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).
1 other identifier
interventional
71
4 countries
64
Brief Summary
- 1.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.
- 2.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.
- 3.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.
- 4.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%.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2007
Longer than P75 for phase_2
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2016
CompletedFirst Submitted
Initial submission to the registry
August 19, 2016
CompletedFirst Posted
Study publicly available on registry
September 5, 2016
CompletedSeptember 5, 2016
August 1, 2016
3.8 years
August 19, 2016
August 30, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival at 12 months
12 months
Secondary Outcomes (12)
The proportion of Complete haematological remission
5 years
The proportion of Major molecular response defined by a BCR-ABL/ABL ≤ 0.1% in bone marrow
5 years
The proportion of Complete molecular response
5 years
Event free survival
5 years
Relapse free survival
5 years
- +7 more secondary outcomes
Study Arms (1)
Treatment Arm
EXPERIMENTALstandard treatment + dasatinib
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (64)
Cliniques Universitaires Saint-Luc
Brussels, Belgium
CHU Ambroise Paré
Mons, Belgium
Centre Hospitalier Départemental FELIX GUYON
Saint-Denis, La Reunion, France
Ch D'Aix En Provence
Aix-en-Provence, France
Groupe Hospitalier Sud
Amiens, France
CHU Angers
Angers, France
Chr Annecienne
Annecy, France
Ch Victor Dupouy
Argenteuil, France
CHG D'Avignon Henri Duffaut
Avignon, France
C.H. de la Côte Basque
Bayonne, France
Hôpital JEAN MINJOZ
Besançon, France
CH Blois
Blois, France
Avicenne
Bobigny, France
CHU Brest
Brest, France
Hôpital CLEMENCEAU
Caen, France
HIA Percy
Clamart, France
Hotel Dieu
Clermont-Ferrand, France
Hôpital PASTEUR
Colmar, France
Centre Hospitalier Sud Francilien
Corbeil-Essonnes, France
Henry Mondor
Créteil, France
Hôpital du BOCAGE
Dijon, France
CH Dunkerque
Dunkirk, France
Hôpital A. MICHALLON
Grenoble, France
CH Versailles
Le Chesnay, France
CH Lens
Lens, France
Hopital Claude Huriez
Lille, France
Hôpital Dupuytren
Limoges, France
Edouard Herriot
Lyon, France
IPC
Marseille, France
CH Meaux
Meaux, France
Hôpital Notre Dame de Bon Secours
Metz, France
Hôpital LAPEYRONIE
Montpellier, France
CH E Muller
Mulhouse, France
Hotel Dieu
Nantes, France
Archet 1
Nice, France
CHU Nimes
Nîmes, France
Hôpital de la Source
Orléans, France
Cochin
Paris, France
Hopital St louis
Paris, France
Necker
Paris, France
Pitie Salpetrière
Paris, France
St Antoine
Paris, France
CH Perpignan
Perpignan, France
Hôpital du HAUT LEVEQUE
Pessac, France
Hopital Lyon Sud
Pierre-Bénite, France
CHU Mileterie
Poitiers, France
Hopital R Debre
Reims, France
Hôpital de PONTCHAILLOU
Rennes, France
CH Victor PROVO
Roubaix, France
Centre HENRI BECQUEREL
Rouen, France
centre rene Huguenin
Saint-Cloud, France
Institut de Cancérologie de la Loire
Saint-Priest-en-Jarez, France
CHU Hautepierre
Strasbourg, France
HIA Ste Anne
Toulon, France
Hôpital de PURPAN
Toulouse, France
CHU Tours
Tours, France
Hotel Dieu
Valenciennes, France
CH Brabois
Vandœuvre-lès-Nancy, France
IGR
Villejuif, France
St. Johannes-Hospital
Duisburg, Germany
Robert Bosch-Krankenhaus
Stuttgart, Germany
Ospedali Riuniti di Bergamo
Bergamo, Italy
Ospedale San Gerardo
Monza, Italy
Dipartimento Oncologico La Maddalena
Palermo, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rousselot Philippe, MD
CH Versailles
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- study coordinator
Study Record Dates
First Submitted
August 19, 2016
First Posted
September 5, 2016
Study Start
August 1, 2007
Primary Completion
May 1, 2011
Study Completion
January 1, 2016
Last Updated
September 5, 2016
Record last verified: 2016-08
Data Sharing
- IPD Sharing
- Will not share