A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML (ENESTPath)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01743989
First received: December 4, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This study aims to assess the optimal duration of nilotinib 300 mg BID consolidation treatment, in order that patients remain in treatment-free remission (≥MR4.0) 12 months after starting the Treatment-Free Remission (TFR) phase of the study.

Rationale:

CP-CML patients who have received 2 or more calendar years of first-line imatinib treatment, and who have failed to achieve the molecular response threshold for treatment cessation (≥MR4.0) have a 50% greater chance of doing by switching to nilotinib; however the optimal duration of consolidation treatment with nilotinib to ensure the highest rate of patients remaining in ≥MR4.0 after entering the TFR phase is not yet known. This protocol therefore aims to assess the potential impact of a longer duration of consolidation treatment with nilotinib, i.e. 12 months versus 24 months, on molecular relapse rate in the first 12 months of treatment-free remission.


Condition Intervention Phase
Leukemia, Myeloid, Ph1-Positive
Drug: Nilotinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open Label, Two Arm Phase III Study to Evaluate Treatment Free Remission (TFR) Rate in Patients With Philadelphia-positive CML After Two Different Durations of Consolidation Treatment With Nilotinib 300mg BID

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • optimal duration of consolidation treatment with nilotinib 300 mg BID to ensure the highest rate of patients remaining in ≥MR4.0 12months after entering the TFR phase. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    the primary endpoint is the number of patients who remain in treatment free remission (≥MR4.0) ,without molecular relapse, at the end of 12 months in the TFR phase of the study, in the nilotinib 12 months consolidation treatment arm (arm 1) versus the nilotinib 24 months consolidation treatment arm (arm 2).


Secondary Outcome Measures:
  • To evaluate the proportion of patients who are eligible to suspend nilotinib therapy by achieving and maintaining a sustained ≥MR4.0 for at least 12 months during consolidation treatment with nilotinib 300 mg BID [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The proportion of patients who have achieved a sustained ≥MR4.0 (defined as having 4 out of 5 quarterly assessments of ≥MR4.0 by a EUTOS standardized laboratory over the last 12 months and the last assessment before randomization is at least MR4.0) during the consolidation treatment phase of the study.

  • The kinetics of the molecular response in patients during induction/consolidation treatment with nilotinib 300 mg BID. [ Time Frame: 24 or 36 months depending on randomized arm ] [ Designated as safety issue: No ]
    The proportion of patients who achieve MR4.0 or MR4.5 on the study at selected time points during the induction/consolidation phase of the study.

  • The kinetics of the molecular response in patients during the TFR phase of the study in the two treatment arms. [ Time Frame: 36months (arm1); 24 months (arm2) ] [ Designated as safety issue: No ]
    The proportion of patients who maintain in MR4.0 or MR4.5 on the study at selected time points during the TFR phase in each one of the two treatment arms

  • Progression-free survival (PFS) rate during the TFR phase of the study. [ Time Frame: 36 months (arm1); 24 months (arm2) ] [ Designated as safety issue: Yes ]
    PFS defined as progression to AP/BP or death, where the "failure" event is the earliest occurrence of either of these events; Kaplan-Meier (KM) estimation of PFS is measured from the date of start of the nilotinib TFR phase to the date of the earliest failure event. Patients not known to have recurred or died on or before the cut-off date for the KM analysis will have their PFS interval censored at the earlier of the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who are still on study, and at the date of last contact for patients who are in follow-up.

  • Treatment -free survival (TFS) during the TFR phase of the study [ Time Frame: 36 months (arm1); 24 months (arm 2) ] [ Designated as safety issue: Yes ]
    TFS is defined as lack of any of the following events: loss of MMR, confirmed loss of MR4.0, re-start of nilotinib treatment, progression to AP/BP, or death from any cause;KM estimation of TFS, which is measured from the date of the start of the nilotinib TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4.0, re-start of nilotinib treatment, progression to AP/BP, or death from any cause.

  • Overall survival (OS) rate during of the TFR phase of the study. [ Time Frame: 36 months (arm1); 24 months (arm2) ] [ Designated as safety issue: Yes ]
    Overall survival is defined as the time from start of the TFR phase to the time of death due to any cause. For patients without any event on or before the cut-off date, survival time will be censored at the date of their last assessment for patients who are still on study, and at the date of last contact for patients who are in follow-up -

  • Safety profile of nilotinib during the induction/consolidation treatment phase, the TFR phase, and during the treatment re-initiation phase. [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]
    Descriptive statistics on adverse events, laboratory abnormalities and clinically notable ECG and other safety parameters during the study


Estimated Enrollment: 1058
Study Start Date: May 2005
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: arm 1
12 months of nilotinib consolidation (arm 1) plus 36 months of TFR phase
Drug: Nilotinib
Nilotinib will be provided to patients for at least 24 or 36months. (depending if nilotinib re-initiation is necessary- nilotinib will be provided during nilotinib re-initiation phase)
Active Comparator: arm 2
24 months of nilotinib consolidation plus 24 months of TFR phase
Drug: Nilotinib
Nilotinib will be provided to patients for at least 24 or 36months. (depending if nilotinib re-initiation is necessary- nilotinib will be provided during nilotinib re-initiation phase)

  Eligibility

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

Key Inclusion Criteria:

  • Confirmed diagnosis of chronic phase Ph+ CML
  • Previous first-line treatment with imatinib for a minimum of 2 years;
  • Patient in complete cytogenetic response;

Key Exclusion Criteria:

  • Previous achievement of MR4.0 at study entry;
  • Previous treatment with other target cells inhibitors other than imatinib;
  • Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening;
  • Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction;
  • Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol;
  • History of other active malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively;
  • Patients who have not recovered from prior surgery;
  • Treatment with other investigational agents within 4 weeks of Day 1;
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug;
  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: NCT01743989

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

  Show 325 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01743989     History of Changes
Other Study ID Numbers: CAMN107AIC05, 2012-005124-15
Study First Received: December 4, 2012
Last Updated: June 23, 2014
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Norway: Directorate of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Slovak Republic: Ethics Committee
Slovenia: Agency for Medicinal Products - Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: The Italian Medicines Agency
Bulgaria: Bulgarian Drug Agency
Croatia: Agency for Medicinal Product and Medical Devices
Hungary: National Institute of Pharmacy
Romania: National Medicines Agency
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Austria: Federal Office for Safety in Health Care
European Union: European Medicines Agency

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

ClinicalTrials.gov processed this record on October 20, 2014