S0535, Gemtuzumab and Combination Chemotherapy in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00551460
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 78
• Locations: 192
• Arm: 1
• Duration (Months): 115
• Patients Per Site: 0.4
• 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 find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Gemtuzumab may also stop the growth of promyelocytic leukemia by blocking blood flow to the cancer. Giving gemtuzumab together with combination chemotherapy may be more effective in treating promyelocytic leukemia.

PURPOSE: This phase II trial is studying how well giving gemtuzumab together with combination chemotherapy works in treating patients with previously untreated promyelocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: arsenic trioxide; Drug: gemtuzumab ozogamicin; Drug: mercaptopurine; Drug: methotrexate; Drug: tretinoin	Phase 2

Detailed Description

OBJECTIVES:

• To assess the event-free survival and death during the first six weeks in patients with previously untreated, high-risk acute promyelocytic leukemia treated with a combined regimen of tretinoin, arsenic trioxide, and gemtuzumab ozogamicin.

• To estimate the frequency and severity of toxicities of this regimen in this group of patients.

• To investigate the molecular response rate utilizing this regimen in high-risk patients.

OUTLINE:

• Induction chemotherapy: Patients receive oral tretinoin twice daily beginning on day 1 until CR (up to 90 days), gemtuzumab ozogamicin IV over 2 hours on day 1, and arsenic trioxide IV over 2 hours 5 days a week beginning on day 10 until CR (up to 60 days) in the absence of disease progression or unacceptable toxicity. Patients achieving A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to consolidation therapy after maintaining B1 peripheral blood status for ≥ 7 days.

• Consolidation therapy: Beginning between 2-8 weeks after documentation of complete response (CR), patients receive consolidation therapy.

• Consolidation courses 1 and 2: Patients receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks. Treatment repeats every 7 weeks for up to 2 courses. Patients remaining in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status continue with consolidation courses 3 and 4.

• Consolidation courses 3 and 4: Within 4 weeks of completing consolidation course 2, patients receive oral tretinoin twice daily on days 1-7 and daunomycin IV bolus or over 1 hour on days 1-3. Within 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 4 as in course 3. Patients who remain in B1 peripheral blood and C1 extramedullary disease status continue on consolidation courses 5 and 6.

• Consolidation courses 5 and 6: Beginning between 2-8 weeks after recovery to B1 peripheral blood status, patients receive gemtuzumab IV over 2 hours on day 1. Between 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 6 as in course 5. Patients who remain in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to maintenance therapy.

• Maintenance therapy: Beginning 2-8 weeks after recovery of blood counts, patients receive oral tretinoin twice daily on days 1-7 every other week for 1 year, oral mercaptopurine once daily for 1 year, and oral methotrexate once weekly for 1 year.

Patients undergo bone marrow aspirates and biopsies periodically during study. Samples are analyzed for cytogenetics by fluorescence in situ hybridization (FISH) and for PML-RARα by polymerase chain reaction (PCR).

After completion of study treatment, patients are evaluated at 3, 6, 9, 12, 18, 24, and 36 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: S0535, A Phase II Study of ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin in Patients With Previously Untreated High-Risk Acute Promyelocytic Leukemia
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment Induction: ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR Consolidation 1 and 2: Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest Consolidation 2 and 3: ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3 Consolidation 5 and 6: GO 9mg/m2 IV D1 Maintenance: ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year

Drug: arsenic trioxide; Drug: gemtuzumab ozogamicin; Drug: mercaptopurine; Drug: methotrexate; Drug: tretinoin

Outcome Measures

Primary Outcome Measures

1. Continuous Complete Remission at 3 Years [3 years]

   Binary variable: yes if the patient achieves complete remission and remains in continuous complete remission until at least 3 years after entering the study; otherwise no.

2. Mortality Rate at 6 Weeks [6 weeks]

Secondary Outcome Measures

1. Frequency of Toxicities [Up to 3 years]

   Adverse events that were 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:

• Morphologically confirmed acute promyelocytic leukemia (APL) based on bone marrow examination

• APL-RARα-negative by RT-PCR are not eligible

• High-risk disease, defined as WBC > 100,000/mm^3

• Bone marrow specimens must be made available for cytogenetic studies

PATIENT CHARACTERISTICS:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No prolonged QTc > 0.47 sec

• No other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or stage II cancer from which the patients is currently in complete remission

PRIOR CONCURRENT THERAPY:

• No prior systemic chemotherapy for acute leukemia

• At least 3 days since prior tretinoin (ATRA) allowed

• Prior hydroxyurea, corticosteroids, or leukapheresis to control high cell counts allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sutter Cancer Center at Roseville Medical Center	Roseville	California	United States	95661
2	Sutter Cancer Center	Sacramento	California	United States	95816
3	Stanford Cancer Center	Stanford	California	United States	94305-5824
4	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
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	M.D. Anderson Cancer Center at Orlando	Orlando	Florida	United States	32806
8	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida	United States	33612-9497
9	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
10	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
11	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
12	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
13	Kellogg Cancer Care Center	Highland Park	Illinois	United States	60035
14	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois	United States	60901
15	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
16	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
17	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
18	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
19	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
20	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46845
21	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
22	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
23	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
24	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
25	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
26	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
27	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
28	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
29	Providence Medical Center	Kansas City	Kansas	United States	66112
30	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
31	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
32	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
33	Cancer Center of Kansas, PA - McPherson	McPherson	Kansas	United States	67460
34	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
35	Menorah Medical Center	Overland Park	Kansas	United States	66209
36	Saint Luke's Hospital - South	Overland Park	Kansas	United States	66213
37	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
38	CCOP - Kansas City	Prairie Village	Kansas	United States	66208
39	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
40	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
41	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
42	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
43	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
44	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
45	CCOP - Wichita	Wichita	Kansas	United States	67214
46	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
47	Wesley Medical Center	Wichita	Kansas	United States	67214
48	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
49	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
50	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
51	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
52	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
53	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts	United States	02115
54	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
55	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
56	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
57	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
58	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
59	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
60	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
61	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
62	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
63	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
64	Hurley Medical Center	Flint	Michigan	United States	48503
65	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
66	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
67	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
68	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
69	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
70	Foote Memorial Hospital	Jackson	Michigan	United States	49201
71	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
72	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
73	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
74	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
75	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
76	Mercy General Health Partners	Muskegon	Michigan	United States	49444
77	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
78	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
79	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
80	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
81	Munson Medical Center	Traverse City	Michigan	United States	49684
82	St. John Macomb Hospital	Warren	Michigan	United States	48093
83	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
84	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
85	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
86	CCOP - Duluth	Duluth	Minnesota	United States	55805
87	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
88	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
89	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
90	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
91	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
92	Minnesota Oncology - Maplewood	Maplewood	Minnesota	United States	55109
93	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
94	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
95	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
96	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
97	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
98	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
99	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
100	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
101	United Hospital	Saint Paul	Minnesota	United States	55102
102	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
103	Lakeview Hospital	Stillwater	Minnesota	United States	55082
104	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
105	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
106	Minnesota Oncology - Woodbury	Woodbury	Minnesota	United States	55125
107	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216
108	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
109	North Kansas City Hospital	Kansas City	Missouri	United States	64116
110	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri	United States	64118
111	Research Medical Center	Kansas City	Missouri	United States	64132
112	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
113	Parvin Radiation Oncology	Liberty	Missouri	United States	64068
114	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
115	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri	United States	64507
116	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
117	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
118	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
119	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
120	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
121	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
122	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
123	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
124	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
125	St. Peter's Hospital	Helena	Montana	United States	59601
126	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
127	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
128	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
129	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
130	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
131	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
132	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
133	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York	United States	11042
134	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
135	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
136	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
137	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
138	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
139	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
140	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
141	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
142	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
143	St. Rita's Medical Center	Lima	Ohio	United States	45801
144	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
145	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
146	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
147	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
148	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
149	AnMed Cancer Center	Anderson	South Carolina	United States	29621
150	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
151	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
152	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
153	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
154	American Fork Hospital	American Fork	Utah	United States	84003
155	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
156	Logan Regional Hospital	Logan	Utah	United States	84321
157	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
158	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
159	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
160	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
161	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
162	LDS Hospital	Salt Lake City	Utah	United States	84143
163	Island Hospital Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
164	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
165	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
166	Highline Medical Center Cancer Center	Burien	Washington	United States	98166
167	Swedish Medical Center - Issaquah Campus	Issaquah	Washington	United States	98029
168	Columbia Basin Hematology	Kennewick	Washington	United States	99336
169	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington	United States	98274
170	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington	United States	98370
171	Harborview Medical Center	Seattle	Washington	United States	98104
172	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
173	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
174	Group Health Central Hospital	Seattle	Washington	United States	98112
175	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
176	Polyclinic First Hill	Seattle	Washington	United States	98122
177	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
178	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington	United States	98284
179	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
180	Evergreen Hematology and Oncology, PS	Spokane	Washington	United States	99218
181	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
182	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
183	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
184	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
185	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
186	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
187	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
188	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
189	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
190	St. Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
191	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
192	Rocky Mountain Oncology	Casper	Wyoming	United States	82609

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Jeffrey E. Lancet, MD, H. Lee Moffitt Cancer Center and Research Institute
• Study Chair: Rami Komrokji, MD, H. Lee Moffitt Cancer Center and Research Institute
• Study Chair: Cheryl L. Willman, MD, University of New Mexico Cancer Center
• Study Chair: Marilyn L. Slovak, PhD, City of Hope Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Oct 1, 2015

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00551460
• Other Study ID Numbers: S0535; S0535; U10CA032102
• First Posted: Oct 31, 2007
• Last Update Posted: Dec 22, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by Southwest Oncology Group: adult acute promyelocytic leukemia (M3); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); untreated adult acute myeloid leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute; Methotrexate; Mercaptopurine; Arsenic Trioxide; Tretinoin; Gemtuzumab

Study Results

Participant Flow

Arm/Group Title	ATRA + GO + Arsenic
Arm/Group Description	Induction: ATRA 45mg/m2 PO D1-CR; Gemtuzumab Ozogamicin 9 mg/m2 IV D1; Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR Consolidation 1 and 2: Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest Consolidation 2 and 3: ATRA 45 mg/m2 PO D1-7; Daunomycin 50 mg/m2/d IV D1-3 Consolidation 5 and 6: GO 9mg/m2 IV D1 Maintenance: ATRA 45 mg/m2/d PO D1-7 every 14 days; 6-MP 60 mg/m2/d PO daily for 1 year; Methotrexate 20 mg/m2 PO once/wk for 1 year
Period Title: Overall Study
STARTED	78
COMPLETED	60
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	ATRA + GO + Arsenic
Arm/Group Description	Induction: ATRA 45mg/m2 PO D1-CR; Gemtuzumab Ozogamicin 9 mg/m2 IV D1; Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR Consolidation 1 and 2: Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest Consolidation 2 and 3: ATRA 45 mg/m2 PO D1-7; Daunomycin 50 mg/m2/d IV D1-3 Consolidation 5 and 6: GO 9mg/m2 IV D1 Maintenance: ATRA 45 mg/m2/d PO D1-7 every 14 days; 6-MP 60 mg/m2/d PO daily for 1 year; Methotrexate 20 mg/m2 PO once/wk for 1 year
Overall Participants	70
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	46.5
Sex: Female, Male (Count of Participants)
Female	37 52.9%
Male	33 47.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.4%
Native Hawaiian or Other Pacific Islander	1 1.4%
Black or African American	7 10%
White	58 82.9%
More than one race	0 0%
Unknown or Not Reported	3 4.3%

Outcome Measures

1. Primary Outcome

Title	Continuous Complete Remission at 3 Years
Description	Binary variable: yes if the patient achieves complete remission and remains in continuous complete remission until at least 3 years after entering the study; otherwise no.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

The Analysis Population includes eligible and analyzable patients. Ineligible patients and not analyzable patients from Participant Flow are excluded.

Arm/Group Title	ATRA + GO + Arsenic
Arm/Group Description	Induction: ATRA 45mg/m2 PO D1-CR; Gemtuzumab Ozogamicin 9 mg/m2 IV D1; Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR Consolidation 1 and 2: Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest Consolidation 2 and 3: ATRA 45 mg/m2 PO D1-7; Daunomycin 50 mg/m2/d IV D1-3 Consolidation 5 and 6: GO 9mg/m2 IV D1 Maintenance: ATRA 45 mg/m2/d PO D1-7 every 14 days; 6-MP 60 mg/m2/d PO daily for 1 year; Methotrexate 20 mg/m2 PO once/wk for 1 year
Measure Participants	70
Number (95% Confidence Interval) [percentage of participants]	74 105.7%

2. Primary Outcome

Title	Mortality Rate at 6 Weeks
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The Analysis Population includes eligible and analyzable patients. Ineligible patients and not analyzable patients from Participant Flow are excluded.

Arm/Group Title	ATRA + GO + Arsenic
Arm/Group Description	Induction: ATRA 45mg/m2 PO D1-CR; Gemtuzumab Ozogamicin 9 mg/m2 IV D1; Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR Consolidation 1 and 2: Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest Consolidation 2 and 3: ATRA 45 mg/m2 PO D1-7; Daunomycin 50 mg/m2/d IV D1-3 Consolidation 5 and 6: GO 9mg/m2 IV D1 Maintenance: ATRA 45 mg/m2/d PO D1-7 every 14 days; 6-MP 60 mg/m2/d PO daily for 1 year; Methotrexate 20 mg/m2 PO once/wk for 1 year
Measure Participants	70
Number (95% Confidence Interval) [percentage of participants]	11 15.7%

3. Secondary Outcome

Title	Frequency of Toxicities
Description	Adverse events that were possibly, probably or definitely related to study drug are reported.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

The Analysis Population includes eligible and analyzable patients. Ineligible patients and not analyzable patients from Participant Flow are excluded.

Arm/Group Title	ATRA + GO + Arsenic
Arm/Group Description	Induction: ATRA 45mg/m2 PO D1-CR; Gemtuzumab Ozogamicin 9 mg/m2 IV D1; Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR Consolidation 1 and 2: Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest Consolidation 2 and 3: ATRA 45 mg/m2 PO D1-7; Daunomycin 50 mg/m2/d IV D1-3 Consolidation 5 and 6: GO 9mg/m2 IV D1 Maintenance: ATRA 45 mg/m2/d PO D1-7 every 14 days; 6-MP 60 mg/m2/d PO daily for 1 year; Methotrexate 20 mg/m2 PO once/wk for 1 year
Measure Participants	70
ALT, SGPT (serum glutamic pyruvic transaminase)	37 52.9%
AST, SGOT	46 65.7%
Acidosis (metabolic or respiratory)	4 5.7%
Acute vascular leak syndrome	1 1.4%
Adult respiratory distress syndrome (ARDS)	3 4.3%
Albumin, serum-low (hypoalbuminemia)	24 34.3%
Alkaline phosphatase	23 32.9%
Alkalosis (metabolic or respiratory)	4 5.7%
Allergic reaction/hypersensitivity	8 11.4%
Allergic rhinitis	6 8.6%
Allergy/Immunology-Other	1 1.4%
Anorexia	18 25.7%
Arthritis (non-septic)	1 1.4%
Ascites (non-malignant)	2 2.9%
Atelectasis	2 2.9%
Atrioventricular block - 2nd degree Mobitz Type II	1 1.4%
Atrioventricular block - first degree	1 1.4%
Auditory/Ear-Other	2 2.9%
Bicarbonate, serum-low	7 10%
Bilirubin (hyperbilirubinemia)	23 32.9%
Blood/Bone Marrow-Other	4 5.7%
Bronchospasm, wheezing	1 1.4%
Bruising (in absence of Gr 3-4 thrombocytopenia)	8 11.4%
CNS cerebrovascular ischemia	4 5.7%
Calcium, serum-high (hypercalcemia)	1 1.4%
Calcium, serum-low (hypocalcemia)	22 31.4%
Carbon monoxide diffusion capacity (DL(co))	1 1.4%
Cardiac Arrhythmia-Other	1 1.4%
Cardiac General-Other	2 2.9%
Cardiac troponin I (cTnI)	1 1.4%
Cardiac troponin T (cTnT)	1 1.4%
Cardiac-ischemia/infarction	3 4.3%
Chelitis	1 1.4%
Cholesterol, serum-high (hypercholesterolemia)	4 5.7%
Confusion	6 8.6%
Constipation	26 37.1%
Cough	17 24.3%
Creatinine	5 7.1%
Cytokine release syndrome/acute infusion reaction	1 1.4%
DIC (disseminated intravascular coagulation)	19 27.1%
Dental: periodontal disease	1 1.4%
Dermal change lymphedema, phlebolymphedema	1 1.4%
Dermatology/Skin-Other	3 4.3%
Diarrhea	23 32.9%
Distention/bloating, abdominal	10 14.3%
Dizziness	4 5.7%
Dry mouth/salivary gland (xerostomia)	1 1.4%
Dry skin	11 15.7%
Dysphagia (difficulty swallowing)	3 4.3%
Dyspnea (shortness of breath)	27 38.6%
Edema, larynx	1 1.4%
Edema: head and neck	5 7.1%
Edema: limb	33 47.1%
Edema: viscera	2 2.9%
Encephalopathy	1 1.4%
Esophagitis	2 2.9%
Eyelid dysfunction	1 1.4%
Fatigue (asthenia, lethargy, malaise)	34 48.6%
Febrile neutropenia	29 41.4%
Fever in absence of neutropenia, ANC lt1.0x10e9/L	22 31.4%
Fibrinogen	13 18.6%
Flatulence	2 2.9%
Flushing	2 2.9%
GGT (gamma-glutamyl transpeptidase)	1 1.4%
Gastrointestinal-Other	1 1.4%
Glomerular filtration rate	2 2.9%
Glucose, serum-high (hyperglycemia)	39 55.7%
Glucose, serum-low (hypoglycemia)	1 1.4%
Hair loss/Alopecia (scalp or body)	6 8.6%
Hearing: pts w/o audiogram not enroll monitor prgm	1 1.4%
Heartburn/dyspepsia	2 2.9%
Hematoma	3 4.3%
Hemoglobin	41 58.6%
Hemorrhage, Respiratory tract NOS	3 4.3%
Hemorrhage, CNS	8 11.4%
Hemorrhage, GI - Lower GI NOS	2 2.9%
Hemorrhage, GI - Oral cavity	4 5.7%
Hemorrhage, GI - Rectum	1 1.4%
Hemorrhage, GI - Upper GI NOS	2 2.9%
Hemorrhage, GU - Bladder	1 1.4%
Hemorrhage, GU - Urinary NOS	10 14.3%
Hemorrhage, GU - Vagina	4 5.7%
Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS	3 4.3%
Hemorrhage, pulmonary/upper respiratory - Lung	1 1.4%
Hemorrhage, pulmonary/upper respiratory - Nose	9 12.9%
Hemorrhage/Bleeding-Other	8 11.4%
Hemorrhoids	2 2.9%
Hepatobiliary/Pancreas-Other	2 2.9%
Hiccoughs (hiccups, singultus)	2 2.9%
Hot flashes/flushes	1 1.4%
Hypertension	25 35.7%
Hypotension	4 5.7%
Hypoxia	14 20%
INR (of prothrombin time)	8 11.4%
Ileus, GI (functional obstruction of bowel)	1 1.4%
Incontinence, anal	1 1.4%
Induration/fibrosis (skin and subcutaneous tissue)	1 1.4%
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	1 1.4%
Inf (clin/microbio) w/Gr 3-4 neuts - Colon	1 1.4%
Inf (clin/microbio) w/Gr 3-4 neuts - Dental-tooth	1 1.4%
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	4 5.7%
Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums	3 4.3%
Inf (clin/microbio) w/Gr 3-4 neuts - Skin	1 1.4%
Inf (clin/microbio) w/Gr 3-4 neuts - Stomach	1 1.4%
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	2 2.9%
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	2 2.9%
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	3 4.3%
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	1 1.4%
Inf w/normal ANC or Gr 1-2 neutrophils - Vagina	2 2.9%
Inf w/unknown ANC - Oral cavity-gums (gingivitis)	1 1.4%
Infection (documented clinically or microbiologica	1 1.4%
Infection with unknown ANC - Blood	2 2.9%
Infection with unknown ANC - Lung (pneumonia)	5 7.1%
Infection-Other	1 1.4%
Injection site reaction/extravasation changes	3 4.3%
Insomnia	19 27.1%
Leak (including anastomotic), GU - Bladder	1 1.4%
Left ventricular systolic dysfunction	3 4.3%
Leukocytes (total WBC)	26 37.1%
Liver dysfunction/failure (clinical)	1 1.4%
Lymphopenia	19 27.1%
Magnesium, serum-high (hypermagnesemia)	16 22.9%
Magnesium, serum-low (hypomagnesemia)	8 11.4%
Mental status	1 1.4%
Metabolic/Laboratory-Other	8 11.4%
Mood alteration - agitation	3 4.3%
Mood alteration - anxiety	14 20%
Mood alteration - depression	10 14.3%
Mucositis/stomatitis (clinical exam) - Oral cavity	2 2.9%
Mucositis/stomatitis (functional/symp) - Oral cav	6 8.6%
Muscle weakness, not d/t neuropathy - Extrem-lower	1 1.4%
Muscle weakness, not d/t neuropathy - body/general	9 12.9%
Musculoskeletal/Soft Tissue-Other	3 4.3%
Nasal cavity/paranasal sinus reactions	3 4.3%
Nausea	40 57.1%
Neurology-Other	2 2.9%
Neuropathy: cranial - CN II Vision	1 1.4%
Neuropathy: motor	4 5.7%
Neuropathy: sensory	3 4.3%
Neutrophils/granulocytes (ANC/AGC)	38 54.3%
Obstruction, GU - Bladder	1 1.4%
Ocular/Visual-Other	5 7.1%
Optic disc edema	2 2.9%
PTT (Partial thromboplastin time)	13 18.6%
Pain - Abdomen NOS	14 20%
Pain - Back	8 11.4%
Pain - Bone	2 2.9%
Pain - Buttock	1 1.4%
Pain - Cardiac/heart	1 1.4%
Pain - Chest/thorax NOS	9 12.9%
Pain - Dental/teeth/peridontal	1 1.4%
Pain - Esophagus	2 2.9%
Pain - Extremity-limb	5 7.1%
Pain - Eye	2 2.9%
Pain - Face	1 1.4%
Pain - Head/headache	44 62.9%
Pain - Joint	7 10%
Pain - Muscle	7 10%
Pain - Neck	3 4.3%
Pain - Oral cavity	2 2.9%
Pain - Pleura	1 1.4%
Pain - Sinus	1 1.4%
Pain - Stomach	1 1.4%
Pain - Throat/pharynx/larynx	8 11.4%
Pain - Urethra	2 2.9%
Pain-Other	6 8.6%
Petechiae/purpura (hemorrhage into skin or mucosa)	15 21.4%
Phosphate, serum-low (hypophosphatemia)	7 10%
Platelets	40 57.1%
Pleural effusion (non-malignant)	9 12.9%
Pneumonitis/pulmonary infiltrates	3 4.3%
Potassium, serum-high (hyperkalemia)	9 12.9%
Potassium, serum-low (hypokalemia)	28 40%
Prolonged QTc interval	21 30%
Proteinuria	6 8.6%
Pruritus/itching	12 17.1%
Psychosis (hallucinations/delusions)	1 1.4%
Pulmonary/Upper Respiratory-Other	5 7.1%
Rash/desquamation	26 37.1%
Renal failure	4 5.7%
Renal/Genitourinary-Other	2 2.9%
Retinoic acid syndrome	6 8.6%
Rigors/chills	7 10%
SVT and nodal arrhythmia - Atrial fibrillation	1 1.4%
SVT and nodal arrhythmia - SVT arrhythmia NOS	1 1.4%
SVT and nodal arrhythmia - Sinus arrhythmia	3 4.3%
SVT and nodal arrhythmia - Sinus bradycardia	5 7.1%
SVT and nodal arrhythmia - Sinus tachycardia	20 28.6%
Seizure	1 1.4%
Sodium, serum-high (hypernatremia)	5 7.1%
Sodium, serum-low (hyponatremia)	19 27.1%
Soft tissue necrosis - Extremity-lower	1 1.4%
Somnolence/depressed level of consciousness	6 8.6%
Speech impairment (e.g., dysphasia or aphasia)	1 1.4%
Stricture/stenosis (incl anastomotic) GI - Pharynx	1 1.4%
Sweating (diaphoresis)	9 12.9%
Syncope (fainting)	2 2.9%
Syndromes-Other	4 5.7%
Taste alteration (dysgeusia)	2 2.9%
Thrombosis/embolism (vascular access-related)	1 1.4%
Thrombosis/thrombus/embolism	2 2.9%
Thyroid function, low (hypothyroidism)	1 1.4%
Triglyceride, serum-high (hypertriglyceridemia)	11 15.7%
Ulceration	2 2.9%
Uric acid, serum-high (hyperuricemia)	2 2.9%
Urinary frequency/urgency	1 1.4%
Urinary retention (including neurogenic bladder)	4 5.7%
Urine color change	1 1.4%
Vaginal discharge (non-infectious)	1 1.4%
Ventricular arrhythmia - PVCs	1 1.4%
Ventricular arrhythmia - Ventricular tachycardia	1 1.4%
Vision-blurred vision	7 10%
Vision-flashing lights/floaters	2 2.9%
Vision-photophobia	4 5.7%
Vitreous hemorrhage	3 4.3%
Voice changes/dysarthria	1 1.4%
Vomiting	33 47.1%
Watery eye (epiphora, tearing)	2 2.9%
Weight gain	3 4.3%
Weight loss	9 12.9%

Adverse Events

Time Frame	Up to 3 years
Adverse Event Reporting Description	Only adverse events and serious adverse events that are possibly, probably or definitely related to study drug are reported.
Arm/Group Title	ATRA + GO + Arsenic
Arm/Group Description	Induction: ATRA 45mg/m2 PO D1-CR; Gemtuzumab Ozogamicin 9 mg/m2 IV D1; Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR
All Cause Mortality
	ATRA + GO + Arsenic
	Affected / at Risk (%)	# Events
Total	10/70 (14.3%)
Serious Adverse Events
	ATRA + GO + Arsenic
	Affected / at Risk (%)	# Events
Total	11/70 (15.7%)
Blood and lymphatic system disorders
DIC (disseminated intravascular coagulation)	2/70 (2.9%)
Hemoglobin	1/70 (1.4%)
Cardiac disorders
Cardiac General-Other	1/70 (1.4%)
SVT and nodal arrhythmia - Sinus tachycardia	1/70 (1.4%)
Gastrointestinal disorders
Ileus, GI (functional obstruction of bowel)	1/70 (1.4%)
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	1/70 (1.4%)
Infections and infestations
Infection with unknown ANC - Blood	2/70 (2.9%)
Infection with unknown ANC - Lung (pneumonia)	2/70 (2.9%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	1/70 (1.4%)
AST, SGOT	2/70 (2.9%)
Bilirubin (hyperbilirubinemia)	1/70 (1.4%)
Carbon monoxide diffusion capacity (DL(co))	1/70 (1.4%)
Leukocytes (total WBC)	1/70 (1.4%)
Neutrophils/granulocytes (ANC/AGC)	1/70 (1.4%)
Platelets	3/70 (4.3%)
Nervous system disorders
CNS cerebrovascular ischemia	1/70 (1.4%)
Hemorrhage, CNS	1/70 (1.4%)
Somnolence/depressed level of consciousness	1/70 (1.4%)
Renal and urinary disorders
Renal/Genitourinary-Other	2/70 (2.9%)
Respiratory, thoracic and mediastinal disorders
Carbon monoxide diffusion capacity (DL(co))	1/70 (1.4%)
Dyspnea (shortness of breath)	1/70 (1.4%)
Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS	1/70 (1.4%)
Hypoxia	2/70 (2.9%)
Pneumonitis/pulmonary infiltrates	1/70 (1.4%)
Pulmonary/Upper Respiratory-Other	1/70 (1.4%)
Retinoic acid syndrome	1/70 (1.4%)
Vascular disorders
Hypertension	1/70 (1.4%)
Other (Not Including Serious) Adverse Events
	ATRA + GO + Arsenic
	Affected / at Risk (%)	# Events
Total	68/70 (97.1%)
Blood and lymphatic system disorders
Blood/Bone Marrow-Other	4/70 (5.7%)
DIC (disseminated intravascular coagulation)	17/70 (24.3%)
Febrile neutropenia	29/70 (41.4%)
Hemoglobin	40/70 (57.1%)
Cardiac disorders
SVT and nodal arrhythmia - Sinus bradycardia	5/70 (7.1%)
SVT and nodal arrhythmia - Sinus tachycardia	19/70 (27.1%)
Eye disorders
Ocular/Visual-Other	5/70 (7.1%)
Vision-blurred vision	7/70 (10%)
Vision-photophobia	4/70 (5.7%)
Gastrointestinal disorders
Constipation	26/70 (37.1%)
Diarrhea	23/70 (32.9%)
Distention/bloating, abdominal	10/70 (14.3%)
Hemorrhage, GI - Oral cavity	4/70 (5.7%)
Mucositis/stomatitis (functional/symp) - Oral cav	6/70 (8.6%)
Nausea	40/70 (57.1%)
Pain - Abdomen NOS	14/70 (20%)
Vomiting	33/70 (47.1%)
General disorders
Edema: head and neck	5/70 (7.1%)
Edema: limb	33/70 (47.1%)
Fatigue (asthenia, lethargy, malaise)	34/70 (48.6%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	22/70 (31.4%)
Pain - Chest/thorax NOS	9/70 (12.9%)
Pain-Other	6/70 (8.6%)
Rigors/chills	7/70 (10%)
Syndromes-Other	4/70 (5.7%)
Immune system disorders
Allergic reaction/hypersensitivity	8/70 (11.4%)
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	4/70 (5.7%)
Injury, poisoning and procedural complications
Bruising (in absence of Gr 3-4 thrombocytopenia)	8/70 (11.4%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	36/70 (51.4%)
AST, SGOT	44/70 (62.9%)
Alkaline phosphatase	23/70 (32.9%)
Bilirubin (hyperbilirubinemia)	22/70 (31.4%)
Cholesterol, serum-high (hypercholesterolemia)	4/70 (5.7%)
Creatinine	5/70 (7.1%)
Fibrinogen	13/70 (18.6%)
INR (of prothrombin time)	8/70 (11.4%)
Leukocytes (total WBC)	25/70 (35.7%)
Lymphopenia	19/70 (27.1%)
Metabolic/Laboratory-Other	8/70 (11.4%)
Neutrophils/granulocytes (ANC/AGC)	37/70 (52.9%)
PTT (Partial thromboplastin time)	13/70 (18.6%)
Platelets	37/70 (52.9%)
Prolonged QTc interval	21/70 (30%)
Weight loss	9/70 (12.9%)
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)	4/70 (5.7%)
Albumin, serum-low (hypoalbuminemia)	24/70 (34.3%)
Alkalosis (metabolic or respiratory)	4/70 (5.7%)
Anorexia	18/70 (25.7%)
Bicarbonate, serum-low	7/70 (10%)
Calcium, serum-low (hypocalcemia)	22/70 (31.4%)
Glucose, serum-high (hyperglycemia)	39/70 (55.7%)
Magnesium, serum-high (hypermagnesemia)	16/70 (22.9%)
Magnesium, serum-low (hypomagnesemia)	8/70 (11.4%)
Phosphate, serum-low (hypophosphatemia)	7/70 (10%)
Potassium, serum-high (hyperkalemia)	9/70 (12.9%)
Potassium, serum-low (hypokalemia)	28/70 (40%)
Sodium, serum-high (hypernatremia)	5/70 (7.1%)
Sodium, serum-low (hyponatremia)	19/70 (27.1%)
Triglyceride, serum-high (hypertriglyceridemia)	11/70 (15.7%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	9/70 (12.9%)
Pain - Back	8/70 (11.4%)
Pain - Extremity-limb	5/70 (7.1%)
Pain - Joint	7/70 (10%)
Pain - Muscle	7/70 (10%)
Nervous system disorders
Dizziness	4/70 (5.7%)
Hemorrhage, CNS	7/70 (10%)
Neuropathy: motor	4/70 (5.7%)
Ocular/Visual-Other	5/70 (7.1%)
Pain - Head/headache	44/70 (62.9%)
Somnolence/depressed level of consciousness	5/70 (7.1%)
Psychiatric disorders
Confusion	6/70 (8.6%)
Insomnia	19/70 (27.1%)
Mood alteration - anxiety	14/70 (20%)
Mood alteration - depression	10/70 (14.3%)
Renal and urinary disorders
Hemorrhage, GU - Urinary NOS	10/70 (14.3%)
Proteinuria	6/70 (8.6%)
Renal failure	4/70 (5.7%)
Urinary retention (including neurogenic bladder)	4/70 (5.7%)
Reproductive system and breast disorders
Hemorrhage, GU - Vagina	4/70 (5.7%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	6/70 (8.6%)
Cough	17/70 (24.3%)
Dyspnea (shortness of breath)	26/70 (37.1%)
Hemorrhage, pulmonary/upper respiratory - Nose	9/70 (12.9%)
Hypoxia	12/70 (17.1%)
Pain - Throat/pharynx/larynx	8/70 (11.4%)
Pleural effusion (non-malignant)	9/70 (12.9%)
Pulmonary/Upper Respiratory-Other	5/70 (7.1%)
Retinoic acid syndrome	5/70 (7.1%)
Skin and subcutaneous tissue disorders
Dry skin	11/70 (15.7%)
Hair loss/Alopecia (scalp or body)	6/70 (8.6%)
Petechiae/purpura (hemorrhage into skin or mucosa)	15/70 (21.4%)
Pruritus/itching	12/70 (17.1%)
Rash/desquamation	26/70 (37.1%)
Sweating (diaphoresis)	9/70 (12.9%)
Vascular disorders
Hemorrhage/Bleeding-Other	8/70 (11.4%)
Hypertension	24/70 (34.3%)
Hypotension	4/70 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.