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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Johann Wolfgang Goethe University Hospitals
Sponsor:
Information provided by (Responsible Party):
Oliver G. Ottmann, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01724879
First received: February 3, 2012
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

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 Intervention Phase
Philadelphia Positive Acute Lymphoblastic Leukemia
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • Treatment-related discontinuation of study treatment (Proportion of Patients) [ Time Frame: Day 120 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Molecular complete remission rate (CR) [ Time Frame: Day 120 ] [ Designated as safety issue: No ]
  • Hematologic complete remission rate [ Time Frame: Day 120 ] [ Designated as safety issue: No ]
  • Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3 [ Time Frame: Day 120 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: November 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01724879

Contacts
Contact: Oliver G. Ottmann, Prof.Dr.med +49 (0)69-6301 ext 3947 ottmann@em.uni-frankfurt.de
Contact: Nicola Gökbuget, Dr. med. +49 (0)69-6301 ext 6365 goekbuget@em.uni-frankfurt.de

Locations
Germany
Robert Bosch Krankenhaus Recruiting
Stuttgart, Baden-Württemberg, Germany, 70376
Klinikum der Universität Regensburg Recruiting
Regensburg, Bayern, Germany, 93042
University Hospital of Frankfurt, Medical Dept. II Recruiting
Frankfurt, Hessen, Germany, 60590
Medizinische Hochschule Hannover Recruiting
Hannover, Niedersachsen, Germany, 30625
Universitätsklinikum Essen Recruiting
Essen, NRW, Germany, 45147
Universitätsklinik Münster Recruiting
Münster, NRW, Germany, 48149
Universitätsklinik Dresden Recruiting
Dresden, Sachsen, Germany, 01307
Uniklinik Aachen Recruiting
Aachen, Germany, 52074
Charité Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13353
St. Johannes-Hospital Duisburg Recruiting
Duisburg, Germany, 47166
University Hospital Düsseldorf Recruiting
Düsseldorf, Germany, 40225
Universitätsklinikum Göttingen Recruiting
Göttingen, Germany, 37075
Asklepios Klinik St. Georg Recruiting
Hamburg, Germany, 20099
Universitätsklinik Köln Recruiting
Köln, Germany, 50937
Universität Leipzig, José-Carreras-Haus Recruiting
Leipzig, Germany, 04103
Universitätskliniken Mainz Recruiting
Mainz, Germany, 55101
Klinikum Mannheim Recruiting
Mannheim, Germany, 68167
Universitätsklinikum Großhadern Recruiting
München, Germany, 81377
Klinikum Nürnberg Nord Recruiting
Nürnberg, Germany, 90419
Klinikum Oldenburg Recruiting
Oldenburg, Germany, 26133
Universität Rostock Recruiting
Rostock, Germany, 18055
Medizinische Universitätsklinik Ulm Recruiting
Ulm, Germany, 89070
Medizinische Poliklinik der Universität Würzburg Recruiting
Würzburg, Germany, 97070
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
Investigators
Principal Investigator: Oliver G. Ottmann, Prof.Dr.med Johann Wolfgang Goethe University Hospitals
  More Information

Additional Information:
No publications provided

Responsible Party: Oliver G. Ottmann, Dr. med., Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT01724879     History of Changes
Other Study ID Numbers: GMALL-PH-01, 2010-022854-18
Study First Received: February 3, 2012
Last Updated: November 7, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Johann Wolfgang Goethe University Hospitals:
philadelphia chromosome
BCR-ABL
ALL
acute lymphoblastic leukemia
dasatinib
Sprycel

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Philadelphia Chromosome
Abnormal Karyotype
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014