Clinical Trial: Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome & /or BCR-ABL Positive Chronic Myeloid Leukaemia in Chronic Phase

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase IIIb, Multicentre, Open-label Study of Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome and/or BCR-ABL Positive CML in Chronic Phase

Brief Summary: This study will assess the efficacy and safety of nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive/BCR-ABL positive chronic myeloid leukaemia in chronic phase. The aim of the study is to confirm the rates of complete molecular remission (CMR) of nilotinib in newly diagnosed CML chronic phase patients in a pan-European population using the EUTOS standardized laboratories.

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Percentage of Participants With Molecular Response (MR4^0) at 18 Months [ Time Frame: at 18 months ]

MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.


Original Primary Outcome: Rate of complete molecular response (CMR). [ Time Frame: after 18 months of study drug ]

Current Secondary Outcome:

  • Percentage of Participants Free From Progression to Accelerated Phase/Blast Crisis (AP/BC) at 12 and 24 Months [ Time Frame: at 12 and 24 months ]

    The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC.

    BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.

  • Rate of Event Free Survival at 12 and 24 Months [ Time Frame: at 12 and 24 months ]
    EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (ie, 91 + 15 days), Not achieving CCyR up to 18 months (ie, 548 + 15 days), whichever is earlier.
  • Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months [ Time Frame: 12 months, 24 months ]
    MMR was defined as BCR-ABL ratio (IS) ≤ 0.1% in a peripheral blood sample. BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 to a part of the BCR ("breakpoint cluster region") gene on chromosome 22. Depending upon the breakpoints on the BCR gene, there are several forms of fusion proteins.
  • Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months [ Time Frame: 12 and 24 months ]
    CCyR parameters were defined as 0% Philadelphia positive (Ph+) metaphases. Loss of CCyR was defined as a patient exceeding the CCyR criteria (ie, > 0% Ph+ metaphases) at a subsequent visit after the patient had achieved CCyR.
  • Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months [ Time Frame: 12 and 24 months ]
    Major cytogenetic response (MCyR) parameters were defined as 0 to 35% Philadelphia positive (Ph+) metaphases.
  • Percentage of Participants Free From Progression to AP/BC With MR4^0 at 12 Months [ Time Frame: at 12 months ]

    The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC.

    BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.

  • Percentage of Participants With Event Free Survival in Participants Achieving MR4^0 at 12 Months [ Time Frame: at 12 months ]
    EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (i.e. 91 + 15 days).
  • Percentage of Participants With Progression Free Survival (PFS) at 12 and 24 Months [ Time Frame: 12 months, 24 months ]
    PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.
  • Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months [ Time Frame: 12 and 24 months ]
    MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
  • Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months [ Time Frame: 12 and 24 months ]
    MR4^5 was defined as either (i) detectable disease ≤

    Original Secondary Outcome:

    • To evaluate the rate of annual disease progression and annual events at 12 and 24 months of treatment. [ Time Frame: at 12 and 24 months ]
    • To evaluate the rate of major molecular response (MMR) after 12 and 24 months of study treatment. [ Time Frame: at 12 and 24 months ]
    • To evaluate the rate of complete cytogenetic response after 12 and 24 months of study drug [ Time Frame: at 12 and 24 months ]
    • To evaluate the rate of CMR (Complete Molecular response) after 12 and 24 months of study drug. [ Time Frame: at 12 and 24 months ]
    • evaluate the annual rate of events in patients achieving a CMR at 12 months. [ Time Frame: at 12 months ]


    Information By: Novartis

    Dates:
    Date Received: February 1, 2010
    Date Started: May 2010
    Date Completion:
    Last Updated: January 4, 2017
    Last Verified: December 2016