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
  Show All Outcome Measures

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


  Other 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.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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

Other Adverse Events
    Arm 1: (HDAC)     Arm 2:(LDAC)  
Total, other (not including serious) adverse events      
# participants affected / at risk     107/109     112/114  
Blood and lymphatic system disorders      
DIC (disseminated intravascular coagulation) * 1    
# participants affected / at risk     6/109 (5.50%)     0/114 (0.00%)  
# events     6     0  
Epistaxis * 1    
# participants affected / at risk     7/109 (6.42%)     9/114 (7.89%)  
# events     9     14  
Hemorrhage-Other * 1    
# participants affected / at risk     0/109 (0.00%)     12/114 (10.53%)  
# events     0     14  
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia * 1    
# participants affected / at risk     0/109 (0.00%)     6/114 (5.26%)  
# events     0     6  
Cardiac disorders      
Hypertension * 1    
# participants affected / at risk     8/109 (7.34%)     7/114 (6.14%)  
# events     9     9  
Hypotension * 1    
# participants affected / at risk     11/109 (10.09%)     20/114 (17.54%)  
# events     14     21  
Eye disorders      
Conjunctivitis * 1    
# participants affected / at risk     7/109 (6.42%)     0/114 (0.00%)  
# events     7     0  
Gastrointestinal disorders      
Anorexia * 1    
# participants affected / at risk     23/109 (21.10%)     16/114 (14.04%)  
# events     28     26  
Colitis * 1    
# participants affected / at risk     6/109 (5.50%)     0/114 (0.00%)  
# events     7     0  
Dehydration * 1    
# participants affected / at risk     0/109 (0.00%)     6/114 (5.26%)  
# events     0     6  
Diarrhea patients without colostomy * 1    
# participants affected / at risk     21/109 (19.27%)     20/114 (17.54%)  
# events     26     27  
Gastrointestinal-Other * 1    
# participants affected / at risk     8/109 (7.34%)     0/114 (0.00%)  
# events     8     0  
Nausea * 1    
# participants affected / at risk     6/109 (5.50%)     8/114 (7.02%)  
# events     6     11  
Stomatitis/pharyngitis (oral/pharyngeal mucositis) * 1    
# participants affected / at risk     15/109 (13.76%)     19/114 (16.67%)  
# events     18     22  
Typhlitis (inflammation of cecum) * 1    
# participants affected / at risk     8/109 (7.34%)     16/114 (14.04%)  
# events     10     17  
Vomiting * 1    
# participants affected / at risk     14/109 (12.84%)     15/114 (13.16%)  
# events     15     20  
General disorders      
Abdominal pain or cramping * 1    
# participants affected / at risk     11/109 (10.09%)     0/114 (0.00%)  
# events     12     0  
Headache * 1    
# participants affected / at risk     6/109 (5.50%)     9/114 (7.89%)  
# events     7     11  
Pain-Other * 1    
# participants affected / at risk     6/109 (5.50%)     0/114 (0.00%)  
# events     6     0  
Hepatobiliary disorders      
Bilirubin * 1    
# participants affected / at risk     7/109 (6.42%)     0/114 (0.00%)  
# events     8     0  
GGT (Gamma-Glutamyl transpeptidase) * 1    
# participants affected / at risk     14/109 (12.84%)     8/114 (7.02%)  
# events     21     9  
SGOT (AST) (serum glutamic oxaloacetic transaminase) * 1    
# participants affected / at risk     10/109 (9.17%)     0/114 (0.00%)  
# events     10     0  
SGPT (ALT) (serum glutamic pyruvic transaminase) * 1    
# participants affected / at risk     18/109 (16.51%)     8/114 (7.02%)  
# events     21     9  
Immune system disorders      
Allergic reaction/hypersensitivity (including drug fever) * 1    
# participants affected / at risk     17/109 (15.60%)     16/114 (14.04%)  
# events     19     19  
Infections and infestations      
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe * 1    
# participants affected / at risk     69/109 (63.30%)     92/114 (80.70%)  
# events     138     181  
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L) * 1    
# participants affected / at risk     0/109 (0.00%)     8/114 (7.02%)  
# events     0     9  
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia (ANC <1.0 x 10e * 1    
# participants affected / at risk     83/109 (76.15%)     82/114 (71.93%)  
# events     193     178  
Infection without neutropenia * 1    
# participants affected / at risk     10/109 (9.17%)     13/114 (11.40%)  
# events     10     15  
Metabolism and nutrition disorders      
Acidosis (metabolic or respiratory) * 1    
# participants affected / at risk     6/109 (5.50%)     0/114 (0.00%)  
# events     8     0  
Hyperglycemia * 1    
# participants affected / at risk     15/109 (13.76%)     10/114 (8.77%)  
# events     21     13  
Hyperkalemia * 1    
# participants affected / at risk     7/109 (6.42%)     6/114 (5.26%)  
# events     8     14  
Hypocalcemia * 1    
# participants affected / at risk     12/109 (11.01%)     12/114 (10.53%)  
# events     13     17  
Hypokalemia * 1    
# participants affected / at risk     37/109 (33.94%)     38/114 (33.33%)  
# events     79     84  
Hypomagnesmia * 1    
# participants affected / at risk     8/109 (7.34%)     7/114 (6.14%)  
# events     9     11  
Hyponatremia * 1    
# participants affected / at risk     6/109 (5.50%)     9/114 (7.89%)  
# events     8     11  
Hypophosphatemia * 1    
# participants affected / at risk     12/109 (11.01%)     12/114 (10.53%)  
# events     14     14  
Lipase * 1    
# participants affected / at risk     6/109 (5.50%)     0/114 (0.00%)  
# events     7     0  
Respiratory, thoracic and mediastinal disorders      
Hypoxia * 1    
# participants affected / at risk     19/109 (17.43%)     17/114 (14.91%)  
# events     20     19  
Pleural effusion (non-malignant) * 1    
# participants affected / at risk     0/109 (0.00%)     7/114 (6.14%)  
# events     0     7  
Pneumonitis/pulmonary infiltrates * 1    
# participants affected / at risk     10/109 (9.17%)     0/114 (0.00%)  
# events     12     0  
Skin and subcutaneous tissue disorders      
Rash/desquamation * 1    
# participants affected / at risk     0/109 (0.00%)     8/114 (7.02%)  
# events     0     9  
Wound-infectious * 1    
# participants affected / at risk     0/109 (0.00%)     11/114 (9.65%)  
# events     0     12  
Wound-non-infectious * 1    
# participants affected / at risk     9/109 (8.26%)     6/114 (5.26%)  
# events     10     6  
* Events were collected by non-systematic assessment
1 Term from vocabulary, CTCAE (2.0)



  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


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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