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Trial record 1 of 1 for:    CALGB 10603
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Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00651261
First received: April 1, 2008
Last updated: February 6, 2017
Last verified: February 2017
Results First Received: December 12, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Participant, Investigator;   Primary Purpose: Treatment
Condition: Leukemia
Interventions: Drug: cytarabine
Drug: daunorubicin
Drug: midostaurin
Other: placebo
Drug: dexamethasone acetate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between May 2008 and October 2001, 3,277 participants were pre-registered. Of those, 900 participants had a documented FLT3 mutation. 717 participants were enrolled onto this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Induction and Consolidation Chemotherapy Plus Midostaurin Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.
Induction and Consolidation Chemotherapy Plus Placebo Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.

Participant Flow:   Overall Study
    Induction and Consolidation Chemotherapy Plus Midostaurin   Induction and Consolidation Chemotherapy Plus Placebo
STARTED   360   357 
COMPLETED   69   51 
NOT COMPLETED   291   306 
Adverse Event                32                22 
Death                18                18 
Withdrawal by Subject                22                40 
Induction failure                24                35 
Disease progression                58                58 
Alternative therapy                109                107 
Other disease or participant decisions                23                23 
Never treated                5                3 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Induction and Consolidation Chemotherapy Plus Midostaurin Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.
Induction and Consolidation Chemotherapy Plus Placebo Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Total Total of all reporting groups

Baseline Measures
   Induction and Consolidation Chemotherapy Plus Midostaurin   Induction and Consolidation Chemotherapy Plus Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 360   357   717 
Age 
[Units: Years]
Median (Full Range)
 47.1 
 (19 to 59.8) 
 48.6 
 (18 to 60.9) 
 47.9 
 (18.0 to 60.9) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      186  51.7%      212  59.4%      398  55.5% 
Male      174  48.3%      145  40.6%      319  44.5% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      9   2.5%      7   2.0%      16   2.2% 
Not Hispanic or Latino      103  28.6%      107  30.0%      210  29.3% 
Unknown or Not Reported      248  68.9%      243  68.1%      491  68.5% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      0   0.0%      1   0.3%      1   0.1% 
Asian      8   2.2%      5   1.4%      13   1.8% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      8   2.2%      9   2.5%      17   2.4% 
White      147  40.8%      128  35.9%      275  38.4% 
More than one race      2   0.6%      1   0.3%      3   0.4% 
Unknown or Not Reported      195  54.2%      213  59.7%      408  56.9% 
Region of Enrollment 
[Units: Participants]
     
Canada   4   9   13 
United States   117   106   223 
Germany   148   157   305 
Belgium   3   5   8 
France   3   2   5 
Netherlands   3   2   5 
Australia   0   2   2 
Spain   7   15   22 
Austria   7   5   12 
Italy   61   44   105 
Czech Republic   5   6   11 
Slovakia   2   2   4 
Hungary   0   2   2 
FLT3 mutational subtype [1] 
[Units: Participants]
     
TKD (No ITD)   81   81   162 
ITD Allelic ratio <0.7   171   170   341 
ITD Allelic ratio >=0.7   108   106   214 
[1] Mutations in the gene encoding the trans-membrane tyrosine kinase FLT3. FLT3 internal tandem duplications (ITD) mutation which results in a duplication between 3 and greater than 100 amino acids most commonly located in the juxtamembrane region. Tyrosine kinase domain (TKD) point mutations are the remainder of those with FLT3 mutations. FLT3 testing was done centrally.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Survival (OS)   [ Time Frame: Duration of study (Up to 10 years) ]

2.  Secondary:   Event- Free Survival   [ Time Frame: Duration of study (Up to 10 years) ]

3.  Secondary:   Overall Survival, Censoring Participants Who Receive a Stem Cell Transplant at the Time of the Transplant   [ Time Frame: Duration of study (Up to 10 years) ]

4.  Secondary:   Complete Response Rate   [ Time Frame: Induction therapy (up to 60 days) ]

5.  Secondary:   Disease-free Survival (DFS)   [ Time Frame: Duration of study (Up to 10 years) ]

6.  Secondary:   DFS Rate One Year After Completing the Planned Continuation Phase   [ Time Frame: 30 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Richard Stone, MD
Organization: Dana Farber Cancer Institute
e-mail: rstone@partners.org


Publications of Results:
Stone RM, Dohner H, Ehninger G, et al.: CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. [Abstract] J Clin Oncol 29 (Suppl 15): A-TPS199, 2011.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00651261     History of Changes
Other Study ID Numbers: CALGB-10603
EUDRACT-2006-006852-37
CDR0000590404 ( Registry Identifier: Phyisician Data Query )
Study First Received: April 1, 2008
Results First Received: December 12, 2016
Last Updated: February 6, 2017