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 ]


  Serious Adverse Events
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Time Frame Adverse events have been collected from study inception (October, 2002) through February, 2009.
Additional Description No text entered.

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

Serious Adverse Events
    Arm 1: (HDAC)     Arm 2:(LDAC)  
Total, serious adverse events      
# participants affected / at risk     23/109 (21.10%)     19/114 (16.67%)  
Blood and lymphatic system disorders      
DIC (disseminated intravascular coagulation * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Hemorrhage-Other * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Hemorrhage/bleeding associated with surgery * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Cardiac disorders      
Acute vascular leak syndrome * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Cardiac left ventricular function * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Cardiovascular/Arrhythmia-Other * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Hypertension * 1    
# participants affected / at risk     0/109 (0.00%)     0/114 (0.00%)  
# events     0     0  
Hypotension * 1    
# participants affected / at risk     2/109 (1.83%)     0/114 (0.00%)  
# events     2     0  
Peripheral arterial ischemia * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Sinus tachycardia * 1    
# participants affected / at risk     0/109 (0.00%)     2/114 (1.75%)  
# events     0     2  
Thrombosis/embolism * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Gastrointestinal disorders      
Anorexia * 1    
# participants affected / at risk     5/109 (4.59%)     3/114 (2.63%)  
# events     8     3  
Diarrhea patients without colostomy * 1    
# participants affected / at risk     0/109 (0.00%)     2/114 (1.75%)  
# events     0     2  
Gastritis * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Pancreatitis * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Typhlitis (inflammation of cecum) * 1    
# participants affected / at risk     0/109 (0.00%)     2/114 (1.75%)  
# events     0     2  
Vomiting * 1    
# participants affected / at risk     0/109 (0.00%)     2/114 (1.75%)  
# events     0     2  
Hepatobiliary disorders      
Liver dysfunction/failure (clinical) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
SGOT (AST) (serum glutamic oxaloacetic transaminase) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
SGPT (ALT) (serum glutamic pyruvic transaminase) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Infections and infestations      
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe * 1    
# participants affected / at risk     1/109 (0.92%)     4/114 (3.51%)  
# events     1     7  
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia (ANC <1.0 x 10e * 1    
# participants affected / at risk     13/109 (11.93%)     10/114 (8.77%)  
# events     19     15  
Infection with unknown ANC * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     3  
Infection without neutropenia * 1    
# participants affected / at risk     1/109 (0.92%)     1/114 (0.88%)  
# events         1  
Infection/Febrile Neutropenia-Other * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     3  
Metabolism and nutrition disorders      
Acidosis (metabolic or respiratory) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Hyperglycemia * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Hyperkalemia * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Hypernatremia * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Hypocalcemia * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Hypokalemia * 1    
# participants affected / at risk     6/109 (5.50%)     4/114 (3.51%)  
# events     8     4  
Lipase * 1    
# participants affected / at risk     2/109 (1.83%)     0/114 (0.00%)  
# events     2     0  
Nervous system disorders      
Arachnoiditis/meningismus/radiculitis * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
CNS cerebrovascular ischemia * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
CNS hemorrhage/bleeding * 1    
# participants affected / at risk     0/109 (0.00%)     2/114 (1.75%)  
# events     0     4  
Confusion * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Depressed level of consciousness * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Hallucinations * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
Seizure(s) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Renal and urinary disorders      
Renal failure * 1    
# participants affected / at risk     3/109 (2.75%)     0/114 (0.00%)  
# events     3     0  
Respiratory, thoracic and mediastinal disorders      
Adult respiratory distress syndrome (ARDS) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Dyspnea (shortness of breath) * 1    
# participants affected / at risk     1/109 (0.92%)     0/114 (0.00%)  
# events     1     0  
Hypoxia * 1    
# participants affected / at risk     1/109 (0.92%)     1/114 (0.88%)  
# events     1     1  
Pneumonitis/pulmonary infiltrates * 1    
# participants affected / at risk     3/109 (2.75%)     0/114 (0.00%)  
# events     4     0  
Pulmonary-Other * 1    
# participants affected / at risk     0/109 (0.00%)     3/114 (2.63%)  
# events     0     3  
Skin and subcutaneous tissue disorders      
Wound-infectious * 1    
# participants affected / at risk     1/109 (0.92%)     1/114 (0.88%)  
# events     1     1  
Vascular disorders      
Veno-Occlusive Dease (VOD) * 1    
# participants affected / at risk     0/109 (0.00%)     1/114 (0.88%)  
# events     0     1  
* Events were collected by non-systematic assessment
1 Term from vocabulary, CTCAE (2.0)




  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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