Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00136084
First received: August 24, 2005
Last updated: November 2, 2012
Last verified: November 2012
Results First Received: March 5, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukemia, Myelocytic, Acute
Interventions: Drug: Cladribine, Cyclophosphamide, Cytarabine, Daunorubicin, Dexamethasone
Drug: Etoposide, Cytarabine, Gemtuzumab, L-asparaginase, Mercaptopurine, methotrexate, Mitoxantrone, Prednisone, Vincristine

  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
238 patients were recruited between October, 2002 and June, 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
238 patients were enrolled on the study. This report is based on results for 223 patients. 15 patients were excluded for the following reasons: 7 were switched to lymphoid-directed therapy shortly after enrollment, 6 were determined to be ineligible shortly after enrollment (wrong diagnosis), and 2 were not randomized.

Reporting Groups
  Description
Arm 1: (HDAC) High-dose Cytarabine (HDAC)
Arm 2:(LDAC) Low-dose Cytarabine (LDAC)

Participant Flow:   Overall Study
    Arm 1: (HDAC)     Arm 2:(LDAC)  
STARTED     109     114  
COMPLETED     61     72  
NOT COMPLETED     48     42  
Death                 12                 5  
Unacceptable toxicity                 8                 11  
Relapse                 20                 23  
Lost to Follow-up                 2                 0  
No Response                 1                 2  
Withdrawal by Subject                 5                 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 1: (HDAC) High-dose Cytarabine (HDAC)
Arm 2:(LDAC) Low-dose Cytarabine (LDAC)
Total Total of all reporting groups

Baseline Measures
    Arm 1: (HDAC)     Arm 2:(LDAC)     Total  
Number of Participants  
[units: participants]
  109     114     223  
Age  
[units: years]
Mean ± Standard Deviation
  8.57  ± 6.08     8.48  ± 6.32     8.49  ± 6.19  
Gender  
[units: participants]
     
Female     50     48     98  
Male     59     66     125  



  Outcome Measures
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1.  Primary:   Minimal Residual Disease (MRD).   [ Time Frame: Day 22 MRD measurement ]

2.  Secondary:   Proportion of Minimal Residual Disease (MRD)+ Patients Who Become MRD- After One Course of Gemtuzumab Ozogamicin (GO)   [ Time Frame: Consolidation I ]

3.  Secondary:   Proportion of MRD Reduction After One Course of Cytarabine + Daunomycin + Etoposide (ADE) + GO   [ Time Frame: Induction II ]

4.  Secondary:   Proportion of Patients Experienced Toxicity of Cytarabine + Daunomycin + Etoposide (ADE) + GO.   [ Time Frame: Induction II ]

5.  Secondary:   To Estimate the Overall Event-free Survival (EFS) of AML Patients Who Undergo Risk-adapted and Genotype-directed Therapy   [ Time Frame: Five Year ]

6.  Secondary:   To Assess Whether Inhibition of DNA Synthesis is Greater After High-dose Ara-C (HDAC) Than After Low-dose Ara-C (LDAC) Therapy   [ Time Frame: Measurements were assessed in Induction I chemotherapy ]

7.  Secondary:   Relationship of Inhibition of DNA Synthesis and Clinical Response   [ Time Frame: Measurements were assessed in Induction I chemotherapy ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Relationship of Inhibition of DNA Synthesis and Clinical Response
Measure Description Clinical response is defined as MRD (minimal residual disease) measured by flow cytometry at day 22. The MRD at day 22 is classified as positive (with MRD) or negative (no detectable MRD). The relation between inhibition of DNA synthesis and MRD was performed by logistic regression. In the model, logit of probability of MRD positive was regressed on inhibition of DNA synthesis.
Time Frame Measurements were assessed in Induction I chemotherapy  
Safety Issue No  

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.
Of 232 eligible patients, 49 had DNA synthesis rate performed prior to araC treatment. Of the 49 patients, 23 had no 24-hr samples and 3 did not have enough cells in 24-hr samples. 21 patients with both pre and post araC samples were included in the DNA inhibition study. 17 of the 21 patients had evaluable day 22 MRD.

Reporting Groups
  Description
Overall 17 of the 232 eligible patients

Measured Values
    Overall  
Number of Participants Analyzed  
[units: participants]
  17  
Relationship of Inhibition of DNA Synthesis and Clinical Response  
[units: Percent inhibition of DNA Synthesis]
Mean ± Standard Error
  66.7  ± 12.6  


Statistical Analysis 1 for Relationship of Inhibition of DNA Synthesis and Clinical Response
Groups [1] Overall
Method [2] Regression, Logistic
P Value [3] 0.2287
Odds Ratio, log [4] -0.0139
95% Confidence Interval ( -0.0365 to 0.00873 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
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  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


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.  


Results Point of Contact:  
Name/Title: Jeffrey Rubnitz, M.D
Organization: St. Jude Children's Research Hospital
phone: 1-866-278-5833
e-mail: info@stjude.org


No publications provided by St. Jude Children's Research Hospital

Publications automatically indexed to this study:

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00136084     History of Changes
Other Study ID Numbers: AML02, 5R01CA113482
Study First Received: August 24, 2005
Results First Received: March 5, 2010
Last Updated: November 2, 2012
Health Authority: United States: Institutional Review Board