Suboptimal Study Comparing Nilotinib and Imatinib (LASOR) 

Tracking Information

Start Date  ICMJEMay 2009
Estimated Primary Completion DateJanuary 2012   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2008)
to determine the comparative efficacy between imatinib dose escalation and nilotinib, in terms of CCyR) after 6 months of treatment, for patients with CML in chronic phase with suboptimal response to imatinib standard dose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Original Primary Outcome Measures ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00802841 on Archive Site
Current Secondary Outcome Measures ICMJE 
 (submitted: December 4, 2008)
  • to compare the rate of major molecular response (MMolR defined as ≥ to 3 log reduction in BCR-ABL transcript levels from standardized baseline at 12 months) between the 2 arms [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • to correlate the dose administered with plasma levels of imatinib and with response to therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • to establish predictors of response to imatinib dose escalation among patients with CML in chronic phase with suboptimal response to 400mg imatinib; 600mg/daily and nilotinib 400mg twice daily [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Rate of complete hematologic response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • to evaluate safety and tolerability of imatinib [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures ICMJESame as current

Descriptive Information

Brief Title  ICMJESuboptimal Study Comparing Nilotinib and Imatinib
Official Title  ICMJERandomized Phase Lll Study of Imatinib Dose Optimization Compared With Nilotinib in Patients With Chronic Myelogenous Leukemia and Suboptimal Response to Standard-dose Imatinib
Brief Summary

There is no available data on the clinical benefit of dose escalation for patients with suboptimal response to imatinib, and patients may still improve their response with continuation of therapy at the standard dose as shown in the IRIS trial after 5 years of follow-up. However, there is no data yet regarding the potential benefit of using nilotinib in the group of patients with suboptimal response. In this study, the efficacy of nilotinib 400mg BID will be compared to imatinib 600mg QD.

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Open Label, Parallel Assignment
Condition  ICMJEChronic Myelogenous Leukemia
Intervention  ICMJE
  • Drug: nilotinib
    400 mg twice a day
    Other Name: Tasigna
  • Drug: imatinib
    600 mg daily
    Other Name: Gleevec/Glivec
Study Arms / Comparison Groups
  • Nilotinib: Experimental
    Intervention: Drug: nilotinib
  • Imatinib: Active Comparator
    Intervention: Drug: imatinib

Recruitment Information

Estimated Enrollment  ICMJE188
Completion Date 
Estimated Primary Completion DateJanuary 2012   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female, aged ≥ 18 years;
  2. ECOG Performance Status of 0, 1, or 2 (see Appendix A);
  3. Diagnosis of Ph-positive CML in chronic phase (CP) at the start of therapy with imatinib 400mg. CP is defined as follows:

    • <15% blasts in peripheral blood and bone marrow;
    • <30% blasts plus promyelocytes in peripheral blood and bone marrow;
    • <20% basophils in the peripheral blood;
    • ≥100x 109/L (≥ 100,000/mm3) platelets;
    • no evidence of extramedullary leukemia involvement, with the exception of hepatosplenomegaly;
  4. Patients with a suboptimal cytogenetic response to 400 mg of imatinib, as follows25 (cytogenetic analysis to document suboptimal response must have been done a maximum of 6 weeks before the first dose of study drug):

    • No partial cytogenetic response at ≥ 6 to <12 months of treatment (and at least 36% to 95% Ph+ metaphases on bone marrow); or
    • No complete cytogenetic response at ≥ 12 to <18 months of treatment (and have at least 1% to 35% Ph+ metaphases on bone marrow);
    • Bone marrow karyotyping (BMK) is required on a minimum of 20 metaphases;
  5. Patients receiving 400mg/daily imatinib standard dose for at least 6 months and no more than 18 months;
  6. No prior use of imatinib dose higher than 400 mg daily;

Exclusion Criteria:

  1. Prior accelerated phase or blast crisis CML;
  2. Prior therapy with imatinib in combination to any other drug;
  3. More than 18 months (+ 8 weeks) of therapy with 400mg/daily imatinib;
  4. Patients receiving imatinib dose of 300 mg daily;
  5. Patients with myelotoxicity > Grade 2 (receiving 400mg or less) at the time of randomization,
  6. Previously documented T315I mutations;
  7. Achieved prior PCyR or CCyR on imatinib and lost that response before entering the study;
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Novartis Pharmaceuticals+1 800-340-6843
Location Countries  ICMJEArgentina,   Brazil,   Colombia,   Costa Rica,   Finland,   Germany,   Guatemala,   Mexico,   Panama,   Peru,   Poland,   Russian Federation,   Uruguay,   Venezuela

Administrative Information

Responsible PartyExternal Affairs, Novartis
Study ID Numbers  ICMJECAMN107A2404
Study Sponsor  ICMJENovartis Pharmaceuticals
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:Novartis PharmaceuticalsNovartis Pharmaceuticals
Information Provided ByNovartis