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Trial record 2 of 7 for:    "Acute Promyelocytic Leukemia" | "Hormone Antagonists"

All-trans Retinoic Acid, and Arsenic +/- Idarubicin

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ClinicalTrials.gov Identifier: NCT00413166
Recruitment Status : Completed
First Posted : December 19, 2006
Results First Posted : April 18, 2019
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Promyelocytic Leukemia
Interventions Drug: All-Trans Retinoic Acid (ATRA)
Drug: Arsenic Trioxide (ATO)
Drug: Idarubicin
Drug: Gemtuzumab Ozogamicin
Enrollment 78
Recruitment Details Recruitment Period: December 5, 2006 to April 3, 2012. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Details Pfizer withdrew gemtuzumab ozogamycin (GO) from market based Food & Drug Administration recommendation. As such, protocol modified to Idarubicin Day 1 of induction in high-risk participants & in low risk participants with rising white blood count (WBC), Idarubicin administered to low-risk patients in whom WBC >10,000 after initiation of ATRA + ATO.
Arm/Group Title ATRA + ATO: Low Risk (WBC<10,000) ATRA+ATO+IDA: High Risk (WBC >10,000) ATO+ATRA+GO
Hide Arm/Group Description

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Post CR

1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a “2-weeks on -2-weeks off” basis until therapy with ATO completed.

Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days.

ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1.

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed.

Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.

Period Title: Overall Study
Started 57 5 16
Completed 57 5 16
Not Completed 0 0 0
Arm/Group Title ATRA + ATO: Low Risk (WBC<10,000) ATRA+ATO+IDA: High Risk (WBC >10,000) ATO+ATRA+GO Total
Hide Arm/Group Description

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Post CR

1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a “2-weeks on -2-weeks off” basis until therapy with ATO completed.

Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days.

ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1.

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Induction ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed.

Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.

Total of all reporting groups
Overall Number of Baseline Participants 57 5 16 78
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 5 participants 16 participants 78 participants
<=18 years
1
   1.8%
0
   0.0%
0
   0.0%
1
   1.3%
Between 18 and 65 years
46
  80.7%
5
 100.0%
15
  93.8%
66
  84.6%
>=65 years
10
  17.5%
0
   0.0%
1
   6.3%
11
  14.1%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 57 participants 5 participants 16 participants 78 participants
49
(16 to 84)
38
(28 to 63)
44
(19 to 75)
47
(16 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 5 participants 16 participants 78 participants
Female
33
  57.9%
2
  40.0%
12
  75.0%
47
  60.3%
Male
24
  42.1%
3
  60.0%
4
  25.0%
31
  39.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 5 participants 16 participants 78 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   3.5%
0
   0.0%
0
   0.0%
2
   2.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
  10.5%
1
  20.0%
4
  25.0%
11
  14.1%
White
46
  80.7%
2
  40.0%
12
  75.0%
60
  76.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   5.3%
2
  40.0%
0
   0.0%
5
   6.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 57 participants 5 participants 16 participants 78 participants
57 5 16 78
1.Primary Outcome
Title Complete Response (CR) Rate
Hide Description

Response defined as CR (marrow with <5% blasts and no abnormal promyelocytes together with neutrophil count >1000 and platelet count >100,000) and toxicity as Acute promyelocytic leukemia (APL) differentiation syndrome, arrhythmia, peripheral neuropathy.

Bone marrow aspirate performed to check the status of the disease.

Time Frame 1 month, up to day 85 of treatment
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Hide Analysis Population Description
Of the 57 participants treated on the ATRA + ATO: Low Risk treatment arm, 56 participants were evaluable for response.
Arm/Group Title ATRA + ATO: Low Risk (WBC<10,000) ATRA+ATO+IDA: High Risk (WBC >10,000) ATO+ATRA+GO
Hide Arm/Group Description:

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Post CR

1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a “2-weeks on -2-weeks off” basis until therapy with ATO completed.

Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days.

ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1.

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Induction ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed.

Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.

Overall Number of Participants Analyzed 56 5 16
Measure Type: Count of Participants
Unit of Measure: Participants
55
  98.2%
5
 100.0%
15
  93.8%
Time Frame Up to 7 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ATRA + ATO: Low Risk (WBC<10,000) ATRA+ATO+IDA: High Risk (WBC >10,000) ATO+ATRA+GO
Hide Arm/Group Description

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Post CR

1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a “2-weeks on -2-weeks off” basis until therapy with ATO completed.

Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days.

ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1.

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Induction ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed.

Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.

All-Cause Mortality
ATRA + ATO: Low Risk (WBC<10,000) ATRA+ATO+IDA: High Risk (WBC >10,000) ATO+ATRA+GO
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/57 (1.75%)      0/5 (0.00%)      1/16 (6.25%)    
Show Serious Adverse Events Hide Serious Adverse Events
ATRA + ATO: Low Risk (WBC<10,000) ATRA+ATO+IDA: High Risk (WBC >10,000) ATO+ATRA+GO
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/57 (38.60%)      4/5 (80.00%)      4/16 (25.00%)    
Blood and lymphatic system disorders       
Hemorrhage  1  2/57 (3.51%)  2 0/5 (0.00%)  0 1/16 (6.25%)  1
Cardiac disorders       
Cardiac Troponin I  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Chest Pain  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Left Ventricular Diastolic Dysfunction  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Prolonged QTc interval  1  2/57 (3.51%)  3 0/5 (0.00%)  0 1/16 (6.25%)  2
Gastrointestinal disorders       
Appendectomy  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Nausea/Vomiting  1  0/57 (0.00%)  0 0/5 (0.00%)  0 1/16 (6.25%)  2
General disorders       
Fatigue  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Headache  1  9/57 (15.79%)  13 2/5 (40.00%)  2 0/16 (0.00%)  0
Death  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Pain  1  2/57 (3.51%)  2 0/5 (0.00%)  0 2/16 (12.50%)  2
Infections and infestations       
Infection  1  5/57 (8.77%)  6 0/5 (0.00%)  0 3/16 (18.75%)  3
Investigations       
Retinoic acid syndrome  1  4/57 (7.02%)  4 2/5 (40.00%)  2 1/16 (6.25%)  1
Metabolism and nutrition disorders       
Elevated Transaminases  1  1/57 (1.75%)  2 2/5 (40.00%)  4 0/16 (0.00%)  0
Elevated Amylase  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Elevated Creatinine  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Elevated Lipase  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Hyperbilirubinemia  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Hypoglycemia  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Nervous system disorders       
Depressed level of Consciousness  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Peripharal Neuropathy  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Sensory Neuropathy  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Renal and urinary disorders       
Renal Insufficiency  1  1/57 (1.75%)  1 0/5 (0.00%)  0 1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders       
Hemoptysis  1  0/57 (0.00%)  0 0/5 (0.00%)  0 1/16 (6.25%)  1
Pulmonary Embolism  1  0/57 (0.00%)  0 0/5 (0.00%)  0 1/16 (6.25%)  1
Respiratory Failure  1  2/57 (3.51%)  2 0/5 (0.00%)  0 0/16 (0.00%)  0
Skin and subcutaneous tissue disorders       
Rash/desquamation  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
Surgical and medical procedures       
Hernia Repair  1  1/57 (1.75%)  1 0/5 (0.00%)  0 0/16 (0.00%)  0
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ATRA + ATO: Low Risk (WBC<10,000) ATRA+ATO+IDA: High Risk (WBC >10,000) ATO+ATRA+GO
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/57 (8.77%)      0/5 (0.00%)      1/16 (6.25%)    
Infections and infestations       
Infection  1  5/57 (8.77%)  5 0/5 (0.00%)  0 1/16 (6.25%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Farhad Ravandi-Kashani, Professor, Leukemia
Organization: The University of Texas (UT) MD Anderson Cancer Center
Phone: 7137927734
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00413166     History of Changes
Other Study ID Numbers: 2006-0706
NCI-2012-01395 ( Registry Identifier: NCI CTRP )
First Submitted: December 15, 2006
First Posted: December 19, 2006
Results First Submitted: March 28, 2019
Results First Posted: April 18, 2019
Last Update Posted: May 7, 2019