Study of Frontline Dasatinib Plus Chemotherapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)
- Conditions
- Philadelphia Positive Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT01724879
- Lead Sponsor
- Goethe University
- Brief Summary
The current standard treatment approach for young patients with Positive Acute Lymphoblastic Leukemia (Ph+ALL) is the combination of a chemotherapy protocol employing four to five cytotoxic agents typically used for ALL together with imatinib. It is recommended to propose allogeneic Standard Induction and Consolidation Therapy (SCT) to all eligible patients with a suitable donor and to continue imatinib with or without additional therapy in patients not undergoing SCT.
This protocol is a study for newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia in patients aged 18 to 55 years.
The objective of this strategy is to improve the overall results in the treatment of adult ALL with the addition of specific molecules to the common chemotherapeutic schedule.
- Detailed Description
In the present study, the potent ABL tyrosine kinase inhibitor, Dasatinib will be added to standard induction and consolidation chemotherapy for the Philadelphia positive chromosome sub-group of ALL patients aged 18 to 55 years.
The Study hypothesis is, that Dasatinib in combination with standard chemotherapy according to GMALL protocol 07/2003 is feasible and induces cytologic and molecular remission rates comparable to chemotherapy in combination with imatinib without increased treatment-related mortality.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
- Confirmed new diagnosis of Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia
- Male or female patients aged 18-55 years
- Not previously treated except for prephase (corticosteroids, cyclophosphamide, single dose VCR will be permitted) therapy during establishment of the diagnosis
- Signed written inform consent, willingness and ability to comply with all study procedures
- Molecular detection of BCR-ABL transcripts
- Willingness of women of child-bearing potential (WOCBP) and male subjects whose sexual partners are WOCBP, to use an effective form of contraception (pearl index < 1%), such as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients or male partners during the study and at least 6 months thereafter. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).
- Negative pregnancy test for women of child-bearing potential.
- Patients with ECOG status > 2
- Patients with QTcF > 470 ms
- Cardiac insufficiency NYHA grade III/IV, LEVF < 50%, myocardial infarction within the past 6 months prior to study
- Active secondary malignancy requiring treatment
- Patients with active, uncontrolled bacterial, viral or fungal infection
- Known infection with HIV, Hepatitis B (except post vaccinal profile) or C
- 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
- Expected non-compliance or inability to understand informed consent
- Female patients who are pregnant or breast feeding
- Treatment with other investigational antileukemic agents after informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dasatinib and chemotherapy Dasatinib Dasatinib, QD p.o. administration, day 1 to EOS
- Primary Outcome Measures
Name Time Method Treatment-related discontinuation of study treatment (Proportion of Patients) Day 120
- Secondary Outcome Measures
Name Time Method Molecular complete remission rate (CR) Day 120 Hematologic complete remission rate Day 120 Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3 Day 120
Trial Locations
- Locations (22)
University Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
Asklepios Klinik St. Georg
🇩🇪Hamburg, Germany
Universitätsklinikum Großhadern
🇩🇪München, Germany
Klinikum Nürnberg Nord
🇩🇪Nürnberg, Germany
Medizinische Universitätsklinik Ulm
🇩🇪Ulm, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Uniklinik Aachen
🇩🇪Aachen, Germany
Universitätsklinikum Göttingen
🇩🇪Göttingen, Germany
Universitätsklinik Köln
🇩🇪Köln, Germany
Universitätsklinikum Essen
🇩🇪Essen, NRW, Germany
Medizinische Poliklinik der Universität Würzburg
🇩🇪Würzburg, Germany
University Hospital of Frankfurt, Medical Dept. II
🇩🇪Frankfurt, Hessen, Germany
Klinikum der Universität Regensburg
🇩🇪Regensburg, Bayern, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Universitätskliniken Mainz
🇩🇪Mainz, Germany
Klinikum Mannheim
🇩🇪Mannheim, Germany
Universitätsklinik Münster
🇩🇪Münster, NRW, Germany
Universitätsklinik Dresden
🇩🇪Dresden, Sachsen, Germany
Universität Leipzig, José-Carreras-Haus
🇩🇪Leipzig, Germany
Robert Bosch Krankenhaus
🇩🇪Stuttgart, Baden-Württemberg, Germany
Universität Rostock
🇩🇪Rostock, Germany