Back to resultsNilotinib + Pegylated Interferon Alpha 2a for Untreated Chronic Phase Chronic Myelogenous Leukemia (NILOPEG)
Primary Purpose
Chronic Myelogenous Leukemia
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
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.
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myelogenous Leukemia focused on measuring 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
Eligibility 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.
Sites / Locations
- Hospices Civils de Lyon
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
nilotinib + pegylated interferon alpha 2a (PEG-IFN).
Arm Description
Outcomes
Primary Outcome Measures
Cumulative incidence of complete molecular remissions after 12 months of treatment with nilotinib + Pegylated Interferon (PEG-IFN)
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.
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
Kinetics of Major Molecular Response (MMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months.
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
Cumulative Complete Cytogenetic Remission (CCyR) rates at 3, 6 and 12 months.
Safety (hematologic and non-hematologic) of the combination nilotinib + PEG-IFN
Dose reductions or interruptions of each treatment studied
Progression free survival.
Overall survival.
Quality of life on nilotinib + PEG-IFN
Event free survival.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01294618
Brief Title
Nilotinib + Pegylated Interferon Alpha 2a for Untreated Chronic Phase Chronic Myelogenous Leukemia
Acronym
NILOPEG
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"
Study Type
Interventional
2. Study Status
Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelogenous Leukemia
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
nilotinib + pegylated interferon alpha 2a (PEG-IFN).
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
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.
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cumulative incidence of complete molecular remissions after 12 months of treatment with nilotinib + Pegylated Interferon (PEG-IFN)
Description
The trial opens for enrolment in 2011 March 7th for 18 months. Each patient will be followed for 24 months after entry.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Kinetics of Complete Molecular Response (CMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months.
Description
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.
Time Frame
Patients will be enrolled for 18 months and will be followed for 24 months
Title
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
Title
Kinetics of Major Molecular Response (MMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months.
Description
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.
Time Frame
Patients will be enrolled for 18 months and will be followed for 24 months
Title
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
Title
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
Title
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
Title
Dose reductions or interruptions of each treatment studied
Time Frame
Patients will be enrolled for 18 months and will be followed for 24 months
Title
Progression free survival.
Time Frame
Patients will be enrolled for 18 months and will be followed for 24 months
Title
Overall survival.
Time Frame
Patients will be enrolled for 18 months and will be followed for 24 months
Title
Quality of life on nilotinib + PEG-IFN
Time Frame
Patients will be enrolled for 18 months and will be followed for 24 months
Title
Event free survival.
Time Frame
Patients will be enrolled for 18 months and will be followed for 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Franck Nicolini, Dr
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospices Civils de Lyon
City
Lyon
ZIP/Postal Code
69003
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
26687426
Citation
Nicolini FE, Etienne G, Dubruille V, Roy L, Huguet F, Legros L, Giraudier S, Coiteux V, Guerci-Bresler A, Lenain P, Cony-Makhoul P, Gardembas M, Hermet E, Rousselot P, Ame S, Gagnieu MC, Pivot C, Hayette S, Maguer-Satta V, Etienne M, Dulucq S, Rea D, Mahon FX. Nilotinib and peginterferon alfa-2a for newly diagnosed chronic-phase chronic myeloid leukaemia (NiloPeg): a multicentre, non-randomised, open-label phase 2 study. Lancet Haematol. 2015 Jan;2(1):e37-46. doi: 10.1016/S2352-3026(14)00027-1. Epub 2015 Jan 7.
Results Reference
result
Links:
URL
http://medicine.iupui.edu/flockhart/table.htm
Description
Related Info
Learn more about this trial
Nilotinib + Pegylated Interferon Alpha 2a for Untreated Chronic Phase Chronic Myelogenous Leukemia
We'll reach out to this number within 24 hrs