Conditions: Leukemia, Myeloid, Acute Myelodysplastic Syndromes
Keywords: LBH589 Decitabine panobinostat histone deacetylase methylation hypomethylation
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 52
Healthy volunteers: no

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 efficacy of LBH 589 and decitabine administered in combination.

Decitabine is an epigenetic modifier of gene expression that has been shown to be well-tolerated in this population at the dose schedule proposed in this study, with reasonable efficacy. Although its precise mechanism of action is incompletely understood, it is postulated to work by reactivating the expression of key tumor suppressor genes silenced in tumor cells by reversing a pattern of hypermethylation of promotor elements.

LBH389 is likewise an epigenetic modifier that inhibits the deacetylation of both histones and non-histone proteins, including HSP90 and p53. Although clinical experience with LBH589 in AML is limited, aberrant histone deacetylase activity has been previously shown to play a significant role in the pathogenesis of AML. The addition of LBH589 to a decitabine regimen of previously established efficacy and tolerability will allow us to evaluate the hypothesis that two epigenetic modifiers that are believed to work through distinct mechanisms of action may act together to improve the responses of patients treated with decitabine alone, without significant additional toxicity.

Arms:
arm 1: LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle.

Decitabine 20 mg/m\^2 IV on days 1-5 in a 28 day cycle. arm 2: LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle.

Decitabine 20 mg/m\^2 IV on days 1-5 in a 28 day cycle. arm 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle.

Decitabine 20 mg/m\^2 IV on days 1-5 in a 28 day cycle. arm 4: LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle.

Decitabine 20 mg/m\^2 IV on days 1-5 in a 28 day cycle. arm 5: LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle.

Decitabine 20 mg/m\^2 IV on days 1-5 in a 28 day cycle. arm 6: LBH589 40 mg/day three times a week on nonconsecutive days for the first 2 weeks in a 28 day cycle.

Decitabine 20 mg/m\^2 IV on days 1-5 in a 28 day cycle. arm 7: LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was Level 5B.

Decitabine 20 mg/m\^2 IV on days 1-5 in a 28 day cycle.

Interventions: intervention 1: LBH589 intervention 2: Decitabine
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document: