Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00866918
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 108
• Locations: 111
• Arms: 2
• Patients Per Site: 1

Study Details

Study Description

Brief Summary

This phase III trial is studying combination chemotherapy to see how well it works in treating young patients with newly diagnosed acute promyelocytic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Childhood Acute Promyelocytic Leukemia (M3); Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies	Drug: arsenic trioxide; Drug: mitoxantrone hydrochloride; Other: diagnostic laboratory biomarker analysis; Drug: idarubicin; Drug: tretinoin; Drug: cytarabine; Drug: mercaptopurine tablet; Drug: methotrexate	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To decrease the total anthracycline dose from the best current published results in standard risk childhood acute promyelocytic leukemia (APL) while still maintaining a comparable event-free survival (EFS).

SECONDARY OBJECTIVES:

1. To assign treatment based on risk stratification by white blood cell count (WBC) at diagnosis.

2. To estimate the induction failure rate, toxic death rate, disease-free survival rate and overall survival rate in both standard and high risk APL patients.

3. To monitor for cardiotoxicity in an idarubicin/mitoxantrone based regimen. IV. To document the toxicity of a traditional chemotherapy/all-trans retinoic acid (ATRA) (tretinoin) based regimen combined with arsenic trioxide therapy.

4. To study the relationship of Fms-like tyrosine kinase 3 (FLT3) mutations to clinical features and outcome in APL.

5. To study risk factors for pseudotumor cerebri in APL. VII. To study the relationship of early progenitor cell involvement to treatment failure in FLT3 positive APL.

6. To compare the EFS of children enrolled on AAML0631 with the EFS of children enrolled on C9710 who were between the ages of 2 and 21 and did not receive arsenic trioxide.

7. To estimate the proportion of patients who carry a cryptic t(15;17), i.e., those who are positive for a promyelocytes.(PML)-retinoic acid receptor alpha (RARA) fusion transcript by polymerase chain reaction (PCR) analysis but have normal chromosomes.

8. To estimate the proportion of patients with variant RARA partners. XI. To compare the outcome of patients with only a t(15;17) with that of patients who carry a t(15;17) and other chromosomal abnormalities.

OUTLINE: This is a multicenter study. Patients are treated based on risk factor (standard-risk [WBC less than 10,000/mm^{3] or high-risk [WBC 10,000/mm}3 or higher]).

INDUCTION THERAPY:

STANDARD-RISK: Patients receive tretinoin orally (PO) twice daily (BID) on days 1-30 and idarubicin intravenously (IV) over 15 minutes once on days 3, 5, and 7.

HIGH-RISK: Patients receive tretinoin PO BID on days 1-30 and idarubicin IV over 15 minutes once on days 1, 3, and 5. Patients proceed to consolidation therapy one week later or when blood counts recover.

CONSOLIDATION THERAPY:

CONSOLIDATION 1: Patients receive arsenic trioxide IV over 2 hours on days 1-5, 8-12, 15-19, 22-26, and 29-33 and tretinoin PO BID on days 1-14. Treatment repeats every 5 weeks for 2 courses, followed by a 2-week break, and then treatment repeats for 2 more courses. Beginning 1 week later or when blood counts recover, patients proceed to consolidation 2.

CONSOLIDATION 2: Patients receive cytarabine intrathecally (IT) on day 1, tretinoin PO BID on days 1-14, high-dose cytarabine IV over 3 hours every 12 hours on days 1-3, and mitoxantrone hydrochloride IV over 15-30 minutes once on days 3 and 4. Patients proceed to consolidation 3 1 week later or when blood counts recover.

CONSOLIDATION 3: Patients receive cytarabine IT on day 1, tretinoin PO BID on days 1-14, and idarubicin IV over 15 minutes once daily on days 1, 3, and 5. High-risk patients and those standard-risk patients who are positive for minimal residual disease by real-time quantitative (RQ)-PCR receive consolidation 4 one week later or when blood counts recover. All other standard-risk patients proceed to maintenance therapy.

CONSOLIDATION 4 (patients with high-risk cytology): Patients receive cytarabine IT on day 1, tretinoin PO BID on days 1-14, high-dose cytarabine IV over 3 hours every 12 hours on days 1-3, and idarubicin IV over 15 minutes once on day 4. Patients who demonstrate molecular complete remission (CR) and remain in hematological CR proceed to maintenance therapy 1 week later or when blood counts recover.

MAINTENANCE THERAPY: Patients receive cytarabine IT on day 1 (course 1 only), tretinoin PO BID on days 1-14, mercaptopurine PO once daily (QD) on days 1-84, methotrexate PO once on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 9 courses.

After completion of study treatment, patients are followed every month for 1 year, every 3 months for 2 years, every 6 months for 2 years, and then annually for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Risk Adapted Treatment of Newly Diagnosed Childhood Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide (Trisenox® IND# 103, 331) During Consolidation
• Actual Study Start Date: Mar 9, 2009
• Actual Primary Completion Date: Jun 30, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Standard Risk (WBC < 10000/uL) See Detailed Description	Drug: arsenic trioxide; Given IV; Other Names: Arsenic (III) Oxide Arsenic Sesquioxide Arsenous Acid Anhydride AS2O3 Trisenox ; Drug: mitoxantrone hydrochloride; Given IV; Other Names: CL 232315 DHAD DHAQ Novantrone ; Other: diagnostic laboratory biomarker analysis; Correlative studies; Drug: idarubicin; Given IV; Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA ; Drug: tretinoin; Given orally; Other Names: ATRA Retin-A TRA ; Drug: cytarabine; Given IT or IV; Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside ; Drug: mercaptopurine tablet; Given orally; Other Names: 6-mercaptopurine 6-MP Leukerin MP ; Drug: methotrexate; Given orally; Other Names: amethopterin Folex methylaminopterin Mexate MTX
Active Comparator: High Risk (WBC > 10000/uL) See Detailed Description	Drug: arsenic trioxide; Given IV; Other Names: Arsenic (III) Oxide Arsenic Sesquioxide Arsenous Acid Anhydride AS2O3 Trisenox ; Drug: mitoxantrone hydrochloride; Given IV; Other Names: CL 232315 DHAD DHAQ Novantrone ; Other: diagnostic laboratory biomarker analysis; Correlative studies; Drug: idarubicin; Given IV; Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA ; Drug: tretinoin; Given orally; Other Names: ATRA Retin-A TRA ; Drug: cytarabine; Given IT or IV; Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside ; Drug: mercaptopurine tablet; Given orally; Other Names: 6-mercaptopurine 6-MP Leukerin MP ; Drug: methotrexate; Given orally; Other Names: amethopterin Folex methylaminopterin Mexate MTX

Outcome Measures

Primary Outcome Measures

1. Event-free Survival (EFS) [At 3 years from study entry]

   EFS - time from study entry until failure to achieve complete remission during consolidation, relapse, or death. For further clarification see definitions provided in the protocol.

Secondary Outcome Measures

1. Hematologic Remission Rate [End of consolidation, course 1: up to 5 months]

   Proportion of patients in hematologic remission at end of consolidation, course 1 are reported.

2. Hematologic, Molecular, and Cytogenetic Remission Rate [End of consolidation, course 3; up to 7 months (for Standard Risk) or end of consolidation, course 4; up to 9 months (for High Risk)]

   Proportion of patients in hematologic, molecular, and cytogenetic remission at end of consolidation, course 3 and 4 are reported. Patients were determined to be in remission by all three criteria.

3. Overall Survival (OS) [At 3 years from study entry]

   OS - time from study entry to death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be newly diagnosed with a clinical diagnosis of acute promyelocytic leukemia initially by morphology (bone marrow or peripheral blood); bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted; APL is considered a hematological emergency and treatment should be initiated as quickly as possible without waiting for molecular or cytogenetic/fluorescence in situ hybridization (FISH) confirmation; for patients who are unable to begin receiving ATRA in a timely manner following a presumed diagnosis of APL, consideration should be given to initiating ATRA and proceeding with treatment outside of the AAML0631 protocol; if the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate PML-RARA and/or RARA-PML transcripts by RQ-PCR to be eligible; patients without evidence of APL by bone marrow or peripheral blood morphology but with isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis) are eligible provided that the t(15;17) translocation is documented on either marrow or tumor tissue by cytogenetics, FISH, or PCR prior to study enrollment; in this situation, touch preps from the tumor site can be evaluated by FISH with PML-RARA probes; NOTE: A lumbar puncture is not required to be enrolled on study; if the diagnosis of APL is known or suspected, extreme caution must be exercised in performing a lumbar puncture during active coagulopathy; in addition a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma if central nervous system (CNS) disease is suspected or proven; if CNS disease is documented, patients are still eligible

• No minimal performance status criteria

• The patient must not have received systemic definitive treatment for APL or other suspected leukemia, including cytotoxic chemotherapy, retinoids, or arsenic; prior therapy with corticosteroids, hydroxyurea, or leukopheresis will not exclude the patient; if a patient received intrathecal cytarabine prior to the diagnosis of APL being known, the patient will still be eligible as long as they meet all other eligibility requirements

Exclusion Criteria:

• Pregnant women or nursing mothers are excluded; treatment under this protocol would expose an unborn child to significant risks; patients should not be pregnant or plan to become pregnant while on treatment; women and men of reproductive potential should agree to use an effective means of birth control; there is an extremely high risk of fetal malformation if pregnancy occurs while on ATRA in any amount even for short periods

• Patients with a pre-existing prolonged QT Syndrome will not be eligible for this protocol due to the use of arsenic trioxide which can prolong the QT interval

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Children's Oncology Group	Arcadia	California	United States	91006-3776
5	Southern California Permanente Medical Group	Downey	California	United States	90242
6	Loma Linda University Medical Center	Loma Linda	California	United States	92354
7	Miller Children's Hospital	Long Beach	California	United States	90806
8	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
9	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
10	Children's Hospital Central California	Madera	California	United States	93636-8762
11	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
12	Childrens Hospital of Orange County	Orange	California	United States	92868-3874
13	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
14	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
15	University of California San Francisco Medical Center-Parnassus	San Francisco	California	United States	94143
16	Children's Hospital Colorado	Aurora	Colorado	United States	80045
17	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
18	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
19	Children's National Medical Center	Washington	District of Columbia	United States	20010
20	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia	United States	20057
21	Lee Memorial Health System	Fort Myers	Florida	United States	33901
22	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida	United States	32207-8426
23	Florida Hospital	Orlando	Florida	United States	32803
24	Nemours Childrens Clinic - Orlando	Orlando	Florida	United States	32806
25	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
26	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
27	All Children's Hospital	Saint Petersburg	Florida	United States	33701
28	Saint Joseph Children's Hospital of Tampa	Tampa	Florida	United States	33607
29	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
30	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
31	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
32	University of Hawaii	Honolulu	Hawaii	United States	96813
33	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60614
34	Loyola University Medical Center	Maywood	Illinois	United States	60153
35	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois	United States	60453
36	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61602
37	Southern Illinois University	Springfield	Illinois	United States	62702
38	Indiana University Medical Center	Indianapolis	Indiana	United States	46202
39	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
40	Saint Vincent Hospital and Health Services	Indianapolis	Indiana	United States	46260
41	University of Kentucky	Lexington	Kentucky	United States	40536
42	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
43	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
44	Eastern Maine Medical Center	Bangor	Maine	United States	04401
45	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
46	Johns Hopkins University	Baltimore	Maryland	United States	21287
47	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
48	Baystate Medical Center	Springfield	Massachusetts	United States	01199
49	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
50	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
51	Wayne State University-Karmanos Cancer Institute	Detroit	Michigan	United States	48201
52	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
53	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
54	Michigan State University - Breslin Cancer Center	Lansing	Michigan	United States	48910
55	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
56	Mayo Clinic	Rochester	Minnesota	United States	55905
57	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
58	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
59	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
60	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
61	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
62	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
63	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
64	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
65	Saint Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
66	Overlook Hospital	Summit	New Jersey	United States	07902
67	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
68	Montefiore Medical Center	Bronx	New York	United States	10467-2490
69	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
70	Columbia University Medical Center	New York	New York	United States	10032
71	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
72	University of North Carolina	Chapel Hill	North Carolina	United States	27599
73	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
74	Presbyterian Hospital	Charlotte	North Carolina	United States	28204
75	Duke University Medical Center	Durham	North Carolina	United States	27710
76	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
77	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
78	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
79	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
80	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
81	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
82	The Children's Medical Center of Dayton	Dayton	Ohio	United States	45404
83	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
84	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
85	Oregon Health and Science University	Portland	Oregon	United States	97239
86	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
87	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
88	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
89	Palmetto Health Richland	Columbia	South Carolina	United States	29203
90	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
91	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
92	T C Thompson Children's Hospital	Chattanooga	Tennessee	United States	37403
93	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
94	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
95	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
96	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
97	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
98	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
99	Seattle Children's Hospital	Seattle	Washington	United States	98105
100	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
101	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
102	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
103	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
104	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
105	IWK Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9
106	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
107	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
108	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
109	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
110	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec	Canada	G1V 4G2
111	San Jorge Children's Hospital	Santurce		Puerto Rico	00912

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Gregory, MD, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00866918
• Other Study ID Numbers: AAML0631; NCI-2011-01904; CDR0000637184; AAML0631; AAML0631; U10CA098543
• First Posted: Mar 23, 2009
• Last Update Posted: Mar 25, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute; Cytarabine; Methotrexate; Mercaptopurine; Mitoxantrone; Idarubicin; Arsenic Trioxide; Tretinoin

Study Results

Participant Flow

Arm/Group Title	Standard Risk	High Risk
Arm/Group Description	WBC<10,000/MicroLiter	WBC>=10,000/MicroLiter
Period Title: Overall Study
STARTED	69	39
COMPLETED	53	27
NOT COMPLETED	16	12

Baseline Characteristics

Arm/Group Title	Standard Risk	High Risk	Total
Arm/Group Description	WBC<10,000/MicroLiter	WBC>=10,000/MicroLiter	Total of all reporting groups
Overall Participants	69	39	108
Age (Count of Participants)
<=18 years	68 98.6%	38 97.4%	106 98.1%
Between 18 and 65 years	1 1.4%	1 2.6%	2 1.9%
>=65 years	0 0%	0 0%	0 0%
Age (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	4915.25 (1627.27)	4921.33 (1747.04)	4917.44 (1663.37)
Sex: Female, Male (Count of Participants)
Female	37 53.6%	25 64.1%	62 57.4%
Male	32 46.4%	14 35.9%	46 42.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 23.2%	7 17.9%	23 21.3%
Not Hispanic or Latino	51 73.9%	31 79.5%	82 75.9%
Unknown or Not Reported	2 2.9%	1 2.6%	3 2.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2.9%	0 0%	2 1.9%
Asian	0 0%	3 7.7%	3 2.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 11.6%	4 10.3%	12 11.1%
White	52 75.4%	30 76.9%	82 75.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	7 10.1%	2 5.1%	9 8.3%
Region of Enrollment (participants) [Number]
Canada	2 2.9%	2 5.1%	4 3.7%
United States	67 97.1%	37 94.9%	104 96.3%

Outcome Measures

1. Primary Outcome

Title	Event-free Survival (EFS)
Description	EFS - time from study entry until failure to achieve complete remission during consolidation, relapse, or death. For further clarification see definitions provided in the protocol.
Time Frame	At 3 years from study entry

Outcome Measure Data

Analysis Population Description

Ineligible and inevaluable patients are excluded from analyses of EFS.

Arm/Group Title	Standard Risk	High Risk
Arm/Group Description	WBC<10,000/MicroLiter	WBC>=10,000/MicroLiter
Measure Participants	66	35
Number (95% Confidence Interval) [Percentage of participants]	95.4 138.3%	82.9 212.6%

2. Secondary Outcome

Title	Hematologic Remission Rate
Description	Proportion of patients in hematologic remission at end of consolidation, course 1 are reported.
Time Frame	End of consolidation, course 1: up to 5 months

Outcome Measure Data

Analysis Population Description

Patients who were ineligible (n=6), inevaluable (n=1), or who electively withdrew during Induction (n=4) were excluded.

Arm/Group Title	Standard Risk	High Risk
Arm/Group Description	WBC<10,000/MicroLiter	WBC>=10,000/MicroLiter
Measure Participants	63	34
Number [Proportion of participants]	1.0000 1.4%	0.8824 2.3%

3. Secondary Outcome

Title	Hematologic, Molecular, and Cytogenetic Remission Rate
Description	Proportion of patients in hematologic, molecular, and cytogenetic remission at end of consolidation, course 3 and 4 are reported. Patients were determined to be in remission by all three criteria.
Time Frame	End of consolidation, course 3; up to 7 months (for Standard Risk) or end of consolidation, course 4; up to 9 months (for High Risk)

Outcome Measure Data

Analysis Population Description

Patients who were ineligible (n=6), inevaluable (n=1), or who electively withdrew during Induction (n=4) were excluded.

Arm/Group Title	Standard Risk	High Risk
Arm/Group Description	WBC<10,000/MicroLiter	WBC>=10,000/MicroLiter
Measure Participants	63	34
Number [Proportion of participants]	0.8095 1.2%	0.5882 1.5%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS - time from study entry to death.
Time Frame	At 3 years from study entry

Outcome Measure Data

Analysis Population Description

Ineligible and inevaluable patients are excluded from analyses of OS.

Arm/Group Title	Standard Risk	High Risk
Arm/Group Description	WBC<10,000/MicroLiter	WBC>=10,000/MicroLiter
Measure Participants	66	35
Number (95% Confidence Interval) [Percentage of participants]	98.4 142.6%	85.7 219.7%

Adverse Events

Adverse Event Reporting Description	Patients who were study ineligible (n=6) or inevaluable (n=1, RQ-PCR negative at diagnosis) were excluded from number at risk in the Serious and Other Adverse event data tables.
Arm/Group Title	Standard Risk		High Risk
Arm/Group Description	WBC<10,000/MicroLiter		WBC>=10,000/MicroLiter
All Cause Mortality
	Standard Risk		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Risk		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/66 (25.8%)		14/35 (40%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	0/66 (0%)		1/35 (2.9%)
Febrile neutropenia	6/66 (9.1%)		1/35 (2.9%)
Cardiac disorders
Asystole	0/66 (0%)		1/35 (2.9%)
Sinus tachycardia	0/66 (0%)		1/35 (2.9%)
Gastrointestinal disorders
Abdominal pain	0/66 (0%)		1/35 (2.9%)
Nausea	1/66 (1.5%)		1/35 (2.9%)
Vomiting	1/66 (1.5%)		1/35 (2.9%)
General disorders
Fever	0/66 (0%)		1/35 (2.9%)
Multi-organ failure	0/66 (0%)		2/35 (5.7%)
Pain	1/66 (1.5%)		0/35 (0%)
Infections and infestations
Bronchial infection	1/66 (1.5%)		0/35 (0%)
Catheter related infection	2/66 (3%)		3/35 (8.6%)
Endocarditis infective	0/66 (0%)		1/35 (2.9%)
Infections and infestations - Other, specify	4/66 (6.1%)		3/35 (8.6%)
Sepsis	2/66 (3%)		3/35 (8.6%)
Skin infection	1/66 (1.5%)		0/35 (0%)
Urinary tract infection	1/66 (1.5%)		0/35 (0%)
Investigations
Alanine aminotransferase increased	1/66 (1.5%)		1/35 (2.9%)
Aspartate aminotransferase increased	1/66 (1.5%)		1/35 (2.9%)
Blood bilirubin increased	0/66 (0%)		1/35 (2.9%)
INR increased	0/66 (0%)		1/35 (2.9%)
Neutrophil count decreased	0/66 (0%)		1/35 (2.9%)
Platelet count decreased	0/66 (0%)		1/35 (2.9%)
White blood cell decreased	0/66 (0%)		1/35 (2.9%)
Metabolism and nutrition disorders
Acidosis	0/66 (0%)		1/35 (2.9%)
Anorexia	1/66 (1.5%)		0/35 (0%)
Dehydration	1/66 (1.5%)		1/35 (2.9%)
Hyperglycemia	0/66 (0%)		1/35 (2.9%)
Hyperkalemia	0/66 (0%)		1/35 (2.9%)
Hypocalcemia	0/66 (0%)		1/35 (2.9%)
Hypomagnesemia	0/66 (0%)		1/35 (2.9%)
Hyponatremia	0/66 (0%)		1/35 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	1/66 (1.5%)		0/35 (0%)
Nervous system disorders
Syncope	0/66 (0%)		1/35 (2.9%)
Psychiatric disorders
Depression	0/66 (0%)		1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/66 (1.5%)		2/35 (5.7%)
Dyspnea	0/66 (0%)		1/35 (2.9%)
Respiratory failure	1/66 (1.5%)		1/35 (2.9%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	0/66 (0%)		1/35 (2.9%)
Vascular disorders
Hypotension	3/66 (4.5%)		1/35 (2.9%)
Other (Not Including Serious) Adverse Events
	Standard Risk		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/66 (92.4%)		33/35 (94.3%)
Blood and lymphatic system disorders
Anemia	1/66 (1.5%)		0/35 (0%)
Blood and lymphatic system disorders - Other, specify	2/66 (3%)		0/35 (0%)
Disseminated intravascular coagulation	4/66 (6.1%)		3/35 (8.6%)
Febrile neutropenia	29/66 (43.9%)		20/35 (57.1%)
Cardiac disorders
Cardiac disorders - Other, specify	1/66 (1.5%)		2/35 (5.7%)
Ventricular arrhythmia	1/66 (1.5%)		1/35 (2.9%)
Ventricular tachycardia	0/66 (0%)		1/35 (2.9%)
Ear and labyrinth disorders
Ear pain	1/66 (1.5%)		0/35 (0%)
Eye disorders
Eye disorders - Other, specify	1/66 (1.5%)		1/35 (2.9%)
Papilledema	0/66 (0%)		1/35 (2.9%)
Retinopathy	0/66 (0%)		1/35 (2.9%)
Vitreous hemorrhage	2/66 (3%)		0/35 (0%)
Gastrointestinal disorders
Abdominal pain	3/66 (4.5%)		4/35 (11.4%)
Anal pain	1/66 (1.5%)		1/35 (2.9%)
Ascites	1/66 (1.5%)		0/35 (0%)
Colitis	1/66 (1.5%)		1/35 (2.9%)
Constipation	2/66 (3%)		0/35 (0%)
Diarrhea	3/66 (4.5%)		2/35 (5.7%)
Dysphagia	1/66 (1.5%)		0/35 (0%)
Enterocolitis	1/66 (1.5%)		0/35 (0%)
Esophageal pain	0/66 (0%)		1/35 (2.9%)
Esophageal ulcer	0/66 (0%)		1/35 (2.9%)
Esophagitis	0/66 (0%)		2/35 (5.7%)
Gastritis	1/66 (1.5%)		0/35 (0%)
Mucositis oral	12/66 (18.2%)		7/35 (20%)
Nausea	6/66 (9.1%)		0/35 (0%)
Oral hemorrhage	1/66 (1.5%)		1/35 (2.9%)
Oral pain	3/66 (4.5%)		2/35 (5.7%)
Pancreatitis	3/66 (4.5%)		0/35 (0%)
Rectal fistula	1/66 (1.5%)		0/35 (0%)
Rectal hemorrhage	1/66 (1.5%)		0/35 (0%)
Rectal pain	1/66 (1.5%)		2/35 (5.7%)
Toothache	1/66 (1.5%)		0/35 (0%)
Typhlitis	2/66 (3%)		1/35 (2.9%)
Vomiting	6/66 (9.1%)		0/35 (0%)
General disorders
Fever	6/66 (9.1%)		2/35 (5.7%)
Pain	1/66 (1.5%)		8/35 (22.9%)
Hepatobiliary disorders
Cholecystitis	0/66 (0%)		1/35 (2.9%)
Immune system disorders
Allergic reaction	1/66 (1.5%)		0/35 (0%)
Infections and infestations
Anorectal infection	1/66 (1.5%)		0/35 (0%)
Appendicitis	0/66 (0%)		1/35 (2.9%)
Appendicitis perforated	0/66 (0%)		1/35 (2.9%)
Bone infection	1/66 (1.5%)		0/35 (0%)
Bronchial infection	1/66 (1.5%)		0/35 (0%)
Catheter related infection	7/66 (10.6%)		4/35 (11.4%)
Enterocolitis infectious	3/66 (4.5%)		1/35 (2.9%)
Esophageal infection	1/66 (1.5%)		0/35 (0%)
Hepatic infection	0/66 (0%)		1/35 (2.9%)
Infections and infestations - Other, specify	15/66 (22.7%)		15/35 (42.9%)
Lip infection	0/66 (0%)		2/35 (5.7%)
Lung infection	3/66 (4.5%)		6/35 (17.1%)
Lymph gland infection	1/66 (1.5%)		0/35 (0%)
Mucosal infection	0/66 (0%)		1/35 (2.9%)
Nail infection	1/66 (1.5%)		0/35 (0%)
Otitis externa	1/66 (1.5%)		0/35 (0%)
Otitis media	2/66 (3%)		1/35 (2.9%)
Papulopustular rash	1/66 (1.5%)		0/35 (0%)
Pharyngitis	1/66 (1.5%)		0/35 (0%)
Sepsis	1/66 (1.5%)		0/35 (0%)
Sinusitis	2/66 (3%)		1/35 (2.9%)
Skin infection	5/66 (7.6%)		1/35 (2.9%)
Small intestine infection	0/66 (0%)		1/35 (2.9%)
Soft tissue infection	2/66 (3%)		0/35 (0%)
Splenic infection	0/66 (0%)		1/35 (2.9%)
Stoma site infection	1/66 (1.5%)		0/35 (0%)
Tooth infection	0/66 (0%)		1/35 (2.9%)
Upper respiratory infection	2/66 (3%)		3/35 (8.6%)
Urinary tract infection	3/66 (4.5%)		0/35 (0%)
Vaginal infection	1/66 (1.5%)		0/35 (0%)
Vulval infection	1/66 (1.5%)		0/35 (0%)
Wound infection	2/66 (3%)		0/35 (0%)
Injury, poisoning and procedural complications
Vascular access complication	0/66 (0%)		1/35 (2.9%)
Investigations
Activated partial thromboplastin time prolonged	2/66 (3%)		2/35 (5.7%)
Alanine aminotransferase increased	14/66 (21.2%)		7/35 (20%)
Alkaline phosphatase increased	0/66 (0%)		2/35 (5.7%)
Aspartate aminotransferase increased	8/66 (12.1%)		2/35 (5.7%)
Blood bilirubin increased	5/66 (7.6%)		2/35 (5.7%)
Creatinine increased	0/66 (0%)		1/35 (2.9%)
Electrocardiogram QT corrected interval prolonged	16/66 (24.2%)		6/35 (17.1%)
Fibrinogen decreased	2/66 (3%)		2/35 (5.7%)
GGT increased	3/66 (4.5%)		0/35 (0%)
Investigations - Other, specify	0/66 (0%)		1/35 (2.9%)
Lipase increased	1/66 (1.5%)		0/35 (0%)
Lymphocyte count decreased	2/66 (3%)		1/35 (2.9%)
Neutrophil count decreased	4/66 (6.1%)		2/35 (5.7%)
Platelet count decreased	3/66 (4.5%)		0/35 (0%)
Weight gain	1/66 (1.5%)		0/35 (0%)
Weight loss	3/66 (4.5%)		0/35 (0%)
White blood cell decreased	3/66 (4.5%)		0/35 (0%)
Metabolism and nutrition disorders
Acidosis	0/66 (0%)		1/35 (2.9%)
Anorexia	5/66 (7.6%)		5/35 (14.3%)
Dehydration	2/66 (3%)		1/35 (2.9%)
Hypercalcemia	1/66 (1.5%)		0/35 (0%)
Hyperglycemia	13/66 (19.7%)		4/35 (11.4%)
Hyperkalemia	2/66 (3%)		1/35 (2.9%)
Hypernatremia	2/66 (3%)		1/35 (2.9%)
Hypertriglyceridemia	1/66 (1.5%)		2/35 (5.7%)
Hypocalcemia	4/66 (6.1%)		2/35 (5.7%)
Hypokalemia	13/66 (19.7%)		9/35 (25.7%)
Hyponatremia	4/66 (6.1%)		2/35 (5.7%)
Hypophosphatemia	5/66 (7.6%)		3/35 (8.6%)
Metabolism and nutrition disorders - Other, specify	1/66 (1.5%)		0/35 (0%)
Tumor lysis syndrome	0/66 (0%)		1/35 (2.9%)
Musculoskeletal and connective tissue disorders
Back pain	1/66 (1.5%)		0/35 (0%)
Muscle weakness right-sided	0/66 (0%)		1/35 (2.9%)
Pain in extremity	2/66 (3%)		0/35 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/66 (1.5%)		0/35 (0%)
Nervous system disorders
Arachnoiditis	1/66 (1.5%)		0/35 (0%)
Dysarthria	1/66 (1.5%)		0/35 (0%)
Headache	16/66 (24.2%)		4/35 (11.4%)
Intracranial hemorrhage	0/66 (0%)		1/35 (2.9%)
Nervous system disorders - Other, specify	1/66 (1.5%)		0/35 (0%)
Psychiatric disorders
Agitation	1/66 (1.5%)		0/35 (0%)
Depression	1/66 (1.5%)		0/35 (0%)
Insomnia	0/66 (0%)		1/35 (2.9%)
Suicide attempt	1/66 (1.5%)		1/35 (2.9%)
Renal and urinary disorders
Acute kidney injury	1/66 (1.5%)		2/35 (5.7%)
Hematuria	1/66 (1.5%)		0/35 (0%)
Renal and urinary disorders - Other, specify	1/66 (1.5%)		0/35 (0%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	2/66 (3%)		1/35 (2.9%)
Atelectasis	0/66 (0%)		1/35 (2.9%)
Bronchopulmonary hemorrhage	3/66 (4.5%)		0/35 (0%)
Bronchospasm	1/66 (1.5%)		0/35 (0%)
Dyspnea	2/66 (3%)		2/35 (5.7%)
Epistaxis	3/66 (4.5%)		1/35 (2.9%)
Hypoxia	8/66 (12.1%)		3/35 (8.6%)
Laryngeal mucositis	1/66 (1.5%)		0/35 (0%)
Laryngeal obstruction	1/66 (1.5%)		0/35 (0%)
Pleural effusion	1/66 (1.5%)		3/35 (8.6%)
Pleural hemorrhage	1/66 (1.5%)		0/35 (0%)
Pneumonitis	2/66 (3%)		0/35 (0%)
Pulmonary edema	1/66 (1.5%)		1/35 (2.9%)
Respiratory failure	0/66 (0%)		1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders - Other, specify	2/66 (3%)		0/35 (0%)
Retinoic acid syndrome	4/66 (6.1%)		1/35 (2.9%)
Sore throat	0/66 (0%)		2/35 (5.7%)
Stridor	1/66 (1.5%)		0/35 (0%)
Tracheal stenosis	1/66 (1.5%)		0/35 (0%)
Skin and subcutaneous tissue disorders
Pain of skin	1/66 (1.5%)		0/35 (0%)
Rash maculo-papular	1/66 (1.5%)		3/35 (8.6%)
Skin and subcutaneous tissue disorders - Other, specify	1/66 (1.5%)		0/35 (0%)
Skin ulceration	0/66 (0%)		1/35 (2.9%)
Surgical and medical procedures
Surgical and medical procedures - Other, specify	1/66 (1.5%)		0/35 (0%)
Vascular disorders
Hematoma	1/66 (1.5%)		0/35 (0%)
Hypertension	3/66 (4.5%)		2/35 (5.7%)
Hypotension	4/66 (6.1%)		5/35 (14.3%)
Thromboembolic event	3/66 (4.5%)		1/35 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Must obtain prior Sponsor approval.