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Lestaurtinib, Cytarabine, and Idarubicin in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT00469859
Recruitment Status : Completed
First Posted : May 7, 2007
Results First Posted : December 20, 2013
Last Update Posted : March 15, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia
Interventions Drug: cytarabine
Drug: idarubicin
Drug: lestaurtinib
Enrollment 14
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group 1 (Lestaurtinib Dose 50 mg/m2) Group 2 (Lestaurtinib: Dose 62.5 mg/m2)
Hide Arm/Group Description

COURSE 1: Cytarabine IV over 2 hours twice daily days 1-4, idarubicin IV over 15 minutes days 2-4, and oral lestaurtinib twice daily days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a safe, tolerable and biologically active dose (TBAD) is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

COURSE 1: Cytarabine IV over 2 hours twice daily days 1-4, idarubicin IV over 15 minutes days 2-4, and oral lestaurtinib twice daily days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a safe, tolerable and biologically active dose (TBAD) is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

cytarabine

Period Title: Overall Study
Started 6 8
Completed 6 6
Not Completed 0 2
Reason Not Completed
Inevaluable             0             2
Arm/Group Title Group 1 (Lestaurtinib Dose 50 mg/m2 Group 2 (Lestaurtinib: Dose 62.5 mg/m2 Total
Hide Arm/Group Description

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

Total of all reporting groups
Overall Number of Baseline Participants 6 8 14
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 8 participants 14 participants
<=18 years
6
 100.0%
8
 100.0%
14
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 8 participants 14 participants
Female
4
  66.7%
2
  25.0%
6
  42.9%
Male
2
  33.3%
6
  75.0%
8
  57.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 8 participants 14 participants
Hispanic or Latino
1
  16.7%
0
   0.0%
1
   7.1%
Not Hispanic or Latino
4
  66.7%
8
 100.0%
12
  85.7%
Unknown or Not Reported
1
  16.7%
0
   0.0%
1
   7.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 8 participants 14 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  16.7%
2
  25.0%
3
  21.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  16.7%
1
  12.5%
2
  14.3%
White
4
  66.7%
5
  62.5%
9
  64.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 8 participants 14 participants
6 8 14
1.Primary Outcome
Title Dose-limiting Toxicity
Hide Description Number of patients with dose-limiting toxicity (DLT)
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 (Lestaurtinib Dose 50 mg/m2 Group 2 (Lestaurtinib: Dose 62.5 mg/m2
Hide Arm/Group Description:

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

Overall Number of Participants Analyzed 6 6
Measure Type: Number
Unit of Measure: participants
0 0
2.Primary Outcome
Title >80% Inhibition of FLT3 Phosphorylation in a Majority of Post-treatment Trough Time Points
Time Frame Course 1 day 7, day 14, day 21, and day 28.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 (Lestaurtinib Dose 50 mg/m2 Group 2 (Lestaurtinib: Dose 62.5 mg/m2
Hide Arm/Group Description:

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

Overall Number of Participants Analyzed 6 6
Measure Type: Number
Unit of Measure: participants
5 5
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1 (Lestaurtinib Dose 50 mg/m2 Group 2 (Lestaurtinib: Dose 62.5 mg/m2
Hide Arm/Group Description

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

COURSE 1: Patients receive cytarabine IV over 2 hours twice daily on days 1-4, idarubicin IV over 15 minutes on days 2-4, and oral lestaurtinib twice daily on days 5-28. Patients achieving complete or partial response proceed to course 2. Cohorts of 6 patients receive escalating doses of lestaurtinib until a TBAD is determined. The TBAD is defined as the dose at which no more than 2 of 6 patients experience DLT and biologic activity is confirmed by PIA assay.

COURSE 2: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-4 and oral lestaurtinib (at the dose determined in course 1) twice daily on days 5-28. Patients achieving complete or partial response proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive oral lestaurtinib twice daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Continued (see detailed description)

All-Cause Mortality
Group 1 (Lestaurtinib Dose 50 mg/m2 Group 2 (Lestaurtinib: Dose 62.5 mg/m2
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Group 1 (Lestaurtinib Dose 50 mg/m2 Group 2 (Lestaurtinib: Dose 62.5 mg/m2
Affected / at Risk (%) Affected / at Risk (%)
Total   2/6 (33.33%)   6/8 (75.00%) 
Blood and lymphatic system disorders     
Anemia  1/6 (16.67%)  0/8 (0.00%) 
Disseminated intravascular coagulation  0/6 (0.00%)  1/8 (12.50%) 
Febrile neutropenia  0/6 (0.00%)  1/8 (12.50%) 
Cardiac disorders     
Cardiac disorders - Other  0/6 (0.00%)  1/8 (12.50%) 
Left ventricular systolic dysfunction  0/6 (0.00%)  1/8 (12.50%) 
Pericardial effusion  0/6 (0.00%)  1/8 (12.50%) 
Sinus tachycardia  0/6 (0.00%)  1/8 (12.50%) 
Gastrointestinal disorders     
Abdominal pain  0/6 (0.00%)  2/8 (25.00%) 
Ascites  0/6 (0.00%)  1/8 (12.50%) 
Colitis  0/6 (0.00%)  1/8 (12.50%) 
Diarrhea  0/6 (0.00%)  1/8 (12.50%) 
Mucositis oral  1/6 (16.67%)  0/8 (0.00%) 
Typhlitis  0/6 (0.00%)  1/8 (12.50%) 
Infections and infestations     
Appendicitis perforated  0/6 (0.00%)  1/8 (12.50%) 
Infections and infestations - Other  1/6 (16.67%)  4/8 (50.00%) 
Investigations     
Activated partial thromboplastin time prolonged  1/6 (16.67%)  0/8 (0.00%) 
Alanine aminotransferase increased  0/6 (0.00%)  1/8 (12.50%) 
Aspartate aminotransferase increased  0/6 (0.00%)  1/8 (12.50%) 
Lymphocyte count decreased  0/6 (0.00%)  1/8 (12.50%) 
Neutrophil count decreased  0/6 (0.00%)  1/8 (12.50%) 
Platelet count decreased  0/6 (0.00%)  1/8 (12.50%) 
Weight gain  0/6 (0.00%)  1/8 (12.50%) 
White blood cell decreased  0/6 (0.00%)  2/8 (25.00%) 
Metabolism and nutrition disorders     
Acidosis  0/6 (0.00%)  1/8 (12.50%) 
Alkalosis  0/6 (0.00%)  1/8 (12.50%) 
Anorexia  0/6 (0.00%)  3/8 (37.50%) 
Hyperglycemia  1/6 (16.67%)  0/8 (0.00%) 
Hyperkalemia  1/6 (16.67%)  1/8 (12.50%) 
Hypoalbuminemia  0/6 (0.00%)  1/8 (12.50%) 
Hypokalemia  1/6 (16.67%)  4/8 (50.00%) 
Musculoskeletal and connective tissue disorders     
Chest wall pain  0/6 (0.00%)  1/8 (12.50%) 
Pain in extremity  0/6 (0.00%)  1/8 (12.50%) 
Nervous system disorders     
Intracranial hemorrhage  0/6 (0.00%)  1/8 (12.50%) 
Seizure  0/6 (0.00%)  1/8 (12.50%) 
Psychiatric disorders     
Anxiety  0/6 (0.00%)  1/8 (12.50%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  0/6 (0.00%)  1/8 (12.50%) 
Epistaxis  1/6 (16.67%)  1/8 (12.50%) 
Hypoxia  0/6 (0.00%)  3/8 (37.50%) 
Pneumonitis  0/6 (0.00%)  1/8 (12.50%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  0/6 (0.00%)  1/8 (12.50%) 
Vascular disorders     
Hypotension  0/6 (0.00%)  1/8 (12.50%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1 (Lestaurtinib Dose 50 mg/m2 Group 2 (Lestaurtinib: Dose 62.5 mg/m2
Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   8/8 (100.00%) 
Blood and lymphatic system disorders     
Anemia  3/6 (50.00%)  6/8 (75.00%) 
Febrile neutropenia  1/6 (16.67%)  3/8 (37.50%) 
Gastrointestinal disorders     
Abdominal pain  0/6 (0.00%)  1/8 (12.50%) 
Hemorrhoids  1/6 (16.67%)  0/8 (0.00%) 
Nausea  1/6 (16.67%)  1/8 (12.50%) 
Rectal pain  1/6 (16.67%)  0/8 (0.00%) 
Upper gastrointestinal hemorrhage  0/6 (0.00%)  1/8 (12.50%) 
Vomiting  0/6 (0.00%)  1/8 (12.50%) 
General disorders     
Fever  0/6 (0.00%)  1/8 (12.50%) 
Infections and infestations     
Infections and infestations - Other  1/6 (16.67%)  2/8 (25.00%) 
Investigations     
Alanine aminotransferase increased  2/6 (33.33%)  1/8 (12.50%) 
Aspartate aminotransferase increased  1/6 (16.67%)  1/8 (12.50%) 
Lipase increased  0/6 (0.00%)  1/8 (12.50%) 
Lymphocyte count decreased  1/6 (16.67%)  5/8 (62.50%) 
Neutrophil count decreased  4/6 (66.67%)  5/8 (62.50%) 
Platelet count decreased  4/6 (66.67%)  6/8 (75.00%) 
Weight loss  0/6 (0.00%)  1/8 (12.50%) 
White blood cell decreased  4/6 (66.67%)  3/8 (37.50%) 
Metabolism and nutrition disorders     
Anorexia  1/6 (16.67%)  1/8 (12.50%) 
Hypertriglyceridemia  0/6 (0.00%)  1/8 (12.50%) 
Hypoalbuminemia  0/6 (0.00%)  2/8 (25.00%) 
Hypokalemia  1/6 (16.67%)  2/8 (25.00%) 
Hyponatremia  0/6 (0.00%)  1/8 (12.50%) 
Hypophosphatemia  1/6 (16.67%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1/6 (16.67%)  0/8 (0.00%) 
Psychiatric disorders     
Depression  1/6 (16.67%)  0/8 (0.00%) 
Reproductive system and breast disorders     
Uterine hemorrhage  1/6 (16.67%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  0/6 (0.00%)  1/8 (12.50%) 
Hypoxia  0/6 (0.00%)  2/8 (25.00%) 
Pharyngolaryngeal pain  0/6 (0.00%)  1/8 (12.50%) 
Skin and subcutaneous tissue disorders     
Erythema multiforme  0/6 (0.00%)  1/8 (12.50%) 
Rash maculo-papular  1/6 (16.67%)  1/8 (12.50%) 
Vascular disorders     
Hypertension  0/6 (0.00%)  1/8 (12.50%) 
Hypotension  1/6 (16.67%)  0/8 (0.00%) 
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.
Must obtain prior Sponsor approval.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00469859     History of Changes
Other Study ID Numbers: AAML06P1
CDR0000543398 ( Other Identifier: Clinical Trials.gov )
COG-AAML06P1 ( Other Identifier: Children's Oncology Group )
First Submitted: May 3, 2007
First Posted: May 7, 2007
Results First Submitted: August 29, 2013
Results First Posted: December 20, 2013
Last Update Posted: March 15, 2017