Study of Nilotinib as First Line Treatment in Philadelphia Chromosome Positive(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Condition: Chronic Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
Intervention: Nilotinib
Intervention description: administered orally at a dose of 300 mg twice daily for 24 months
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 112.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: First line treatment; newly diagnosed; Philadelphia chromosome positive; Chronic Myelogenous Leukemia; Ph+; CML-CP; major molecular response; Social risk

Summary:

      The study was a local multicentric, open-label, non-randomized phase II study of nilotinib as
      a first line treatment in adult patients with newly-diagnosed Philadelphia
      chromosome-positive (Ph+) and chronic phase myeloid leukemia (CML-CP).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

          -  First cytogenetic diagnosis of CML-CP with cytogenetic confirmation of Philadelphia
             chromosome of (9;22) translocations within 6 months. Standard conventional cytogenetic
             analysis must be performed.

          -  Previously untreated for CML, except for hydroxyurea and/or anagrelide (except
             imatinib treatment for max. 31 days long)

          -  Adequate end organ function with following laboratory criteria: total bilirubin < 1.5
             x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) < 2.5 x upper limit of normal (ULN); creatinine < 1.5 x upper
             limit of normal (ULN); serum amylase and lipase ≤ 1.5 x upper limit of normal (ULN);
             alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) unless considered tumor
             related

          -  Serum potassium, magnesium, and phosphorus levels are equal or above the lower limit
             of normal prior to the first dose of study medication

        Exclusion Criteria:

          -  Treatment with tyrosine kinase inhibitor(s) prior to study (in emergent cases where
             the patient requires disease management while awaiting study start, commercial
             supplies of imatinib at any dose may be prescribed to the patient but for no longer
             than 31 days in duration)

          -  Known cytopathologically confirmed Central Nervous System CNS infiltration

          -  Impaired cardiac function

          -  Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or
             uncontrolled infection)

          -  Acute or chronic liver, pancreatic or severe renal disease considered unrelated to
             disease

          -  Patients with another primary malignancy except if the other primary malignancy is
             neither currently clinically significant or requiring active intervention

          -  History of significant congenital or acquired bleeding disorder unrelated to cancer

          -  Previous radiotherapy to ≥25% of the bone marrow

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea,
             vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass
             surgery)

          -  Use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)

          -  Patients actively receiving therapy with strong Cytochrome P450 3A4 isoenzyme (CYP3A4)
             inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole,
             clarithromycin, telithromycin, ritonavir, mibefradil)

          -  Patients actively receiving therapy with medications that have the potential to
             prolong the QT interval and the treatment cannot be either discontinued or switched to
             a different medication prior to starting study drug

        Other protocol-defined inclusion/exclusion criteria may apply