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Nilotinib Versus Standard Imatinib (400/600 mg Every Day (QD)) Comparing the Kinetics of Complete Molecular Response for Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Pts With Evidence of Persistent Leukemia by Real-time Quantitative Polymerase Chain Reaction (RQ-PCR) (ENESTcmr).

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00760877
First received: September 25, 2008
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
The primary goal of this study was to determine the rate of confirmed best cumulative complete molecular response within the first year of study therapy with imatinib or nilotinib. The study also explored the impact and significance of the achieved CMR on patient outcomes (PFS, EFS and OS), characterized the kinetics of CMR achieved in both treatment arms and after the cross-over.

Condition Intervention Phase
CHRONIC MYELOGENOUS LEUKEMIA
Drug: Nilotinib
Drug: Imatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Randomized Study of Nilotinib vs. Standard Imatinib (400/600 mg QD) Comparing the Kinetics of Complete Molecular Response for CML-CP Patients With Evidence of Persistent Leukemia by RQ-PCR.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Rate of Confirmed Best Cumulative Complete Molecular Response (CMR) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The rate of confirmed best cumulative CMR was defined as the percentage of participants who had confirmed CMR during the first 12 months of treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by real-time quantitative polymerase chain reaction (RQ-PCR) where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.


Secondary Outcome Measures:
  • Rate of Confirmed Best Cumulative CMR [ Time Frame: 24 months, 36 month, 48 months ] [ Designated as safety issue: No ]
    The rate of confirmed best cumulative CMR was defined as the percentage of participants who had confirmed CMR during the 24, 36 and 48 months post treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.

  • Number of Cross-over Participants With CMR [ Time Frame: 24 months, 36 months, 48 months ] [ Designated as safety issue: No ]
    The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.

  • Progression Free Survival (PFS) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    PFS was defined as the time from the date of randomization to the date of the earliest documented progression-defining event as follows: transformation to blast crisis or accelerated phase disease, or death from any cause.

  • Event-free Survival [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest.

  • Overall Survival [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of randomization to the date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.


Enrollment: 207
Study Start Date: June 2009
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib
Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.
Drug: Nilotinib
Supplied in 200 mg capsules
Active Comparator: Imatinib
Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Drug: Imatinib
Supplied in 100 mg and 400 mg capsules
Other Name: Glivec/Gleevec

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Diagnosis of chronic myeloid leukemia associated with BCR-ABL quantifiable by RQ-PCR Documented CCyR by bone marrow or BCR-ABL<1% IS in the past 12 months Persistent disease demonstrated by two PCR positive tests 3 months apart both during the past 6 months.

Treatment with imatinib for at least 2 years with 400 mg or 600 mg and a stable dose No other current or planned anti-leukemia therapies

Exclusion Criteria:

Patient has evidence of rising PCR (a confirmed >1 log increase in previous 6 months) Patient has received another investigational agent within last 6 months or TKIs other than imatinib Prior allogeneic stem cell transplantation

Impaired cardiac function including any one of the following:

Inability to monitor the QT interval on ECG Long QT syndrome or a known family history of long QT syndrome. Clinically significant resting brachycardia (<50 beats per minute) QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc Myocardial infarction within 12 months prior to starting study Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) History of or presence of clinically significant ventricular or atrial tachyarrhythmias Administration of cytokine therapy (e.g. G-CSF, GM-CSF or SCF) within 4 weeks prior to study entry

  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: NCT00760877

  Show 30 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00760877     History of Changes
Other Study ID Numbers: CAMN107A2405  2009-012616-40 
Study First Received: September 25, 2008
Results First Received: July 1, 2016
Last Updated: July 1, 2016
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Brazil: Ministry of Health
Canada: Health Canada

Keywords provided by Novartis:
MYELOGENOUS
LEUKEMIA
Chronic Phase
CML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016