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

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00413166
• Collaborator: (none)
• Enrollment: 78
• Location: 1
• Arms: 3
• Duration (Months): 110
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if the combination of arsenic trioxide (ATO) with ATRA and possibly idarubicin is effective in treating patients with newly-diagnosed APL.

Condition or Disease	Intervention/Treatment	Phase
Acute Promyelocytic Leukemia	Drug: All-Trans Retinoic Acid (ATRA); Drug: Arsenic Trioxide (ATO); Drug: Idarubicin; Drug: Gemtuzumab Ozogamicin	Phase 2

Detailed Description

All-trans retinoic acid (ATRA) and ATO are designed to cause the APL cells to mature and function normally. Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells).

If you are found to be eligible to take part in this study, you will begin induction. During induction, you will receive ATRA, by mouth starting on Day 1. You will also receive ATO through a needle in your vein over 2 hours starting on Day 1. You will continue receiving the drugs every day until your bone marrow no longer shows APL cells.

If you had a high white blood cell count at screening, you will receive idarubicin through a needle in your vein over about 30 minutes one dose only on any day of Day 1 through 5.

During induction, blood (about 1-3 tablespoons) will be drawn every day during Week 1, and then 2 times a week after that. This blood will be drawn for routine tests.

During induction (about 21-28 days after beginning treatment), you will have a bone marrow aspirate to check the status of the disease. This may be performed more often if the doctor thinks it is needed.

If you achieve a complete remission during the induction phase, you will continue to the maintenance phase. During the maintenance phase, you will receive ATO by vein over 2 hours Monday-Friday for 4 weeks. After the 4 weeks of receiving the study drug, you will have a 4-week period "off" (when no study drug is given). ATRA is given by mouth every day for 2 weeks. This 2 weeks is followed by 2 additional weeks when no study drug will be given. You will continue to take ATRA until treatment with ATO is complete.

During maintenance, blood (about 1-3 tablespoons) will be drawn before every 4-week cycle of ATO, and then every week for routine tests. You will also have an ECG before every 4 week cycle when you take ATO.

If you do not achieve a complete remission during induction you will be taken off study.

If at any point during the study your white blood cell count rises above 10,000, you will receive idarubicin by vein over 30 minutes.

You will remain in the hospital for about the first 7 days of induction. After that, you must remain in Houston for the next 3-4 weeks. Once in the maintenance phase, you may be treated at home, but must return to M. D. Anderson for study visits.

After maintenance is complete, you will have follow-up visits for an additional 2 years. If at any time during the active study or follow-up the disease gets worse or intolerable side effects occur, you will be taken off the study.

If you had a low or high white blood cell count when you joined the study, you will have follow-up visits every 3 months for 2 years. At these visits, blood (about 1 tablespoon) will be drawn for routine tests and you will have a bone marrow aspirate.

This is an investigational study. Idarubicin, ATRA and ATO are FDA approved and commercially available. However, their use in this study and in this combination is considered investigational. Its use in APL patients is investigational. Up to 80 patients will take part in this multicenter study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Acute Promyelocytic Leukemia (APL) With All-Trans Retinoic Acid, and Arsenic +/- Idarubicin
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Induction ATRA + ATO + Idarubicin All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATRA 45 mg/m2 daily by mouth beginning day 1; ATO 0.15 mg/kg by vein daily beginning on day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days starting on day 1.	Drug: All-Trans Retinoic Acid (ATRA); Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; Drug: Arsenic Trioxide (ATO); Induction: 0.15 mg/kg daily IV beginning day 1; Drug: Idarubicin; 12 mg/m2 one dose only (may be given on day 1 to 5 of induction) If either ATRA or ATO are discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses will be administered once every 4 to 5 weeks (depending on the recovery of counts) until 28 weeks has elapsed from the Complete Recovery date.; Other Names: Idamycin
Experimental: Maintenance All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATO 0.15 mg/kg by vein over 2 hours Monday-Friday for 4 weeks, then a 4-week break. ATRA 45 mg/m2 by mouth every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.	Drug: All-Trans Retinoic Acid (ATRA); Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; Drug: Arsenic Trioxide (ATO); Induction: 0.15 mg/kg daily IV beginning day 1; Drug: Idarubicin; 12 mg/m2 one dose only (may be given on day 1 to 5 of induction) If either ATRA or ATO are discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses will be administered once every 4 to 5 weeks (depending on the recovery of counts) until 28 weeks has elapsed from the Complete Recovery date.; Other Names: Idamycin
Experimental: Induction ATRA + ATO + GO All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) + Gemtuzumab Ozogamicin (GO) ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1; ATO 0.15 mg/kg IV daily beginning on day 1; GO 9 mg/m2 on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1. 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.	Drug: All-Trans Retinoic Acid (ATRA); Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; Drug: Arsenic Trioxide (ATO); Induction: 0.15 mg/kg daily IV beginning day 1; Drug: Idarubicin; 12 mg/m2 one dose only (may be given on day 1 to 5 of induction) If either ATRA or ATO are discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses will be administered once every 4 to 5 weeks (depending on the recovery of counts) until 28 weeks has elapsed from the Complete Recovery date.; Other Names: Idamycin ; Drug: Gemtuzumab Ozogamicin; Induction: 9 mg/m2 on day 1 of induction

Outcome Measures

Primary Outcome Measures

1. Complete Response (CR) Rate [1 month, up to day 85 of treatment]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. A diagnosis of APL based on the presence of the PML-RAR alpha fusion gene by cytogenetics, PCR, or POD test.

2. Provision of written informed consent.

3. Patients in whom therapy for APL was initiated on an emergent basis are eligible

Exclusion Criteria:

1. First trimester of pregnancy (ATRA is teratogenic)

2. Corrected QT (QTC) interval must not be greater than 480 milliseconds.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Farhad Ravandi-Kashani, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00413166
• Other Study ID Numbers: 2006-0706; NCI-2012-01395
• First Posted: Dec 19, 2006
• Last Update Posted: May 7, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by M.D. Anderson Cancer Center: Acute Promyelocytic Leukemia; APL; ATRA; All-Trans Retinoic Acid; Arsenic Trioxide; Theophylline; Gemtuzumab
• Additional relevant MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute; Idarubicin; Tretinoin; Arsenic Trioxide; Gemtuzumab

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	ATRA + ATO: Low Risk (WBC<10,000)	ATRA+ATO+IDA: High Risk (WBC >10,000)	ATO+ATRA+GO	Total
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 Participants	57	5	16	78
Age (Count of Participants)
<=18 years	1 1.8%	0 0%	0 0%	1 1.3%
Between 18 and 65 years	46 80.7%	5 100%	15 93.8%	66 84.6%
>=65 years	10 17.5%	0 0%	1 6.3%	11 14.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49	38	44	47
Sex: Female, Male (Count of Participants)
Female	33 57.9%	2 40%	12 75%	47 60.3%
Male	24 42.1%	3 60%	4 25%	31 39.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 3.5%	0 0%	0 0%	2 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	6 10.5%	1 20%	4 25%	11 14.1%
White	46 80.7%	2 40%	12 75%	60 76.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	3 5.3%	2 40%	0 0%	5 6.4%
Region of Enrollment (participants) [Number]
United States	57 100%	5 100%	16 100%	78 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response (CR) Rate
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

Outcome Measure Data

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
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.
Measure Participants	56	5	16
Count of Participants [Participants]	55 96.5%	5 100%	15 93.8%

Adverse Events

Time Frame	Up to 7 years
Arm/Group Title	ATRA + ATO: Low Risk (WBC<10,000)		ATRA+ATO+IDA: High Risk (WBC >10,000)		ATO+ATRA+GO
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/57 (1.8%)		0/5 (0%)		1/16 (6.3%)
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 (38.6%)		4/5 (80%)		4/16 (25%)
Blood and lymphatic system disorders
Hemorrhage	2/57 (3.5%)	2	0/5 (0%)	0	1/16 (6.3%)	1
Cardiac disorders
Cardiac Troponin I	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Chest Pain	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Left Ventricular Diastolic Dysfunction	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Prolonged QTc interval	2/57 (3.5%)	3	0/5 (0%)	0	1/16 (6.3%)	2
Gastrointestinal disorders
Appendectomy	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Nausea/Vomiting	0/57 (0%)	0	0/5 (0%)	0	1/16 (6.3%)	2
General disorders
Fatigue	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Headache	9/57 (15.8%)	13	2/5 (40%)	2	0/16 (0%)	0
Death	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Pain	2/57 (3.5%)	2	0/5 (0%)	0	2/16 (12.5%)	2
Infections and infestations
Infection	5/57 (8.8%)	6	0/5 (0%)	0	3/16 (18.8%)	3
Investigations
Retinoic acid syndrome	4/57 (7%)	4	2/5 (40%)	2	1/16 (6.3%)	1
Metabolism and nutrition disorders
Elevated Transaminases	1/57 (1.8%)	2	2/5 (40%)	4	0/16 (0%)	0
Elevated Amylase	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Elevated Creatinine	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Elevated Lipase	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Hyperbilirubinemia	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Hypoglycemia	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Nervous system disorders
Depressed level of Consciousness	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Peripharal Neuropathy	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Sensory Neuropathy	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Renal and urinary disorders
Renal Insufficiency	1/57 (1.8%)	1	0/5 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Hemoptysis	0/57 (0%)	0	0/5 (0%)	0	1/16 (6.3%)	1
Pulmonary Embolism	0/57 (0%)	0	0/5 (0%)	0	1/16 (6.3%)	1
Respiratory Failure	2/57 (3.5%)	2	0/5 (0%)	0	0/16 (0%)	0
Skin and subcutaneous tissue disorders
Rash/desquamation	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Surgical and medical procedures
Hernia Repair	1/57 (1.8%)	1	0/5 (0%)	0	0/16 (0%)	0
Other (Not Including 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	5/57 (8.8%)		0/5 (0%)		1/16 (6.3%)
Infections and infestations
Infection	5/57 (8.8%)	5	0/5 (0%)	0	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.