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History of Changes for Study: NCT02201459
Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients (PETALs)
Latest version (submitted August 6, 2014) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 25, 2014 None (earliest Version on record)
2 August 6, 2014 Recruitment Status, Study Status and Contacts/Locations
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Study NCT02201459
Submitted Date:  July 25, 2014 (v1)

Open or close this module Study Identification
Unique Protocol ID: 2013.837
Brief Title: Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients (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)
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2014
Overall Status: Not yet recruiting
Study Start: July 2014
Primary Completion: July 2015 [Anticipated]
Study Completion: July 2019 [Anticipated]
First Submitted: June 24, 2014
First Submitted that
Met QC Criteria:
July 25, 2014
First Posted: July 28, 2014 [Estimate]
Last Update Submitted that
Met QC Criteria:
July 25, 2014
Last Update Posted: July 28, 2014 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Hospices Civils de Lyon
Responsible Party: Sponsor
Collaborators: Novartis
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module 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.
Detailed Description:
Open or close this module Conditions
Conditions: Chronic Myeloid Leukemia
Keywords: Peg-IFN, nilotinib, MR4.5, CML, chronic phase, first-line
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 200 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Nilotinib
Control arm, this compound been licensed in this indication.
Drug: Nilotinib (Tasigna ®), capsules of 150 mg
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
Experimental: Peg-IFN alfa 2a (Pegasys®) and Nilotinib
Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.
Drug: Nilotinib (Tasigna ®), capsules of 150 mg
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
Drug: Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)
  • 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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
[ Time Frame: 12 months ]

Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation
Secondary Outcome Measures:
1. 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).
[ Time Frame: 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.
2. 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).
[ Time Frame: 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.
3. Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.
[ Time Frame: 3 months after nilotinib initiation ]

Centralised assessment of the BCR-ABL transcripts at 3 months.
4. Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib.
[ Time Frame: Assessment at 3, 6 and 12 months ]

Local bone marrow cytogenetic assessment (on 20 metaphases)
5. 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).
[ Time Frame: 36 months ]

Continuous evaluation of the AEs and SAEs reported during 36 months
6. Quality of life of patients treated in both arms
[ Time Frame: 36 months ]

EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36.
7. Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered.
[ Time Frame: 24 months for Peg-IFN, and 36 months for both drugs ]

Continuous recording of dose intensity along the study for 24-36 months.
8. Compliance to drugs in each arms
[ Time Frame: 36 months ]

Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation.
9. Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.
[ Time Frame: 36 months ]

Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.
10. Event-free survival.
[ Time Frame: 36 months ]

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.
11. Progression-free survival
[ Time Frame: 36 months ]

Survival without progression towards accelerated of blast phase, death.
12. Overall survival.
[ Time Frame: 36 months ]

Survival without death from any cause
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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
Open or close this module Contacts/Locations
Central Contact Person: Madeleine ETIENNE, CRA
Telephone: 4 78 86 22 32 Ext. +33
Email: madeleine.etienne@chu-lyon.fr
Central Contact Backup: jérémy MONFRAY, CRA
Telephone: 4 78 86 22 27 Ext. +33
Email: jeremy.monfray@chu-lyon.fr
Study Officials: Franck NICOLINI, MD
Principal Investigator
Hopsices Civils de Lyon
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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