efficacy and safety of lbh589 in adult patients with refractory chronic myeloid leukemia (cml) in chronic phase

Conditions: Chronic Myeloid Leukemia in Chronic Phase

Summary: 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


Eligibility criteria:
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

Keywords: refractory chronic myeloid leukemia in chronic phase adults oral lbh589