Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

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:
NCT00369317
First received: August 24, 2006
Last updated: March 16, 2016
Last verified: March 2016
Results First Received: January 6, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Childhood Acute Basophilic Leukemia
Childhood Acute Eosinophilic Leukemia
Childhood Acute Erythroleukemia (M6)
Childhood Acute Megakaryocytic Leukemia (M7)
Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
Childhood Acute Monoblastic Leukemia (M5a)
Childhood Acute Monocytic Leukemia (M5b)
Childhood Acute Myeloblastic Leukemia With Maturation (M2)
Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
Childhood Acute Myelomonocytic Leukemia (M4)
Childhood Myelodysplastic Syndromes
de Novo Myelodysplastic Syndromes
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Interventions: Drug: asparaginase
Drug: daunorubicin hydrochloride
Drug: cytarabine
Drug: thioguanine
Drug: etoposide
Other: laboratory biomarker analysis

  Participant Flow
  Hide Participant Flow

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
Treatment (Combination Chemotherapy)

INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.

COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I

INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

asparaginase: Given IM

daunorubicin hydrochloride: Given IV

cytarabine: Given IV or IT

thioguanine: Given orally

etoposide: Given IV

laboratory biomarker analysis: Correlative studies


Participant Flow:   Overall Study
    Treatment (Combination Chemotherapy)
STARTED   205 
COMPLETED   185 
NOT COMPLETED   20 
Adverse Event                3 
Death                1 
Lack of Efficacy                5 
Physician Decision                2 
Withdrawal by Subject                8 
Ineligible                1 



  Baseline Characteristics
  Hide Baseline Characteristics

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
Treatment (Combination Chemotherapy)

INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.

COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I

INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

asparaginase: Given IM

daunorubicin hydrochloride: Given IV

cytarabine: Given IV or IT

thioguanine: Given orally

etoposide: Given IV

laboratory biomarker analysis: Correlative studies


Baseline Measures
   Treatment (Combination Chemotherapy) 
Overall Participants Analyzed 
[Units: Participants]
 205 
Age 
[Units: Days]
Mean (Standard Deviation)
 616.41  (265.73) 
Age 
[Units: Participants]
 
<=18 years   205 
Between 18 and 65 years   0 
>=65 years   0 
Gender 
[Units: Participants]
 
Female   106 
Male   99 
Race (NIH/OMB) 
[Units: Participants]
 
American Indian or Alaska Native   0 
Asian   12 
Native Hawaiian or Other Pacific Islander   2 
Black or African American   28 
White   141 
More than one race   0 
Unknown or Not Reported   22 
Ethnicity (NIH/OMB) 
[Units: Participants]
 
Hispanic or Latino   48 
Not Hispanic or Latino   154 
Unknown or Not Reported   3 
Region of Enrollment 
[Units: Participants]
 
United States   187 
Canada   11 
Australia   7 


  Outcome Measures
  Show All Outcome Measures

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

2.  Primary:   Overall Survival (OS) at 3 Years   [ Time Frame: Time from study entry to death, assessed at 3 years. ]

3.  Secondary:   Induction Remission Rate   [ Time Frame: End of induction therapy ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Percentage of Patients Experiencing Grade 3 or 4 Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0   [ Time Frame: From the beginning of induction therapy to the end of intensification therapy ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes

5.  Secondary:   Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry   [ Time Frame: At baseline and at the end of therapy (intensification) or disease relapse ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

6.  Secondary:   Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis   [ Time Frame: At baseline and at the end of therapy (intensification) or disease relapse ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

7.  Secondary:   Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry   [ Time Frame: After completion of induction therapy (I, IV) and after completion of intensification therapy ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

8.  Secondary:   Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program.   [ Time Frame: Days 1, 2, 8, and 9 of induction II ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

9.  Secondary:   Gene Expression Profiles by Microarrays   [ Time Frame: At baseline and at the time of relapse (if available) ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  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
  Hide More Information

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: resultsreportingcoordintator@childrensoncologygroup.org



Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00369317     History of Changes
Other Study ID Numbers: AAML0431
NCI-2009-00318 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000492776 ( Other Identifier: Clinical Trials.gov )
COG-AAML0431 ( Other Identifier: Children's Oncology Group )
AAML0431 ( Other Identifier: CTEP )
U10CA098543 ( US NIH Grant/Contract Award Number )
Study First Received: August 24, 2006
Results First Received: January 6, 2015
Last Updated: March 16, 2016
Health Authority: United States: Food and Drug Administration