Dasatinib and Low Intensity Chemotherapy for Ph+ Acute Lymphoblastic Leukemia

NCT ID: NCT02888990

Last Updated: 2016-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2016-01-31

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%.

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.

Conditions

Leukemia, Lymphoblastic, Acute

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

standard treatment + dasatinib

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Interventions

Dasatinib

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female patients ≥ 55 years

2. Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukaemia

3. Not previously treated except with corticosteroids or single dose vincristine (three doses cyclophosphamide accepted but not recommended)

4. With or without documented CNS involvement

5. Signed written inform consent

6. Molecular evaluation for BCR-ABL done

Exclusion Criteria

1. Patients with ECOG status > 2

2. Patient previously treated with Tyrosine Kinase Inhibitors

3. Patients with QTc > 470 ms

4. Heart insufficiency NYHA grade III/IV, LEVF < 50% and or RF < 30%, myocardial infarction within the past 6 months prior to study

5. Active secondary malignancy

6. Patients with active bacterial, viral or fungal infection

7. Known infection with HIV, Hepatitis B (except post vaccinal profile) or C

8. Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study

9. 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

10. Concurrent severe diseases which exclude the administration of therapy

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Versailles Hospital

OTHER

Sponsor Role: lead

Responsible Party

Philippe ROUSSELOT

study coordinator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rousselot Philippe, MD

Role: PRINCIPAL_INVESTIGATOR

CH Versailles

Locations

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

Countries

Belgium; France; Germany; Italy

Other Identifiers

2006-005694-21

Identifier Type: -

Identifier Source: org_study_id