Clinical trial NCT01294618: Nilotinib + Pegylated Interferon Alpha 2a for Untreated Chronic Phase Chronic Myelogenous Leukemia
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2011-02-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Cumulative incidence of complete molecular remissions after 12 months of treatment with nilotinib + Pegylated Interferon (PEG-IFN)
timeFrame: 24 months
Secondary outcomes:
measure: Kinetics of Complete Molecular Response (CMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months.
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Stability of CMR : Proportion of patients maintaining their CMR at 18 and 24 months
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Kinetics of Major Molecular Response (MMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months.
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Stability of MMR : proportion of patients maintaining their MMR at 18 and 24 months
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Cumulative Complete Cytogenetic Remission (CCyR) rates at 3, 6 and 12 months.
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Safety (hematologic and non-hematologic) of the combination nilotinib + PEG-IFN
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Dose reductions or interruptions of each treatment studied
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Progression free survival.
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Overall survival.
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Quality of life on nilotinib + PEG-IFN
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
measure: Event free survival.
timeFrame: Patients will be enrolled for 18 months and will be followed for 24 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hospices Civils de Lyon
Study officials:
affiliation: Hospices Civils de Lyon
name: Franck Nicolini, Dr
role: PRINCIPAL_INVESTIGATOR
References:
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.