Nilotinib + Pegylated Interferon Alpha 2a for Untreated Chronic Phase Chronic Myelogenous Leukemia (NILOPEG)
This study is currently recruiting participants.
Verified February 2011 by Hospices Civils de Lyon
Sponsor:
Hospices Civils de Lyon
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01294618
First received: February 7, 2011
Last updated: January 10, 2012
Last verified: February 2011
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Myelogenous Leukemia |
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. |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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" |
Resource links provided by NLM:
Further study details as provided by Hospices Civils de Lyon:
Primary Outcome Measures:
- Cumulative incidence of complete molecular remissions after 12 months of treatment with nilotinib + Pegylated Interferon (PEG-IFN) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]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. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]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 [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
- Kinetics of Major Molecular Response (MMR) at 1, 2, 3, 6, 9, 12, 15, 18 and 24 months. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]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 [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: Yes ]
- Dose reductions or interruptions of each treatment studied [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
- Progression free survival. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
- Overall survival. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
- Quality of life on nilotinib + PEG-IFN [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
- Event free survival. [ Time Frame: Patients will be enrolled for 18 months and will be followed for 24 months ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 60 |
| Study Start Date: | March 2011 |
| Estimated Study Completion Date: | September 2014 |
| Primary Completion Date: | March 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01294618
Contacts
| Contact: Madeleine ETIENNE, CRAs | 4 72 11 73 96 ext 33 | madeleine.etienne@chu-lyon.fr |
| Contact: Elodie GADOLET, CRAs | 4 72 11 73 01 ext 33 | elodie.gadolet@chu-lyon.fr |
Locations
| France | |
| Hospices Civils de Lyon | Recruiting |
| Lyon, France, 69003 | |
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
| Principal Investigator: | Franck Nicolini, Dr | Hospices Civils de Lyon |
More Information
Additional Information:
No publications provided
| Responsible Party: | Hospices Civils de Lyon |
| ClinicalTrials.gov Identifier: | NCT01294618 History of Changes |
| Other Study ID Numbers: | 2009-560 |
| Study First Received: | February 7, 2011 |
| Last Updated: | January 10, 2012 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by Hospices Civils de Lyon:
|
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 |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Interferon-alpha Interferon Alfa-2a Interferons |
Peginterferon alfa-2a Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 19, 2013