Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients (ENESTxtnd)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01254188
First received: December 2, 2010
Last updated: February 3, 2016
Last verified: February 2016
  Purpose
This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic phase

Condition Intervention Phase
Chronic Myeloid Leukemia
Drug: Nilotinib
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Extending Molecular Responses With Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients in Chronic Phase

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Percentage of Patients Achieving MMR by 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    MMR is defined as BCR-ABL ratio (%) on IS <= 0.1% (corresponds to >=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method


Secondary Outcome Measures:
  • Time to Molecular Response at 24 Months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Estimated median time to first MMR by Kaplan-Meier method

  • Duration of Major Molecular Response [ Time Frame: 3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of duration of first MMR among patients who achieved MMR (FAS) Duration of first MMR (months) = (Minimum date of (loss of first MMR , CML-related death, progression to AP/BC during study treatment, censoring) - date of first MMR + 1) / 30.4375

  • Complete Cytogenetic Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Complete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.

  • Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation. [ Time Frame: 6,12,18 and 24 months ] [ Designated as safety issue: No ]

    * CCyR = 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics.

    Duration of first CCyR (months) = (date of CCyR loss or censoring - date of first CCyR +1) / 30.4375


  • Overall Survival [ Time Frame: 3, 6, 9, 12, 15, 18, 21, 24 Months ] [ Designated as safety issue: No ]
    OS was defined as the time between date of study entry and date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.

  • Kaplan-Meier Estimates of Progression-free Survival [ Time Frame: 3,6,9,12,15,18,21,and 24 months ] [ Designated as safety issue: No ]
    PFS was defined as the time from the date of study entry to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring on treatment.

  • Kaplan-Meier Estimates of Failure-free Survival [ Time Frame: 3,6,9,12,15,18,21,and 24 months ] [ Designated as safety issue: No ]
    Time to event (months) = (date of event or censoring - date of study entry + 1) / 30.4375. Date of event is the earliest date of the following events during treatment : discontinuation of nilotinib for nilotinib-related adverse events, death due to any cause, progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR. Time is censored at the date of last assessment in the trial for patients without event.


Enrollment: 421
Study Start Date: April 2011
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib
300 mg BID
Drug: Nilotinib
This was an open-label, single-arm, prospective, multi-center, Phase IIIb clinical study with nilotinib 300 mg bid treatment in newly diagnosed CML-CP patients not previously treated with imatinib therapy and diagnosed within 6 months of study entry. For patients insufficiently responding to nilotinib 300 mg bid, the dose may have been increased to 400 mg bid. Among patients with adverse events who had dose reduction, this study also allowed a possible re-escalation to 300 mg bid.
Other Name: AMN107

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

-Patients with chronic myeloid leukemia in the chronic phase diagnosed within 6 months of study entry

Exclusion Criteria:

  • Treatment with tyrosine kinase inhibitor or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with exception of hydroxyurea and/or anagrelide
  • Uncontrolled congestive heart failure or hypertension
  • Myocardial infarction or unstable angina pectoris within past 12 months
  • Known T315I mutations
  • QTcF >450 msec
  • Significant arrhythmias

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01254188

  Show 100 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01254188     History of Changes
Obsolete Identifiers: NCT01580059
Other Study ID Numbers: CAMN107E2401 
Study First Received: December 2, 2010
Results First Received: November 2, 2015
Last Updated: February 3, 2016
Health Authority: United States: Food and Drug Administration
Algeria: Ministry of Health
Argentina: Ministry of Health
Australia: Institutional Review Board
Bahrain: Institutional Review Board
Brazil: Ministry of Health
Canada: Health Canada
Egypt: Ministry of Health and Population
India: Drugs Controller General India
Israel: Ministry of Health
Lebanon: Institutional Review Board
Malaysia: Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Morocco: Ministry of Public Health
Philippines: Philippine Food and Drug Administration
Qatar: Institutional Review Board
Russia: Ministry of Health
Saudi Arabia: Saudi Food & Drug Administration
South Africa: Department of Health

Keywords provided by Novartis:
Chronic myeloid leukemia,
CML,
nilotinib,
myelogenous,
Philadelphia chromosome

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on April 27, 2016