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

Sponsor

Goethe University (Other)

Overall Status

Completed

CT.gov ID

NCT01724879

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Philadelphia Positive Acute Lymphoblastic Leukemia	Drug: Dasatinib	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib and chemotherapy Dasatinib, QD p.o. administration, day 1 to EOS	Drug: Dasatinib Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide)) Other Names: Sprycel (R) BMS-354825

Arm

Intervention/Treatment

Experimental: Dasatinib and chemotherapy

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

Drug: Dasatinib

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

Other Names:

Sprycel (R)

BMS-354825

Outcome Measures

Primary Outcome Measures

Treatment-related discontinuation of study treatment (Proportion of Patients) [Day 120]

Secondary Outcome Measures

Molecular complete remission rate (CR) [Day 120]
Hematologic complete remission rate [Day 120]
Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3 [Day 120]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert Bosch Krankenhaus	Stuttgart	Baden-Württemberg	Germany	70376
2	Klinikum der Universität Regensburg	Regensburg	Bayern	Germany	93042
3	University Hospital of Frankfurt, Medical Dept. II	Frankfurt	Hessen	Germany	60590
4	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
5	Universitätsklinikum Essen	Essen	NRW	Germany	45147
6	Universitätsklinik Münster	Münster	NRW	Germany	48149
7	Universitätsklinik Dresden	Dresden	Sachsen	Germany	01307
8	Uniklinik Aachen	Aachen		Germany	52074
9	Charité Universitätsmedizin Berlin	Berlin		Germany	13353
10	University Hospital Düsseldorf	Düsseldorf		Germany	40225
11	Universitätsklinikum Göttingen	Göttingen		Germany	37075
12	Asklepios Klinik St. Georg	Hamburg		Germany	20099
13	Universitätsklinik Köln	Köln		Germany	50937
14	Universität Leipzig, José-Carreras-Haus	Leipzig		Germany	04103
15	Universitätskliniken Mainz	Mainz		Germany	55101
16	Klinikum Mannheim	Mannheim		Germany	68167
17	Universitätsklinikum Großhadern	München		Germany	81377
18	Klinikum Nürnberg Nord	Nürnberg		Germany	90419
19	Klinikum Oldenburg	Oldenburg		Germany	26133
20	Universität Rostock	Rostock		Germany	18055
21	Medizinische Universitätsklinik Ulm	Ulm		Germany	89070
22	Medizinische Poliklinik der Universität Würzburg	Würzburg		Germany	97070