Clinical Trials /

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

NCT02201459

Description:

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.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 2013.837
  • NCT ID: NCT02201459

Conditions

  • Chronic Myeloid Leukemia

Interventions

DrugSynonymsArms
Nilotinib (Tasigna ®), capsules of 150 mgNilotinib
Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)Peg-IFN alfa 2a (Pegasys®) and Nilotinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
NilotinibActive ComparatorControl arm, this compound been licensed in this indication.
  • Nilotinib (Tasigna ®), capsules of 150 mg
Peg-IFN alfa 2a (Pegasys®) and NilotinibExperimentalArm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.
  • Nilotinib (Tasigna ®), capsules of 150 mg
  • Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)

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
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation

Secondary Outcome Measures

Measure: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
Safety Issue:
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.
Measure: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
Safety Issue:
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.
Measure:Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.
Time Frame:3 months after nilotinib initiation
Safety Issue:
Description:Centralised assessment of the BCR-ABL transcripts at 3 months.
Measure: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
Safety Issue:
Description:Local bone marrow cytogenetic assessment (on 20 metaphases)
Measure: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
Safety Issue:
Description:Continuous evaluation of the AEs and SAEs reported during 36 months
Measure:Quality of life of patients treated in both arms
Time Frame:36 months
Safety Issue:
Description:EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36.
Measure: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
Safety Issue:
Description:Continuous recording of dose intensity along the study for 24-36 months.
Measure:Compliance to drugs in each arms
Time Frame:36 months
Safety Issue:
Description:Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation.
Measure:Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.
Time Frame:36 months
Safety Issue:
Description:Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.
Measure:Event-free survival.
Time Frame:36 months
Safety Issue:
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.
Measure:Progression-free survival
Time Frame:36 months
Safety Issue:
Description:Survival without progression towards accelerated of blast phase, death.
Measure:Overall survival.
Time Frame:36 months
Safety Issue:
Description:Survival without death from any cause

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hospices Civils de Lyon

Trial Keywords

  • Peg-IFN, nilotinib, MR4.5, CML, chronic phase, first-line

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