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

Chronic Myelogenous Leukemia Clinical Trial

— 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"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01294618
• Other study ID #: 2009-560
• Status: Completed
• Phase: Phase 2
• Start date: March 2011
• Est. completion date: September 2013

Study information

• Verified date: February 2011
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: September 2013
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase

Intervention

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.

Locations

Country	Name	City	State
France	Hospices Civils de Lyon	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

References & Publications (1)

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, Amé S, Gagnieu MC, Pivot C, Hayette S, Maguer-Satta V, Etienne M, Dulucq S, Rea D, Maho — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Dose reductions or interruptions of each treatment studied		Patients will be enrolled for 18 months and will be followed for 24 months
Secondary	Progression free survival.		Patients will be enrolled for 18 months and will be followed for 24 months
Secondary	Overall survival.		Patients will be enrolled for 18 months and will be followed for 24 months
Secondary	Quality of life on nilotinib + PEG-IFN		Patients will be enrolled for 18 months and will be followed for 24 months
Secondary	Event free survival.		Patients will be enrolled for 18 months and will be followed for 24 months

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