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

NCT ID: NCT01724879

Last Updated: 2022-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-09-30

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.

Conditions

Philadelphia Positive Acute Lymphoblastic Leukemia

Study Design

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

Study Groups

Dasatinib and chemotherapy

Dasatinib, QD p.o. administration, day 1 to EOS

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide))

Interventions

Dasatinib

Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide))

Intervention Type: DRUG

Other Intervention Names

Sprycel (R); BMS-354825

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Goethe University

OTHER

Sponsor Role: lead

Responsible Party

Nicola Goekbuget

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nicola Gökbuget, Dr.med

Role: PRINCIPAL_INVESTIGATOR

Johann Wolfgang Goethe University Hospital

Locations

Robert Bosch Krankenhaus

Stuttgart, Baden-Wurttemberg, Germany

Klinikum der Universität Regensburg

Regensburg, Bavaria, Germany

University Hospital of Frankfurt, Medical Dept. II

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Universitätsklinik Münster

Münster, North Rhine-Westphalia, Germany

Universitätsklinik Dresden

Dresden, Saxony, Germany

Uniklinik Aachen

Aachen, , Germany

Charité Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinik Köln

Cologne, , Germany

University Hospital Düsseldorf

Düsseldorf, , Germany

Universitätsklinikum Göttingen

Göttingen, , Germany

Asklepios Klinik St. Georg

Hamburg, , Germany

Universität Leipzig, José-Carreras-Haus

Leipzig, , Germany

Universitätskliniken Mainz

Mainz, , Germany

Klinikum Mannheim

Mannheim, , Germany

Universitätsklinikum Großhadern

München, , Germany

Klinikum Nürnberg Nord

Nuremberg, , Germany

Klinikum Oldenburg

Oldenburg, , Germany

Universität Rostock

Rostock, , Germany

Medizinische Universitätsklinik Ulm

Ulm, , Germany

Medizinische Poliklinik der Universität Würzburg

Würzburg, , Germany

Countries

Germany

Other Identifiers

2010-022854-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GMALL-PH-01

Identifier Type: -

Identifier Source: org_study_id