LBH589 Plus Decitabine for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)

• Status: Completed
• Trial end date: 2014-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Treatments: Azacitidine; Decitabine; Panobinostat

Criteria

Inclusion Criteria:

• 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 Criteria:

• 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.