Efficacy and Safety of LBH589B in Adult Patients With Refractory Chronic Myeloid Leukemia in Accelerated or Blast Phase

Inclusion criteria:

* Male or female patients aged ≥ 18 years old
* Diagnosis of Philadelphia chromosome positive accelerated or blast phase chronic myeloid leukemia defined as:

Accelerated phase - the presence of at least one of the following:

* ≥15% but \<30% blasts in blood or bone marrow
* ≥30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that \<30% blasts present in bone marrow)
* ≥ 20% basophiles in the peripheral blood
* Thrombocytopenia \<100 X 109 /L unrelated to sole therapy

Blast phase (blast crisis) - the presence of one of the following:

* ≥ 30% blasts in the blood, in bone marrow or both
* Extramedullary infiltrates of leukemic cells other than liver or spleen involvement
* Prior treatment with at least two a fusion gene of the BCR and ABL genes (BCR-ABL) tyrosine kinase inhibitors (i.e., imatinib, nilotinib, or dasatinib) and demonstrated resistance to the most recent kinase inhibitor therapy. Resistance to a BCR-ABL tyrosine kinase inhibitors (TKI) for this study was defined as:

  * Progression from chronic phase to either accelerated phase or blast crisis
  * Progression from accelerated phase to blast crisis
  * No hematologic response (defined as not achieving complete hematologic response (CHR), no evidence of leukemia (NEL) or return to chronic phase (RTC)) within 3 months of starting therapy
  * Increasing blast counts in peripheral blood of increasing marrow leukemic infiltrate (MLI, the percent marrow blasts multiplied by marrow cellularity)
* Patients with a history of intolerance to one BCR-ABL kinase inhibitors (defined as discontinuation of treatment due grade 3 or 4 adverse events related to treatment) will be considered eligible to enter the study if they demonstrate resistance to their most recent BCR-ABL kinase inhibitor. Intolerance was defined as discontinuation of treatment due to either grade 3 or 4 treatment-related Adverse Event (AE) or a grade 2 treatment-related AE persisting for ≥ one month or recurring more than three times despite dose reduction.
* Patients must have adequate laboratory values:

  * Serum albumin ≥ 3g/dL
  * Aspartate Aminotransferase (AST)/Serum Glutamate Oxalacetate Transaminase (SGOT) and Alanine Aminotransferase (ALT)/Serum Glutamate Pyruvate Transaminase (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, phosphorus, magnesium, and serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ Lower Limit of Normal (LLN). Supplementation was allowed to correct potassium, calcium, and magnesium values prior to enrollment.
  * Thyroid Stimulating Hormone (TSH) and free Thyroxine (T4) within normal limits (WNL) (patients may have been on thyroid hormone replacement)
* Baseline measurement of left ventricular ejection fraction \[assessment of the hearts ability to pump effectively\]
* Assessment of patients ability to perform every day activities. Assessment by the Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

Exclusion criteria:

* A candidate for hematopoietic stem cell transplantation
* Prior therapy with certain medications:

  * Therapeutic doses of sodium warfarin or any other anti-vitamin K drug (low doses for line patency were allowed).
  * Candidate for hematopoietic stem cell transplantation (HSCT)
  * Prior histone deacetylase (HDAC) inhibitor treatment of Chronic Myelogenous Leukemia (CML)
  * Concomitant use of drugs with a risk of causing QT complex (QTc) prolongation or torsades de pointes, CYP3A4/5 inhibitors, anti-cancer therapy or radiation therapy, valproic acid (within 5 days prior to study drug treatment or during the study), chemotherapy (within 3 weeks), immunotherapy (within 1 week), BCR-ABL kinase inhibitor ≤ 1 week of first treatment with panobinostat
* Patients who are in chronic phase chronic myeloid leukemia
* Impaired cardiac function or clinically significant cardiac diseases
* Concomitant use of drugs with a risk of possible risk of causing QTc prolongation or torsades de pointes
* Concomitant use of certain medications
* Impairment of Gastrointestinal (GI) function or GI disease
* Patients with unresolved diarrhea
* Women who are pregnant or breast feeding or women of childbearing potential not using an effective method of birth control
* Male patients whose sexual partners are women of child bearing potential not using effective birth control Other protocol-defined inclusion/exclusion criteria may apply