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

Primary Purpose

Philadelphia Positive Acute Lymphoblastic Leukemia

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Dasatinib
Sponsored by
Goethe University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Philadelphia Positive Acute Lymphoblastic Leukemia focused on measuring philadelphia chromosome, BCR-ABL, ALL, acute lymphoblastic leukemia, dasatinib, Sprycel

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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.

Sites / Locations

  • Robert Bosch Krankenhaus
  • Klinikum der Universität Regensburg
  • University Hospital of Frankfurt, Medical Dept. II
  • Medizinische Hochschule Hannover
  • Universitätsklinikum Essen
  • Universitätsklinik Münster
  • Universitätsklinik Dresden
  • Uniklinik Aachen
  • Charité Universitätsmedizin Berlin
  • University Hospital Düsseldorf
  • Universitätsklinikum Göttingen
  • Asklepios Klinik St. Georg
  • Universitätsklinik Köln
  • Universität Leipzig, José-Carreras-Haus
  • Universitätskliniken Mainz
  • Klinikum Mannheim
  • Universitätsklinikum Großhadern
  • Klinikum Nürnberg Nord
  • Klinikum Oldenburg
  • Universität Rostock
  • Medizinische Universitätsklinik Ulm
  • Medizinische Poliklinik der Universität Würzburg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dasatinib and chemotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

Treatment-related discontinuation of study treatment (Proportion of Patients)

Secondary Outcome Measures

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

Full Information

First Posted
February 3, 2012
Last Updated
January 10, 2022
Sponsor
Goethe University
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1. Study Identification

Unique Protocol Identification Number
NCT01724879
Brief Title
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

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Goethe University

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Philadelphia Positive Acute Lymphoblastic Leukemia
Keywords
philadelphia chromosome, BCR-ABL, ALL, acute lymphoblastic leukemia, dasatinib, Sprycel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dasatinib and chemotherapy
Arm Type
Experimental
Arm Description
Dasatinib, QD p.o. administration, day 1 to EOS
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
Sprycel (R), BMS-354825
Intervention Description
Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide))
Primary Outcome Measure Information:
Title
Treatment-related discontinuation of study treatment (Proportion of Patients)
Time Frame
Day 120
Secondary Outcome Measure Information:
Title
Molecular complete remission rate (CR)
Time Frame
Day 120
Title
Hematologic complete remission rate
Time Frame
Day 120
Title
Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3
Time Frame
Day 120

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicola Gökbuget, Dr.med
Organizational Affiliation
Johann Wolfgang Goethe University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Robert Bosch Krankenhaus
City
Stuttgart
State/Province
Baden-Württemberg
ZIP/Postal Code
70376
Country
Germany
Facility Name
Klinikum der Universität Regensburg
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93042
Country
Germany
Facility Name
University Hospital of Frankfurt, Medical Dept. II
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
State/Province
NRW
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitätsklinik Münster
City
Münster
State/Province
NRW
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universitätsklinik Dresden
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
Uniklinik Aachen
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
University Hospital Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Universitätsklinikum Göttingen
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Asklepios Klinik St. Georg
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Universitätsklinik Köln
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universität Leipzig, José-Carreras-Haus
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universitätskliniken Mainz
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Klinikum Mannheim
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Universitätsklinikum Großhadern
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Klinikum Nürnberg Nord
City
Nürnberg
ZIP/Postal Code
90419
Country
Germany
Facility Name
Klinikum Oldenburg
City
Oldenburg
ZIP/Postal Code
26133
Country
Germany
Facility Name
Universität Rostock
City
Rostock
ZIP/Postal Code
18055
Country
Germany
Facility Name
Medizinische Universitätsklinik Ulm
City
Ulm
ZIP/Postal Code
89070
Country
Germany
Facility Name
Medizinische Poliklinik der Universität Würzburg
City
Würzburg
ZIP/Postal Code
97070
Country
Germany

12. IPD Sharing Statement

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

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