<clinical_study>
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  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01724879</url>
  </required_header>
  <id_info>
    <org_study_id>GMALL-PH-01</org_study_id>
    <secondary_id>2010-022854-18</secondary_id>
    <nct_id>NCT01724879</nct_id>
  </id_info>
  <brief_title>Study of Frontline Dasatinib Plus Chemotherapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)</brief_title>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Goethe University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Goethe University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current standard treatment approach for young patients with Positive Acute Lymphoblastic&#xD;
      Leukemia (Ph+ALL) is the combination of a chemotherapy protocol employing four to five&#xD;
      cytotoxic agents typically used for ALL together with imatinib. It is recommended to propose&#xD;
      allogeneic Standard Induction and Consolidation Therapy (SCT) to all eligible patients with a&#xD;
      suitable donor and to continue imatinib with or without additional therapy in patients not&#xD;
      undergoing SCT.&#xD;
&#xD;
      This protocol is a study for newly diagnosed Philadelphia chromosome positive acute&#xD;
      lymphoblastic leukemia in patients aged 18 to 55 years.&#xD;
&#xD;
      The objective of this strategy is to improve the overall results in the treatment of adult&#xD;
      ALL with the addition of specific molecules to the common chemotherapeutic schedule.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the present study, the potent ABL tyrosine kinase inhibitor, Dasatinib will be added to&#xD;
      standard induction and consolidation chemotherapy for the Philadelphia positive chromosome&#xD;
      sub-group of ALL patients aged 18 to 55 years.&#xD;
&#xD;
      The Study hypothesis is, that Dasatinib in combination with standard chemotherapy according&#xD;
      to GMALL protocol 07/2003 is feasible and induces cytologic and molecular remission rates&#xD;
      comparable to chemotherapy in combination with imatinib without increased treatment-related&#xD;
      mortality.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2011</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment-related discontinuation of study treatment (Proportion of Patients)</measure>
    <time_frame>Day 120</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Molecular complete remission rate (CR)</measure>
    <time_frame>Day 120</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic complete remission rate</measure>
    <time_frame>Day 120</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3</measure>
    <time_frame>Day 120</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Philadelphia Positive Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>Dasatinib and chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dasatinib, QD p.o. administration, day 1 to EOS</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dasatinib</intervention_name>
    <description>Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide))</description>
    <arm_group_label>Dasatinib and chemotherapy</arm_group_label>
    <other_name>Sprycel (R)</other_name>
    <other_name>BMS-354825</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed new diagnosis of Philadelphia chromosome or BCR-ABL positive acute&#xD;
             lymphoblastic leukemia&#xD;
&#xD;
          -  Male or female patients aged 18-55 years&#xD;
&#xD;
          -  Not previously treated except for prephase (corticosteroids, cyclophosphamide, single&#xD;
             dose VCR will be permitted) therapy during establishment of the diagnosis&#xD;
&#xD;
          -  Signed written inform consent, willingness and ability to comply with all study&#xD;
             procedures&#xD;
&#xD;
          -  Molecular detection of BCR-ABL transcripts&#xD;
&#xD;
          -  Willingness of women of child-bearing potential (WOCBP) and male subjects whose sexual&#xD;
             partners are WOCBP, to use an effective form of contraception (pearl index &lt; 1%), such&#xD;
             as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal&#xD;
             hormone ring, transdermal contraceptive patch, contraceptive implant or depot&#xD;
             contraceptive injection in combination with a second method of contraception like a&#xD;
             condom or a cervical cap / diaphragm with spermicide or surgical sterilisation&#xD;
             (vasectomy) in male patients or male partners during the study and at least 6 months&#xD;
             thereafter. WOCBP are defined as sexually mature women who have not undergone a&#xD;
             hysterectomy or surgical sterilization or who have not been naturally postmenopausal&#xD;
             for at least 12 consecutive months (i.e., who has had menses any time in the preceding&#xD;
             12 consecutive months).&#xD;
&#xD;
          -  Negative pregnancy test for women of child-bearing potential.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with ECOG status &gt; 2&#xD;
&#xD;
          -  Patients with QTcF &gt; 470 ms&#xD;
&#xD;
          -  Cardiac insufficiency NYHA grade III/IV, LEVF &lt; 50%, myocardial infarction within the&#xD;
             past 6 months prior to study&#xD;
&#xD;
          -  Active secondary malignancy requiring treatment&#xD;
&#xD;
          -  Patients with active, uncontrolled bacterial, viral or fungal infection&#xD;
&#xD;
          -  Known infection with HIV, Hepatitis B (except post vaccinal profile) or C&#xD;
&#xD;
          -  Inadequate hepatic functions defined as ASAT or ALAT &gt; 2,5 times the institutional&#xD;
             upper limit of normal and total bilirubin &gt; 2 fold the institutional upper limit&#xD;
             unless considered to be due to organ involvement by the leukemia&#xD;
&#xD;
          -  Concurrent severe diseases which exclude the administration of therapy&#xD;
&#xD;
          -  Expected non-compliance or inability to understand informed consent&#xD;
&#xD;
          -  Female patients who are pregnant or breast feeding&#xD;
&#xD;
          -  Treatment with other investigational antileukemic agents after informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicola Gökbuget, Dr.med</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johann Wolfgang Goethe University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Robert Bosch Krankenhaus</name>
      <address>
        <city>Stuttgart</city>
        <state>Baden-Württemberg</state>
        <zip>70376</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universität Regensburg</name>
      <address>
        <city>Regensburg</city>
        <state>Bayern</state>
        <zip>93042</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Frankfurt, Medical Dept. II</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen</name>
      <address>
        <city>Essen</city>
        <state>NRW</state>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik Münster</name>
      <address>
        <city>Münster</city>
        <state>NRW</state>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik Dresden</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinik Aachen</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Düsseldorf</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Göttingen</name>
      <address>
        <city>Göttingen</city>
        <zip>37075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asklepios Klinik St. Georg</name>
      <address>
        <city>Hamburg</city>
        <zip>20099</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik Köln</name>
      <address>
        <city>Köln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universität Leipzig, José-Carreras-Haus</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätskliniken Mainz</name>
      <address>
        <city>Mainz</city>
        <zip>55101</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Mannheim</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Großhadern</name>
      <address>
        <city>München</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Nürnberg Nord</name>
      <address>
        <city>Nürnberg</city>
        <zip>90419</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Oldenburg</name>
      <address>
        <city>Oldenburg</city>
        <zip>26133</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universität Rostock</name>
      <address>
        <city>Rostock</city>
        <zip>18055</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universitätsklinik Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89070</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Poliklinik der Universität Würzburg</name>
      <address>
        <city>Würzburg</city>
        <zip>97070</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>February 3, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>January 10, 2022</last_update_submitted>
  <last_update_submitted_qc>January 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Goethe University</investigator_affiliation>
    <investigator_full_name>Nicola Goekbuget</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>philadelphia chromosome</keyword>
  <keyword>BCR-ABL</keyword>
  <keyword>ALL</keyword>
  <keyword>acute lymphoblastic leukemia</keyword>
  <keyword>dasatinib</keyword>
  <keyword>Sprycel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Philadelphia Chromosome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dasatinib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01724879
org study id: GMALL-PH-01
secondary id: 2010-022854-18
nct id: NCT01724879
lead sponsor: 
has dmc: Yes
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Treatment-related discontinuation of study treatment (Proportion of Patients)
time frame: Day 120
measure: Molecular complete remission rate (CR)
time frame: Day 120
measure: Hematologic complete remission rate
time frame: Day 120
measure: Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3
time frame: Day 120
arm group label: Dasatinib and chemotherapy
arm group type: Experimental
description: Dasatinib, QD p.o. administration, day 1 to EOS
intervention type: Drug
intervention name: Dasatinib
description: Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide))
arm group label: Dasatinib and chemotherapy
other name: Sprycel (R)
other name: BMS-354825
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Nicola Gökbuget, Dr.med
role: Principal Investigator
affiliation: Johann Wolfgang Goethe University Hospital
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country: Germany
responsible party type: Principal Investigator
investigator affiliation: Goethe University
investigator full name: Nicola Goekbuget
investigator title: MD
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Philadelphia Chromosome
mesh term: Dasatinib