S0521, Combination Chemotherapy With or Without Gemtuzumab Followed By Tretinoin, Mercaptopurine, and Methotrexate or Observation in Treating Patients With Acute Promyelocytic Leukemia

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00492856
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 105
• Locations: 210
• Arms: 2
• Duration (Months): 101
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: 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. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Sometimes the cancer may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether combination chemotherapy is more effective than observation when given as maintenance therapy in treating acute promyelocytic leukemia.

PURPOSE: This randomized phase III trial is studying tretinoin, mercaptopurine, and methotrexate to see how well they work when given as maintenance therapy compared with observation after combination chemotherapy in treating patients with acute promyelocytic leukemia. (Randomization and observation group closed as of 8/15/10)

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: mercaptopurine; Drug: methotrexate; Drug: tretinoin	Phase 3

Detailed Description

OBJECTIVES:

• Compare disease-free survival (DFS) among patients with previously untreated low and intermediate risk acute promyelocytic leukemia (APL) who are PCR-negative for Promyelocytic-retinoic acid receptor alpha (PML-RARα) after consolidation therapy and receive maintenance therapy versus patients who receive no maintenance therapy. (Randomization and observation arm closed as of 8/15/10)

• Assess the toxicity of induction, consolidation and maintenance in these patients.

• Test whether gene expression profiles assessed prior to treatment are predictive of resistance to remission induction chemotherapy and correlate with detectable minimal residual disease post-consolidation therapy. (Only one patient was not in molecular remission after receiving consolidation. Therefore, the predictive value of pre-treatment gene expression profiling could not be determined and is not reported here).

• Investigate in a preliminarily manner the outcomes of patients who fail to achieve or maintain PCR-negative PML-RARα fusion gene after consolidation therapy when treated with gemtuzumab ozogamicin. (Only one patient was treated with gemtuzumab ozogamicin as part of protocol treatment. Therefore, results for this objective are not reported).

OUTLINE: This is a randomized, multicenter study.

• Induction therapy: Patients receive oral tretinoin twice daily until morphologic complete remission (CR) or for a maximum of 90 days in the absence of disease progression or unacceptable toxicity. Patients also receive cytarabine IV continuously on days 3-9 and daunorubicin hydrochloride IV on days 3-6.

• Consolidation therapy: Patients who achieve CR, CR with incomplete blood count recovery (CRi), or partial remission (PR) after induction therapy receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks. After a 2-week rest period, patients receive a second course of arsenic trioxide. Within 14-30 days after blood count recovery, patients receive oral tretinoin twice daily on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients receive a second course of tretinoin and daunorubicin hydrochloride after adequate blood count recovery.

• Post-consolidation therapy: Patients who do not achieve molecular CR (CRm), but do achieve CR or CRi and are still PML-RARα-positive after consolidation therapy, receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment repeats every 14 days for up to 6 courses or until PML-RARα-negative by PCR. (closed as of 8/15/10)Patients are stratified according to age (18 to 60 years vs > 60 years), acute promyelocytic leukemia (APL) risk group (low vs intermediate), and if the patient received consolidation therapy courses 3 or 4 (yes vs no) regardless of their CRm response. These patients are randomized to 1 of 2 treatment arms. (Randomization and observation arm closed as of 8/15/10) All patients are non-randomly assigned to receive post-consolidation therapy.

• Arm I: Beginning 14-30 days after blood count recovery, patients receive oral tretinoin twice daily on days 1-7, oral mercaptopurine once daily on days 1-14, and oral methotrexate on day 1. Treatment repeats every 2 weeks for up to 1 year.

• Arm II: Patients receive no further chemotherapy. Patients are followed every 3 months for 1 year. (Randomization and observation arm closed as of 8/15/10) Patients undergo blood collection periodically for cytogenetic studies. Samples are analyzed for PML-RARα fusion gene via reverse transcriptase-polymerase chain reaction (RT-PCR) assay and gene expression profiling.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: S0521, A Randomized Trial of Maintenance Versus Observation for Patients With Previously Untreated Low and Intermediate Risk Acute Promyelocytic Leukemia (APL), Phase III
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Post-consolidation therapy arm I Patients receive oral tretinoin twice daily on days 1-7, oral mercaptopurine once daily on days 1-14, and oral methotrexate on day 1. Treatment repeats every 2 weeks for up to 1 year.	Drug: mercaptopurine; Given orally; Drug: methotrexate; Given orally; Drug: tretinoin; Given orally
No Intervention: Post-consolidation therapy arm II Patients receive no further chemotherapy. Patients are followed every 3 months for 1 year. (Randomization and observation arm closed as of 8/15/10)

Outcome Measures

Primary Outcome Measures

1. 3-year Disease-free Survival (DFS) Rate [Up to 3 years]

   DFS measured from date of post-consolidation randomization until relapse of any kind or death from any cause. Observation censored at date of last follow-up for patients last known to be alive without report of relapse. Relapse from CR/CRi is occurrence of marrow blasts ≥ 5% or presence of Auer rods or presence of neoplastic promyelocytes; (re)appearance of leukemic blasts or neoplastic promyelocytes in the peripheral blood; or (re)appearance of extramedullary disease. Relapse from PR is sum of marrow blasts and promyelocytes ≥ 20%, or sum of marrow blasts and promyelocytes 6-19% with Auer rods and/or neoplastic promyelocytes; or (re)appearance of leukemic blasts or neoplastic promyelocytes in the peripheral blood; or (re)appearance of extramedullary disease. Relapse from CRc is reappearance of t(15;17) in cytogenetic analysis. Relapse from CRm/PRm is reappearance of PML-RARα by RT-PCR as defined by a normalized quotient > 10^-5 based on RT-PCR performed at appropriate central lab.

Secondary Outcome Measures

1. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [Up to 5 years]

   Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included. Only adverse events that are possibly, probably, or definitely related to study drug are reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Cytologically confirmed acute promyelocytic leukemia (APL) or the variant form of APL

• Previously untreated disease

• Low- or intermediate-risk disease

• Low-risk disease, defined as white blood cell (WBC) ≤ 10,000/mm^{3 and platelet count > 40,000/mm}3

• Intermediate-risk disease, defined as WBC ≤ 10,000/mm^{3 and platelet count ≤ 40,000/mm}3

• WBC and platelet count confirming low- or intermediate-risk disease must be obtained within 48 hours prior to study registration unless the patient received tretinoin therapy prior to study registration in which case the WBC and platelet count must be obtained within 48 hours prior to study therapy

• PML-RARα fusion gene positive by reverse transcriptase-polymerase chain reaction (RT-PCR) assay

• No recurrent disease

• Must be registered on clinical trials SWOG-9007 and SWOG-S9910

• Specimens must be collected prior to tretinoin therapy and may be collected after tretinoin therapy

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-3

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception for ≥ 1 month prior to, during, and for 2 months after completion of study treatment

• No unstable cardiac arrhythmia or unstable angina

• No other malignancy within the past 5 years except for the following:

• Adequately treated basal cell or squamous cell skin cancer

• Carcinoma in situ of the cervix

• Adequately treated stage I or II cancer (except for highly aggressive malignancies with a high rate of early relapse) currently in complete remission

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No more than 1 prior dose of intrathecal chemotherapy for acute leukemia

• No prior systemic chemotherapy, hydroxyurea, or leukapheresis for acute leukemia

• Prior tretinoin at a dose of ≤ 45 mg/m^2/day allowed provided it was received ≤ 5 days prior to study registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Sutter Cancer Center at Roseville Medical Center	Roseville	California	United States	95661
3	Sutter Cancer Center	Sacramento	California	United States	95816
4	Stanford Cancer Center	Stanford	California	United States	94305-5824
5	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
6	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
7	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
8	Hematology Oncology Associates of Illinois - Berwyn	Berwyn	Illinois	United States	60402
9	Illinois CancerCare - Bloomington	Bloomington%	Illinois	United States	61701
10	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
11	Graham Hospital	Canton	Illinois	United States	61520
12	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
13	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
14	Memorial Hospital	Carthage	Illinois	United States	62321
15	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
16	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
17	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
18	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
19	Eureka Community Hospital	Eureka	Illinois	United States	61530
20	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
21	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
22	Illinois CancerCare - Galesburg	Galesburg	Illinois	United States	61401
23	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
24	Mason District Hospital	Havana	Illinois	United States	62644
25	Kellogg Cancer Care Center	Highland Park	Illinois	United States	60035
26	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
27	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
28	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
29	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
30	McDonough District Hospital	Macomb	Illinois	United States	61455
31	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
32	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
33	La Grange Oncology Associates - Geneva	Naperville	Illinois	United States	60563
34	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
35	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
36	Community Cancer Center	Normal	Illinois	United States	61761
37	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
38	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
39	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
40	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
41	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
42	Proctor Hospital	Peoria	Illinois	United States	61614
43	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
44	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
45	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
46	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
47	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
48	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
49	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
50	Perry Memorial Hospital	Princeton	Illinois	United States	61356
51	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
52	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
53	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
54	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46845
55	McFarland Clinic, PC	Ames	Iowa	United States	50010
56	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
57	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
58	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
59	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
60	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
61	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
62	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
63	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
64	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
65	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
66	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
67	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
68	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
69	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
70	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
71	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
72	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
73	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
74	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67905
75	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
76	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
77	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
78	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
79	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
80	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
81	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
82	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
83	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
84	CCOP - Wichita	Wichita	Kansas	United States	67214
85	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
86	Wesley Medical Center	Wichita	Kansas	United States	67214
87	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
88	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
89	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine	United States	04401
90	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
91	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
92	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland	United States	21921
93	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
94	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
95	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
96	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
97	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
98	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
99	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
100	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
101	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
102	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
103	Hurley Medical Center	Flint	Michigan	United States	48503
104	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
105	Foote Memorial Hospital	Jackson	Michigan	United States	49201
106	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
107	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
108	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
109	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
110	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
111	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
112	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
113	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
114	St. John Macomb Hospital	Warren	Michigan	United States	48093
115	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
116	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
117	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
118	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
119	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
120	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
121	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
122	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
123	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
124	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
125	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
126	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
127	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
128	United Hospital	Saint Paul	Minnesota	United States	55102
129	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
130	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
131	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
132	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
133	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
134	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
135	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
136	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
137	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
138	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
139	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
140	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
141	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
142	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
143	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
144		Great Falls	Montana	United States	59405
145	Northern Montana Hospital	Havre	Montana	United States	59501
146	St. Peter's Hospital	Helena	Montana	United States	59601
147	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
148	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
149	Community Medical Center	Missoula	Montana	United States	59801
150	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
151	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
152	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
153	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
154	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
155	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
156	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York	United States	10466
157	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
158	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
159	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York	United States	11042
160	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
161	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
162	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
163	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
164	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
165	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
166	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
167	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
168	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
169	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
170	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
171	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
172	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
173	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
174	St. Rita's Medical Center	Lima	Ohio	United States	45801
175	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
176	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
177	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
178	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
179	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
180	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
181	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
182	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
183	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
184	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
185	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
186	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
187	Columbia Basin Hematology	Kennewick	Washington	United States	99336
188	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington	United States	98273
189	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington	United States	98370
190	Harborview Medical Center	Seattle	Washington	United States	98104
191	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
192	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
193	Group Health Central Hospital	Seattle	Washington	United States	98112
194	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
195	Polyclinic First Hill	Seattle	Washington	United States	98122
196	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
197	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
198	Evergreen Hematology and Oncology, PS	Spokane	Washington	United States	99218
199	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
200	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
201	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
202	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
203	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
204	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
205	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
206	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
207	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
208	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
209	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
210	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Steven E. Coutre, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00492856
• Other Study ID Numbers: S0521; S0521; U10CA032102
• First Posted: Jun 27, 2007
• Last Update Posted: May 17, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Southwest Oncology Group: adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute promyelocytic leukemia (M3); untreated adult acute myeloid leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute; Methotrexate; Mercaptopurine; Tretinoin

Study Results

Participant Flow

Arm/Group Title	Low and Intermediate Risk APL Patients	Post-consolidation ATRA, 6-MP, MTX	Post-consolidation Observation	Post-consolidation Gemtuzumab Ozogamicin
Arm/Group Description	All patients received induction: ATRA 45 mg/m^2/day orally, divided BID, Ara-C 200 mg/m^2/day continuous IV infusion days 3-9, Daunorubicin 50 mg/m^2/day IV bolus days 3-6. If CR (CRm), CRi, or PR, patients received consolidation: Arsenic trioxide 0.15 mg/kg/day IV infusion over 2 hours, 5 days per week for 5 weeks followed by 2 weeks of rest (2 courses). ATRA 45 mg/m^2/day orally divided BID days 1-7, Daunorubicin 50 mg/m^2/day IV bolus days 1-3 (2 courses).	Patients who achieved CRm after consolidation and were randomized or assigned to the treatment arm received ATRA 45 mg/m^2/day orally divided BID 7 days repeated every other week, 6-MP 60 mg/m^2/day orally daily, Methotrexate 20 mg/m^2 orally once a week (1 year cycle). Effective with Revision #6, all eligible patients were non-randomly assigned to receive maintenance with ATRA, 6-MP, and MTX.	Patients who achieved CRm after consolidation and were randomized to the observation arm.	Patients who did not achieve CRm, but achieved CR/CRi and are PML-RARα-positive after consolidation received maintenance gemtuzumab ozogamicin 6 mg/m^2/day IV over 2 hours days 1 and 15 (up to 6 does).
Period Title: Induction
STARTED	105	0	0	0
COMPLETED	99	0	0	0
NOT COMPLETED	6	0	0	0
Period Title: Induction
STARTED	92	0	0	0
COMPLETED	83	0	0	0
NOT COMPLETED	9	0	0	0
Period Title: Induction
STARTED	0	41	27	1
COMPLETED	0	29	0	0
NOT COMPLETED	0	12	27	1

Baseline Characteristics

Arm/Group Title	Low and Intermediate Risk APL Patients
Arm/Group Description	All patients received induction: ATRA 45 mg/m^2/day orally, divided BID, Ara-C 200 mg/m^2/day continuous IV infusion days 3-9, Daunorubicin 50 mg/m^2/day IV bolus days 3-6. If CR (CRm), CRi, or PR, patients received consolidation: Arsenic trioxide 0.15 mg/kg/day IV infusion over 2 hours, 5 days per week for 5 weeks followed by 2 weeks of rest (2 courses). ATRA 45 mg/m^2/day orally divided BID days 1-7, Daunorubicin 50 mg/m^2/day IV bolus days 1-3 (2 courses). If CRm, patients randomized to either (1) maintenance: ATRA 45 mg/m^2/day orally divided BID 7 days repeated every other week, 6-MP 60 mg/m^2/day orally daily, Methotrexate 20 mg/m^2 orally once a week (1 year cycle), or (2) observation. If CR or CRi, but not CRm, patients received maintenance gemtuzumab ozogamicin 6 mg/m^2/day IV over 2 hours days 1 and 15 (up to 6 does). Effective with Revision #6, all eligible patients were non-randomly assigned to receive maintenance with ATRA, 6-MP, and MTX.
Overall Participants	105
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49
Sex: Female, Male (Count of Participants)
Female	44 41.9%
Male	61 58.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%
Asian	7 6.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 7.6%
White	87 82.9%
More than one race	0 0%
Unknown or Not Reported	2 1.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 5.7%
Not Hispanic or Latino	87 82.9%
Unknown or Not Reported	12 11.4%

Outcome Measures

1. Secondary Outcome

Title	Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Description	Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included. Only adverse events that are possibly, probably, or definitely related to study drug are reported.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible patients who received any treatment and were assessed for adverse events were included in the adverse event summaries.

Arm/Group Title	ATRA + Ara-C + Daunorubicin	Consolidation	ATRA+6-MP+MTX	Gemtuzumab Ozogamicin
Arm/Group Description	ATRA 45 mg/m^2/day orally, divided BID, Ara-C 200 mg/m^2/day continuous IV infusion days 3-9, Daunorubicin 50 mg/m^2/day IV bolus days 3-6	Arsenic trioxide 0.15 mg/kg/day IV infusion over 2 hours, 5 days per week for 5 weeks followed by 2 weeks of rest (2 courses). ATRA 45 mg/m^2/day orally divided BID days 1-7, Daunorubicin 50 mg/m^2/day IV bolus days 1-3 (2 courses).	ATRA 45 mg/m^2/day orally divided BID 7 days repeated every other week, 6-MP 60 mg/m^2/day orally daily, Methotrexate 20 mg/m^2 orally once a week (1 year cycle).	Gemtuzumab Ozogamicin 6 mg/m^2/day IV over 2 hours days 1 and 15 (up to 6 does)
Measure Participants	105	90	38	1
ALT, SGPT (serum glutamic pyruvic transaminase)	5 4.8%	3 NaN	2 NaN	0 NaN
AST, SGOT	2 1.9%	2 NaN	1 NaN	0 NaN
Acidosis (metabolic or respiratory)	1 1%	0 NaN	0 NaN	0 NaN
Albumin, serum-low (hypoalbuminemia)	4 3.8%	0 NaN	0 NaN	0 NaN
Alkaline phosphatase	1 1%	0 NaN	0 NaN	0 NaN
Alkalosis (metabolic or respiratory)	2 1.9%	0 NaN	0 NaN	0 NaN
Anorexia	4 3.8%	1 NaN	0 NaN	0 NaN
Bilirubin (hyperbilirubinemia)	7 6.7%	0 NaN	1 NaN	0 NaN
CPK (creatine phosphokinase)	2 1.9%	0 NaN	0 NaN	0 NaN
Calcium, serum-low (hypocalcemia)	3 2.9%	1 NaN	0 NaN	0 NaN
Cardiac Arrhythmia-Other (Specify)	1 1%	0 NaN	0 NaN	0 NaN
Cardiac troponin T (cTnT)	2 1.9%	0 NaN	0 NaN	0 NaN
Cholesterol, serum-high (hypercholesterolemia)	1 1%	0 NaN	0 NaN	0 NaN
Coagulation-Other (Specify)	2 1.9%	0 NaN	0 NaN	0 NaN
Confusion	4 3.8%	0 NaN	0 NaN	0 NaN
Creatinine	2 1.9%	0 NaN	0 NaN	0 NaN
DIC (disseminated intravascular coagulation)	11 10.5%	0 NaN	0 NaN	0 NaN
Dehydration	0 0%	1 NaN	0 NaN	0 NaN
Diarrhea	11 10.5%	0 NaN	0 NaN	0 NaN
Distention/bloating, abdominal	2 1.9%	0 NaN	0 NaN	0 NaN
Dizziness	1 1%	0 NaN	0 NaN	0 NaN
Dry skin	1 1%	0 NaN	0 NaN	0 NaN
Dysphagia (difficulty swallowing)	0 0%	1 NaN	0 NaN	0 NaN
Dyspnea (shortness of breath)	11 10.5%	0 NaN	0 NaN	0 NaN
Enteritis (inflammation of the small bowel)	1 1%	0 NaN	0 NaN	0 NaN
Extremity-lower (gait/walking)	1 1%	0 NaN	0 NaN	0 NaN
Fatigue (asthenia, lethargy, malaise)	8 7.6%	5 NaN	1 NaN	0 NaN
Febrile neutropenia	58 55.2%	8 NaN	0 NaN	1 NaN
Fever in absence of neutropenia, ANC lt1.0x10e9/L	1 1%	1 NaN	0 NaN	0 NaN
Flu-like syndrome	0 0%	1 NaN	0 NaN	0 NaN
Glucose, serum-high (hyperglycemia)	4 3.8%	5 NaN	0 NaN	0 NaN
Hemoglobin	37 35.2%	4 NaN	3 NaN	0 NaN
Hemorrhage, CNS	1 1%	0 NaN	0 NaN	0 NaN
Hemorrhage, GI - Rectum	1 1%	0 NaN	0 NaN	0 NaN
Hemorrhage, GU - Vagina	1 1%	0 NaN	0 NaN	0 NaN
Hemorrhage, pulmonary/upper respiratory - Lung	1 1%	0 NaN	0 NaN	0 NaN
Hemorrhage, pulmonary/upper respiratory - Nose	2 1.9%	0 NaN	0 NaN	0 NaN
Hypertension	3 2.9%	1 NaN	0 NaN	0 NaN
Hypotension	1 1%	2 NaN	0 NaN	0 NaN
Hypoxia	6 5.7%	0 NaN	0 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	10 9.5%	1 NaN	0 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Cecum	1 1%	0 NaN	0 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Colon	4 3.8%	0 NaN	1 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Dental-tooth	1 1%	0 NaN	0 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	8 7.6%	0 NaN	1 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums	1 1%	0 NaN	0 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Sinus	0 0%	0 NaN	1 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Skin	3 2.9%	0 NaN	0 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - UTI	1 1%	0 NaN	0 NaN	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Up aerodigest	1 1%	0 NaN	0 NaN	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Bladder	0 0%	0 NaN	1 NaN	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	1 1%	5 NaN	0 NaN	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter	0 0%	1 NaN	0 NaN	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Gallbladd	1 1%	0 NaN	0 NaN	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	3 2.9%	1 NaN	0 NaN	0 NaN
Inf w/unknown ANC - Oral cavity-gums (gingivitis)	1 1%	0 NaN	0 NaN	0 NaN
Infection with unknown ANC - Bladder (urinary)	1 1%	0 NaN	0 NaN	0 NaN
Infection with unknown ANC - Lung (pneumonia)	1 1%	0 NaN	0 NaN	0 NaN
Infection with unknown ANC - Rectum	1 1%	0 NaN	0 NaN	0 NaN
Infection with unknown ANC - Skin (cellulitis)	1 1%	0 NaN	0 NaN	0 NaN
Infection-Other (Specify)	2 1.9%	0 NaN	0 NaN	0 NaN
Left ventricular systolic dysfunction	0 0%	3 NaN	3 NaN	0 NaN
Leukocytes (total WBC)	34 32.4%	37 NaN	3 NaN	0 NaN
Lymphopenia	20 19%	20 NaN	7 NaN	0 NaN
Metabolic/Laboratory-Other (Specify)	1 1%	0 NaN	0 NaN	0 NaN
Mood alteration - agitation	1 1%	0 NaN	0 NaN	0 NaN
Mood alteration - anxiety	0 0%	1 NaN	0 NaN	0 NaN
Mood alteration - depression	1 1%	0 NaN	0 NaN	0 NaN
Mucositis/stomatitis (clinical exam) - Oral cavity	3 2.9%	0 NaN	1 NaN	0 NaN
Mucositis/stomatitis (clinical exam) - Rectum	1 1%	0 NaN	0 NaN	0 NaN
Mucositis/stomatitis (functional/symp) - Oral cav	0 0%	1 NaN	0 NaN	0 NaN
Muscle weakness, not d/t neuropathy - Extrem-lower	1 1%	0 NaN	0 NaN	0 NaN
Muscle weakness, not d/t neuropathy - Extrem-upper	1 1%	0 NaN	0 NaN	0 NaN
Muscle weakness, not d/t neuropathy - body/general	2 1.9%	0 NaN	0 NaN	0 NaN
Myositis (inflammation/damage of muscle)	2 1.9%	0 NaN	0 NaN	0 NaN
Nausea	6 5.7%	4 NaN	1 NaN	0 NaN
Neuropathy: motor	1 1%	0 NaN	0 NaN	0 NaN
Neuropathy: sensory	0 0%	2 NaN	0 NaN	0 NaN
Neutrophils/granulocytes (ANC/AGC)	34 32.4%	55 NaN	4 NaN	0 NaN
Opportunistic inf associated w/gt=Gr 2 lymphopenia	0 0%	1 NaN	0 NaN	0 NaN
Pain - Abdomen NOS	3 2.9%	1 NaN	0 NaN	0 NaN
Pain - Back	2 1.9%	0 NaN	0 NaN	0 NaN
Pain - Chest/thorax NOS	0 0%	2 NaN	0 NaN	0 NaN
Pain - Extremity-limb	1 1%	1 NaN	0 NaN	0 NaN
Pain - Head/headache	10 9.5%	3 NaN	6 NaN	0 NaN
Pain - Joint	0 0%	4 NaN	0 NaN	0 NaN
Pain - Muscle	3 2.9%	2 NaN	0 NaN	0 NaN
Pain - Neck	1 1%	0 NaN	0 NaN	0 NaN
Pain - Rectum	0 0%	1 NaN	0 NaN	0 NaN
Pain - Scrotum	1 1%	0 NaN	0 NaN	0 NaN
Pain - Throat/pharynx/larynx	0 0%	1 NaN	0 NaN	0 NaN
Pericardial effusion (non-malignant)	1 1%	1 NaN	0 NaN	0 NaN
Pericarditis	0 0%	1 NaN	0 NaN	0 NaN
Petechiae/purpura (hemorrhage into skin or mucosa)	2 1.9%	0 NaN	0 NaN	0 NaN
Phosphate, serum-low (hypophosphatemia)	7 6.7%	1 NaN	0 NaN	0 NaN
Photosensitivity	1 1%	0 NaN	0 NaN	0 NaN
Platelets	42 40%	18 NaN	2 NaN	0 NaN
Pleural effusion (non-malignant)	1 1%	0 NaN	0 NaN	0 NaN
Pneumonitis/pulmonary infiltrates	0 0%	1 NaN	0 NaN	0 NaN
Potassium, serum-low (hypokalemia)	4 3.8%	0 NaN	0 NaN	0 NaN
Prolonged QTc interval	3 2.9%	6 NaN	0 NaN	0 NaN
Pruritus/itching	0 0%	0 NaN	1 NaN	0 NaN
Rash/desquamation	3 2.9%	1 NaN	0 NaN	0 NaN
Renal failure	7 6.7%	1 NaN	0 NaN	0 NaN
Renal/Genitourinary-Other (Specify)	1 1%	0 NaN	0 NaN	0 NaN
Restrictive cardiomyopathy	0 0%	1 NaN	0 NaN	0 NaN
Retinal detachment	1 1%	0 NaN	0 NaN	0 NaN
Retinoic acid syndrome	13 12.4%	0 NaN	0 NaN	0 NaN
Sodium, serum-low (hyponatremia)	4 3.8%	0 NaN	0 NaN	0 NaN
Syncope (fainting)	3 2.9%	0 NaN	0 NaN	0 NaN
Thrombosis/thrombus/embolism	1 1%	0 NaN	0 NaN	0 NaN
Triglyceride, serum-high (hypertriglyceridemia)	5 4.8%	2 NaN	3 NaN	0 NaN
Typhlitis (cecal inflammation)	3 2.9%	0 NaN	0 NaN	0 NaN
Uric acid, serum-high (hyperuricemia)	0 0%	1 NaN	0 NaN	0 NaN
Vasovagal episode	1 1%	1 NaN	0 NaN	0 NaN
Ventricular arrhythmia - Ventricular tachycardia	1 1%	1 NaN	0 NaN	0 NaN
Vomiting	1 1%	1 NaN	0 NaN	0 NaN
Weight gain	1 1%	0 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	3-year Disease-free Survival (DFS) Rate
Description	DFS measured from date of post-consolidation randomization until relapse of any kind or death from any cause. Observation censored at date of last follow-up for patients last known to be alive without report of relapse. Relapse from CR/CRi is occurrence of marrow blasts ≥ 5% or presence of Auer rods or presence of neoplastic promyelocytes; (re)appearance of leukemic blasts or neoplastic promyelocytes in the peripheral blood; or (re)appearance of extramedullary disease. Relapse from PR is sum of marrow blasts and promyelocytes ≥ 20%, or sum of marrow blasts and promyelocytes 6-19% with Auer rods and/or neoplastic promyelocytes; or (re)appearance of leukemic blasts or neoplastic promyelocytes in the peripheral blood; or (re)appearance of extramedullary disease. Relapse from CRc is reappearance of t(15;17) in cytogenetic analysis. Relapse from CRm/PRm is reappearance of PML-RARα by RT-PCR as defined by a normalized quotient > 10^-5 based on RT-PCR performed at appropriate central lab.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible patients in molecular remission after receiving consolidation and randomized to either maintenance chemotherapy or observation. As of 8/15/10, all eligible patients were non-randomly assigned to receive maintenance chemotherapy. Only those that were randomized to either maintenance treatment or observation were included.

Arm/Group Title	Post-consolidation Therapy Arm I	Post-consolidation Therapy Arm II
Arm/Group Description	Patients receive oral tretinoin twice daily on days 1-7, oral mercaptopurine once daily on days 1-14, and oral methotrexate on day 1. Treatment repeats every 2 weeks for up to 1 year. mercaptopurine: Given orally methotrexate: Given orally tretinoin: Given orally	Patients receive no further chemotherapy. (Randomization and observation arm closed as of 05/27/10)
Measure Participants	28	27
Number [percentage of patients]	96	100

Adverse Events

Time Frame	Up to 5 years
Adverse Event Reporting Description	Eligible patients who received any treatment and were assessed for adverse events were included in the adverse event summaries.
Arm/Group Title	ATRA + Ara-C + Daunorubicin		Consolidation		ATRA+6-MP+MTX		Gemtuzumab Ozogamicin
Arm/Group Description	ATRA 45 mg/m^2/day orally, divided BID, Ara-C 200 mg/m^2/day continuous IV infusion days 3-9, Daunorubicin 50 mg/m^2/day IV bolus days 3-6		Arsenic trioxide 0.15 mg/kg/day IV infusion over 2 hours, 5 days per week for 5 weeks followed by 2 weeks of rest (2 courses). ATRA 45 mg/m^2/day orally divided BID days 1-7, Daunorubicin 50 mg/m^2/day IV bolus days 1-3 (2 courses).		ATRA 45 mg/m^2/day orally divided BID 7 days repeated every other week, 6-MP 60 mg/m^2/day orally daily, Methotrexate 20 mg/m^2 orally once a week (1 year cycle).		Gemtuzumab Ozogamicin 6 mg/m^2/day IV over 2 hours days 1 and 15 (up to 6 does)
All Cause Mortality
	ATRA + Ara-C + Daunorubicin		Consolidation		ATRA+6-MP+MTX		Gemtuzumab Ozogamicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ATRA + Ara-C + Daunorubicin		Consolidation		ATRA+6-MP+MTX		Gemtuzumab Ozogamicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/105 (7.6%)		4/90 (4.4%)		1/38 (2.6%)		0/1 (0%)
Cardiac disorders
Left ventricular systolic dysfunction	0/105 (0%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
Pericardial effusion (non-malignant)	1/105 (1%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
SVT and nodal arrhythmia - Atrial flutter	0/105 (0%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
Eye disorders
Retinal detachment	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Gastrointestinal disorders
Typhlitis (cecal inflammation)	2/105 (1.9%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
General disorders
Extremity-lower (gait/walking)	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Sudden death	1/105 (1%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	0/105 (0%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
Infection-Other	0/105 (0%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	0/105 (0%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
AST, SGOT	0/105 (0%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
Amylase	0/105 (0%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
CPK (creatine phosphokinase)	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Myositis (inflammation/damage of muscle)	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Pain - Muscle	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Renal and urinary disorders
Renal failure	1/105 (1%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	0/105 (0%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
Hemorrhage, pulmonary/upper respiratory - Lung	1/105 (1%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Pneumonitis/pulmonary infiltrates	0/105 (0%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
Vascular disorders
Hypotension	0/105 (0%)		1/90 (1.1%)		1/38 (2.6%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	ATRA + Ara-C + Daunorubicin		Consolidation		ATRA+6-MP+MTX		Gemtuzumab Ozogamicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/105 (100%)		89/90 (98.9%)		37/38 (97.4%)		1/1 (100%)
Blood and lymphatic system disorders
DIC (disseminated intravascular coagulation)	24/105 (22.9%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
Febrile neutropenia	62/105 (59%)		8/90 (8.9%)		0/38 (0%)		1/1 (100%)
Hemoglobin	43/105 (41%)		59/90 (65.6%)		22/38 (57.9%)		0/1 (0%)
Cardiac disorders
Left ventricular systolic dysfunction	4/105 (3.8%)		7/90 (7.8%)		3/38 (7.9%)		0/1 (0%)
SVT and nodal arrhythmia - Atrial fibrillation	3/105 (2.9%)		2/90 (2.2%)		2/38 (5.3%)		0/1 (0%)
SVT and nodal arrhythmia - Sinus tachycardia	13/105 (12.4%)		10/90 (11.1%)		0/38 (0%)		0/1 (0%)
Ventricular arrhythmia - Ventricular tachycardia	5/105 (4.8%)		6/90 (6.7%)		0/38 (0%)		0/1 (0%)
Eye disorders
Ocular/Visual-Other	4/105 (3.8%)		5/90 (5.6%)		1/38 (2.6%)		0/1 (0%)
Vision-blurred vision	6/105 (5.7%)		7/90 (7.8%)		2/38 (5.3%)		0/1 (0%)
Vision-photophobia	0/105 (0%)		0/90 (0%)		2/38 (5.3%)		0/1 (0%)
Watery eye (epiphora, tearing)	1/105 (1%)		5/90 (5.6%)		0/38 (0%)		0/1 (0%)
Gastrointestinal disorders
Chelitis	5/105 (4.8%)		0/90 (0%)		3/38 (7.9%)		0/1 (0%)
Constipation	20/105 (19%)		22/90 (24.4%)		4/38 (10.5%)		0/1 (0%)
Diarrhea	77/105 (73.3%)		35/90 (38.9%)		11/38 (28.9%)		0/1 (0%)
Dysphagia (difficulty swallowing)	6/105 (5.7%)		4/90 (4.4%)		2/38 (5.3%)		0/1 (0%)
Heartburn/dyspepsia	11/105 (10.5%)		6/90 (6.7%)		3/38 (7.9%)		0/1 (0%)
Hemorrhage, GI - Oral cavity	6/105 (5.7%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Hemorrhoids	1/105 (1%)		2/90 (2.2%)		2/38 (5.3%)		0/1 (0%)
Mucositis/stomatitis (clinical exam) - Oral cavity	38/105 (36.2%)		14/90 (15.6%)		4/38 (10.5%)		0/1 (0%)
Mucositis/stomatitis (functional/symp) - Oral cav	9/105 (8.6%)		2/90 (2.2%)		2/38 (5.3%)		0/1 (0%)
Nausea	72/105 (68.6%)		66/90 (73.3%)		26/38 (68.4%)		0/1 (0%)
Pain - Abdomen NOS	21/105 (20%)		7/90 (7.8%)		3/38 (7.9%)		1/1 (100%)
Vomiting	42/105 (40%)		29/90 (32.2%)		6/38 (15.8%)		0/1 (0%)
General disorders
Edema: limb	25/105 (23.8%)		13/90 (14.4%)		4/38 (10.5%)		1/1 (100%)
Fatigue (asthenia, lethargy, malaise)	67/105 (63.8%)		70/90 (77.8%)		27/38 (71.1%)		1/1 (100%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	29/105 (27.6%)		16/90 (17.8%)		3/38 (7.9%)		0/1 (0%)
Pain - Chest/thorax NOS	8/105 (7.6%)		16/90 (17.8%)		4/38 (10.5%)		0/1 (0%)
Pain-Other	5/105 (4.8%)		3/90 (3.3%)		1/38 (2.6%)		1/1 (100%)
Rigors/chills	31/105 (29.5%)		13/90 (14.4%)		1/38 (2.6%)		0/1 (0%)
Immune system disorders
Allergic reaction/hypersensitivity	12/105 (11.4%)		2/90 (2.2%)		1/38 (2.6%)		0/1 (0%)
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	12/105 (11.4%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Colon	6/105 (5.7%)		0/90 (0%)		1/38 (2.6%)		0/1 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	15/105 (14.3%)		2/90 (2.2%)		1/38 (2.6%)		0/1 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	4/105 (3.8%)		10/90 (11.1%)		0/38 (0%)		0/1 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	3/105 (2.9%)		3/90 (3.3%)		2/38 (5.3%)		0/1 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Pharynx	0/105 (0%)		2/90 (2.2%)		2/38 (5.3%)		0/1 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	6/105 (5.7%)		6/90 (6.7%)		2/38 (5.3%)		0/1 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	0/105 (0%)		2/90 (2.2%)		3/38 (7.9%)		0/1 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Vagina	0/105 (0%)		1/90 (1.1%)		2/38 (5.3%)		0/1 (0%)
Inf w/unknown ANC - Oral cavity-gums (gingivitis)	1/105 (1%)		0/90 (0%)		0/38 (0%)		1/1 (100%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	47/105 (44.8%)		46/90 (51.1%)		19/38 (50%)		0/1 (0%)
AST, SGOT	54/105 (51.4%)		43/90 (47.8%)		19/38 (50%)		0/1 (0%)
Alkaline phosphatase	17/105 (16.2%)		27/90 (30%)		5/38 (13.2%)		0/1 (0%)
Bilirubin (hyperbilirubinemia)	37/105 (35.2%)		14/90 (15.6%)		8/38 (21.1%)		0/1 (0%)
Cholesterol, serum-high (hypercholesterolemia)	18/105 (17.1%)		22/90 (24.4%)		11/38 (28.9%)		0/1 (0%)
Creatinine	19/105 (18.1%)		13/90 (14.4%)		2/38 (5.3%)		0/1 (0%)
Fibrinogen	6/105 (5.7%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
INR (of prothrombin time)	11/105 (10.5%)		1/90 (1.1%)		4/38 (10.5%)		0/1 (0%)
Leukocytes (total WBC)	35/105 (33.3%)		46/90 (51.1%)		16/38 (42.1%)		0/1 (0%)
Lymphopenia	21/105 (20%)		28/90 (31.1%)		13/38 (34.2%)		0/1 (0%)
Metabolic/Laboratory-Other	14/105 (13.3%)		15/90 (16.7%)		4/38 (10.5%)		0/1 (0%)
Neutrophils/granulocytes (ANC/AGC)	36/105 (34.3%)		61/90 (67.8%)		10/38 (26.3%)		0/1 (0%)
PTT (Partial thromboplastin time)	16/105 (15.2%)		6/90 (6.7%)		4/38 (10.5%)		0/1 (0%)
Platelets	44/105 (41.9%)		54/90 (60%)		11/38 (28.9%)		0/1 (0%)
Prolonged QTc interval	10/105 (9.5%)		28/90 (31.1%)		0/38 (0%)		0/1 (0%)
Weight gain	5/105 (4.8%)		6/90 (6.7%)		4/38 (10.5%)		0/1 (0%)
Weight loss	15/105 (14.3%)		6/90 (6.7%)		1/38 (2.6%)		0/1 (0%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	37/105 (35.2%)		19/90 (21.1%)		6/38 (15.8%)		0/1 (0%)
Anorexia	45/105 (42.9%)		16/90 (17.8%)		5/38 (13.2%)		0/1 (0%)
Bicarbonate, serum-low	7/105 (6.7%)		5/90 (5.6%)		1/38 (2.6%)		0/1 (0%)
Calcium, serum-low (hypocalcemia)	33/105 (31.4%)		20/90 (22.2%)		5/38 (13.2%)		0/1 (0%)
Dehydration	2/105 (1.9%)		5/90 (5.6%)		0/38 (0%)		0/1 (0%)
Glucose, serum-high (hyperglycemia)	36/105 (34.3%)		40/90 (44.4%)		15/38 (39.5%)		0/1 (0%)
Glucose, serum-low (hypoglycemia)	5/105 (4.8%)		10/90 (11.1%)		1/38 (2.6%)		0/1 (0%)
Magnesium, serum-high (hypermagnesemia)	12/105 (11.4%)		4/90 (4.4%)		1/38 (2.6%)		0/1 (0%)
Magnesium, serum-low (hypomagnesemia)	17/105 (16.2%)		16/90 (17.8%)		6/38 (15.8%)		0/1 (0%)
Phosphate, serum-low (hypophosphatemia)	16/105 (15.2%)		4/90 (4.4%)		0/38 (0%)		0/1 (0%)
Potassium, serum-high (hyperkalemia)	3/105 (2.9%)		5/90 (5.6%)		2/38 (5.3%)		0/1 (0%)
Potassium, serum-low (hypokalemia)	37/105 (35.2%)		19/90 (21.1%)		4/38 (10.5%)		0/1 (0%)
Sodium, serum-low (hyponatremia)	30/105 (28.6%)		15/90 (16.7%)		6/38 (15.8%)		0/1 (0%)
Triglyceride, serum-high (hypertriglyceridemia)	46/105 (43.8%)		30/90 (33.3%)		18/38 (47.4%)		0/1 (0%)
Uric acid, serum-high (hyperuricemia)	4/105 (3.8%)		7/90 (7.8%)		1/38 (2.6%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	5/105 (4.8%)		6/90 (6.7%)		1/38 (2.6%)		0/1 (0%)
Pain - Back	10/105 (9.5%)		15/90 (16.7%)		3/38 (7.9%)		0/1 (0%)
Pain - Bone	4/105 (3.8%)		3/90 (3.3%)		2/38 (5.3%)		0/1 (0%)
Pain - Chest wall	4/105 (3.8%)		2/90 (2.2%)		2/38 (5.3%)		0/1 (0%)
Pain - Extremity-limb	12/105 (11.4%)		10/90 (11.1%)		3/38 (7.9%)		0/1 (0%)
Pain - Joint	5/105 (4.8%)		20/90 (22.2%)		6/38 (15.8%)		0/1 (0%)
Pain - Muscle	17/105 (16.2%)		17/90 (18.9%)		7/38 (18.4%)		0/1 (0%)
Pain - Neck	7/105 (6.7%)		3/90 (3.3%)		1/38 (2.6%)		0/1 (0%)
Nervous system disorders
Ataxia (incoordination)	0/105 (0%)		1/90 (1.1%)		2/38 (5.3%)		0/1 (0%)
Dizziness	12/105 (11.4%)		21/90 (23.3%)		6/38 (15.8%)		0/1 (0%)
Hemorrhage, CNS	7/105 (6.7%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Neuropathy: sensory	5/105 (4.8%)		35/90 (38.9%)		4/38 (10.5%)		0/1 (0%)
Ocular/Visual-Other	4/105 (3.8%)		5/90 (5.6%)		1/38 (2.6%)		0/1 (0%)
Pain - Head/headache	60/105 (57.1%)		54/90 (60%)		20/38 (52.6%)		0/1 (0%)
Taste alteration (dysgeusia)	4/105 (3.8%)		10/90 (11.1%)		3/38 (7.9%)		0/1 (0%)
Tremor	2/105 (1.9%)		5/90 (5.6%)		1/38 (2.6%)		0/1 (0%)
Psychiatric disorders
Confusion	14/105 (13.3%)		2/90 (2.2%)		0/38 (0%)		0/1 (0%)
Insomnia	18/105 (17.1%)		17/90 (18.9%)		6/38 (15.8%)		1/1 (100%)
Mood alteration - anxiety	15/105 (14.3%)		11/90 (12.2%)		5/38 (13.2%)		0/1 (0%)
Mood alteration - depression	14/105 (13.3%)		4/90 (4.4%)		4/38 (10.5%)		0/1 (0%)
Renal and urinary disorders
Renal failure	8/105 (7.6%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
Urinary frequency/urgency	4/105 (3.8%)		8/90 (8.9%)		2/38 (5.3%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/105 (3.8%)		18/90 (20%)		4/38 (10.5%)		0/1 (0%)
Cough	19/105 (18.1%)		24/90 (26.7%)		11/38 (28.9%)		0/1 (0%)
Dyspnea (shortness of breath)	39/105 (37.1%)		22/90 (24.4%)		6/38 (15.8%)		0/1 (0%)
Hemorrhage, pulmonary/upper respiratory - Lung	6/105 (5.7%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Hemorrhage, pulmonary/upper respiratory - Nose	16/105 (15.2%)		1/90 (1.1%)		4/38 (10.5%)		0/1 (0%)
Hypoxia	11/105 (10.5%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Pain - Throat/pharynx/larynx	2/105 (1.9%)		11/90 (12.2%)		3/38 (7.9%)		0/1 (0%)
Pleural effusion (non-malignant)	11/105 (10.5%)		3/90 (3.3%)		0/38 (0%)		0/1 (0%)
Pulmonary/Upper Respiratory-Other	5/105 (4.8%)		5/90 (5.6%)		1/38 (2.6%)		0/1 (0%)
Retinoic acid syndrome	24/105 (22.9%)		0/90 (0%)		0/38 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other	7/105 (6.7%)		12/90 (13.3%)		4/38 (10.5%)		0/1 (0%)
Dry skin	20/105 (19%)		23/90 (25.6%)		10/38 (26.3%)		0/1 (0%)
Hair loss/Alopecia (scalp or body)	36/105 (34.3%)		28/90 (31.1%)		5/38 (13.2%)		0/1 (0%)
Nail changes	0/105 (0%)		6/90 (6.7%)		2/38 (5.3%)		0/1 (0%)
Petechiae/purpura (hemorrhage into skin or mucosa)	15/105 (14.3%)		1/90 (1.1%)		0/38 (0%)		0/1 (0%)
Pruritus/itching	22/105 (21%)		15/90 (16.7%)		5/38 (13.2%)		1/1 (100%)
Rash/desquamation	53/105 (50.5%)		32/90 (35.6%)		12/38 (31.6%)		0/1 (0%)
Sweating (diaphoresis)	16/105 (15.2%)		5/90 (5.6%)		3/38 (7.9%)		0/1 (0%)
Vascular disorders
Hemorrhage/Bleeding-Other	6/105 (5.7%)		2/90 (2.2%)		1/38 (2.6%)		0/1 (0%)
Hypertension	21/105 (20%)		5/90 (5.6%)		3/38 (7.9%)		0/1 (0%)
Hypotension	14/105 (13.3%)		6/90 (6.7%)		2/38 (5.3%)		0/1 (0%)
Thrombosis/thrombus/embolism	9/105 (8.6%)		5/90 (5.6%)		0/38 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT 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.