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Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients (PETALs)

Primary Purpose

Chronic Myeloid Leukemia

Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Nilotinib (Tasigna ®), capsules of 150 mg
Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Peg-IFN, nilotinib, MR4.5, CML, chronic phase, first-line

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male and female patients
  • CP-CML, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript), diagnosed less than 3 months prior to study entry
  • Age of at least 18 years-old and less than 65 years
  • Patient for whom treatment with Nilotinib is expected
  • No other CML treatment except for hydroxyurea and/or anagrelide
  • No previous TKI treatment.
  • No previous treatment with IFN even for other purposes.
  • SGOT and SGPT < 2.5 UNL
  • Serum creatinine < 2 UNL
  • No planned allogeneic stem cell transplantation
  • Signed informed consent
  • ECOG score 0 to 2

Exclusion Criteria:

  • Contra-indication to IFN
  • Transcripts other than M-Bcr
  • Pregnancy, lactation
  • HIV positivity, chronic hepatitis B or C.
  • Prior or concurrent malignancy other than CML (exceptions to be mentioned)
  • History of arterial occlusive disease or (peripheral, carotids or severe coronary heart disease).
  • Permanent elevation of total cholesterol and triglycerides despite treatment
  • Severe psychiatric/neurological disease (previous or ongoing)
  • Concomitant auto-immune disease
  • Other investigational product ongoing
  • Ongoing immunosuppressive treatment
  • Ongoing treatment at risk for inducing torsades de pointes
  • QTcF > 450ms despite correction of predisposing factors (i.e electrolytes…)
  • Congenital long QTcF
  • Unstabilised thyroid disorder
  • No health insurance coverage

Sites / Locations

  • Franck NICOLINIRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Nilotinib

Peg-IFN alfa 2a (Pegasys®) and Nilotinib

Arm Description

Control arm, this compound been licensed in this indication.

Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.

Outcomes

Primary Outcome Measures

Molecular response (MR) 4.5 at 12 months of nilotinib 300 mg twice a day versus a combination of low-dose Peg-Interferon (Peg-IFN) to nilotinib 300 mg twice a day in newly diagnosed CP-CML Chronic Phase Chronic Myelogenous Leukemia patients.
Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation

Secondary Outcome Measures

Molecular Response 4.5 at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MR4.5 during the second year of treatment (18, 24 and 36 months).
Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.
Major Molecular Response at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MMR during the second year of treatment (18, 24 and 36 months).
Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.
Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.
Centralised assessment of the BCR-ABL transcripts at 3 months.
Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib.
Local bone marrow cytogenetic assessment (on 20 metaphases)
Safety of the nilotinib combined to Peg-IFN or not (hematological and non-hematological adverse events (AE) graded according to the NCI CTC AE v3).
Continuous evaluation of the AEs and SAEs reported during 36 months
Quality of life of patients treated in both arms
EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36.
Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered.
Continuous recording of dose intensity along the study for 24-36 months.
Compliance to drugs in each arms
Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation.
Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.
Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.
Event-free survival.
Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.
Progression-free survival
Survival without progression towards accelerated of blast phase, death.
Overall survival.
Survival without death from any cause

Full Information

First Posted
June 24, 2014
Last Updated
August 6, 2014
Sponsor
Hospices Civils de Lyon
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT02201459
Brief Title
Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients
Acronym
PETALs
Official Title
Randomized Multicenter Phase III Study Comparing the Rate of Molecular Response 4.5 at 12 Months in Newly Diagnosed Philadelphia Positive Chronic Phase Chronic Myelogenous Leukemia Patients Receiving Either Frontline Nilotinib 600 mg Daily or Nilotinib 600 mg Daily Combined to Pegylated Interferon-alfa 2a (Peg-IFN)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Unknown status
Study Start Date
August 2014 (undefined)
Primary Completion Date
January 2018 (Anticipated)
Study Completion Date
August 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase III trial comparing, for newly diagnosed chronic phase CML patients, nilotinib 600 mg BID as a standard arm and nilotinib 600 mg BID combined to interferon alfa 2 a (pegylated form improving tolerance and maybe enhancing is efficacy) at increased doses for a total of 24 months of combination, in a 1:1 randomized manner. The assessment for the primary efficacy endpoint will be performed at 12 months (since nilotinib initiation) and is the rate patients obtaining MR4.5 will be measured at this time point.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia
Keywords
Peg-IFN, nilotinib, MR4.5, CML, chronic phase, first-line

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nilotinib
Arm Type
Active Comparator
Arm Description
Control arm, this compound been licensed in this indication.
Arm Title
Peg-IFN alfa 2a (Pegasys®) and Nilotinib
Arm Type
Experimental
Arm Description
Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.
Intervention Type
Drug
Intervention Name(s)
Nilotinib (Tasigna ®), capsules of 150 mg
Intervention Description
Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months
Intervention Type
Drug
Intervention Name(s)
Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)
Intervention Description
Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months and Pegylated interferon alfa 2a subcutaneously once a week (auto-injection syringes of 135 and 90 micrograms) at 30 micrograms/week the first month alone (= priming procedure), then at 30 micrograms/2weeks the first month of combination to nilotinib and then at 45 micrograms/week thereafter until month 24 after nilotinib initiation.
Primary Outcome Measure Information:
Title
Molecular response (MR) 4.5 at 12 months of nilotinib 300 mg twice a day versus a combination of low-dose Peg-Interferon (Peg-IFN) to nilotinib 300 mg twice a day in newly diagnosed CP-CML Chronic Phase Chronic Myelogenous Leukemia patients.
Description
Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Molecular Response 4.5 at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MR4.5 during the second year of treatment (18, 24 and 36 months).
Description
Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.
Time Frame
36 months
Title
Major Molecular Response at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MMR during the second year of treatment (18, 24 and 36 months).
Description
Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.
Time Frame
36 months
Title
Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.
Description
Centralised assessment of the BCR-ABL transcripts at 3 months.
Time Frame
3 months after nilotinib initiation
Title
Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib.
Description
Local bone marrow cytogenetic assessment (on 20 metaphases)
Time Frame
Assessment at 3, 6 and 12 months
Title
Safety of the nilotinib combined to Peg-IFN or not (hematological and non-hematological adverse events (AE) graded according to the NCI CTC AE v3).
Description
Continuous evaluation of the AEs and SAEs reported during 36 months
Time Frame
36 months
Title
Quality of life of patients treated in both arms
Description
EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36.
Time Frame
36 months
Title
Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered.
Description
Continuous recording of dose intensity along the study for 24-36 months.
Time Frame
24 months for Peg-IFN, and 36 months for both drugs
Title
Compliance to drugs in each arms
Description
Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation.
Time Frame
36 months
Title
Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.
Description
Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.
Time Frame
36 months
Title
Event-free survival.
Description
Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.
Time Frame
36 months
Title
Progression-free survival
Description
Survival without progression towards accelerated of blast phase, death.
Time Frame
36 months
Title
Overall survival.
Description
Survival without death from any cause
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female patients CP-CML, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript), diagnosed less than 3 months prior to study entry Age of at least 18 years-old and less than 65 years Patient for whom treatment with Nilotinib is expected No other CML treatment except for hydroxyurea and/or anagrelide No previous TKI treatment. No previous treatment with IFN even for other purposes. SGOT and SGPT < 2.5 UNL Serum creatinine < 2 UNL No planned allogeneic stem cell transplantation Signed informed consent ECOG score 0 to 2 Exclusion Criteria: Contra-indication to IFN Transcripts other than M-Bcr Pregnancy, lactation HIV positivity, chronic hepatitis B or C. Prior or concurrent malignancy other than CML (exceptions to be mentioned) History of arterial occlusive disease or (peripheral, carotids or severe coronary heart disease). Permanent elevation of total cholesterol and triglycerides despite treatment Severe psychiatric/neurological disease (previous or ongoing) Concomitant auto-immune disease Other investigational product ongoing Ongoing immunosuppressive treatment Ongoing treatment at risk for inducing torsades de pointes QTcF > 450ms despite correction of predisposing factors (i.e electrolytes…) Congenital long QTcF Unstabilised thyroid disorder No health insurance coverage
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Madeleine ETIENNE, CRA
Phone
4 78 86 22 32
Ext
+33
Email
madeleine.etienne@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
jérémy MONFRAY, CRA
Phone
4 78 86 22 27
Ext
+33
Email
jeremy.monfray@chu-lyon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Franck NICOLINI, MD
Organizational Affiliation
Hopsices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Franck NICOLINI
City
Lyon
ZIP/Postal Code
04 78 86 22 50
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Franck Nicolini, MD
Phone
4 78 86 22 50
Ext
33
Email
franck-emmanuel.nicolini@chu-lyon.fr

12. IPD Sharing Statement

Learn more about this trial

Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients

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