Efficacy and Safety of LBH589 in Adult Patients With Refractory Chronic Myeloid Leukemia (CML) in Chronic Phase

A Phase II, Multicentre Study of Oral LBH589 in Patients With Chronic Phase Chronic Myeloid Leukemia With Resistant Disease Following Treatment With at Least Two Fusion Gene of the BCR and ABL Genes (BCR-ABL) Tyrosine Kinase Inhibitors

This study will evaluate the efficacy and safety of LBH589B in adult patients with chronic phase chronic myeloid leukemia with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors

Inclusion criteria:

• Male or female patients aged ≥ 18 years old

• Diagnosis of Philadelphia chromosome positive, chronic phase chronic myeloid leukemia

• Prior treatment with at least two BCR-ABL tyrosine kinase inhibitors with demonstrated resistance to the most recent kinase inhibitor therapy.

• Patients with a history of intolerance to one BCR-ABL kinase inhibitors will be considered eligible to enter the study if they demonstrate resistance to their most recent BCR-ABL kinase inhibitor.

• Patients who are intolerant of at least 2 BCR-ABL kinase inhibitors will be considered eligible to enter this study if they also demonstrate resistance to or intolerance of interferon-alpha (IFN-α) by the same criteria defined above.

• Patients must have adequate laboratory values:

  1. Hematology: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 8.0 g/dL.
  2. Serum chemistry: albumin ≥ 3 g/dL; aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement; bilirubin ≤ 1.5 x ULN; creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 mL/min; potassium, phosphorus, magnesium and total calcium (corrected for serum albumin) or serum ionized calcium ≥ lower limit of normal (LLN), thyroid stimulating hormone (TSH) and free T4 (thyroxine) within normal limits.

Note: Potassium, calcium, and magnesium supplements to correct values that are < LLN, were allowed when documented as corrected prior to enrollment.

• 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

Exclusion criteria:

• A candidate for hematopoietic stem cell transplantation
• Prior therapy with certain medications
• Patients with a prior history of accelerated phase or blast crisis CML
• Impaired cardiac function or clinically significant cardiac diseases
• Concomitant use of certain medications. Therapeutic doses of sodium warfarin or any other anti-vitamin K drug (low doses for line patency were allowed). Prior HDACi treatment of CML, concomitant use of drugs with a risk of causing QT interval (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 or major surgery (within 3 weeks), immunotherapy (within 1 week), BCR-ABL tyrosine kinase inhibitors (TKI) ≤ 1 week of first treatment with panobinostat
• Impairment of GI function or GI disease
• Patients with unresolved diarrhea
• Patients who have received chemotherapy, any investigational drugs or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Patients who have received a BCR-ABL tyrosine-kinase inhibitor within 1 week of first treatment with LBH589
• 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