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Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00666588
First Posted: April 25, 2008
Last Update Posted: May 28, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
Results First Submitted: December 18, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myelomonocytic Leukemia (M4)
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)
Recurrent Adult Acute Myeloid Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Interventions: Drug: idarubicin
Drug: cytarabine
Drug: bortezomib
Drug: etoposide
Other: laboratory biomarker analysis

  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
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure

Bortezomib 1.3mg/m2 to assess efficacy in low prior anthracycline exposure. Patients receive idarubicin IV (12 mg/m2/day) over 15 minutes on days 1-3, low-dose cytarabine IV (100 mg/m2/day) continuously over days 1-7, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (closed as of 08/01/10). Dosage modification based on age < 3 years old.

idarubicin: Given IV

cytarabine: Given IV or IT

bortezomib: Given IV

laboratory biomarker analysis: Correlative studies

Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp

Bortezomib 1.0 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.0 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

cytarabine: Given IV or IT

bortezomib: Given IV

etoposide: Given IV

laboratory biomarker analysis: Correlative studies

Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp

Bortezomib 1.3 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (dose-finding phase closed as of 10/10).

cytarabine: Given IV or IT

bortezomib: Given IV

etoposide: Given IV

laboratory biomarker analysis: Correlative studies

Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp

Bortezomib 1.3 mg/m2 to assess efficacy in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity

cytarabine: Given IV or IT

bortezomib: Given IV

etoposide: Given IV

laboratory biomarker analysis: Correlative studies


Participant Flow:   Overall Study
    Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure   Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp   Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp   Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp
STARTED   18   6   6   22 
COMPLETED   14   6   6   20 
NOT COMPLETED   4   0   0   2 
ineligible                2                0                0                2 
inevaluable                2                0                0                0 



  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
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure

Bortezomib 1.3mg/m2 to assess efficacy in low prior anthracycline exposure. Patients receive idarubicin IV (12 mg/m2/day) over 15 minutes on days 1-3, low-dose cytarabine IV (100 mg/m2/day) continuously over days 1-7, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (closed as of 08/01/10). Dosage modification based on age < 3 years old.

idarubicin: Given IV

cytarabine: Given IV or IT

bortezomib: Given IV

laboratory biomarker analysis: Correlative studies

Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp

Bortezomib 1.0 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.0 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

cytarabine: Given IV or IT

bortezomib: Given IV

etoposide: Given IV

laboratory biomarker analysis: Correlative studies

Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp

Bortezomib 1.3 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (dose-finding phase closed as of 10/10).

cytarabine: Given IV or IT

bortezomib: Given IV

etoposide: Given IV

laboratory biomarker analysis: Correlative studies

Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp

Bortezomib 1.3 mg/m2 to assess efficacy in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity

cytarabine: Given IV or IT

bortezomib: Given IV

etoposide: Given IV

laboratory biomarker analysis: Correlative studies

Total Total of all reporting groups

Baseline Measures
   Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure   Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp   Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp   Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp   Total 
Overall Participants Analyzed 
[Units: Participants]
 18   6   6   22   52 
Age 
[Units: Days]
Mean (Standard Deviation)
 4121.72  (2569.95)   5637.0  (1757.39)   2812.5  (1769.83)   3365.0  (2227.99)   3984.06  (2081.29) 
Age 
[Units: Participants]
         
<=18 years   15   4   6   21   46 
Between 18 and 65 years   3   2   0   1   6 
>=65 years   0   0   0   0   0 
Gender 
[Units: Participants]
         
Female   11   2   4   13   30 
Male   7   4   2   9   22 
Race (NIH/OMB) 
[Units: Participants]
         
American Indian or Alaska Native   0   0   0   0   0 
Asian   1   2   1   1   5 
Native Hawaiian or Other Pacific Islander   0   0   0   0   0 
Black or African American   3   1   1   2   7 
White   11   3   3   18   35 
More than one race   0   0   0   0   0 
Unknown or Not Reported   3   0   1   1   5 
Ethnicity (NIH/OMB) 
[Units: Participants]
         
Hispanic or Latino   3   0   1   3   7 
Not Hispanic or Latino   13   6   5   17   41 
Unknown or Not Reported   2   0   0   2   4 
Region of Enrollment 
[Units: Participants]
         
United States   17   5   6   20   48 
Canada   1   1   0   1   3 
Australia   0   0   0   1   1 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Dose Limiting Toxicity   [ Time Frame: During Course 1 ]

2.  Primary:   Overall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 1   [ Time Frame: After course 1 ]

3.  Secondary:   NF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)   [ Time Frame: At baseline, prior to and up to 24 hours after bortezomib treatment ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

4.  Secondary:   Proteasome Inhibition Activity   [ Time Frame: At baseline, 2 hours prior to and 3 hours after first bortezomib dose ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

5.  Secondary:   Protein Expression Assessed by Western Blot   [ Time Frame: At baseline, prior to and up to 24 hours after bortezomib treatment ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

6.  Secondary:   Feasibility of Stem Cell Quantitation   [ Time Frame: At baseline and after completion of course 1 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  


  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
No text entered.


  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


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



Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00666588     History of Changes
Other Study ID Numbers: NCI-2009-00323
U10CA098543 ( U.S. NIH Grant/Contract )
CDR0000594224 ( Registry Identifier: PDQ (Physician Data Query) )
COG-AAML07P1 ( Other Identifier: Children's Oncology Group )
NCI-2009-00323 ( Other Identifier: NCI )
First Submitted: April 24, 2008
First Posted: April 25, 2008
Results First Submitted: December 18, 2013
Results First Posted: February 6, 2014
Last Update Posted: May 28, 2014