Clinical trial NCT02201459: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Myeloid Leukemia
Keywords: Peg-IFN, nilotinib, MR4.5, CML, chronic phase, first-line
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2014-07-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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.
timeFrame: 12 months
Secondary outcomes:
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).
timeFrame: 36 months
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).
timeFrame: 36 months
measure: Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.
timeFrame: 3 months after nilotinib initiation
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.
timeFrame: Assessment at 3, 6 and 12 months
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).
timeFrame: 36 months
measure: Quality of life of patients treated in both arms
timeFrame: 36 months
measure: Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered.
timeFrame: 24 months for Peg-IFN, and 36 months for both drugs
measure: Compliance to drugs in each arms
timeFrame: 36 months
measure: Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.
timeFrame: 36 months
measure: Event-free survival.
timeFrame: 36 months
measure: Progression-free survival
timeFrame: 36 months
measure: Overall survival.
timeFrame: 36 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Franck NICOLINI
Study officials:
affiliation: Hopsices Civils de Lyon
name: Franck NICOLINI, MD
role: PRINCIPAL_INVESTIGATOR
References: