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

Goethe University

Status and phase

Completed

Phase 2

Conditions

Philadelphia Positive Acute Lymphoblastic Leukemia

Treatments

Drug: Dasatinib

Study type

Interventional

Funder types

Other

Identifiers

NCT01724879

GMALL-PH-01

2010-022854-18 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

19 patients

Sex

All

Ages

18 to 55 years old

Volunteers

No Healthy Volunteers

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.