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

• ClinicalTrials.gov Identifier: NCT02201459
• Recruitment Status: Unknown
• First Posted: July 28, 2014
• Last Update Posted: August 7, 2014
• Sponsor: Hospices Civils de Lyon
• Collaborator: Novartis
• Information provided by (Responsible Party): Hospices Civils de Lyon

Tracking Information

• First Submitted Date: June 24, 2014
• First Posted Date: July 28, 2014
• Last Update Posted Date: August 7, 2014
• Study Start Date: August 2014
• Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 25, 2014)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 25, 2014)

• 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.
• 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.
• 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.
• 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)
• 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
• 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.
• 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.
• 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.
• 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.
• 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.
• Progression-free survival [ Time Frame: 36 months ]
  Survival without progression towards accelerated of blast phase, death.
• Overall survival. [ Time Frame: 36 months ]
  Survival without death from any cause

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients
• 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)
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Myeloid Leukemia

Intervention

• 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.

Study Arms

• Active Comparator: Nilotinib
  Control arm, this compound been licensed in this indication.
  Intervention: Drug: Nilotinib (Tasigna ®), capsules of 150 mg
• 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.
  Interventions:

  • Drug: Nilotinib (Tasigna ®), capsules of 150 mg
  • Drug: Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 25, 2014): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2019
• Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02201459
• Other Study ID Numbers: 2013.837
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hospices Civils de Lyon
• Original Responsible Party: Same as current
• Current Study Sponsor: Hospices Civils de Lyon
• Original Study Sponsor: Same as current
• Collaborators: Novartis

Investigators

• Principal Investigator: Franck NICOLINI, MD; Hopsices Civils de Lyon

• PRS Account: Hospices Civils de Lyon
• Verification Date: August 2014