Efficacy and Safety of LBH589 in Adult Patients With Refractory Chronic Myeloid Leukemia (CML) in Chronic Phase
Condition: Chronic Myeloid Leukemia in Chronic Phase
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: LBH589
Intervention MeSH terms: Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Refractory Chronic Myeloid Leukemia in Chronic Phase; adults; oral LBH589

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