Dasatinib and Low Intensity Chemotherapy for Ph+ Acute Lymphoblastic Leukemia (EWALLPH01)
An Open Label Phase II Study to Evaluate the Efficacy and Safety of Induction and Consolidation Therapy With Dasatinib in Combination With Chemotherapy in Patients Aged 55 Years and Over With Philadelphia Chromosome Positive (Ph+ or BCR-ABL+) Acute Lymphoblastic Leukemia (ALL).
- The use of imatinib in combination or in association with chemotherapy is now considered as the gold standard for the treatment of Ph+ ALL. The complete remission (CR) rate is 90% versus 20% to 40% with chemotherapy alone. The combination of imatinib, vincristine and dexamethasone is a well tolerated regimen in aged patients and is also associated with a high CR rate of 80% to 90% in patient aged 55 years and over.
- However, despite high CR rates, the progression free survival rate at 12 months of patients treated with the combination of imatinib and chemotherapy is 30% to 50%. Relapses remain frequent and only patients intensified with allogenic haematopoietic stem cell transplantation are in long term remission. This strategy is not fully applicable to most patients aged 55 years and over.
- Relapses after or during imatinib therapy in patients with Ph+ ALL are associated with BCR-ABL tyrosine kinase domain mutation in 80% of cases, predominantly of the p-loop. The exact incidence of the T315I mutation is controversial and can be estimated to be near 50%. Conversely, the detection of the T315I or F317 mutation in a patient is a very strong predictor of relapse.
- Dasatinib is a potent SCR and BCR-ABL tyrosine kinase inhibitor with preserved in vitro activity in most of the BCR-ABL mutated cell lines, except for the T315I and F317 mutations. This is also the case in vivo, with patients harbouring BCR-ABL TK domain mutations remaining sensitive to dasatinib. The CHR rate in Ph+ ALL resistant to imatinib is 33% and the median progression-free survival is 3.7 months. Progression free survival (PFS) rate at 12 months is 22%.
The goal of this trial is to evaluate the efficacy and the tolerance of the combination of dasatinib with chemotherapy in the front-line setting as induction and consolidation therapy in Ph+ ALL patient aged 55 years and over. A European consensus has been reached to adopt a common chemotherapeutic schedule for patients aged 55 years and over. This schedule will be used in this trial with the addition of dasatinib as concomitant therapy during induction and alternating with chemotherapy during consolidation and maintenance. A CR rate of 90% and a progression free survival of 60% at 12 months are expected. The patients will be prospectively monitored for minimal residual disease and mutation.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Duisburg、德国
- St. Johannes-Hospital
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Stuttgart、德国
- Robert Bosch-Krankenhaus
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Bergamo、意大利
- Ospedali Riuniti di Bergamo
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Monza、意大利
- Ospedale San Gerardo
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Palermo、意大利
- Dipartimento Oncologico La Maddalena
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Bruxelles、比利时
- Cliniques Universitaires Saint-Luc
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Mons、比利时
- CHU Ambroise Pare
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Aix en provence、法国
- Ch D'Aix En Provence
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Amiens、法国
- Groupe Hospitalier Sud
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Angers、法国
- Chu Angers
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Annecy、法国
- Chr Annecienne
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Argenteuil、法国
- CH Victor Dupouy
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Avignon、法国
- CHG D'Avignon Henri Duffaut
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Bayonne、法国
- C.H. de la Côte Basque
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Besancon、法国
- Hopital Jean Minjoz
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Blois、法国
- CH BLOIS
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Bobigny、法国
- Avicenne
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Brest、法国
- CHU Brest
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Caen、法国
- Hôpital Clémenceau
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Clamart、法国
- HIA Percy
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Clermont ferrand、法国
- Hotel Dieu
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Colmar、法国
- Hôpital Pasteur
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Corbeil Essonnes、法国
- Centre Hospitalier Sud Francilien
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Creteil、法国
- HEnry Mondor
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Dijon、法国
- Hopital Du Bocage
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Dunkerque、法国
- Ch Dunkerque
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Grenoble、法国
- Hôpital A. MICHALLON
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Le Chesnay、法国
- CH Versailles
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Lens、法国
- CH LENS
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Lille、法国
- Hopital Claude Huriez
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Limoges、法国
- Hôpital Dupuytren
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Lyon、法国
- Edouard Herriot
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Marseille、法国
- IPC
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Meaux、法国
- CH Meaux
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Metz、法国
- Hôpital Notre Dame de Bon Secours
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Montpellier、法国
- Hôpital Lapeyronie
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Mulhouse、法国
- CH E Muller
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Nantes、法国
- Hotel Dieu
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Nice、法国
- Archet 1
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Nimes、法国
- Chu Nimes
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Orléans、法国
- Hôpital de la Source
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Paris、法国
- Hopital St Louis
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Paris、法国
- Cochin
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Paris、法国
- NECKER
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Paris、法国
- Pitie Salpetriere
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Paris、法国
- St Antoine
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Perpignan、法国
- Ch Perpignan
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Pessac、法国
- Hôpital du Haut Lévêque
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Pierre Benite、法国
- Hopital Lyon Sud
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Poitiers、法国
- CHU Mileterie
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Reims、法国
- Hopital R Debre
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Rennes、法国
- Hôpital de Pontchaillou
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Roubaix、法国
- CH Victor PROVO
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Rouen、法国
- Centre Henri Becquerel
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Saint-priest-en-jarez、法国
- Institut de Cancerologie de La Loire
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St Cloud、法国
- Centre René Huguenin
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Strasbourg、法国
- CHU HautePierre
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Toulon、法国
- HIA Ste Anne
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Toulouse、法国
- Hôpital de Purpan
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Tours、法国
- Chu Tours
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Valenciennes、法国
- Hotel Dieu
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Vandoeuvre Les Nancy、法国
- CH Brabois
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Villejuif、法国
- IGR
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La Reunion
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St Denis、La Reunion、法国
- Centre Hospitalier Départemental FELIX GUYON
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Male or female patients ≥ 55 years
- Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukaemia
- Not previously treated except with corticosteroids or single dose vincristine (three doses cyclophosphamide accepted but not recommended)
- With or without documented CNS involvement
- Signed written inform consent
- Molecular evaluation for BCR-ABL done
Exclusion Criteria:
- Patients with ECOG status > 2
- Patient previously treated with Tyrosine Kinase Inhibitors
- Patients with QTc > 470 ms
- Heart insufficiency NYHA grade III/IV, LEVF < 50% and or RF < 30%, myocardial infarction within the past 6 months prior to study
- Active secondary malignancy
- Patients with active bacterial, viral or fungal infection
- Known infection with HIV, Hepatitis B (except post vaccinal profile) or C
- Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
- Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal and total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia
- Concurrent severe diseases which exclude the administration of therapy
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Treatment Arm
standard treatment + dasatinib
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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Progression free survival at 12 months
大体时间:12 months
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12 months
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次要结果测量
结果测量 |
大体时间 |
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总生存期
大体时间:5年
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5年
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无事件生存
大体时间:5年
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5年
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无进展生存期
大体时间:5年
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5年
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无复发生存期
大体时间:5年
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5年
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根据 CTCAE v4.0 评估的发生治疗相关不良事件的参与者人数
大体时间:5年
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5年
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The proportion of Complete haematological remission
大体时间:5 years
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5 years
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The proportion of Major molecular response defined by a BCR-ABL/ABL ≤ 0.1% in bone marrow
大体时间:5 years
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5 years
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The proportion of Complete molecular response
大体时间:5 years
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5 years
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The proportion of Detection of a T315I or F317 BCR-ABL TK mutation
大体时间:5 years
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5 years
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The proportion of Molecular progression
大体时间:5 years
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5 years
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Death during induction
大体时间:2 months
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2 months
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Death in complete remission
大体时间:5 years
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5 years
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合作者和调查者
调查人员
- 首席研究员:Rousselot Philippe, MD、CH Versailles
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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