Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients
- Conditions
- Chronic Myeloid Leukemia
- Interventions
- Registration Number
- NCT02201459
- Lead Sponsor
- Hospices Civils de Lyon
- 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 available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 200
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nilotinib Nilotinib (Tasigna ®), capsules of 150 mg Control arm, this compound been licensed in this indication. Peg-IFN alfa 2a (Pegasys®) and Nilotinib Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®) Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients. Peg-IFN alfa 2a (Pegasys®) and Nilotinib Nilotinib (Tasigna ®), capsules of 150 mg Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.
- Primary Outcome Measures
Name Time Method 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. 12 months Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation
- Secondary Outcome Measures
Name Time Method Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months. 3 months after nilotinib initiation Centralised assessment of the BCR-ABL transcripts at 3 months.
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). 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). 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 CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib. 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). 36 months Continuous evaluation of the AEs and SAEs reported during 36 months
Quality of life of patients treated in both arms 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. 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 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. 36 months Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.
Event-free survival. 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 36 months Survival without progression towards accelerated of blast phase, death.
Overall survival. 36 months Survival without death from any cause
Trial Locations
- Locations (1)
Franck NICOLINI
🇫🇷Lyon, France