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

Philadelphia Positive Acute Lymphoblastic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01724879
• Other study ID #: GMALL-PH-01
• Secondary ID: 2010-022854-18
• Status: Completed
• Phase: Phase 2
• Start date: November 2011
• Est. completion date: September 2015

Study information

• Verified date: January 2022
• Source: Goethe University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Philadelphia Positive Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
Germany	Uniklinik Aachen	Aachen
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinik Dresden	Dresden	Sachsen
Germany	University Hospital Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Essen	Essen	NRW
Germany	University Hospital of Frankfurt, Medical Dept. II	Frankfurt	Hessen
Germany	Universitätsklinikum Göttingen	Göttingen
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Universitätsklinik Köln	Köln
Germany	Universität Leipzig, José-Carreras-Haus	Leipzig
Germany	Universitätskliniken Mainz	Mainz
Germany	Klinikum Mannheim	Mannheim
Germany	Universitätsklinikum Großhadern	München
Germany	Universitätsklinik Münster	Münster	NRW
Germany	Klinikum Nürnberg Nord	Nürnberg
Germany	Klinikum Oldenburg	Oldenburg
Germany	Klinikum der Universität Regensburg	Regensburg	Bayern
Germany	Universität Rostock	Rostock
Germany	Robert Bosch Krankenhaus	Stuttgart	Baden-Württemberg
Germany	Medizinische Universitätsklinik Ulm	Ulm
Germany	Medizinische Poliklinik der Universität Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Goethe University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related discontinuation of study treatment (Proportion of Patients)		Day 120
Secondary	Molecular complete remission rate (CR)		Day 120
Secondary	Hematologic complete remission rate		Day 120
Secondary	Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3		Day 120