Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00372593
First received: September 6, 2006
Last updated: March 10, 2016
Last verified: March 2016
Results First Received: January 6, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukemia
Interventions: Drug: asparaginase
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: etoposide
Drug: gemtuzumab ozogamicin
Drug: mitoxantrone hydrochloride

  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
No text entered.

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
Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, & 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of gemtuzumab ozogamicin (GMTZ) (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.

Participant Flow:   Overall Study
    Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome     Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome     Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome  
STARTED     531     532     7  
COMPLETED     327     334     3  
NOT COMPLETED     204     198     4  
Adverse Event                 43                 45                 0  
Death                 16                 20                 1  
Lack of Efficacy                 82                 71                 2  
Lost to Follow-up                 1                 0                 0  
Physician Decision                 42                 41                 0  
Ineligible                 20                 21                 1  



  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
Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, & 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Total Total of all reporting groups

Baseline Measures
    Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome     Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome     Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome     Total  
Number of Participants  
[units: participants]
  531     532     7     1070  
Age  
[units: days]
Mean (Standard Deviation)
  3352.86  (2336.55)     3466  (2283.45)     4206.71  (1979.95)     3409.43  (2310)  
Age  
[units: participants]
       
<=18 years     516     510     7     1033  
Between 18 and 65 years     15     22     0     37  
>=65 years     0     0     0     0  
Gender  
[units: participants]
       
Female     260     277     4     541  
Male     271     255     3     529  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     3     1     0     4  
Asian     28     24     0     52  
Native Hawaiian or Other Pacific Islander     1     1     0     2  
Black or African American     62     58     2     122  
White     383     394     5     782  
More than one race     0     0     0     0  
Unknown or Not Reported     54     54     0     108  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     100     97     0     197  
Not Hispanic or Latino     411     416     7     834  
Unknown or Not Reported     20     19     0     39  
Region of Enrollment  
[units: participants]
       
United States     473     480     5     958  
Canada     34     32     2     68  
Australia     19     15     0     34  
Switzerland     1     0     0     1  
New Zealand     4     5     0     9  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Event-free Survival at 3 Years   [ Time Frame: Time from study entry to time of induction failure, relapse, or death, assessed at 3 years ]

2.  Primary:   Overall Survival at 3 Years   [ Time Frame: Time from study entry, assessed at 3 years ]

3.  Secondary:   Remission Induction Rate After 2 Courses of Induction Therapy   [ Time Frame: After 2 courses of induction (I and II) therapy, assessed for up to 10 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Disease-free Survival   [ Time Frame: Time from the end of course 3 (Intensification I) to death or relapse; assessed for up to 10 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

5.  Secondary:   Mortality   [ Time Frame: During the first three courses of therapy ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

6.  Secondary:   Time to Marrow Recovery   [ Time Frame: At 25 days after treatment with Induction I, Induction II, and Intensification I ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

7.  Secondary:   Toxicities, Including Infectious Complications   [ Time Frame: From the time therapy is initiated, assessed up to 10 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
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.


Results Point of Contact:  
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
phone: 626-447-0064
e-mail: resultsreportingcoordinator@childrensoncologygroup.org


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

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00372593     History of Changes
Other Study ID Numbers: AAML0531
COG-AAML0531 ( Other Identifier: Children's Oncology Group )
CDR0000487497 ( Other Identifier: Clinical Trials.gov )
Study First Received: September 6, 2006
Results First Received: January 6, 2015
Last Updated: March 10, 2016
Health Authority: United States: Federal Government