Study of Frontline Dasatinib Plus Chemotherapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.