted : June 18, 2015
Last Update Posted : August 23, 2018
Novartis Pharmaceuticals
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Drug: LBH589 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome
Study Start Date : August 2009
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: LBH589
LBH589 20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle.
Drug: LBH589
20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle.

Primary Outcome Measures :
  1. 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 .

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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).
  2. 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.
  3. Age >/= 18 years old
  4. 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.
  5. Previously untreated patients are eligible for this study.
  6. 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)
  7. Baseline MUGA or ECHO must demonstrate LVEF >/= the lower limit of the institutional normal of 50%.
  8. ECOG Performance Status of </= 2
  9. 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.
  10. Male patients who agree to use a condom during sexual contact with a female of child bearing potential.
  11. Patients with a heart rate >/= 50 beats per minute with or without a pacemaker.

Exclusion Criteria:

  1. Prior treatment with an HDAC inhibitor for MDS or any other malignancy.
  2. Patients currently treated with valproic acid for neurological or other conditions who can not be changed to another therapy.
  3. 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)
  4. 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.
  5. Concomitant use of CYP3A4 inhibitors. A wash-out period of at least 72 hours is required.
  6. Patients with unresolved diarrhea greater than CTCAE grade 1
  7. 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.
  8. 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.
  9. Concomitant use of any anti-cancer therapy or radiation therapy.
  10. 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
  11. Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C.
  12. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
  13. Female patients who are pregnant or breastfeeding.
  14. Uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen.
  15. Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
  16. Peripheral neuropathy greater than CTCAE grade 2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00939159

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis Pharmaceuticals
Study Chair: Guillermo Garcia-Manero, MD UT MD Anderson Cancer Center

Additional Information:
Publications of Results:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00939159     History of Changes
Other Study ID Numbers: 2007-0713
First Posted: July 14, 2009    Key Record Dates
Results First Posted: June 18, 2015
Last Update Posted: August 23, 2018
Last Verified: July 2018

Keywords provided by M.D. Anderson Cancer Center:
Low or Intermediate-1 Risk Myelodysplastic Syndrome

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action