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)
概览
- 阶段
- 3 期
- 干预措施
- Nilotinib (Tasigna ®), capsules of 150 mg
- 疾病 / 适应症
- Chronic Myeloid Leukemia
- 发起方
- Hospices Civils de Lyon
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- 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.
- 状态
- 已完成
- 最后更新
- 7个月前
概览
简要总结
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Nilotinib
Control arm, this compound been licensed in this indication.
干预措施: Nilotinib (Tasigna ®), capsules of 150 mg
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.
干预措施: Nilotinib (Tasigna ®), capsules of 150 mg
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.
干预措施: Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)
结局指标
主要结局
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.
时间窗: 12 months
Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation
次要结局
- Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.(3 months after nilotinib initiation)
- 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)
- 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)
- 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)
- 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)
- Quality of life of patients treated in both arms(36 months)
- 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)
- Compliance to drugs in each arms(36 months)
- Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.(36 months)
- Event-free survival.(36 months)
- Progression-free survival(36 months)
- Overall survival.(36 months)