Efficacy of Nilotinib Versus Imatinib in Ph+ CML in Early CP Who Have a Suboptimal Molecular Response to Imatinib

• Status: Unknown status
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

In this study, the efficacy of nilotinib at 400 mg BID will be compared with imatinib at 400 mg BID in suboptimal molecular response patients. To determine study eligibility, suboptimal molecular response will be defined as patients who have achieved a complete cytogenetic response (CCyR) but have not achieved a MMR, after at least 18 months of treatment on first line imatinib therapy at a minimum dose of 400mg daily (Baccarani 2006).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seoul St. Mary's Hospital
• Collaborator: Novartis
• Treatments: Imatinib Mesylate

Criteria

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.