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

Phase 3CompletedNCT02201459

Hospices Civils de Lyon200 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

200

Conditions

Chronic Myeloid Leukemia

Interventions

Nilotinib (Tasigna ®), capsules of 150 mgDRUG

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

Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)DRUG

* 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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Franck NICOLINI

Lyon, France

Outcomes

Primary Outcomes

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

Time frame: 12 months

Secondary Outcomes

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.

Time frame: 36 months

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.

Time frame: 36 months

Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.

Centralised assessment of the BCR-ABL transcripts at 3 months.

Time frame: 3 months after nilotinib initiation

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)

Time frame: Assessment at 3, 6 and 12 months

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).

Data from ClinicalTrials.gov

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