Status:
COMPLETED
LBH589 Plus Decitabine for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)
Lead Sponsor:
Washington University School of Medicine
Conditions:
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Eligibility:
All Genders
60+ years
Phase:
PHASE1
PHASE2
Brief Summary
This study is designed to evaluate the combination of LBH589 and decitabine in patients age ≥ 60 years with high risk Myelodysplastic Syndrome (IPSS Int-2 or High) or Acute Myeloid Leukemia.
Detailed Description
To address the need for less toxic, more effective treatments for older patients with advanced MDS and AML, the purpose of this Phase 1-2 single institution study is to evaluate the safety and efficac...
Eligibility Criteria
Inclusion
- AML (except t(15;17), inv(16) or t(8;21) and variants) or high risk MDS (IPSS Int-2 or High) diagnosed according to WHO criteria (see Appendix 1)
- Age ≥ 60 years old
- Not a candidate for allogeneic stem cell transplantation within next 12 weeks
- Ability to provide written informed consent, obtained prior to participation in the study and any related procedures being performed
- Patients must meet the following laboratory criteria:
- Serum albumin ≥ 3 g/dL
- Aspartate aminotransferase (AST)/SGOT and alanine aminotransferase (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 phosphorus ≥ LLN
- Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
- Serum magnesium ≥ LLN, thyroid stimulating hormone (TSH) and free thyroxine (T4) within normal limits (WNL) (patients may be on thyroid hormone replacement)
- Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
Exclusion
- Prior treatment for MDS / AML with Histone deacetylase (HDAC) inhibitor or hypomethylating agent (e.g., Decitabine, azacitidine etc.)
- Active central nervous system (CNS) involvement with MDS/AML
- Impaired cardiac function including any one of the following:
- Screening electrocardiogram (ECG) with a QTc \> 450 msec confirmed by central laboratory prior to enrollment to the study
- Patients with congenital long QT syndrome
- History of sustained ventricular tachycardia
- Any history of ventricular fibrillation or torsades de pointes
- Bradycardia defined as heart rate \< 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
- Patients with a myocardial infarction or unstable angina within 6 months of study entry
- Congestive heart failure (NY Heart Association class III or IV)
- Right bundle branch block and left anterior hemiblock (bifasicular block)
- Uncontrolled hypertension
- Concomitant use of drugs with a risk of causing torsades de pointes
- Patients with unresolved diarrhea \> CTCAE grade 1
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
- Other concurrent severe and/or uncontrolled medical conditions
- Patients who have received chemotherapy or any investigational drug \< 2 weeks or hydroxyurea \< 48 hours prior to starting study drug or who have not recovered from side effects of such therapy.
- Concomitant use of any anti-cancer therapy or radiation therapy
- Male patients whose sexual partners are women of child bearing potential (WOCBP) not using effective birth control
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
- Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
- Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
Key Trial Info
Start Date :
June 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 1 2014
Estimated Enrollment :
52 Patients enrolled
Trial Details
Trial ID
NCT00691938
Start Date
June 1 2008
End Date
August 1 2014
Last Update
October 13 2016
Active Locations (1)
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1
Washington University
St Louis, Missouri, United States, 63110