<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <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/NCT01690065</url>
  </required_header>
  <id_info>
    <org_study_id>CAMN107AKR07T</org_study_id>
    <nct_id>NCT01690065</nct_id>
  </id_info>
  <brief_title>Nilotinib-Chemotherapy in CML Myeloid BP or Bcr-abl(+) AML</brief_title>
  <acronym>NICE-BORA</acronym>
  <official_title>Nilotinib Combined by Chemotherapy for Myeloid Blastic Phase of Chronic Myeloid Leukemia or Bcr-abl Positive Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ulsan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Korean Society of Hematology CML working party</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ulsan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current standard therapy in previously untreated adults with chronic phase (CP) of CML is&#xD;
      imatinib and the result of long-term follow-up of IRIS study proves that imatinib for CML CP&#xD;
      is reasonable therapy.(1, 2) However, some patients were initially diagnosed as advanced CML,&#xD;
      accelerated phase (AP) or blastic phase (BP). Various chemotherapies were tried and were&#xD;
      found that there were no highly effective chemotherapies for CML BP.(3-11) Imatinib in&#xD;
      patients with these advanced CML is also disappointing because of low response rates as well&#xD;
      as short response duration, and sudden transformation to BC is found even in initial CML CP&#xD;
      patients. (12-17). Recent studies showed that nilotinib or dasatinib is better than imatinib&#xD;
      in terms of rapid response and higher molecular response in newly diagnosed CML&#xD;
      patients.(18-21) More potent bcr-abl suppression of nilotinib is supposed to be more active&#xD;
      than imatinib even in patients with advanced CML. However, nilotinib in patients with&#xD;
      imatinib-resistant or -intolerant CML BP showed low hematologic response and major&#xD;
      cytogenetic response.(22, 23)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. IMATINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE ACUTE LYMPHOBLASTIC&#xD;
           LYMPHOMA (PH+ ALL) The trials combining imatinib with high-dose chemotherapy were&#xD;
           successfully resulting in high response rate and longer survival and a role for bridging&#xD;
           therapy to allogeneic hematopoietic stem cell transplantation (alloHSCT) by means of&#xD;
           concurrent or alternating regimen in patients with Philadelphia-positive (Ph+) acute&#xD;
           lymphoblastic leukemia (ALL).(24-29) Current combination therapy of imatinib and&#xD;
           chemotherapy became standard therapy of Ph+ ALL and new 2nd generation TKIs are&#xD;
           investigating. These experiences may be translated into the treatment of CML BP.&#xD;
&#xD;
        2. HIGH-DOSE DAUNORUBICIN IN ACUTE MYELOID LEUKEMIA (AML) INDUCTION CHEMOTHERAPY Two&#xD;
           recently published papers of randomized trials comparing standard dose daunorubicin (45&#xD;
           mg/m2 for 3 days) and high dose daunorubicin (90 mg/m2 for 3 days) demonstrated improved&#xD;
           CR rate and survival with high dose daunorubicin in younger (60 years or younger) and&#xD;
           older (over 60 years) patients, respectively.(30, 31) Therefore high-dose daunorubicin&#xD;
           can be applied safely and effectively to the treatment of CML BP.&#xD;
&#xD;
        3. NILOTINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE CML MYELOID BLASTIC PHASE&#xD;
           (MBP) OR PHYLADELPHIA POSITIVE AML We will try 2nd generation TKI, nilotinib and&#xD;
           high-dose daunorubicin induction chemotherapy combination to find out the combination&#xD;
           therapy can improve response rate and survival in patients with CML MBP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">September 2019</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>Complete remission rate</measure>
    <time_frame>Within 8 weeks after induction therapy</time_frame>
    <description>Primary purpose of this study is to define the efficacy of combined chemotherapy and nilotinib in chronic myeloid leukemia (CML) myeloid blastic phase (MBP) and bcr-abl positive acute myeloid leukemia (AML). The efficacy will be evaluated by complete remission (CR) rate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>Within 8 weeks after induction therapy</time_frame>
    <description>This study will also evaluate the safety of nilotinib and chemotherapy combination therapy.&#xD;
CTCAE ver. 4.03 will be used for safety measurement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time-dependent variables</measure>
    <time_frame>at least 2 years</time_frame>
    <description>• This study will evaluate the impacts of nilotinib combined with chemotherapy on duration of CR, relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">46</enrollment>
  <condition>Chronic Myeloid Leukemia in Myeloid Blast Crisis</condition>
  <condition>Untreated Adult Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Nilotinib+AD induction</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nilotinib plus AD induction chemotherapy&#xD;
AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days (D 1-7) plus Daunorubicin 90 mg/m2/day iv daily for 3 days (D 1-3)&#xD;
Nilotinib 400mg bid PO (continuous without interruption from D8 of induction chemotherapy)&#xD;
Re-induction chemotherapy AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 5 days (D 1-5) plus Daunorubicin 45 mg/m2/day iv daily for 2 days (D 1-2)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nilotinib+AD induction</intervention_name>
    <description>• Post-remission consolidation chemotherapy&#xD;
4 courses of high-dose cytarabine will be given as post-remission therapy. Cytarabine 3 g/m2 will be administered in a 3-hour iv infusion every 12 hours on days 1, 3, and 5 (a total of six doses per course).&#xD;
Nilotinib 400mg bid PO will be administered continuously during consolidation chemotherapy and for 2 years after the consolidation therapy or until allogeneic hematopoietic stem cell transplantation</description>
    <arm_group_label>Nilotinib+AD induction</arm_group_label>
    <other_name>Tasigna</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with previously-untreated patients having bcr-abl gene rearrangement (or&#xD;
             t(9;22)) and 20% or more of myeloid blasts in bone marrow and/or blood, or converted&#xD;
             CML CP/AP to MBP after initial imatinib treatment.&#xD;
&#xD;
          -  15 years old or older, but 65 years or younger&#xD;
&#xD;
          -  Adequate performance status (Karnofsky score of 50 or more)&#xD;
&#xD;
          -  Adequate hepatic and renal function (AST, ALT, bilirubin and creatinine &lt; 2.5 x upper&#xD;
             normal limit). Elevation of AST or ALT due to hepatic infiltration of leukemic cells&#xD;
             will be permitted.&#xD;
&#xD;
          -  Adequate cardiac function (left ventricular ejection fraction of 45% or more on heart&#xD;
             scan or echocardiogram)&#xD;
&#xD;
          -  Signed and dated informed consent must be obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients without bcr-abl gene rearrangement&#xD;
&#xD;
          -  Acute lymphoblastic leukemia with bcr-abl gene rearrangement or t(9;22)&#xD;
&#xD;
          -  Any previous history of TKIs except for imatinib in CML CP.&#xD;
&#xD;
          -  Therapy-related leukemia or leukemia after myelodysplastic syndrome.&#xD;
&#xD;
          -  Patients with CNS leukemia&#xD;
&#xD;
          -  Patients with primary granulocytic sarcoma without bone marrow involvement&#xD;
&#xD;
          -  Prior chemotherapy for leukemia or anthracycline treatment for any malignancy.&#xD;
             Hydroxyurea for reduction of leukemic cell burden before induction chemotherapy will&#xD;
             be permitted.&#xD;
&#xD;
          -  Presence of significant active infection&#xD;
&#xD;
          -  Presence of uncontrolled bleeding&#xD;
&#xD;
          -  Significant cardiovascular disease including myocardial infarction within previous 6&#xD;
             months&#xD;
&#xD;
          -  Cardiac dysfunction: LVEF &lt; 45% or institutional lower normal range (any higher value&#xD;
             of them) by echocardiogram or MUGA scan; Long QT syndrome or its family history;&#xD;
             Clinically significant resting bradycardia (&lt;50 beats/minute); QTc &gt; 450 msec (by QTcF&#xD;
             formula) on baseline ECG . If QTcF &gt; 450 msec and electrolytes are abnormal, retest&#xD;
             QTc after the correction of electrolytes; Myocardial infarction within 12 months;&#xD;
             Other clinically significant cardiac diseases (for example, unstable angina,&#xD;
             congestive heart failure, uncontrolled hypertension or uncontrolled arrhythmia)&#xD;
&#xD;
          -  Chronic or acute hepatic disease, pancreatic disease or severe renal disease&#xD;
&#xD;
          -  Severe or life-threatening other medical conditions&#xD;
&#xD;
          -  Any coexisting major illness or organ failure&#xD;
&#xD;
          -  Patients with psychiatric disorder or mental deficiency severe as to make compliance&#xD;
             with the treatment unlike, and making informed consent impossible History of&#xD;
             congenital or acquired coagulopathy unrelated to malignancy&#xD;
&#xD;
          -  Pregnancy issues: (a) pregnant woman, (b) lactating woman, (c) reproductive woman who&#xD;
             does not confirm negative baseline pregnancy test (d) man or reproductive woman who&#xD;
             cannot continue an appropriate contraceptive method (postmenopausal woman who has no&#xD;
             menstruation for last 12 months is considered as non-reproductive)&#xD;
&#xD;
          -  Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years&#xD;
             following therapy with curative intent (except curatively treated nonmelanoma skin&#xD;
             cancer, in situ carcinoma, or cervical intraepithelial neoplasia)&#xD;
&#xD;
          -  History of non-compliance or patient who cannot sign informed consent&#xD;
&#xD;
          -  Hypersensitivity to nilotinib or any of the experience&#xD;
&#xD;
          -  Concurrent medications (Gastrointestinal dysfunction that can significantly change the&#xD;
             absorption of test drug; - Strong CYP3A4 inhibitor and cannot stop or change the&#xD;
             medication before starting study; Medication to prolong QT interval and cannot stop or&#xD;
             change the medication before starting study) • The capsules contain lactose, and&#xD;
             nilotinib is therefore not recommended for patients with rare hereditary problems of&#xD;
             galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hawk Kim, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ulsan University Hospital, University of Ulsan College of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hawk Kim, M.D., Ph.D.</last_name>
    <phone>+82-52-250-8892</phone>
    <email>kimhawkmd@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Min Jung Kim, R.N.</last_name>
    <phone>+82-52-250-8515</phone>
    <email>enael@nate.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Seoul St Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dong-Wook Kim, M.D., Ph.D.</last_name>
      <email>dwkim@catholic.ac.kr</email>
    </contact>
    <investigator>
      <last_name>Dong-Wook Kim, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ulsan University Hospital</name>
      <address>
        <city>Ulsan</city>
        <zip>682714</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Hawk Kim, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jae-Hoo Park, M.D., Ph.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jae-Cheol Jo, M.D., Ph.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
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    <citation>Rea D, Legros L, Raffoux E, Thomas X, Turlure P, Maury S, Dupriez B, Pigneux A, Choufi B, Reman O, Stephane D, Royer B, Vigier M, Ojeda-Uribe M, Recher C, Dombret H, Huguet F, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chronique; Group for Research in Adult Acute Lymphoblastic Leukemia. High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia. Leukemia. 2006 Mar;20(3):400-3. doi: 10.1038/sj.leu.2404115.</citation>
    <PMID>16437142</PMID>
  </reference>
  <reference>
    <citation>Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun 15;103(12):4396-407. doi: 10.1182/blood-2003-08-2958. Epub 2003 Oct 9.</citation>
    <PMID>14551133</PMID>
  </reference>
  <reference>
    <citation>Wassmann B, Pfeifer H, Goekbuget N, Beelen DW, Beck J, Stelljes M, Bornhauser M, Reichle A, Perz J, Haas R, Ganser A, Schmid M, Kanz L, Lenz G, Kaufmann M, Binckebanck A, Bruck P, Reutzel R, Gschaidmeier H, Schwartz S, Hoelzer D, Ottmann OG. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2006 Sep 1;108(5):1469-77. doi: 10.1182/blood-2005-11-4386. Epub 2006 Apr 25.</citation>
    <PMID>16638934</PMID>
  </reference>
  <reference>
    <citation>Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. doi: 10.1056/NEJMoa0904544.</citation>
    <PMID>19776406</PMID>
  </reference>
  <reference>
    <citation>Lowenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Dohner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. doi: 10.1056/NEJMoa0901409. Erratum In: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text.</citation>
    <PMID>19776405</PMID>
  </reference>
  <reference>
    <citation>Wassmann B, Pfeifer H, Stadler M, Bornhauser M, Bug G, Scheuring UJ, Bruck P, Stelljes M, Schwerdtfeger R, Basara N, Perz J, Bunjes D, Ledderose G, Mahlberg R, Binckebanck A, Gschaidmeier H, Hoelzer D, Ottmann OG. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005 Jul 15;106(2):458-63. doi: 10.1182/blood-2004-05-1746. Epub 2005 Apr 7.</citation>
    <PMID>15817679</PMID>
  </reference>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>May 10, 2016</last_update_submitted>
  <last_update_submitted_qc>May 10, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 11, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ulsan University Hospital</investigator_affiliation>
    <investigator_full_name>Hawk Kim</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>chronic myeloid leukemia</keyword>
  <keyword>myeloid blastic phase</keyword>
  <keyword>bcr-abl(+) acute myeloid leukemia</keyword>
  <keyword>nilotinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Blast Crisis</mesh_term>
  </condition_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/NCT01690065
org study id: CAMN107AKR07T
nct id: NCT01690065
lead sponsor: 
collaborator: 
has dmc: No
The current standard therapy in previously untreated adults with chronic phase (CP) of CML is
      imatinib and the result of long-term follow-up of IRIS study proves that imatinib for CML CP
      is reasonable therapy.(1, 2) However, some patients were initially diagnosed as advanced CML,
      accelerated phase (AP) or blastic phase (BP). Various chemotherapies were tried and were
      found that there were no highly effective chemotherapies for CML BP.(3-11) Imatinib in
      patients with these advanced CML is also disappointing because of low response rates as well
      as short response duration, and sudden transformation to BC is found even in initial CML CP
      patients. (12-17). Recent studies showed that nilotinib or dasatinib is better than imatinib
      in terms of rapid response and higher molecular response in newly diagnosed CML
      patients.(18-21) More potent bcr-abl suppression of nilotinib is supposed to be more active
      than imatinib even in patients with advanced CML. However, nilotinib in patients with
      imatinib-resistant or -intolerant CML BP showed low hematologic response and major
      cytogenetic response.(22, 23)
1. IMATINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE ACUTE LYMPHOBLASTIC
           LYMPHOMA (PH+ ALL) The trials combining imatinib with high-dose chemotherapy were
           successfully resulting in high response rate and longer survival and a role for bridging
           therapy to allogeneic hematopoietic stem cell transplantation (alloHSCT) by means of
           concurrent or alternating regimen in patients with Philadelphia-positive (Ph+) acute
           lymphoblastic leukemia (ALL).(24-29) Current combination therapy of imatinib and
           chemotherapy became standard therapy of Ph+ ALL and new 2nd generation TKIs are
           investigating. These experiences may be translated into the treatment of CML BP.

        2. HIGH-DOSE DAUNORUBICIN IN ACUTE MYELOID LEUKEMIA (AML) INDUCTION CHEMOTHERAPY Two
           recently published papers of randomized trials comparing standard dose daunorubicin (45
           mg/m2 for 3 days) and high dose daunorubicin (90 mg/m2 for 3 days) demonstrated improved
           CR rate and survival with high dose daunorubicin in younger (60 years or younger) and
           older (over 60 years) patients, respectively.(30, 31) Therefore high-dose daunorubicin
           can be applied safely and effectively to the treatment of CML BP.

        3. NILOTINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE CML MYELOID BLASTIC PHASE
           (MBP) OR PHYLADELPHIA POSITIVE AML We will try 2nd generation TKI, nilotinib and
           high-dose daunorubicin induction chemotherapy combination to find out the combination
           therapy can improve response rate and survival in patients with CML MBP.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete remission rate
time frame: Within 8 weeks after induction therapy
description: Primary purpose of this study is to define the efficacy of combined chemotherapy and nilotinib in chronic myeloid leukemia (CML) myeloid blastic phase (MBP) and bcr-abl positive acute myeloid leukemia (AML). The efficacy will be evaluated by complete remission (CR) rate.
measure: Safety
time frame: Within 8 weeks after induction therapy
description: This study will also evaluate the safety of nilotinib and chemotherapy combination therapy.
CTCAE ver. 4.03 will be used for safety measurement.
measure: Time-dependent variables
time frame: at least 2 years
description: • This study will evaluate the impacts of nilotinib combined with chemotherapy on duration of CR, relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS).
arm group label: Nilotinib+AD induction
arm group type: Experimental
description: Nilotinib plus AD induction chemotherapy
AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days (D 1-7) plus Daunorubicin 90 mg/m2/day iv daily for 3 days (D 1-3)
Nilotinib 400mg bid PO (continuous without interruption from D8 of induction chemotherapy)
Re-induction chemotherapy AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 5 days (D 1-5) plus Daunorubicin 45 mg/m2/day iv daily for 2 days (D 1-2)
intervention type: Drug
intervention name: Nilotinib+AD induction
description: • Post-remission consolidation chemotherapy
4 courses of high-dose cytarabine will be given as post-remission therapy. Cytarabine 3 g/m2 will be administered in a 3-hour iv infusion every 12 hours on days 1, 3, and 5 (a total of six doses per course).
Nilotinib 400mg bid PO will be administered continuously during consolidation chemotherapy and for 2 years after the consolidation therapy or until allogeneic hematopoietic stem cell transplantation
arm group label: Nilotinib+AD induction
other name: Tasigna
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Hawk Kim, M.D., Ph.D.
role: Principal Investigator
affiliation: Ulsan University Hospital, University of Ulsan College of Medicine
last name: Hawk Kim, M.D., Ph.D.
phone: +82-52-250-8892
email: kimhawkmd@gmail.com
last name: Min Jung Kim, R.N.
phone: +82-52-250-8515
email: enael@nate.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
investigator: 
investigator: 
country: Korea, Republic of
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citation: Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, Capucci A, Cedrone M, Fava C, Intermesoli T, Cambrin GR, Stagno F, Tiribelli M, Amabile M, Luatti S, Poerio A, Soverini S, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M; GIMEMA CML Working Party. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood. 2009 Dec 3;114(24):4933-8. doi: 10.1182/blood-2009-07-232595. Epub 2009 Oct 12.
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citation: Fava C, Kantarjian HM, Jabbour E, O'Brien S, Jain N, Rios MB, Garcia-Manero G, Ravandi F, Verstovsek S, Borthakur G, Shan J, Cortes J. Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase. Blood. 2009 May 21;113(21):5058-63. doi: 10.1182/blood-2008-10-184960. Epub 2009 Mar 12.
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citation: Rea D, Legros L, Raffoux E, Thomas X, Turlure P, Maury S, Dupriez B, Pigneux A, Choufi B, Reman O, Stephane D, Royer B, Vigier M, Ojeda-Uribe M, Recher C, Dombret H, Huguet F, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chronique; Group for Research in Adult Acute Lymphoblastic Leukemia. High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia. Leukemia. 2006 Mar;20(3):400-3. doi: 10.1038/sj.leu.2404115.
PMID: 16437142
citation: Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun 15;103(12):4396-407. doi: 10.1182/blood-2003-08-2958. Epub 2003 Oct 9.
PMID: 14551133
citation: Wassmann B, Pfeifer H, Goekbuget N, Beelen DW, Beck J, Stelljes M, Bornhauser M, Reichle A, Perz J, Haas R, Ganser A, Schmid M, Kanz L, Lenz G, Kaufmann M, Binckebanck A, Bruck P, Reutzel R, Gschaidmeier H, Schwartz S, Hoelzer D, Ottmann OG. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2006 Sep 1;108(5):1469-77. doi: 10.1182/blood-2005-11-4386. Epub 2006 Apr 25.
PMID: 16638934
citation: Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. doi: 10.1056/NEJMoa0904544.
PMID: 19776406
citation: Lowenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Dohner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. doi: 10.1056/NEJMoa0901409. Erratum In: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text.
PMID: 19776405
citation: Wassmann B, Pfeifer H, Stadler M, Bornhauser M, Bug G, Scheuring UJ, Bruck P, Stelljes M, Schwerdtfeger R, Basara N, Perz J, Bunjes D, Ledderose G, Mahlberg R, Binckebanck A, Gschaidmeier H, Hoelzer D, Ottmann OG. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005 Jul 15;106(2):458-63. doi: 10.1182/blood-2004-05-1746. Epub 2005 Apr 7.
PMID: 15817679
responsible party type: Principal Investigator
investigator affiliation: Ulsan University Hospital
investigator full name: Hawk Kim
investigator title: Associate Professor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Blast Crisis