Efficacy of Nilotinib Versus Imatinib in Ph+ CML in Early CP Who Have a Suboptimal Molecular Response to Imatinib (RE-NICE)

This is an interventional treatment trial for Chronic Myeloid Leukemia Read More

Inclusion Criteria:

• Male or female patients ≥ 18 years of age
• ECOG 0, 1, or 2
• Diagnosis of Ph+ CML in CP

• Patients with suboptimal molecular response defined as:

  • Patients must achieve a CCyR at 12 months and must maintain CCyR until study entry (0% Ph+ chromosomes). Cytogenetic confirmation of Ph+ (9;22 translocation) is required on a minimum of 20 metaphases. FISH analysis will not be accepted.
  • at least 18 months and up to 24 months (≥18 to ≤24 months) of treatment with imatinib as first line therapy, at a dose of 400 mg daily, without achieving a MMR (<0.1% IS of Bcr-Abl transcript by RQ- PCR).

• The following laboratory results must be present:

  • Total bilirubin <1.5 x ULN
  • SGOT and SGPT <2.5 x ULN
  • Creatinine <1.5 x ULN
  • Serum amylase and lipase ≤ 1.5 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
  • Serum potassium, magnesium and calcium ≥ LLN or correctable with supplements to within normal limits prior to the first dose of study medication.
• Ability to provide written informed consent prior to any study related screening procedures being performed.

Exclusion Criteria:

• Late CP who started imatinib more than 6 months after diagnosis
• Prior accelerated phase or blast phase CML
• Rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose galactose malabsorption
• Hypersensitivity to nilotinib or any of the excipients.
• Previously documented T315I mutations.
• Intolerance to imatinib 400 mg daily defined as the inability to maintain at least 400 mg daily for the previous 3 months.
• Patients treated with imatinib more than 400mg daily
• Achieved prior MMR or CCyR on imatinib and lost response to entering the study.
• Previous treatment with interferon or any other tyrosine kinase inhibitor except imatinib (however, allow hydroxyurea or anagrelide before initial imatinib start)
• Impaired cardiac function
• Treatment with inhibitors of CYP3A4 or medications well documented to prolong the QT interval are contraindicated
• Impaired gastrointestinal (GI) function or GI disease
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
• Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
• Any other malignancy that is clinically significant or requires active intervention.
• Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, acute or chronic liver disease, pancreatic, or severe renal disease unrelated to tumor, active or uncontrolled infection).
• History of significant congenital or acquired bleeding disorder unrelated to cancer.
• Previous radiotherapy to ≥ 25% of the bone marrow.
• Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery.
• Use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon).
• Treatment with other investigational agents within 30 days of Day 1.
• History of non-compliance to medical regimens or inability to grant consent.
• Women who are pregnant, breast feeding, or of childbearing potential without a negative serum or urine pregnancy test at baseline.