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

"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"

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.

Study Overview

• Status: Completed
• Conditions: Chronic Myelogenous Leukemia
• Intervention / Treatment: 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69003
    • Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Franck Nicolini, Dr, Hospices Civils de Lyon

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: February 7, 2011
• First Submitted That Met QC Criteria: February 10, 2011
• First Posted (Estimate): February 11, 2011

Study Record Updates

• Last Update Posted (Actual): May 28, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Chronic Myelogenous Leukemia; pegylated interferon; nilotinib; 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: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons
• Other Study ID Numbers: 2009-560