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

Phase 2

Completed

• Conditions: Chronic Myelogenous Leukemia
• Interventions: 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.

• Registration Number: NCT01294618
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2011-02
• Study First Submitted: 2011-02-07
• Study First Submitted QC: 2011-02-10
• Study First Posted: 2011-02-11
• Study Start: 2011-03
• Primary Completion: 2011-03
• Study Completion: 2013-09
• Last Update Submitted: 2019-05-23
• Last Update Posted: 2019-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
nilotinib + pegylated interferon alpha 2a (PEG-IFN).	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.	-

Primary Outcome Measures

Name	Time	Method
Cumulative incidence of complete molecular remissions after 12 months of treatment with nilotinib + Pegylated Interferon (PEG-IFN)	24 months	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

Name	Time	Method
Kinetics of Major Molecular Response (MMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months.	Patients will be enrolled for 18 months and will be followed for 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	Patients will be enrolled for 18 months and will be followed for 24 months
Kinetics of Complete Molecular Response (CMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months.	Patients will be enrolled for 18 months and will be followed for 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	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

Trial Locations

Locations (1)

Hospices Civils de Lyon; 🇫🇷 Lyon, France