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

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ClinicalTrials.gov Identifier: NCT00666588
Recruitment Status : Completed
First Posted : April 25, 2008
Results First Posted : February 6, 2014
Last Update Posted : May 22, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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
Enrollment 52
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 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
Hide Arm/Group Description

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 1.0 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 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 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

Period Title: Overall Study
Started 18 6 6 22
Completed 14 6 6 20
Not Completed 4 0 0 2
Reason Not Completed
ineligible             2             0             0             2
inevaluable             2             0             0             0
Arm/Group Title 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
Hide Arm/Group Description

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 1.0 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 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 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 of all reporting groups
Overall Number of Baseline Participants 18 6 6 22 52
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 18 participants 6 participants 6 participants 22 participants 52 participants
4121.72  (2569.95) 5637.0  (1757.39) 2812.5  (1769.83) 3365.0  (2227.99) 3984.06  (2081.29)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 6 participants 6 participants 22 participants 52 participants
<=18 years
15
  83.3%
4
  66.7%
6
 100.0%
21
  95.5%
46
  88.5%
Between 18 and 65 years
3
  16.7%
2
  33.3%
0
   0.0%
1
   4.5%
6
  11.5%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 6 participants 6 participants 22 participants 52 participants
Female
11
  61.1%
2
  33.3%
4
  66.7%
13
  59.1%
30
  57.7%
Male
7
  38.9%
4
  66.7%
2
  33.3%
9
  40.9%
22
  42.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 6 participants 6 participants 22 participants 52 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   5.6%
2
  33.3%
1
  16.7%
1
   4.5%
5
   9.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  16.7%
1
  16.7%
1
  16.7%
2
   9.1%
7
  13.5%
White
11
  61.1%
3
  50.0%
3
  50.0%
18
  81.8%
35
  67.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
  16.7%
0
   0.0%
1
  16.7%
1
   4.5%
5
   9.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 6 participants 6 participants 22 participants 52 participants
Hispanic or Latino
3
  16.7%
0
   0.0%
1
  16.7%
3
  13.6%
7
  13.5%
Not Hispanic or Latino
13
  72.2%
6
 100.0%
5
  83.3%
17
  77.3%
41
  78.8%
Unknown or Not Reported
2
  11.1%
0
   0.0%
0
   0.0%
2
   9.1%
4
   7.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 6 participants 6 participants 22 participants 52 participants
United States 17 5 6 20 48
Canada 1 1 0 1 3
Australia 0 0 0 1 1
1.Primary Outcome
Title Dose Limiting Toxicity
Hide Description Number of participants with dose limiting toxicity.
Time Frame During Course 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 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
Hide Arm/Group Description:

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 1.0 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 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 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

Overall Number of Participants Analyzed 14 6 6 20
Measure Type: Number
Unit of Measure: participants
0 1 0 0
2.Primary Outcome
Title Overall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 1
Hide Description Overall response (complete remission [CR] and CR with partial recovery [CRp]) during course 1.
Time Frame After course 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 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
Hide Arm/Group Description:

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 1.0 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 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 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

Overall Number of Participants Analyzed 14 6 6 20
Measure Type: Number
Unit of Measure: participants
4 2 2 9
3.Secondary Outcome
Title NF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)
Hide Description NF-kB activity will be measured as a continuous variable (ng NF-kB/Mg protein). Differences in NF-κB activity between time points will be assessed using summary statistics such as mean, standard deviation, and range. We may perform exploratory analyses to determine if single time point measurements, or the difference between time points, correlate with treatment response.
Time Frame At baseline, prior to and up to 24 hours after bortezomib treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Ineligible patients (n=4) are excluded. Patients without available data (n=36) are excluded.
Arm/Group Title 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
Hide Arm/Group Description:

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 1.0 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 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 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

Overall Number of Participants Analyzed 5 1 1 5
Mean (Standard Deviation)
Unit of Measure: ng/Mg protein
Baseline 718.218  (418.149339) 655.4 974.66 408.144  (484.084297)
24 Hrs after treatment 774.1925  (410.667711) 345.46 855.96 497.31  (449.312899)
4.Secondary Outcome
Title Proteasome Inhibition Activity
Hide Description Mean and standard deviation of β1 and β5- Results are ratios (proteasome subunit/β-actin based on loading of 15 µg total protein, normalized to CEM).
Time Frame At baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Ineligible patients (n=4) are excluded. Patients without available data (n=36) are excluded. The data summarized are only at baseline as that is the only data available.
Arm/Group Title 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
Hide Arm/Group Description:

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 1.0 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 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 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

Overall Number of Participants Analyzed 4 1 0 7
Mean (Standard Deviation)
Unit of Measure: ratio
Baseline β1 0.08115  (0.0860893) 0.7894 0.2895143  (0.2974052)
Baseline β5 0.121575  (0.0691725) 0.2576 0.3721286  (0.7140883)
5.Secondary Outcome
Title Protein Expression Assessed by Western Blot
Hide Description Relative expression of apoptotic and cell cycle proteins will be characterized using descriptive statistics. If differences are noted between pre and post-treatment protein expression, pairwise comparisons will be made using paired t-test or an equivalent nonparametric test if the data are non-normally distributed. The normality assumption will be assessed on the log-transformed data prior to paired t-test evaluation.
Time Frame At baseline, prior to and up to 24 hours after bortezomib treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
These data will never be collected because the investigators decided not to perform quantitative biologic analysis.
Arm/Group Title 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
Hide Arm/Group Description:

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 1.0 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 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 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

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Feasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) Depletion
Hide Description Descriptive statistics to assess mean +/- standard deviation for the percentage leukemia initiation cells (LIC) depletion.
Time Frame At baseline and after completion of course 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Ineligible patients (n=4) are excluded. Patients without available data (n=42) are excluded.
Arm/Group Title 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
Hide Arm/Group Description:

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 1.0 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 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 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

Overall Number of Participants Analyzed 3 0 1 2
Mean (Standard Deviation)
Unit of Measure: percentage of LIC depletion
Prior to Treatment 0.013667  (0.02108) 0.2 1.6385  (2.06887)
Post Treatment 0.021  (0.036373) 0.43 0.0435  (0.0615183)
Time Frame [Not Specified]
Adverse Event Reporting Description The ineligible patients are not included in the adverse event reporting.
 
Arm/Group Title 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
Hide Arm/Group Description

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 1.0 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 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 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

All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/16 (18.75%)   3/6 (50.00%)   1/6 (16.67%)   5/20 (25.00%) 
Blood and lymphatic system disorders         
Disseminated intravascular coagulation [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Cardiac disorders         
Left ventricular systolic dysfunction [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Myocarditis [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Right ventricular dysfunction [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Gastrointestinal disorders         
Abdominal pain [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Anal pain [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Diarrhea [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Mucositis oral [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Oral pain [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
General disorders         
Death NOS [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Infections and infestations         
Catheter related infection [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Infections and infestations - Other, specify [1]  0/16 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  1/20 (5.00%) 
Sepsis [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/20 (10.00%) 
Investigations         
Alanine aminotransferase increased [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Aspartate aminotransferase increased [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Blood bilirubin increased [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Creatinine increased [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
GGT increased [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Metabolism and nutrition disorders         
Anorexia [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Hyperglycemia [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Hyperkalemia [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Hyperuricemia [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Hypoalbuminemia [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Hypocalcemia [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Hypokalemia [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/20 (10.00%) 
Hypomagnesemia [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Hypophosphatemia [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Nervous system disorders         
Headache [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Psychiatric disorders         
Psychosis [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Renal and urinary disorders         
Acute kidney injury [1]  1/16 (6.25%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders         
Adult respiratory distress syndrome [1]  1/16 (6.25%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Cough [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Dyspnea [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Hypoxia [1]  1/16 (6.25%)  0/6 (0.00%)  1/6 (16.67%)  2/20 (10.00%) 
Pneumonitis [1]  1/16 (6.25%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Pulmonary edema [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders         
Palmar-plantar erythrodysesthesia syndrome [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Vascular disorders         
Hypotension [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
[1]
Adeers submitted
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/16 (87.50%)   5/6 (83.33%)   5/6 (83.33%)   14/20 (70.00%) 
Blood and lymphatic system disorders         
Anemia [1]  3/16 (18.75%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Febrile neutropenia [1]  6/16 (37.50%)  2/6 (33.33%)  2/6 (33.33%)  5/20 (25.00%) 
Gastrointestinal disorders         
Abdominal pain [1]  1/16 (6.25%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Constipation [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Diarrhea [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Esophageal pain [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Gastric hemorrhage [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Ileus [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Mucositis oral [1]  1/16 (6.25%)  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Nausea [1]  0/16 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  2/20 (10.00%) 
Vomiting [1]  1/16 (6.25%)  2/6 (33.33%)  0/6 (0.00%)  2/20 (10.00%) 
General disorders         
Fatigue [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Fever [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  4/20 (20.00%) 
Non-cardiac chest pain [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Pain [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Immune system disorders         
Allergic reaction [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Anaphylaxis [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Infections and infestations         
Anorectal infection [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Catheter related infection [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Enterocolitis infectious [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Infections and infestations - Other, specify [1]  9/16 (56.25%)  3/6 (50.00%)  4/6 (66.67%)  3/20 (15.00%) 
Lung infection [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Soft tissue infection [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Upper respiratory infection [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications         
Vascular access complication [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Investigations         
Activated partial thromboplastin time prolonged [1]  1/16 (6.25%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Alanine aminotransferase increased [1]  2/16 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  2/20 (10.00%) 
Aspartate aminotransferase increased [1]  1/16 (6.25%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Blood bilirubin increased [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Fibrinogen decreased [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
GGT increased [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
INR increased [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Investigations - Other, specify [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Lymphocyte count decreased [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Neutrophil count decreased [1]  3/16 (18.75%)  2/6 (33.33%)  1/6 (16.67%)  0/20 (0.00%) 
Platelet count decreased [1]  1/16 (6.25%)  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
White blood cell decreased [1]  3/16 (18.75%)  2/6 (33.33%)  1/6 (16.67%)  0/20 (0.00%) 
Metabolism and nutrition disorders         
Anorexia [1]  2/16 (12.50%)  1/6 (16.67%)  3/6 (50.00%)  1/20 (5.00%) 
Hyperglycemia [1]  3/16 (18.75%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Hypoalbuminemia [1]  2/16 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Hypocalcemia [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Hypokalemia [1]  4/16 (25.00%)  3/6 (50.00%)  2/6 (33.33%)  3/20 (15.00%) 
Hypomagnesemia [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Hyponatremia [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Hypophosphatemia [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Bone pain [1]  1/16 (6.25%)  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Generalized muscle weakness [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Pain in extremity [1]  2/16 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Nervous system disorders         
Dysphasia [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Headache [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Peripheral motor neuropathy [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Peripheral sensory neuropathy [1]  1/16 (6.25%)  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Syncope [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Vasovagal reaction [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Psychiatric disorders         
Agitation [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Anxiety [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Depression [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Reproductive system and breast disorders         
Uterine hemorrhage [1]  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Atelectasis [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Dyspnea [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Hypoxia [1]  1/16 (6.25%)  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders         
Alopecia [1]  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Rash maculo-papular [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Vascular disorders         
Capillary leak syndrome [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Hypertension [1]  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Hypotension [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
Vascular disorders - Other, specify [1]  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/20 (0.00%) 
[1]
Adeers not subm
The secondary outcome measure "Protein Expression Assessed by Western Blot" will never be reported as the investigators decided not to perform quantitative biologic analysis.
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.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
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 22, 2018