Clinical trial NCT01724879: Study of Frontline Dasatinib Plus Chemotherapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)
Official title: Open Label Phase II Study to Evaluate the Safety of Standard Induction and Consolidation Therapy in Combination With Dasatinib in Newly Diagnosed Adult Patients With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Philadelphia Positive Acute Lymphoblastic Leukemia
Keywords: philadelphia chromosome
BCR-ABL
ALL
acute lymphoblastic leukemia
dasatinib
Sprycel
Lead sponsor: Goethe University
Sponsor class: OTHER
First posted: 2012-11-12
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment-related discontinuation of study treatment (Proportion of Patients)
timeFrame: Day 120
Secondary outcomes:
measure: Molecular complete remission rate (CR)
timeFrame: Day 120
measure: Hematologic complete remission rate
timeFrame: Day 120
measure: Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3
timeFrame: Day 120
Other outcomes:
Locations:
city: Stuttgart
country: Germany
facility: Robert Bosch Krankenhaus
state: Baden-Württemberg
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg
state: Bayern
city: Frankfurt
country: Germany
facility: University Hospital of Frankfurt, Medical Dept. II
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: NRW
city: Münster
country: Germany
facility: Universitätsklinik Münster
state: NRW
city: Dresden
country: Germany
facility: Universitätsklinik Dresden
state: Sachsen
city: Aachen
country: Germany
facility: Uniklinik Aachen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Köln
country: Germany
facility: Universitätsklinik Köln
city: Leipzig
country: Germany
facility: Universität Leipzig, José-Carreras-Haus
city: Mainz
country: Germany
facility: Universitätskliniken Mainz
city: Mannheim
country: Germany
facility: Klinikum Mannheim
city: München
country: Germany
facility: Universitätsklinikum Großhadern
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Rostock
country: Germany
facility: Universität Rostock
city: Ulm
country: Germany
facility: Medizinische Universitätsklinik Ulm
city: Würzburg
country: Germany
facility: Medizinische Poliklinik der Universität Würzburg
Study officials:
affiliation: Johann Wolfgang Goethe University Hospital
name: Nicola Gökbuget, Dr.med
role: PRINCIPAL_INVESTIGATOR
References: