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Nilotinib + Pegylated Interferon Alpha 2a for Untreated Chronic Phase Chronic Myelogenous Leukemia (NILOPEG)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01294618
First received: February 7, 2011
Last updated: August 25, 2014
Last verified: February 2011
  Purpose

The aim of this study is to demonstrate the safety and the efficacy of a combination of 2 treatments shown to have some efficacy in Chronic Phase Chronic Myelogenous Leukemia (CP CML) separately, but that have never been combined to date, and this combination is expected to substantially increase the molecular response rates.


Condition Intervention Phase
Chronic Myelogenous Leukemia
Drug: Nilotinib,Novartis,300 mg twice a day +Pegylated interferon 2a,Roche, 45 microg weekly starting Month 2-Month 12 or beyond according to investigator choice.
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: "Phase II Multicenter Study Evaluating the Efficacy and the Safety of a Combination of Nilotinib Plus Pegylated Interferon Alpha 2a for de Novo Chronic Phase Chronic Myelogenous Leukemia Patients"

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Cumulative incidence of complete molecular remissions after 12 months of treatment with nilotinib + Pegylated Interferon (PEG-IFN) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    The trial opens for enrolment in 2011 March 7th for 18 months. Each patient will be followed for 24 months after entry.


Secondary Outcome Measures:
  • Kinetics of Complete Molecular Response (CMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
    CMR corresponds to a level of BCR-ABL transcripts < 0.001 % (BCR-ABL/ABL ratio < 0.001%). The BCR-ABL/ABL ratio will be analysed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months to study kinetics of CMR.

  • Stability of CMR : Proportion of patients maintaining their CMR at 18 and 24 months [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Kinetics of Major Molecular Response (MMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
    MMR corresponds to a level of BCR-ABL transcripts < 0.1 % (BCR-ABL/ABL ratio < 0.1%). The BCR-ABL/ABL ratio is analysed by RT-PCR at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months to study kinetics of MMR.

  • Stability of MMR : proportion of patients maintaining their MMR at 18 and 24 months [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Cumulative Complete Cytogenetic Remission (CCyR) rates at 3, 6 and 12 months. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Safety (hematologic and non-hematologic) of the combination nilotinib + PEG-IFN [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Dose reductions or interruptions of each treatment studied [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Progression free survival. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Overall survival. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Quality of life on nilotinib + PEG-IFN [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
  • Event free survival. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: March 2011
Study Completion Date: September 2013
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nilotinib + pegylated interferon alpha 2a (PEG-IFN). Drug: Nilotinib,Novartis,300 mg twice a day +Pegylated interferon 2a,Roche, 45 microg weekly starting Month 2-Month 12 or beyond according to investigator choice.
Combination of both treatments active by different means on the leukemic cells, in order to enhance the response rates of CP CML patients since diagnosis.

  Eligibility

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

Inclusion Criteria:

  • Performans status 0-2
  • CP CML diagnosed since less than 3 months without previous Tyrosine Kinase Inhibitor (TKI) or interferon treatment
  • Adequate organic functions:

    • Total Bilirubin < 1.5xUpper Normal Range (UNR).
    • Aspartate Amino Transferase (ASAT) and Alanine Amino Transferase (ALAT) < 2.5xUNR.
    • Alkaline phosphatase ≤ 2.5xUNR
    • Amylase and lipase ≤ 1.5xUNR.
    • Creatininemia < 1.5xUNR.
  • Biological blood standards :

    • Potassium ≥ Lower Normal Range (LNR)
    • Magnesium ≥ LNR.
    • Phosphorus ≥ LNR
    • Calcium ≥ LNR.
  • Negative pregnancy test within the last 7 days for women with childbearing potential.
  • Informed consent signed up
  • Compliance to tretament ensured,
  • Valid social insurance

Exclusion Criteria:

Prior TKI or interferon treatment for the CML

  • Contra-indication to IFN
  • Pregnancy, breast feeding
  • Human Immunodeficiency Virus positive, chronic hepatitis B or C.
  • Other BCR-ABL transcript than M-bcr
  • Cardiopathy defined as:

    • Left Ventricular Ejection Fraction (LVEF) < 45%.
    • Left bundle branch block
    • Ventricular pacemaker.
    • Congenital prolonged QT
    • Past ventricular or significant auricular tachyarrythmia
    • Clinically significant bradycardia (<50 per minute).
    • QTc (Fredericia) > 450 ms (average on 3 Elektrokardiogramm (EKG)).
    • Myocardial infarction in the last 12 months.
    • Unstable angina within the last 12 months.
    • Other significant cardiac diseases.
  • Other uncontrolled severe disease (such as diabetes melittus etc…)
  • Other ongoing malignant disease.
  • Past history of congenital or acquired clinically significant bleeding disorder.
  • Previous radiotherapy ≥25% of bone marrow.
  • Serious surgery within the past 4 weeks
  • Investigational treatment within the last 30 days prior to day 1.
  • History of non compliance.
  • Cytochrome P450 3A4 (CYP3A4) inhibitors that could not be withdrawn or modified (such as erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil).
  • Severe gastro-intestinal disorders (such as gastric ulcer, uncontrolled nausea, malabsorption syndrome, small intestine resection, gastric shunt).
  • Hepatic, renal or pancreatic chronic disorder unrelated to CML
  • Recent history of acute pancreatitis within a year or history of chronic pancreatic disease .
  • Any concommittant treatment inducing QT prolongation.
  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: NCT01294618

Locations
France
Hospices Civils de Lyon
Lyon, France, 69003
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Franck Nicolini, Dr Hospices Civils de Lyon
  More Information

Additional Information:
No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01294618     History of Changes
Other Study ID Numbers: 2009-560
Study First Received: February 7, 2011
Last Updated: August 25, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
Chronic Myelogenous Leukemia
nilotinib
pegylated interferon
BCR-ABL Philadelphia chromosome
Hematologic, cytogenetic and molecular response rates and kinetics will be studied in addition to the safety of the combination

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Interferon-alpha
Interferons
Peginterferon alfa-2a
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014