Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00651261
Collaborator
National Cancer Institute (NCI) (NIH), Novartis Pharmaceuticals (Industry)
717
Enrollment
176
Locations
2
Arms
4.1
Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effects, good and/or bad, of a standard chemotherapy regimen for AML that includes the drugs daunorubicin and cytarabine combined with or without midostaurin (also known as PKC412), to find out which is better. This research is being done because it is unknown whether the addition of midostaurin to chemotherapy treatment is better than chemotherapy treatment alone. Midostaurin has been tested in over 400 patients and is being studied in a number of illnesses, including AML, colon cancer, and lung cancer. Midostaurin blocks an enzyme, produced by a gene known as FLT3, that may have a role in the survival and growth of AML cells. Not all leukemia cells will have the abnormal FLT3 gene. This study will focus only on patients with leukemia cells with the abnormal FLT3 gene.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

In this study, patients will receive either the experimental agent (midostaurin) or placebo combined with chemotherapy treatment. Patients are stratified according to FLT3 mutation status (internal tandem duplication [ITD] allelic ratio < 0.7 vs ITD allelic ratio ≥ 0.7 vs tandem kinase domain [TKD]). There are three parts to the study treatment: remission induction therapy, remission consolidation therapy and continuation therapy.

Remission Induction Therapy:
  • Cytarabine 200 mg/m2/day by continuous intravenous infusion on days 1-7

  • Daunorubicin 60 mg/m2/day by intravenous push or short infusion on days 1-3

  • Midostaurin 50 mg (two 25 mg capsules) or placebo for midostaurin (2 capsules) twice a day by mouth on days 8-21

  • A bone marrow aspiration will be performed in all patients on Day 21 to determine the need for a second induction cycle.

Remission Consolidation (Four Remission Consolidation Cycles):
  • High dose cytarabine 3000 mg/m2 will be given by intravenous infusion over 3 hours every 12 hours on days 1, 3 and 5. Serial neurologic evaluation will be performed before and following the infusion of high-dose cytarabine.

  • Dexamethasone 0.1% or other corticosteroid ophthalmic solution 2 drops to each eye once daily to begin 6-12 hours prior to the initiation of the cytarabine infusion and to continue for at least 24 hours after the last cytarabine dose.

  • Midostaurin 50 mg (two 25 mg capsules) or placebo for midostaurin (2 capsules) twice a day by mouth on days 8-21

Midostaurin/Placebo Continuation Therapy:
  • Midostaurin 50 mg (two 25 mg capsules) or placebo for midostaurin (2 capsules) by mouth twice a day for 28 days. Each cycle will be 28 days in length. Continuation therapy with midostaurin/placebo will continue until relapse or for 12 cycles maximum.
The primary and secondary objectives of this study are:
Primary objective:
  • To determine if the addition of midostaurin to daunorubicin/cytarabine induction, high-dose cytarabine consolidation, and continuation therapy improves overall survival (OS) in both the mutant FLT3-ITD and FLT3-TKD AML patients
Secondary objectives:
  • To compare the overall survival (OS) in the two groups using an analysis in which patients who receive a stem cell transplant are censored at the time of transplant

  • To compare the complete response (CR) rate between the two treatment groups

  • To compare the event-free survival (EFS) between the two treatment groups

  • To compare the disease free survival (DFS) of the two treatment groups

  • To compare the disease free survival rate one year after completion of the continuation phase of the two groups

  • To assess the toxicity of the experimental combination

  • To describe the interaction between treatment outcome and pretreatment characteristics such as age, performance status, white blood cell (WBC) count, morphology, cytogenetics, and molecular and pharmacodynamic features

  • To assess the population pharmacokinetics (popPK) of midostaurin and its two major metabolites (CGP52421 and CGP62221). The potential association(s) between PK exposure and FLT3 status, OS, EFS and clinical response will be explored

There is a pharmacokinetic sub-study (CALGB 60706) within CALGB 10603. This embedded companion study must be offered to all patients enrolled on CALGB 10603, although patients may opt not to participate in CALGB 60706.

After study entry, patients are followed periodically for up to 10 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
717 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized, Double-Blind Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy + Midostaurin (PKC412) (IND #101261) or Placebo in Newly Diagnosed Patients < 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia (AML)
Actual Study Start Date :
Apr 1, 2008
Actual Primary Completion Date :
Jul 1, 2016

Arms and Interventions

ArmIntervention/Treatment
Experimental: Induction and consolidation chemotherapy plus midostaurin

Patients will receive a standard combination of chemotherapy drugs during remission induction therapy that includes cytarabine, daunorubicin, and the experimental drug midostaurin. Depending on the outcome of remission induction treatment, there may be a decision to discontinue the study treatment or a second remission induction cycle may be given. If remission induction therapy is successfully completed, patients will receive four courses of high-dose cytarabine consolidation chemotherapy plus dexamethasone together with the experimental drug midostaurin. All patients will undergo a bone marrow aspiration (and perhaps a biopsy) after the final course of remission consolidation chemotherapy. If the patient continues to respond to the treatment, the patient will receive continuation therapy with midostaurin for twelve (12) months.

Drug: cytarabine
Given IV

Drug: daunorubicin
Given IV

Drug: midostaurin
Given orally

Drug: dexamethasone acetate
ocular medication administration

Active Comparator: Induction and consolidation chemotherapy plus placebo

Patients will receive a standard combination of chemotherapy drugs during remission induction therapy that includes cytarabine, daunorubicin, and placebo. Depending on the outcome of remission induction treatment, there may be a decision to discontinue the study treatment or a second remission induction cycle may be given. If remission induction therapy is successfully completed, patients will receive four courses of high-dose cytarabine consolidation chemotherapy plus dexamethasone together with placebo. All patients will undergo a bone marrow aspiration (and perhaps a biopsy) after the final course of remission consolidation chemotherapy. If the patient continues to respond to the treatment, the patient will receive continuation therapy with placebo for twelve (12) months.

Drug: cytarabine
Given IV

Drug: daunorubicin
Given IV

Other: placebo
Given orally

Drug: dexamethasone acetate
ocular medication administration

Outcome Measures

Primary Outcome Measures

  1. Overall Survival (OS) [Duration of study (Up to 10 years)]

    Overall survival (OS) was defined as the time interval from randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.

Secondary Outcome Measures

  1. Event- Free Survival [Duration of study (Up to 10 years)]

    Event free survival (EFS) was defined as the time from randomization until the earliest qualifying event, including: failure to obtain a CR on or before 60 days of initiation of protocol therapy; relapse; or death from any cause. Patients alive and event free at the time of analysis were censored on the date of last clinical assessment. The median EFS with 95% CI was estimated using the Kaplan-Meier method. Due to a higher than expected transplant rate, EFS was promoted to be a key secondary endpoint.

  2. Overall Survival, Censoring Participants Who Receive a Stem Cell Transplant at the Time of the Transplant [Duration of study (Up to 10 years)]

    Overall survival (OS) was defined as the time interval from randomization to death from any cause. Any participants who received a stem cell transplant were censored at the time of transplant. The median OS with 95% CI was estimated using the Kaplan-Meier method.

  3. Complete Response Rate [Induction therapy (up to 60 days)]

    Percentage of participants who achieved a complete response (CR). A CR was defined as normalization of blood counts and a marrow showing less than 5% blasts occurring on or before day 60.

  4. Disease-free Survival (DFS) [Duration of study (Up to 10 years)]

    Disease free survival (DFS) is defined as the time from documentation of first CR at any time to the first of relapse or death from any cause in participants who achieved a CR.

  5. DFS Rate One Year After Completing the Planned Continuation Phase [30 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 59 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
  1. Documentation of Disease:
  • Unequivocal diagnosis of AML ( > 20% blasts in the bone marrow based on the WHO classification), excluding M3 (acute promyelocytic leukemia). Patients with neurologic symptoms suggestive of CNS leukemia are recommended to have a lumbar puncture. Patients whose CSF is positive for AML blasts are not eligible.

  • Documented FLT3 mutation (ITD or point mutation), determined by analysis in a protocol- designated FLT3 screening laboratory.

  1. Age Requirement:
  • Age ≥ 18 and < 60 years
  1. Prior Therapy:
  • No prior chemotherapy for leukemia or myelodysplasia with the following exceptions:

  • emergency leukapheresis

  • emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 5 days

  • cranial RT for CNS leukostasis (one dose only)

  • growth factor/cytokine support

  • AML patients with a history of antecedent myelodysplasia (MDS) remain eligible for treatment on this trial, but must not have had prior cytotoxic therapy (e.g., azacitidine or decitabine)

  • Patients who have developed therapy related AML after prior RT or chemotherapy for another cancer or disorder are not eligible.

  1. Cardiac Function: Patients with symptomatic congestive heart failure are not eligible.

  2. Initial Laboratory Value: Total bilirubin < 2.5 x ULN (Upper Limit of Normal)

  3. Pregnancy and Nursing Status:

  • Non-pregnant and non-nursing due to the unknown teratogenic potential of midostaurin in humans, pregnant or nursing patients may not be enrolled.

  • Women of childbearing potential must have a negative serum or urine pregnancy test within a sensitivity of at least 50 mIU/mL within 16 days prior to registration.

  • Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or commit to TWO acceptable methods of birth control:

  • one highly effective method (eg, IUD, hormonal (non-oral contraceptive), tubal ligation, or partner's vasectomy) and

  • one additional effective method (e.g., latex condom, diaphragm or cervical cap)

  • The two acceptable methods of birth control must be used AT THE SAME TIME, before beginning midostaurin/placebo therapy and continuing for 12 weeks after completion of all therapy.

  • Note that oral contraceptives are not considered a high effective method because of the possibility of a drug interaction with midostaurin.

  • Women of childbearing potential is defined as a sexually active mature woman who has not undergone a hysterectomy or who has not had menses at any time in the preceding 24 consecutive months.

  • Men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking midostaurin/placebo and for 12 weeks after therapy is stopped, even if they have undergone a successful vasectomy.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1UAB Comprehensive Cancer CenterBirminghamAlabamaUnited States35294
2Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle RockArkansasUnited States72205
3University of California Davis Cancer CenterSacramentoCaliforniaUnited States95817
4Aurora Presbyterian HospitalAuroraColoradoUnited States80012
5Boulder Community HospitalBoulderColoradoUnited States80301-9019
6Penrose Cancer Center at Penrose HospitalColorado SpringsColoradoUnited States80933
7St. Anthony Central HospitalDenverColoradoUnited States80204
8Porter Adventist HospitalDenverColoradoUnited States80210
9Presbyterian - St. Luke's Medical CenterDenverColoradoUnited States80218
10St. Joseph HospitalDenverColoradoUnited States80218
11Rose Medical CenterDenverColoradoUnited States80220
12CCOP - Colorado Cancer Research ProgramDenverColoradoUnited States80224-2522
13Swedish Medical CenterEnglewoodColoradoUnited States80110
14North Colorado Medical CenterGreeleyColoradoUnited States80631
15Sky Ridge Medical CenterLone TreeColoradoUnited States80124
16Hope Cancer Care Center at Longmont United HospitalLongmontColoradoUnited States80501
17McKee Medical CenterLovelandColoradoUnited States80539
18North Suburban Medical CenterThorntonColoradoUnited States80229
19Exempla Lutheran Medical CenterWheat RidgeColoradoUnited States80033
20Helen and Harry Gray Cancer Center at Hartford HospitalHartfordConnecticutUnited States06102-5037
21Tunnell Cancer Center at Beebe Medical CenterLewesDelawareUnited States19958
22CCOP - Christiana Care Health ServicesNewarkDelawareUnited States19713
23University of Florida Shands Cancer CenterGainesvilleFloridaUnited States32610-0232
24Memorial Cancer Institute at Memorial Regional HospitalHollywoodFloridaUnited States33021
25Baptist Cancer Institute - JacksonvilleJacksonvilleFloridaUnited States32207
26Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlandoFloridaUnited States32803-1273
27H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampaFloridaUnited States33612-9497
28MBCCOP - Medical College of Georgia Cancer CenterAugustaGeorgiaUnited States30912
29Charles B. Eberhart Cancer Center at DeKalb Medical CenterDecaturGeorgiaUnited States30033
30Medical Center of Central GeorgiaMaconGeorgiaUnited States31208
31Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/CandlerSavannahGeorgiaUnited States31405
32Cancer Research Center of HawaiiHonoluluHawaiiUnited States96813
33Queen's Cancer Institute at Queen's Medical CenterHonoluluHawaiiUnited States96813
34Illinois CancerCare - BloomingtonBloomingtonIllinoisUnited States61701
35Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicagoIllinoisUnited States60611-3013
36University of Illinois Cancer CenterChicagoIllinoisUnited States60612-7243
37University of Chicago Cancer Research CenterChicagoIllinoisUnited States60637-1470
38Decatur Memorial Hospital Cancer Care InstituteDecaturIllinoisUnited States62526
39Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywoodIllinoisUnited States60153
40BroMenn Regional Medical CenterNormalIllinoisUnited States61761
41Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoriaIllinoisUnited States61615
42Methodist Medical Center of IllinoisPeoriaIllinoisUnited States61636
43Fort Wayne Medical Oncology and HematologyFort WayneIndianaUnited States46845
44McFarland Clinic, PCAmesIowaUnited States50010
45Holden Comprehensive Cancer Center at University of IowaIowa CityIowaUnited States52242-1002
46Siouxland Hematology-Oncology Associates, LLPSioux CityIowaUnited States51101
47Mercy Medical Center - Sioux CitySioux CityIowaUnited States51104
48St. Luke's Regional Medical CenterSioux CityIowaUnited States51104
49Lucille P. Markey Cancer Center at University of KentuckyLexingtonKentuckyUnited States40536-0093
50Tulane Cancer Center Office of Clinical ResearchAlexandriaLouisianaUnited States71315-3198
51Feist-Weiller Cancer Center at Louisiana State University Health SciencesShreveportLouisianaUnited States71130-3932
52Greenebaum Cancer Center at University of Maryland Medical CenterBaltimoreMarylandUnited States21201
53Massachusetts General HospitalBostonMassachusettsUnited States02114
54Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer InstituteBostonMassachusettsUnited States02115
55Boston University Cancer Research CenterBostonMassachusettsUnited States02118
56Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
57Baystate Regional Cancer Program at D'Amour Center for Cancer CareSpringfieldMassachusettsUnited States01199
58Battle Creek Health System Cancer Care CenterBattle CreekMichiganUnited States49017
59Mecosta County Medical CenterBig RapidsMichiganUnited States49307
60Butterworth Hospital at Spectrum HealthGrand RapidsMichiganUnited States49503
61CCOP - Grand RapidsGrand RapidsMichiganUnited States49503
62Lacks Cancer Center at Saint Mary's Health CareGrand RapidsMichiganUnited States49503
63Borgess Medical CenterKalamazooMichiganUnited States49001
64West Michigan Cancer CenterKalamazooMichiganUnited States49007-3731
65Bronson Methodist HospitalKalamazooMichiganUnited States49007
66Providence Cancer Institute at Providence Hospital - Southfield CampusSouthfieldMichiganUnited States48075
67Munson Medical CenterTraverse CityMichiganUnited States49684
68Metro Health HospitalWyomingMichiganUnited States49519
69Fairview Ridges HospitalBurnsvilleMinnesotaUnited States55337
70Mercy and Unity Cancer Center at Mercy HospitalCoon RapidsMinnesotaUnited States55433
71Fairview Southdale HospitalEdinaMinnesotaUnited States55435
72Mercy and Unity Cancer Center at Unity HospitalFridleyMinnesotaUnited States55432
73HealthEast Cancer Care at St. John's HospitalMaplewoodMinnesotaUnited States55109
74Minnesota Oncology Hematology, PA - MaplewoodMaplewoodMinnesotaUnited States55109
75Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolisMinnesotaUnited States55407
76Hennepin County Medical Center - MinneapolisMinneapolisMinnesotaUnited States55415
77Masonic Cancer Center at University of MinnesotaMinneapolisMinnesotaUnited States55455
78Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdaleMinnesotaUnited States55422-2900
79Mayo Clinic Cancer CenterRochesterMinnesotaUnited States55905
80CCOP - Metro-MinnesotaSaint Louis ParkMinnesotaUnited States55416
81Park Nicollet Cancer CenterSaint Louis ParkMinnesotaUnited States55416
82Regions Hospital Cancer Care CenterSaint PaulMinnesotaUnited States55101
83United HospitalSaint PaulMinnesotaUnited States55102
84Ridgeview Medical CenterWaconiaMinnesotaUnited States55387
85Minnesota Oncology Hematology, PA - WoodburyWoodburyMinnesotaUnited States55125
86University of Mississippi Cancer ClinicJacksonMississippiUnited States39216
87Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbiaMissouriUnited States65203
88Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSaint LouisMissouriUnited States63110
89UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmahaNebraskaUnited States68198-6805
90University Medical Center of Southern NevadaLas VegasNevadaUnited States89102
91CCOP - Nevada Cancer Research FoundationLas VegasNevadaUnited States89106
92Sunrise Hospital and Medical CenterLas VegasNevadaUnited States89109
93Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanonNew HampshireUnited States03756-0002
94University of New Mexico Cancer CenterAlbuquerqueNew MexicoUnited States87131-5636
95Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263-0001
96Monter Cancer Center of the North Shore-LIJ Health SystemLake SuccessNew YorkUnited States11042
97CCOP - North Shore University HospitalManhassetNew YorkUnited States11030
98Don Monti Comprehensive Cancer Center at North Shore University HospitalManhassetNew YorkUnited States11030
99Tucker Center for Cancer Care at Orange Regional Medical CenterMiddletownNew YorkUnited States10940-4199
100Winthrop University HospitalMineolaNew YorkUnited States11501
101Long Island Jewish Medical CenterNew Hyde ParkNew YorkUnited States11040
102New York Weill Cornell Cancer Center at Cornell UniversityNew YorkNew YorkUnited States10021
103Mount Sinai Medical CenterNew YorkNew YorkUnited States10029
104James P. Wilmot Cancer Center at University of Rochester Medical CenterRochesterNew YorkUnited States14642
105SUNY Upstate Medical University HospitalSyracuseNew YorkUnited States13210
106Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel HillNorth CarolinaUnited States27599-7295
107Blumenthal Cancer Center at Carolinas Medical CenterCharlotteNorth CarolinaUnited States28232-2861
108Duke Comprehensive Cancer CenterDurhamNorth CarolinaUnited States27710
109Leo W. Jenkins Cancer Center at ECU Medical SchoolGreenvilleNorth CarolinaUnited States27834
110Kinston Medical SpecialistsKinstonNorth CarolinaUnited States28501
111Wake Forest University Comprehensive Cancer CenterWinston-SalemNorth CarolinaUnited States27157-1096
112Summa Center for Cancer Care at Akron City HospitalAkronOhioUnited States44309-2090
113Barberton Citizens HospitalBarbertonOhioUnited States44203
114Charles M. Barrett Cancer Center at University HospitalCincinnatiOhioUnited States45267
115Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbusOhioUnited States43210-1240
116St. Rita's Medical CenterLimaOhioUnited States45801
117Cleo Craig Cancer Research ClinicLawtonOklahomaUnited States73505
118Oklahoma University Cancer InstituteOklahoma CityOklahomaUnited States73104
119Geisinger Cancer Institute at Geisinger HealthDanvillePennsylvaniaUnited States17822-0001
120Geisinger Hazleton Cancer CenterHazletonPennsylvaniaUnited States18201
121Penn State Hershey Cancer Institute at Milton S. Hershey Medical CenterHersheyPennsylvaniaUnited States17033-0850
122Western Pennsylvania Cancer Institute at Western Pennsylvania HospitalPittsburghPennsylvaniaUnited States15224-1791
123UPMC Cancer CentersPittsburghPennsylvaniaUnited States15232
124Geisinger Medical Group - Scenery ParkState CollegePennsylvaniaUnited States16801
125Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-BarrePennsylvaniaUnited States18711
126Hollings Cancer Center at Medical University of South CarolinaCharlestonSouth CarolinaUnited States29425
127Cancer Centers of the Carolinas - EasleyEasleySouth CarolinaUnited States29640
128Cancer Centers of the Carolinas - Faris RoadGreenvilleSouth CarolinaUnited States29605
129Cancer Centers of the Carolinas - Grove CommonsGreenvilleSouth CarolinaUnited States29605
130Greenville Hospital Cancer CenterGreenvilleSouth CarolinaUnited States29605
131CCOP - GreenvilleGreenvilleSouth CarolinaUnited States29615
132Self Regional Cancer Center at Self Regional Medical CenterGreenwoodSouth CarolinaUnited States29646
133Cancer Centers of the Carolinas - Greer Medical OncologyGreerSouth CarolinaUnited States29650
134Cancer Centers of the Carolinas - SenecaSenecaSouth CarolinaUnited States29672
135Cancer Centers of the Carolinas - SpartanburgSpartanburgSouth CarolinaUnited States29307
136Avera Cancer InstituteSioux FallsSouth DakotaUnited States57105
137Sanford Cancer Center at Sanford USD Medical CenterSioux FallsSouth DakotaUnited States57117-5039
138University of Tennessee Cancer Institute - MemphisMemphisTennesseeUnited States38104
139Tennessee Oncology, PLLC at Sarah Cannon Cancer CenterNashvilleTennesseeUnited States37203
140Vanderbilt-Ingram Cancer CenterNashvilleTennesseeUnited States37232-6838
141Baylor University Medical Center - HoustonHoustonTexasUnited States77030
142Ben Taub General HospitalHoustonTexasUnited States77030
143Veterans Affairs Medical Center - HoustonHoustonTexasUnited States77030
144Mountainview MedicalBerlinVermontUnited States05602
145Fletcher Allen Health Care - University Health Center CampusBurlingtonVermontUnited States05401
146Virginia Commonwealth University Massey Cancer CenterRichmondVirginiaUnited States23298-0037
147West Virginia University Health Sciences Center - CharlestonCharlestonWest VirginiaUnited States25304
148Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantownWest VirginiaUnited States26506
149Marshfield Clinic - Chippewa CenterChippewa FallsWisconsinUnited States54729
150Center for Cancer Treatment & Prevention at Sacred Heart HospitalEau ClaireWisconsinUnited States54701
151Marshfield Clinic Cancer Care at Regional Cancer CenterEau ClaireWisconsinUnited States54701
152Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen BayWisconsinUnited States54301-3526
153Green Bay Oncology, Limited at St. Mary's HospitalGreen BayWisconsinUnited States54303
154St. Mary's Hospital Medical Center - Green BayGreen BayWisconsinUnited States54303
155St. Vincent Hospital Regional Cancer CenterGreen BayWisconsinUnited States54307-3508
156University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadisonWisconsinUnited States53792-6164
157Holy Family Memorial Medical Center Cancer Care CenterManitowocWisconsinUnited States54221-1450
158Bay Area Cancer Care Center at Bay Area Medical CenterMarinetteWisconsinUnited States54143
159Marshfield Clinic - Marshfield CenterMarshfieldWisconsinUnited States54449
160Saint Joseph's HospitalMarshfieldWisconsinUnited States54449
161Marshfield Clinic - Lakeland CenterMinocquaWisconsinUnited States54548
162D.N. Greenwald CenterMukwonagoWisconsinUnited States53149
163Regional Cancer Center at Oconomowoc Memorial HospitalOconomowocWisconsinUnited States53066
164Ministry Medical Group at Saint Mary's HospitalRhinelanderWisconsinUnited States54501
165Marshfield Clinic - Indianhead CenterRice LakeWisconsinUnited States54868
166Marshfield Clinic at Saint Michael's HospitalStevens PointWisconsinUnited States54481
167Waukesha Memorial Hospital Regional Cancer CenterWaukeshaWisconsinUnited States53188
168Marshfield Clinic - Weston CenterWestonWisconsinUnited States54476
169Ministry Saint Clare's HospitalWestonWisconsinUnited States54476
170Marshfield Clinic - Wisconsin Rapids CenterWisconsin RapidsWisconsinUnited States54494
171Tom Baker Cancer Centre - CalgaryCalgaryAlbertaCanadaT2N 4N2
172CancerCare ManitobaWinnipegManitobaCanadaR3E 0V9
173Nova Scotia Cancer CentreHalifaxNova ScotiaCanadaB3H 1V8
174Princess Margaret HospitalTorontoOntarioCanadaM5G 2M9
175Maisonneuve-Rosemont HospitalMontrealQuebecCanadaH1T 2M4
176McGill Cancer Centre at McGill UniversityMontrealQuebecCanadaH2W 1S6

Sponsors and Collaborators

  • Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)
  • Novartis Pharmaceuticals

Investigators

  • Study Chair: Richard M. Stone, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00651261
Other Study ID Numbers:
  • CALGB-10603
  • CALGB-10603
  • EUDRACT-2006-006852-37
  • CDR0000590404
First Posted:
Apr 2, 2008
Last Update Posted:
Aug 18, 2021
Last Verified:
Aug 1, 2021

Study Results

Participant Flow

Recruitment DetailsBetween May 2008 and October 2001, 3,277 participants were pre-registered. Of those, 900 participants had a documented FLT3 mutation. 717 participants were enrolled onto this study.
Pre-assignment Detail
Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Period Title: Overall Study
STARTED360357
COMPLETED6951
NOT COMPLETED291306

Baseline Characteristics

Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus PlaceboTotal
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.Total of all reporting groups
Overall Participants360357717
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
47.1
48.6
47.9
Sex: Female, Male (Count of Participants)
Female
186
51.7%
212
59.4%
398
55.5%
Male
174
48.3%
145
40.6%
319
44.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
9
2.5%
7
2%
16
2.2%
Not Hispanic or Latino
103
28.6%
107
30%
210
29.3%
Unknown or Not Reported
248
68.9%
243
68.1%
491
68.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
1
0.3%
1
0.1%
Asian
8
2.2%
5
1.4%
13
1.8%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
8
2.2%
9
2.5%
17
2.4%
White
147
40.8%
128
35.9%
275
38.4%
More than one race
2
0.6%
1
0.3%
3
0.4%
Unknown or Not Reported
195
54.2%
213
59.7%
408
56.9%
Region of Enrollment (participants) [Number]
Canada
4
1.1%
9
2.5%
13
1.8%
United States
117
32.5%
106
29.7%
223
31.1%
Germany
148
41.1%
157
44%
305
42.5%
Belgium
3
0.8%
5
1.4%
8
1.1%
France
3
0.8%
2
0.6%
5
0.7%
Netherlands
3
0.8%
2
0.6%
5
0.7%
Australia
0
0%
2
0.6%
2
0.3%
Spain
7
1.9%
15
4.2%
22
3.1%
Austria
7
1.9%
5
1.4%
12
1.7%
Italy
61
16.9%
44
12.3%
105
14.6%
Czech Republic
5
1.4%
6
1.7%
11
1.5%
Slovakia
2
0.6%
2
0.6%
4
0.6%
Hungary
0
0%
2
0.6%
2
0.3%
FLT3 mutational subtype (participants) [Number]
TKD (No ITD)
81
22.5%
81
22.7%
162
22.6%
ITD Allelic ratio <0.7
171
47.5%
170
47.6%
341
47.6%
ITD Allelic ratio >=0.7
108
30%
106
29.7%
214
29.8%

Outcome Measures

1. Primary Outcome
TitleOverall Survival (OS)
DescriptionOverall survival (OS) was defined as the time interval from randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Time FrameDuration of study (Up to 10 years)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Measure Participants360357
Median (95% Confidence Interval) [months]
74.7
25.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesisp-Value0.009
Comments
Method1-sided stratified log-rank
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.78
Confidence Interval (2-Sided) 95%
0.63 to 0.96
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
TitleEvent- Free Survival
DescriptionEvent free survival (EFS) was defined as the time from randomization until the earliest qualifying event, including: failure to obtain a CR on or before 60 days of initiation of protocol therapy; relapse; or death from any cause. Patients alive and event free at the time of analysis were censored on the date of last clinical assessment. The median EFS with 95% CI was estimated using the Kaplan-Meier method. Due to a higher than expected transplant rate, EFS was promoted to be a key secondary endpoint.
Time FrameDuration of study (Up to 10 years)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Measure Participants360357
Median (95% Confidence Interval) [months]
8.2
3.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesisp-Value0.0024
Comments
Method1-sided stratified log rank
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.78
Confidence Interval (2-Sided) 95%
0.66 to 0.93
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
TitleOverall Survival, Censoring Participants Who Receive a Stem Cell Transplant at the Time of the Transplant
DescriptionOverall survival (OS) was defined as the time interval from randomization to death from any cause. Any participants who received a stem cell transplant were censored at the time of transplant. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Time FrameDuration of study (Up to 10 years)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Measure Participants360357
Median (95% Confidence Interval) [months]
NA
NA
4. Secondary Outcome
TitleComplete Response Rate
DescriptionPercentage of participants who achieved a complete response (CR). A CR was defined as normalization of blood counts and a marrow showing less than 5% blasts occurring on or before day 60.
Time FrameInduction therapy (up to 60 days)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Measure Participants360357
Number (95% Confidence Interval) [percentage of participants]
59
16.4%
54
15.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesisp-Value0.15
Comments
MethodFisher Exact
Comments
5. Secondary Outcome
TitleDisease-free Survival (DFS)
DescriptionDisease free survival (DFS) is defined as the time from documentation of first CR at any time to the first of relapse or death from any cause in participants who achieved a CR.
Time FrameDuration of study (Up to 10 years)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
Measure Participants360357
Median (95% Confidence Interval) [months]
26.7
15.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction and Consolidation Chemotherapy Plus Midostaurin, Induction and Consolidation Chemotherapy Plus Placebo
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesisp-Value0.0049
Comments
Method1-sided stratified log rank
Comments
6. Secondary Outcome
TitleDFS Rate One Year After Completing the Planned Continuation Phase
Description
Time Frame30 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description

Adverse Events

Time Frame
Adverse Event Reporting Description 709 participants were evaluated for adverse events.
Arm/Group TitleInduction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Arm/Group DescriptionPatients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and midostaurin 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and midostaurin at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of midostaurin 50 mg orally twice daily.Patients will receive daunorubicin 60 mg/m^2 by IV push days 1-3 plus cytarabine 200 mg/m^2 IV days 1-7, and placebo 50 mg orally twice daily days 8-21. Participants achieving remission will receive four 28 day cycles of high dose cytarabine (3000 mg/m^2) days 1, 3, & 5 and placebo at 50 mg orally twice daily days 8-14. Maintenance therapy was given to participants who continued in remission for 12 28-day cycles of placebo 50 mg orally twice daily.
All Cause Mortality
Induction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total/ (NaN) / (NaN)
Serious Adverse Events
Induction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total157/355 (44.2%) 154/354 (43.5%)
Blood and lymphatic system disorders
Blood disorder0/355 (0%) 01/354 (0.3%) 1
Bone marrow hypocellular0/355 (0%) 01/354 (0.3%) 1
Disseminated intravascular coagulation1/355 (0.3%) 10/354 (0%) 0
Febrile neutropenia105/355 (29.6%) 144110/354 (31.1%) 152
Hemoglobin decreased154/355 (43.4%) 237148/354 (41.8%) 230
Hemolysis2/355 (0.6%) 20/354 (0%) 0
Lymph node pain0/355 (0%) 01/354 (0.3%) 1
Lymphatic disorder6/355 (1.7%) 64/354 (1.1%) 4
Cardiac disorders
Arrhythmia1/355 (0.3%) 12/354 (0.6%) 2
Asystole1/355 (0.3%) 10/354 (0%) 0
Atrial fibrillation4/355 (1.1%) 46/354 (1.7%) 6
Atrial flutter2/355 (0.6%) 22/354 (0.6%) 2
Atrial tachycardia1/355 (0.3%) 12/354 (0.6%) 2
Cardiac disorder4/355 (1.1%) 46/354 (1.7%) 6
Cardiac pain3/355 (0.8%) 31/354 (0.3%) 1
Cardiopulmonary arrest0/355 (0%) 01/354 (0.3%) 1
Conduction disorder0/355 (0%) 02/354 (0.6%) 2
Left ventricular dysfunction1/355 (0.3%) 10/354 (0%) 0
Left ventricular failure8/355 (2.3%) 97/354 (2%) 7
Myocardial ischemia3/355 (0.8%) 33/354 (0.8%) 3
Palpitations0/355 (0%) 01/354 (0.3%) 1
Pericardial effusion4/355 (1.1%) 45/354 (1.4%) 5
Pericarditis3/355 (0.8%) 30/354 (0%) 0
Right ventricular dysfunction1/355 (0.3%) 10/354 (0%) 0
Sinus arrhythmia1/355 (0.3%) 10/354 (0%) 0
Sinus bradycardia2/355 (0.6%) 22/354 (0.6%) 2
Sinus tachycardia17/355 (4.8%) 2015/354 (4.2%) 20
Supraventricular tachycardia0/355 (0%) 02/354 (0.6%) 2
Ventricular fibrillation0/355 (0%) 01/354 (0.3%) 1
Ventricular tachycardia0/355 (0%) 03/354 (0.8%) 3
Ear and labyrinth disorders
Ear disorder1/355 (0.3%) 12/354 (0.6%) 2
Ear pain2/355 (0.6%) 23/354 (0.8%) 3
External ear pain0/355 (0%) 01/354 (0.3%) 1
Middle ear inflammation0/355 (0%) 01/354 (0.3%) 1
Tinnitus0/355 (0%) 01/354 (0.3%) 1
Endocrine disorders
Endocrine disorder0/355 (0%) 01/354 (0.3%) 1
Hyperthyroidism0/355 (0%) 01/354 (0.3%) 1
Hypothyroidism0/355 (0%) 01/354 (0.3%) 1
Eye disorders
Cataract1/355 (0.3%) 10/354 (0%) 0
Conjunctivitis2/355 (0.6%) 21/354 (0.3%) 1
Diplopia1/355 (0.3%) 11/354 (0.3%) 1
Dry eye syndrome3/355 (0.8%) 33/354 (0.8%) 3
Eye disorder8/355 (2.3%) 912/354 (3.4%) 12
Eye pain1/355 (0.3%) 11/354 (0.3%) 1
Eyelid function disorder0/355 (0%) 02/354 (0.6%) 2
Flashing vision1/355 (0.3%) 12/354 (0.6%) 2
Keratitis5/355 (1.4%) 68/354 (2.3%) 9
Optic nerve edema0/355 (0%) 01/354 (0.3%) 1
Photophobia2/355 (0.6%) 21/354 (0.3%) 1
Retinal detachment0/355 (0%) 01/354 (0.3%) 1
Scleral disorder0/355 (0%) 01/354 (0.3%) 1
Vision blurred2/355 (0.6%) 24/354 (1.1%) 4
Watering eyes2/355 (0.6%) 23/354 (0.8%) 3
Gastrointestinal disorders
Abdominal distension4/355 (1.1%) 42/354 (0.6%) 2
Abdominal pain29/355 (8.2%) 3328/354 (7.9%) 32
Anal fistula1/355 (0.3%) 11/354 (0.3%) 1
Anal hemorrhage1/355 (0.3%) 12/354 (0.6%) 2
Anal mucositis2/355 (0.6%) 20/354 (0%) 0
Anal pain7/355 (2%) 85/354 (1.4%) 5
Anal ulcer0/355 (0%) 01/354 (0.3%) 1
Ascites2/355 (0.6%) 22/354 (0.6%) 2
Colitis9/355 (2.5%) 99/354 (2.5%) 9
Colonic hemorrhage2/355 (0.6%) 20/354 (0%) 0
Colonic perforation0/355 (0%) 01/354 (0.3%) 1
Constipation16/355 (4.5%) 1817/354 (4.8%) 18
Diarrhea89/355 (25.1%) 11189/354 (25.1%) 108
Dry mouth2/355 (0.6%) 21/354 (0.3%) 1
Duodenal hemorrhage0/355 (0%) 01/354 (0.3%) 1
Duodenal necrosis1/355 (0.3%) 10/354 (0%) 0
Dyspepsia10/355 (2.8%) 118/354 (2.3%) 8
Dysphagia10/355 (2.8%) 1010/354 (2.8%) 12
Ear, nose and throat examination abnormal40/355 (11.3%) 5242/354 (11.9%) 54
Endoscopy small intestine abnormal1/355 (0.3%) 10/354 (0%) 0
Enteritis2/355 (0.6%) 21/354 (0.3%) 1
Esophageal pain1/355 (0.3%) 12/354 (0.6%) 2
Esophageal ulcer1/355 (0.3%) 10/354 (0%) 0
Esophagitis0/355 (0%) 02/354 (0.6%) 2
Flatulence7/355 (2%) 85/354 (1.4%) 6
Gastric hemorrhage2/355 (0.6%) 21/354 (0.3%) 1
Gastrointestinal disorder10/355 (2.8%) 1210/354 (2.8%) 10
Gastrointestinal pain0/355 (0%) 01/354 (0.3%) 1
Gingival pain1/355 (0.3%) 12/354 (0.6%) 2
Hemorrhoidal hemorrhage1/355 (0.3%) 10/354 (0%) 0
Hemorrhoids11/355 (3.1%) 147/354 (2%) 7
Ileal hemorrhage0/355 (0%) 01/354 (0.3%) 1
Ileal necrosis1/355 (0.3%) 10/354 (0%) 0
Ileus2/355 (0.6%) 24/354 (1.1%) 4
Intestinal necrosis2/355 (0.6%) 20/354 (0%) 0
Intra-abdominal hemorrhage1/355 (0.3%) 10/354 (0%) 0
Jejunal necrosis1/355 (0.3%) 10/354 (0%) 0
Lower gastrointestinal hemorrhage2/355 (0.6%) 23/354 (0.8%) 3
Mucositis oral23/355 (6.5%) 2311/354 (3.1%) 13
Nausea98/355 (27.6%) 14991/354 (25.7%) 126
Oral hemorrhage5/355 (1.4%) 610/354 (2.8%) 11
Oral pain5/355 (1.4%) 55/354 (1.4%) 6
Periodontal disease2/355 (0.6%) 21/354 (0.3%) 1
Proctitis1/355 (0.3%) 11/354 (0.3%) 1
Rectal hemorrhage3/355 (0.8%) 33/354 (0.8%) 3
Rectal obstruction2/355 (0.6%) 20/354 (0%) 0
Rectal pain2/355 (0.6%) 21/354 (0.3%) 1
Salivary gland disorder1/355 (0.3%) 12/354 (0.6%) 2
Stomach pain8/355 (2.3%) 129/354 (2.5%) 9
Tooth disorder1/355 (0.3%) 12/354 (0.6%) 2
Toothache3/355 (0.8%) 34/354 (1.1%) 4
Typhlitis1/355 (0.3%) 12/354 (0.6%) 2
Upper gastrointestinal hemorrhage2/355 (0.6%) 21/354 (0.3%) 1
Vomiting70/355 (19.7%) 10165/354 (18.4%) 86
General disorders
Chest pain6/355 (1.7%) 711/354 (3.1%) 12
Chills16/355 (4.5%) 2116/354 (4.5%) 24
Disease progression1/355 (0.3%) 11/354 (0.3%) 1
Edema limbs26/355 (7.3%) 3221/354 (5.9%) 24
Facial pain2/355 (0.6%) 22/354 (0.6%) 2
Fatigue95/355 (26.8%) 13698/354 (27.7%) 130
Fever34/355 (9.6%) 3833/354 (9.3%) 38
Flu-like symptoms1/355 (0.3%) 11/354 (0.3%) 1
General symptom11/355 (3.1%) 1415/354 (4.2%) 16
Ill-defined disorder1/355 (0.3%) 14/354 (1.1%) 4
Injection site reaction14/355 (3.9%) 1717/354 (4.8%) 22
Localized edema5/355 (1.4%) 59/354 (2.5%) 11
Multi-organ failure4/355 (1.1%) 45/354 (1.4%) 5
Pain14/355 (3.9%) 1718/354 (5.1%) 24
Sudden death0/355 (0%) 01/354 (0.3%) 1
Visceral edema1/355 (0.3%) 11/354 (0.3%) 1
Hepatobiliary disorders
Cholecystitis1/355 (0.3%) 12/354 (0.6%) 2
Hepatic failure1/355 (0.3%) 12/354 (0.6%) 2
Hepatobiliary disease4/355 (1.1%) 41/354 (0.3%) 1
Immune system disorders
Cytokine release syndrome0/355 (0%) 01/354 (0.3%) 1
Hypersensitivity7/355 (2%) 814/354 (4%) 15
Immune system disorder3/355 (0.8%) 33/354 (0.8%) 4
Infections and infestations
Abdominal infection1/355 (0.3%) 13/354 (0.8%) 3
Anal infection6/355 (1.7%) 95/354 (1.4%) 5
Anorectal infection1/355 (0.3%) 10/354 (0%) 0
Appendicitis0/355 (0%) 01/354 (0.3%) 1
Bladder infection2/355 (0.6%) 23/354 (0.8%) 3
Bone infection1/355 (0.3%) 11/354 (0.3%) 1
Bronchitis1/355 (0.3%) 13/354 (0.8%) 4
Catheter related infection29/355 (8.2%) 3921/354 (5.9%) 26
Colitis, infectious (e.g., Clostridium difficile)3/355 (0.8%) 32/354 (0.6%) 2
Conjunctivitis infective4/355 (1.1%) 43/354 (0.8%) 3
Eye infection1/355 (0.3%) 11/354 (0.3%) 1
Eye infection intraocular1/355 (0.3%) 10/354 (0%) 0
Gallbladder infection0/355 (0%) 01/354 (0.3%) 1
Gingival infection1/355 (0.3%) 12/354 (0.6%) 3
Hepatic infection2/355 (0.6%) 23/354 (0.8%) 3
Infection30/355 (8.5%) 4126/354 (7.3%) 33
Infectious colitis8/355 (2.3%) 89/354 (2.5%) 10
Joint infection0/355 (0%) 02/354 (0.6%) 2
Kidney infection0/355 (0%) 01/354 (0.3%) 1
Lip infection5/355 (1.4%) 58/354 (2.3%) 9
Lymph gland infection1/355 (0.3%) 10/354 (0%) 0
Mucosal infection1/355 (0.3%) 11/354 (0.3%) 1
Nail infection3/355 (0.8%) 30/354 (0%) 0
Opportunistic infection3/355 (0.8%) 31/354 (0.3%) 1
Otitis externa1/355 (0.3%) 12/354 (0.6%) 2
Otitis media0/355 (0%) 01/354 (0.3%) 1
Paranasal sinus infection1/355 (0.3%) 13/354 (0.8%) 3
Penile infection1/355 (0.3%) 10/354 (0%) 0
Pharyngitis3/355 (0.8%) 42/354 (0.6%) 2
Phlebitis infective2/355 (0.6%) 21/354 (0.3%) 1
Pleural infection1/355 (0.3%) 10/354 (0%) 0
Pneumonia25/355 (7%) 3235/354 (9.9%) 39
Rhinitis infective1/355 (0.3%) 11/354 (0.3%) 1
Salivary gland infection1/355 (0.3%) 10/354 (0%) 0
Sepsis23/355 (6.5%) 2716/354 (4.5%) 17
Sinusitis1/355 (0.3%) 10/354 (0%) 0
Skin infection8/355 (2.3%) 98/354 (2.3%) 9
Small intestine infection1/355 (0.3%) 10/354 (0%) 0
Soft tissue infection0/355 (0%) 04/354 (1.1%) 4
Splenic infection2/355 (0.6%) 21/354 (0.3%) 1
Tooth infection1/355 (0.3%) 14/354 (1.1%) 5
Upper aerodigestive tract infection1/355 (0.3%) 11/354 (0.3%) 1
Urinary tract infection8/355 (2.3%) 1015/354 (4.2%) 19
Vulval infection1/355 (0.3%) 10/354 (0%) 0
Wound infection4/355 (1.1%) 42/354 (0.6%) 2
Injury, poisoning and procedural complications
Bruising1/355 (0.3%) 10/354 (0%) 0
Fracture1/355 (0.3%) 10/354 (0%) 0
Gastrointestinal anastomotic leak0/355 (0%) 01/354 (0.3%) 1
Intraoperative complications2/355 (0.6%) 20/354 (0%) 0
Intraoperative gastrointestinal injury1/355 (0.3%) 10/354 (0%) 0
Intraoperative gastrointestinal injury - Appendix0/355 (0%) 01/354 (0.3%) 1
Intraoperative reproductive tract injury - Ovary0/355 (0%) 01/354 (0.3%) 1
Intraoperative reproductive tract injury - Testis0/355 (0%) 01/354 (0.3%) 1
Kidney anastomotic leak1/355 (0.3%) 10/354 (0%) 0
Postoperative hemorrhage0/355 (0%) 01/354 (0.3%) 1
Thermal burn0/355 (0%) 01/354 (0.3%) 1
Vascular access complication3/355 (0.8%) 33/354 (0.8%) 3
Wound dehiscence1/355 (0.3%) 10/354 (0%) 0
Investigations
Activated partial thromboplastin time prolonged9/355 (2.5%) 159/354 (2.5%) 11
Alanine aminotransferase increased35/355 (9.9%) 4135/354 (9.9%) 41
Alkaline phosphatase increased8/355 (2.3%) 820/354 (5.6%) 24
Amylase increased1/355 (0.3%) 10/354 (0%) 0
Aspartate aminotransferase increased30/355 (8.5%) 3329/354 (8.2%) 32
Blood bilirubin increased25/355 (7%) 3236/354 (10.2%) 42
CD4 lymphocytes decreased1/355 (0.3%) 30/354 (0%) 0
Cardiac troponin T increased2/355 (0.6%) 21/354 (0.3%) 1
Coagulopathy8/355 (2.3%) 147/354 (2%) 11
Creatinine increased15/355 (4.2%) 1616/354 (4.5%) 17
Electrocardiogram QTc interval prolonged17/355 (4.8%) 2219/354 (5.4%) 22
Fibrinogen decreased2/355 (0.6%) 27/354 (2%) 7
Gamma-glutamyltransferase increased19/355 (5.4%) 2522/354 (6.2%) 32
INR increased8/355 (2.3%) 105/354 (1.4%) 5
Laboratory test abnormal18/355 (5.1%) 3328/354 (7.9%) 47
Leukocyte count decreased41/355 (11.5%) 6647/354 (13.3%) 78
Lipase increased2/355 (0.6%) 21/354 (0.3%) 1
Lymphocyte count decreased22/355 (6.2%) 3036/354 (10.2%) 56
Neutrophil count decreased145/355 (40.8%) 227146/354 (41.2%) 224
Platelet count decreased155/355 (43.7%) 239146/354 (41.2%) 227
Serum cholesterol increased1/355 (0.3%) 10/354 (0%) 0
Weight gain3/355 (0.8%) 33/354 (0.8%) 3
Weight loss1/355 (0.3%) 111/354 (3.1%) 13
Metabolism and nutrition disorders
Acidosis2/355 (0.6%) 21/354 (0.3%) 1
Anorexia21/355 (5.9%) 3026/354 (7.3%) 29
Blood glucose increased17/355 (4.8%) 2322/354 (6.2%) 31
Blood uric acid increased6/355 (1.7%) 104/354 (1.1%) 4
Dehydration1/355 (0.3%) 10/354 (0%) 0
Glucose intolerance0/355 (0%) 02/354 (0.6%) 2
Serum albumin decreased19/355 (5.4%) 2822/354 (6.2%) 26
Serum calcium decreased20/355 (5.6%) 2526/354 (7.3%) 30
Serum calcium increased2/355 (0.6%) 21/354 (0.3%) 1
Serum glucose decreased1/355 (0.3%) 12/354 (0.6%) 3
Serum magnesium decreased15/355 (4.2%) 1915/354 (4.2%) 22
Serum phosphate decreased7/355 (2%) 912/354 (3.4%) 13
Serum potassium decreased31/355 (8.7%) 3747/354 (13.3%) 53
Serum potassium increased8/355 (2.3%) 94/354 (1.1%) 4
Serum sodium decreased20/355 (5.6%) 2220/354 (5.6%) 22
Serum sodium increased5/355 (1.4%) 55/354 (1.4%) 5
Serum triglycerides increased3/355 (0.8%) 40/354 (0%) 0
Tumor lysis syndrome1/355 (0.3%) 12/354 (0.6%) 2
Musculoskeletal and connective tissue disorders
Arthralgia8/355 (2.3%) 86/354 (1.7%) 6
Arthritis1/355 (0.3%) 12/354 (0.6%) 2
Back pain15/355 (4.2%) 1913/354 (3.7%) 13
Bone pain7/355 (2%) 84/354 (1.1%) 5
Buttock pain1/355 (0.3%) 10/354 (0%) 0
Chest wall pain1/355 (0.3%) 12/354 (0.6%) 2
Joint effusion1/355 (0.3%) 11/354 (0.3%) 1
Muscle weakness3/355 (0.8%) 32/354 (0.6%) 3
Musculoskeletal disorder4/355 (1.1%) 44/354 (1.1%) 4
Myalgia7/355 (2%) 74/354 (1.1%) 5
Neck pain7/355 (2%) 84/354 (1.1%) 5
Pain in extremity5/355 (1.4%) 66/354 (1.7%) 9
Trismus0/355 (0%) 01/354 (0.3%) 1
Nervous system disorders
Ataxia1/355 (0.3%) 13/354 (0.8%) 3
Depressed level of consciousness2/355 (0.6%) 21/354 (0.3%) 1
Dizziness19/355 (5.4%) 2320/354 (5.6%) 25
Dysgeusia4/355 (1.1%) 47/354 (2%) 9
Encephalopathy1/355 (0.3%) 11/354 (0.3%) 1
Extrapyramidal disorder1/355 (0.3%) 11/354 (0.3%) 1
Headache41/355 (11.5%) 5442/354 (11.9%) 63
Intracranial hemorrhage3/355 (0.8%) 36/354 (1.7%) 6
Ischemia cerebrovascular0/355 (0%) 01/354 (0.3%) 1
Memory impairment2/355 (0.6%) 20/354 (0%) 0
Neuralgia0/355 (0%) 01/354 (0.3%) 1
Neurological disorder NOS9/355 (2.5%) 114/354 (1.1%) 4
Nystagmus1/355 (0.3%) 10/354 (0%) 0
Peripheral motor neuropathy1/355 (0.3%) 10/354 (0%) 0
Peripheral sensory neuropathy5/355 (1.4%) 56/354 (1.7%) 11
Seizure1/355 (0.3%) 11/354 (0.3%) 1
Speech disorder4/355 (1.1%) 41/354 (0.3%) 1
Syncope6/355 (1.7%) 64/354 (1.1%) 4
Syncope vasovagal1/355 (0.3%) 11/354 (0.3%) 1
Tremor4/355 (1.1%) 43/354 (0.8%) 3
Psychiatric disorders
Agitation3/355 (0.8%) 53/354 (0.8%) 3
Anxiety5/355 (1.4%) 59/354 (2.5%) 11
Confusion4/355 (1.1%) 43/354 (0.8%) 3
Depression2/355 (0.6%) 212/354 (3.4%) 12
Euphoria0/355 (0%) 01/354 (0.3%) 1
Insomnia11/355 (3.1%) 147/354 (2%) 11
Personality change0/355 (0%) 01/354 (0.3%) 1
Psychosis4/355 (1.1%) 42/354 (0.6%) 2
Renal and urinary disorders
Bladder hemorrhage0/355 (0%) 01/354 (0.3%) 1
Bladder pain1/355 (0.3%) 10/354 (0%) 0
Cystitis1/355 (0.3%) 10/354 (0%) 0
Glomerular filtration rate decreased2/355 (0.6%) 21/354 (0.3%) 1
Hemorrhage urinary tract2/355 (0.6%) 26/354 (1.7%) 6
Proteinuria0/355 (0%) 01/354 (0.3%) 1
Renal failure13/355 (3.7%) 139/354 (2.5%) 9
Renal hemorrhage1/355 (0.3%) 10/354 (0%) 0
Ureteric obstruction1/355 (0.3%) 10/354 (0%) 0
Urethral pain0/355 (0%) 01/354 (0.3%) 1
Urinary frequency1/355 (0.3%) 12/354 (0.6%) 2
Urinary incontinence2/355 (0.6%) 21/354 (0.3%) 1
Urinary retention2/355 (0.6%) 23/354 (0.8%) 3
Urine discoloration0/355 (0%) 01/354 (0.3%) 1
Urogenital disorder15/355 (4.2%) 2111/354 (3.1%) 15
Reproductive system and breast disorders
Breast pain0/355 (0%) 02/354 (0.6%) 2
Penile pain0/355 (0%) 01/354 (0.3%) 1
Perineal pain1/355 (0.3%) 10/354 (0%) 0
Reproductive tract disorder1/355 (0.3%) 10/354 (0%) 0
Uterine hemorrhage4/355 (1.1%) 53/354 (0.8%) 4
Vaginal hemorrhage5/355 (1.4%) 59/354 (2.5%) 9
Vaginal mucositis1/355 (0.3%) 11/354 (0.3%) 1
Vaginal pain0/355 (0%) 01/354 (0.3%) 1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome9/355 (2.5%) 95/354 (1.4%) 5
Allergic rhinitis1/355 (0.3%) 13/354 (0.8%) 4
Aspiration1/355 (0.3%) 10/354 (0%) 0
Atelectasis0/355 (0%) 01/354 (0.3%) 1
Bronchopulmonary hemorrhage1/355 (0.3%) 10/354 (0%) 0
Bronchospasm1/355 (0.3%) 12/354 (0.6%) 2
Cough17/355 (4.8%) 2119/354 (5.4%) 20
Dyspnea20/355 (5.6%) 2224/354 (6.8%) 24
Epistaxis24/355 (6.8%) 2622/354 (6.2%) 24
Hiccups2/355 (0.6%) 20/354 (0%) 0
Hypoxia8/355 (2.3%) 812/354 (3.4%) 12
Laryngeal edema0/355 (0%) 01/354 (0.3%) 1
Laryngeal mucositis1/355 (0.3%) 10/354 (0%) 0
Laryngeal pain1/355 (0.3%) 10/354 (0%) 0
Laryngoscopy abnormal0/355 (0%) 01/354 (0.3%) 1
Nasal congestion1/355 (0.3%) 10/354 (0%) 0
Pharyngeal examination abnormal3/355 (0.8%) 32/354 (0.6%) 2
Pharyngeal mucositis2/355 (0.6%) 20/354 (0%) 0
Pharyngolaryngeal pain6/355 (1.7%) 611/354 (3.1%) 12
Pleural effusion8/355 (2.3%) 88/354 (2.3%) 8
Pleuritic pain1/355 (0.3%) 11/354 (0.3%) 1
Pneumonitis27/355 (7.6%) 2817/354 (4.8%) 19
Pneumothorax2/355 (0.6%) 21/354 (0.3%) 1
Pulmonary hemorrhage1/355 (0.3%) 11/354 (0.3%) 1
Pulmonary hypertension2/355 (0.6%) 20/354 (0%) 0
Respiratory disorder12/355 (3.4%) 129/354 (2.5%) 9
Respiratory tract hemorrhage2/355 (0.6%) 21/354 (0.3%) 1
Retinoic acid syndrome1/355 (0.3%) 10/354 (0%) 0
Tracheal stenosis1/355 (0.3%) 10/354 (0%) 0
Voice alteration2/355 (0.6%) 20/354 (0%) 0
Skin and subcutaneous tissue disorders
Alopecia6/355 (1.7%) 84/354 (1.1%) 4
Decubitus ulcer1/355 (0.3%) 12/354 (0.6%) 2
Dry skin7/355 (2%) 87/354 (2%) 7
Erythema multiforme3/355 (0.8%) 33/354 (0.8%) 3
Hand-and-foot syndrome2/355 (0.6%) 45/354 (1.4%) 5
Nail disorder1/355 (0.3%) 10/354 (0%) 0
Pain of skin1/355 (0.3%) 11/354 (0.3%) 1
Petechiae35/355 (9.9%) 4534/354 (9.6%) 52
Pruritus11/355 (3.1%) 1312/354 (3.4%) 13
Rash acneiform1/355 (0.3%) 10/354 (0%) 0
Rash desquamating59/355 (16.6%) 7066/354 (18.6%) 71
Skin disorder23/355 (6.5%) 2823/354 (6.5%) 30
Skin hyperpigmentation0/355 (0%) 01/354 (0.3%) 1
Skin ulceration2/355 (0.6%) 22/354 (0.6%) 2
Sweating14/355 (3.9%) 1914/354 (4%) 15
Urticaria3/355 (0.8%) 33/354 (0.8%) 4
Vascular disorders
Flushing1/355 (0.3%) 10/354 (0%) 0
Hematoma14/355 (3.9%) 1713/354 (3.7%) 17
Hemorrhage14/355 (3.9%) 1912/354 (3.4%) 13
Hot flashes1/355 (0.3%) 12/354 (0.6%) 2
Hypertension13/355 (3.7%) 1311/354 (3.1%) 11
Hypotension25/355 (7%) 2619/354 (5.4%) 22
Lymphangitic streak0/355 (0%) 01/354 (0.3%) 1
Lymphedema0/355 (0%) 01/354 (0.3%) 1
Phlebitis6/355 (1.7%) 77/354 (2%) 7
Thrombosis2/355 (0.6%) 20/354 (0%) 0
Vascular disorder2/355 (0.6%) 22/354 (0.6%) 2
Vasculitis1/355 (0.3%) 10/354 (0%) 0
Other (Not Including Serious) Adverse Events
Induction and Consolidation Chemotherapy Plus MidostaurinInduction and Consolidation Chemotherapy Plus Placebo
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total321/355 (90.4%) 324/354 (91.5%)
Blood and lymphatic system disorders
Blood disorder5/355 (1.4%) 114/354 (1.1%) 6
Disseminated intravascular coagulation2/355 (0.6%) 21/354 (0.3%) 1
Febrile neutropenia246/355 (69.3%) 422238/354 (67.2%) 394
Hemoglobin decreased312/355 (87.9%) 1059311/354 (87.9%) 940
Lymph node pain2/355 (0.6%) 20/354 (0%) 0
Lymphatic disorder10/355 (2.8%) 139/354 (2.5%) 11
Cardiac disorders
Arrhythmia1/355 (0.3%) 14/354 (1.1%) 4
Atrial fibrillation3/355 (0.8%) 30/354 (0%) 0
Atrial flutter0/355 (0%) 01/354 (0.3%) 1
Atrial tachycardia1/355 (0.3%) 31/354 (0.3%) 1
Cardiac disorder8/355 (2.3%) 1213/354 (3.7%) 17
Cardiac pain4/355 (1.1%) 61/354 (0.3%) 1
Cardiac valve disease0/355 (0%) 01/354 (0.3%) 1
Conduction disorder1/355 (0.3%) 12/354 (0.6%) 2
Left ventricular failure6/355 (1.7%) 65/354 (1.4%) 9
Myocardial ischemia1/355 (0.3%) 10/354 (0%) 0
Palpitations3/355 (0.8%) 35/354 (1.4%) 13
Pericardial effusion7/355 (2%) 81/354 (0.3%) 1
Pericarditis2/355 (0.6%) 21/354 (0.3%) 1
Premature ventricular contractions1/355 (0.3%) 30/354 (0%) 0
Sinus bradycardia10/355 (2.8%) 105/354 (1.4%) 15
Sinus tachycardia11/355 (3.1%) 1323/354 (6.5%) 29
Supraventricular extrasystoles1/355 (0.3%) 12/354 (0.6%) 7
Supraventricular tachycardia1/355 (0.3%) 12/354 (0.6%) 2
Ventricular arrhythmia1/355 (0.3%) 11/354 (0.3%) 1
Ventricular bigeminy1/355 (0.3%) 20/354 (0%) 0
Ventricular fibrillation1/355 (0.3%) 10/354 (0%) 0
Ventricular tachycardia1/355 (0.3%) 11/354 (0.3%) 1
Ear and labyrinth disorders
Ear disorder5/355 (1.4%) 53/354 (0.8%) 3
Ear pain5/355 (1.4%) 66/354 (1.7%) 6
External ear inflammation0/355 (0%) 02/354 (0.6%) 2
External ear pain3/355 (0.8%) 32/354 (0.6%) 2
Hearing impaired2/355 (0.6%) 42/354 (0.6%) 2
Middle ear inflammation0/355 (0%) 01/354 (0.3%) 1
Tinnitus3/355 (0.8%) 32/354 (0.6%) 2
Endocrine disorders
Endocrine disorder1/355 (0.3%) 12/354 (0.6%) 2
Hyperthyroidism2/355 (0.6%) 71/354 (0.3%) 3
Hypothyroidism2/355 (0.6%) 22/354 (0.6%) 5
Eye disorders
Cataract1/355 (0.3%) 90/354 (0%) 0
Conjunctivitis7/355 (2%) 74/354 (1.1%) 5
Dry eye syndrome5/355 (1.4%) 710/354 (2.8%) 12
Eye disorder21/355 (5.9%) 2816/354 (4.5%) 19
Eye pain5/355 (1.4%) 55/354 (1.4%) 5
Eyelid function disorder0/355 (0%) 01/354 (0.3%) 1
Flashing vision1/355 (0.3%) 14/354 (1.1%) 5
Keratitis14/355 (3.9%) 179/354 (2.5%) 14
Optic nerve disorder0/355 (0%) 01/354 (0.3%) 1
Photophobia2/355 (0.6%) 34/354 (1.1%) 4
Vision blurred5/355 (1.4%) 84/354 (1.1%) 7
Vitreous hemorrhage1/355 (0.3%) 12/354 (0.6%) 2
Watering eyes4/355 (1.1%) 72/354 (0.6%) 2
Gastrointestinal disorders
Abdominal distension6/355 (1.7%) 1510/354 (2.8%) 11
Abdominal pain57/355 (16.1%) 7867/354 (18.9%) 84
Anal exam abnormal0/355 (0%) 03/354 (0.8%) 3
Anal fistula0/355 (0%) 01/354 (0.3%) 1
Anal hemorrhage2/355 (0.6%) 23/354 (0.8%) 3
Anal mucositis2/355 (0.6%) 22/354 (0.6%) 3
Anal pain12/355 (3.4%) 156/354 (1.7%) 8
Anal ulcer1/355 (0.3%) 13/354 (0.8%) 3
Ascites1/355 (0.3%) 11/354 (0.3%) 1
Colitis7/355 (2%) 912/354 (3.4%) 18
Colonic hemorrhage0/355 (0%) 01/354 (0.3%) 1
Colonic perforation0/355 (0%) 01/354 (0.3%) 2
Constipation50/355 (14.1%) 8660/354 (16.9%) 83
Dental prosthesis user1/355 (0.3%) 10/354 (0%) 0
Diarrhea228/355 (64.2%) 432219/354 (61.9%) 310
Dry mouth2/355 (0.6%) 22/354 (0.6%) 2
Dyspepsia22/355 (6.2%) 3616/354 (4.5%) 17
Dysphagia6/355 (1.7%) 610/354 (2.8%) 10
Ear, nose and throat examination abnormal112/355 (31.5%) 178112/354 (31.6%) 169
Endoscopy large bowel abnormal1/355 (0.3%) 10/354 (0%) 0
Enteritis1/355 (0.3%) 13/354 (0.8%) 3
Esophageal mucositis0/355 (0%) 01/354 (0.3%) 1
Esophageal pain1/355 (0.3%) 13/354 (0.8%) 3
Esophageal perforation1/355 (0.3%) 10/354 (0%) 0
Esophageal ulcer1/355 (0.3%) 10/354 (0%) 0
Esophagitis3/355 (0.8%) 34/354 (1.1%) 4
Flatulence10/355 (2.8%) 207/354 (2%) 8
Gastric hemorrhage2/355 (0.6%) 21/354 (0.3%) 1
Gastric mucositis0/355 (0%) 01/354 (0.3%) 1
Gastric ulcer0/355 (0%) 01/354 (0.3%) 1
Gastritis3/355 (0.8%) 34/354 (1.1%) 4
Gastrointestinal disorder28/355 (7.9%) 3526/354 (7.3%) 29
Gastrointestinal pain0/355 (0%) 01/354 (0.3%) 1
Gastroscopy abnormal0/355 (0%) 03/354 (0.8%) 3
Gingival pain3/355 (0.8%) 34/354 (1.1%) 4
Hemorrhoidal hemorrhage1/355 (0.3%) 12/354 (0.6%) 3
Hemorrhoids28/355 (7.9%) 3621/354 (5.9%) 25
Ileal obstruction0/355 (0%) 01/354 (0.3%) 1
Ileus2/355 (0.6%) 33/354 (0.8%) 3
Large intestinal mucositis1/355 (0.3%) 10/354 (0%) 0
Lower gastrointestinal hemorrhage0/355 (0%) 02/354 (0.6%) 2
Mucositis oral49/355 (13.8%) 5931/354 (8.8%) 36
Nausea258/355 (72.7%) 807226/354 (63.8%) 449
Oesophagoscopy abnormal2/355 (0.6%) 21/354 (0.3%) 1
Oral hemorrhage12/355 (3.4%) 1318/354 (5.1%) 27
Oral pain8/355 (2.3%) 1011/354 (3.1%) 11
Periodontal disease4/355 (1.1%) 67/354 (2%) 7
Peritoneal pain1/355 (0.3%) 10/354 (0%) 0
Proctitis1/355 (0.3%) 10/354 (0%) 0
Proctoscopy abnormal3/355 (0.8%) 30/354 (0%) 0
Rectal hemorrhage7/355 (2%) 85/354 (1.4%) 7
Rectal obstruction1/355 (0.3%) 10/354 (0%) 0
Rectal pain5/355 (1.4%) 62/354 (0.6%) 2
Salivary gland disorder0/355 (0%) 02/354 (0.6%) 2
Small intestinal mucositis1/355 (0.3%) 12/354 (0.6%) 2
Stomach pain34/355 (9.6%) 4327/354 (7.6%) 32
Tooth development disorder0/355 (0%) 01/354 (0.3%) 1
Tooth disorder6/355 (1.7%) 62/354 (0.6%) 2
Toothache9/355 (2.5%) 1110/354 (2.8%) 10
Typhlitis3/355 (0.8%) 34/354 (1.1%) 4
Upper gastrointestinal hemorrhage2/355 (0.6%) 20/354 (0%) 0
Vomiting188/355 (53%) 376168/354 (47.5%) 259
General disorders
Chest pain15/355 (4.2%) 1720/354 (5.6%) 28
Chills22/355 (6.2%) 2617/354 (4.8%) 21
Disease progression0/355 (0%) 01/354 (0.3%) 1
Edema limbs33/355 (9.3%) 4339/354 (11%) 56
Facial pain2/355 (0.6%) 21/354 (0.3%) 1
Fatigue221/355 (62.3%) 522220/354 (62.1%) 474
Fever72/355 (20.3%) 11069/354 (19.5%) 107
Flu-like symptoms5/355 (1.4%) 52/354 (0.6%) 2
Gait abnormal1/355 (0.3%) 10/354 (0%) 0
General symptom15/355 (4.2%) 1817/354 (4.8%) 25
Hypothermia1/355 (0.3%) 10/354 (0%) 0
Ill-defined disorder3/355 (0.8%) 44/354 (1.1%) 4
Injection site reaction20/355 (5.6%) 2523/354 (6.5%) 34
Localized edema16/355 (4.5%) 1614/354 (4%) 19
Pain40/355 (11.3%) 5533/354 (9.3%) 44
Visceral edema2/355 (0.6%) 22/354 (0.6%) 2
Hepatobiliary disorders
Cholecystitis1/355 (0.3%) 11/354 (0.3%) 1
Gallbladder pain1/355 (0.3%) 10/354 (0%) 0
Hepatic failure1/355 (0.3%) 10/354 (0%) 0
Hepatobiliary disease4/355 (1.1%) 164/354 (1.1%) 5
Immune system disorders
Cytokine release syndrome1/355 (0.3%) 20/354 (0%) 0
Hypersensitivity36/355 (10.1%) 4130/354 (8.5%) 41
Immune system disorder12/355 (3.4%) 149/354 (2.5%) 14
Infections and infestations
Abdominal infection0/355 (0%) 01/354 (0.3%) 1
Anal infection8/355 (2.3%) 98/354 (2.3%) 12
Anorectal infection2/355 (0.6%) 31/354 (0.3%) 1
Appendicitis0/355 (0%) 02/354 (0.6%) 2
Bladder infection8/355 (2.3%) 1310/354 (2.8%) 11
Bone infection0/355 (0%) 01/354 (0.3%) 1
Bronchitis7/355 (2%) 96/354 (1.7%) 6
Catheter related infection55/355 (15.5%) 7443/354 (12.1%) 54
Cecal infection1/355 (0.3%) 11/354 (0.3%) 2
Colitis, infectious (e.g., Clostridium difficile)4/355 (1.1%) 44/354 (1.1%) 4
Conjunctivitis infective8/355 (2.3%) 105/354 (1.4%) 7
Device related infection1/355 (0.3%) 10/354 (0%) 0
Eye infection2/355 (0.6%) 20/354 (0%) 0
Gastric infection1/355 (0.3%) 12/354 (0.6%) 3
Gingival infection5/355 (1.4%) 63/354 (0.8%) 3
Hepatic infection3/355 (0.8%) 35/354 (1.4%) 14
Infection57/355 (16.1%) 10060/354 (16.9%) 99
Infectious colitis5/355 (1.4%) 75/354 (1.4%) 5
Kidney infection2/355 (0.6%) 21/354 (0.3%) 1
Lip infection17/355 (4.8%) 2221/354 (5.9%) 29
Lymph gland infection1/355 (0.3%) 13/354 (0.8%) 4
Mediastinal infection1/355 (0.3%) 10/354 (0%) 0
Mucosal infection2/355 (0.6%) 20/354 (0%) 0
Nail infection3/355 (0.8%) 42/354 (0.6%) 2
Opportunistic infection4/355 (1.1%) 59/354 (2.5%) 14
Otitis media2/355 (0.6%) 30/354 (0%) 0
Paranasal sinus infection2/355 (0.6%) 21/354 (0.3%) 1
Penile infection2/355 (0.6%) 20/354 (0%) 0
Pharyngitis5/355 (1.4%) 57/354 (2%) 7
Phlebitis infective3/355 (0.8%) 52/354 (0.6%) 2
Pneumonia36/355 (10.1%) 5336/354 (10.2%) 45
Rhinitis infective6/355 (1.7%) 126/354 (1.7%) 7
Scrotal infection0/355 (0%) 01/354 (0.3%) 1
Sepsis26/355 (7.3%) 2920/354 (5.6%) 23
Sinusitis7/355 (2%) 75/354 (1.4%) 6
Skin infection22/355 (6.2%) 2415/354 (4.2%) 19
Soft tissue infection2/355 (0.6%) 21/354 (0.3%) 1
Splenic infection1/355 (0.3%) 12/354 (0.6%) 9
Tooth infection4/355 (1.1%) 44/354 (1.1%) 5
Tracheitis1/355 (0.3%) 10/354 (0%) 0
Upper aerodigestive tract infection0/355 (0%) 04/354 (1.1%) 4
Upper respiratory infection11/355 (3.1%) 178/354 (2.3%) 14
Ureteritis4/355 (1.1%) 64/354 (1.1%) 6
Urinary tract infection15/355 (4.2%) 1715/354 (4.2%) 19
Vaginal infection5/355 (1.4%) 68/354 (2.3%) 12
Viral hepatitis1/355 (0.3%) 10/354 (0%) 0
Vulval infection2/355 (0.6%) 20/354 (0%) 0
Vulvitis0/355 (0%) 02/354 (0.6%) 2
Wound infection3/355 (0.8%) 33/354 (0.8%) 3
Injury, poisoning and procedural complications
Bruising3/355 (0.8%) 31/354 (0.3%) 1
Device complication1/355 (0.3%) 10/354 (0%) 0
Fracture1/355 (0.3%) 10/354 (0%) 0
Injury to inferior vena cava0/355 (0%) 01/354 (0.3%) 1
Injury to jugular vein0/355 (0%) 01/354 (0.3%) 1
Intraoperative complications1/355 (0.3%) 10/354 (0%) 0
Intraoperative gastrointestinal injury0/355 (0%) 01/354 (0.3%) 1
Intraoperative gastrointestinal injury - Teeth0/355 (0%) 01/354 (0.3%) 1
Intraoperative head and neck injury - Neck NOS1/355 (0.3%) 10/354 (0%) 0
Intraoperative ocular injury - Lens1/355 (0.3%) 20/354 (0%) 0
Postoperative hemorrhage1/355 (0.3%) 10/354 (0%) 0
Radiation recall reaction (dermatologic)0/355 (0%) 01/354 (0.3%) 1
Thermal burn0/355 (0%) 03/354 (0.8%) 3
Tracheostomy site bleeding0/355 (0%) 01/354 (0.3%) 1
Vaginal anastomotic leak1/355 (0.3%) 10/354 (0%) 0
Vascular access complication9/355 (2.5%) 156/354 (1.7%) 6
Venous injury - Extremity-lower1/355 (0.3%) 10/354 (0%) 0
Wound dehiscence2/355 (0.6%) 20/354 (0%) 0
Investigations
Activated partial thromboplastin time prolonged26/355 (7.3%) 3622/354 (6.2%) 27
Alanine aminotransferase increased88/355 (24.8%) 31283/354 (23.4%) 184
Alkaline phosphatase increased30/355 (8.5%) 6029/354 (8.2%) 55
Amylase increased1/355 (0.3%) 11/354 (0.3%) 1
Aspartate aminotransferase increased60/355 (16.9%) 20156/354 (15.8%) 102
Blood bilirubin increased49/355 (13.8%) 8660/354 (16.9%) 104
Cardiac troponin T increased1/355 (0.3%) 11/354 (0.3%) 1
Coagulopathy7/355 (2%) 810/354 (2.8%) 14
Creatinine increased13/355 (3.7%) 1815/354 (4.2%) 25
Electrocardiogram QTc interval prolonged45/355 (12.7%) 8136/354 (10.2%) 48
Fibrinogen decreased12/355 (3.4%) 148/354 (2.3%) 10
Forced expiratory volume decreased1/355 (0.3%) 10/354 (0%) 0
Gamma-glutamyltransferase increased25/355 (7%) 5534/354 (9.6%) 57
INR increased9/355 (2.5%) 1112/354 (3.4%) 12
Laboratory test abnormal31/355 (8.7%) 5341/354 (11.6%) 81
Leukocyte count decreased79/355 (22.3%) 24092/354 (26%) 204
Lymphocyte count decreased69/355 (19.4%) 19571/354 (20.1%) 158
Neutrophil count decreased308/355 (86.8%) 952308/354 (87%) 879
Platelet count decreased311/355 (87.6%) 1131313/354 (88.4%) 1020
Serum cholesterol increased0/355 (0%) 05/354 (1.4%) 10
Weight gain15/355 (4.2%) 266/354 (1.7%) 11
Weight loss9/355 (2.5%) 1210/354 (2.8%) 12
Metabolism and nutrition disorders
Alkalosis0/355 (0%) 03/354 (0.8%) 3
Anorexia30/355 (8.5%) 4040/354 (11.3%) 50
Blood glucose increased72/355 (20.3%) 20259/354 (16.7%) 134
Blood uric acid increased21/355 (5.9%) 4215/354 (4.2%) 23
Dehydration1/355 (0.3%) 11/354 (0.3%) 1
Glucose intolerance0/355 (0%) 02/354 (0.6%) 5
Iron overload0/355 (0%) 02/354 (0.6%) 4
Serum albumin decreased56/355 (15.8%) 10156/354 (15.8%) 80
Serum calcium decreased58/355 (16.3%) 8856/354 (15.8%) 79
Serum calcium increased6/355 (1.7%) 111/354 (0.3%) 2
Serum glucose decreased6/355 (1.7%) 89/354 (2.5%) 10
Serum magnesium decreased30/355 (8.5%) 4832/354 (9%) 65
Serum magnesium increased7/355 (2%) 83/354 (0.8%) 3
Serum phosphate decreased27/355 (7.6%) 3127/354 (7.6%) 40
Serum potassium decreased79/355 (22.3%) 11774/354 (20.9%) 112
Serum potassium increased5/355 (1.4%) 55/354 (1.4%) 6
Serum sodium decreased48/355 (13.5%) 6351/354 (14.4%) 64
Serum sodium increased8/355 (2.3%) 88/354 (2.3%) 9
Serum triglycerides increased1/355 (0.3%) 14/354 (1.1%) 5
Tumor lysis syndrome2/355 (0.6%) 23/354 (0.8%) 3
Musculoskeletal and connective tissue disorders
Arthralgia30/355 (8.5%) 6716/354 (4.5%) 25
Arthritis0/355 (0%) 01/354 (0.3%) 1
Back pain46/355 (13%) 7434/354 (9.6%) 53
Bone pain19/355 (5.4%) 3221/354 (5.9%) 37
Buttock pain3/355 (0.8%) 30/354 (0%) 0
Chest wall pain6/355 (1.7%) 93/354 (0.8%) 4
Joint disorder1/355 (0.3%) 10/354 (0%) 0
Joint effusion0/355 (0%) 01/354 (0.3%) 1
Joint range of motion decreased lumbar spine1/355 (0.3%) 20/354 (0%) 0
Muscle weakness6/355 (1.7%) 64/354 (1.1%) 4
Muscle weakness lower limb2/355 (0.6%) 21/354 (0.3%) 1
Musculoskeletal disorder13/355 (3.7%) 196/354 (1.7%) 8
Myalgia13/355 (3.7%) 2416/354 (4.5%) 19
Myositis0/355 (0%) 02/354 (0.6%) 2
Neck pain16/355 (4.5%) 189/354 (2.5%) 9
Osteoporosis0/355 (0%) 01/354 (0.3%) 1
Pain in extremity30/355 (8.5%) 3917/354 (4.8%) 23
Upper extremity dysfunction1/355 (0.3%) 10/354 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplasia0/355 (0%) 01/354 (0.3%) 1
Treatment related secondary malignancy1/355 (0.3%) 11/354 (0.3%) 2
Tumor pain1/355 (0.3%) 10/354 (0%) 0
Nervous system disorders
Ataxia2/355 (0.6%) 210/354 (2.8%) 11
Cognitive disturbance0/355 (0%) 01/354 (0.3%) 1
Depressed level of consciousness2/355 (0.6%) 23/354 (0.8%) 3
Dizziness44/355 (12.4%) 6443/354 (12.1%) 55
Dysgeusia5/355 (1.4%) 511/354 (3.1%) 14
Encephalopathy0/355 (0%) 01/354 (0.3%) 5
Extrapyramidal disorder0/355 (0%) 02/354 (0.6%) 5
Headache105/355 (29.6%) 21885/354 (24%) 143
Intracranial hemorrhage1/355 (0.3%) 12/354 (0.6%) 2
Memory impairment2/355 (0.6%) 41/354 (0.3%) 2
Neuralgia2/355 (0.6%) 23/354 (0.8%) 6
Neurological disorder NOS17/355 (4.8%) 227/354 (2%) 7
Olfactory nerve disorder0/355 (0%) 01/354 (0.3%) 1
Peripheral motor neuropathy2/355 (0.6%) 121/354 (0.3%) 1
Peripheral sensory neuropathy6/355 (1.7%) 2111/354 (3.1%) 26
Pyramidal tract syndrome0/355 (0%) 01/354 (0.3%) 1
Seizure0/355 (0%) 01/354 (0.3%) 1
Speech disorder1/355 (0.3%) 161/354 (0.3%) 1
Syncope8/355 (2.3%) 96/354 (1.7%) 6
Syncope vasovagal2/355 (0.6%) 37/354 (2%) 9
Tremor5/355 (1.4%) 84/354 (1.1%) 4
Psychiatric disorders
Agitation4/355 (1.1%) 43/354 (0.8%) 3
Anxiety16/355 (4.5%) 2118/354 (5.1%) 32
Confusion4/355 (1.1%) 54/354 (1.1%) 4
Depression14/355 (3.9%) 2624/354 (6.8%) 50
Euphoria1/355 (0.3%) 10/354 (0%) 0
Insomnia30/355 (8.5%) 4720/354 (5.6%) 35
Personality change0/355 (0%) 01/354 (0.3%) 1
Psychosis1/355 (0.3%) 11/354 (0.3%) 1
Renal and urinary disorders
Bladder hemorrhage0/355 (0%) 01/354 (0.3%) 1
Bladder pain3/355 (0.8%) 51/354 (0.3%) 1
Bladder spasm2/355 (0.6%) 20/354 (0%) 0
Cystitis5/355 (1.4%) 67/354 (2%) 8
Hemoglobin urine positive0/355 (0%) 01/354 (0.3%) 1
Hemorrhage urinary tract2/355 (0.6%) 24/354 (1.1%) 4
Kidney pain1/355 (0.3%) 20/354 (0%) 0
Proteinuria1/355 (0.3%) 31/354 (0.3%) 1
Renal failure3/355 (0.8%) 31/354 (0.3%) 1
Urethral obstruction1/355 (0.3%) 10/354 (0%) 0
Urethral pain0/355 (0%) 02/354 (0.6%) 2
Urinary frequency1/355 (0.3%) 14/354 (1.1%) 9
Urinary incontinence1/355 (0.3%) 12/354 (0.6%) 2
Urinary retention1/355 (0.3%) 12/354 (0.6%) 3
Urine discoloration0/355 (0%) 01/354 (0.3%) 1
Urogenital disorder11/355 (3.1%) 1210/354 (2.8%) 11
Reproductive system and breast disorders
Breast pain2/355 (0.6%) 20/354 (0%) 0
Gynecomastia1/355 (0.3%) 11/354 (0.3%) 3
Pelvic pain1/355 (0.3%) 12/354 (0.6%) 2
Perineal pain1/355 (0.3%) 11/354 (0.3%) 1
Reproductive tract disorder1/355 (0.3%) 10/354 (0%) 0
Uterine hemorrhage8/355 (2.3%) 126/354 (1.7%) 7
Uterine pain1/355 (0.3%) 13/354 (0.8%) 3
Vaginal discharge1/355 (0.3%) 11/354 (0.3%) 2
Vaginal hemorrhage16/355 (4.5%) 1717/354 (4.8%) 24
Vaginal inflammation1/355 (0.3%) 11/354 (0.3%) 1
Vaginal mucositis2/355 (0.6%) 22/354 (0.6%) 2
Vaginal pain1/355 (0.3%) 12/354 (0.6%) 2
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome1/355 (0.3%) 11/354 (0.3%) 1
Allergic rhinitis3/355 (0.8%) 38/354 (2.3%) 14
Atelectasis1/355 (0.3%) 12/354 (0.6%) 2
Bronchopulmonary hemorrhage0/355 (0%) 01/354 (0.3%) 1
Bronchospasm2/355 (0.6%) 22/354 (0.6%) 2
Cough38/355 (10.7%) 5741/354 (11.6%) 51
Dyspnea28/355 (7.9%) 3329/354 (8.2%) 30
Epistaxis55/355 (15.5%) 6346/354 (13%) 62
Hypoxia9/355 (2.5%) 911/354 (3.1%) 11
Laryngeal edema1/355 (0.3%) 10/354 (0%) 0
Laryngeal mucositis1/355 (0.3%) 12/354 (0.6%) 3
Laryngeal pain2/355 (0.6%) 21/354 (0.3%) 1
Laryngoscopy abnormal2/355 (0.6%) 21/354 (0.3%) 2
Nasal congestion4/355 (1.1%) 44/354 (1.1%) 6
Pharyngeal examination abnormal2/355 (0.6%) 26/354 (1.7%) 6
Pharyngeal mucositis4/355 (1.1%) 41/354 (0.3%) 1
Pharyngeal stenosis1/355 (0.3%) 10/354 (0%) 0
Pharyngolaryngeal pain28/355 (7.9%) 3525/354 (7.1%) 30
Pleural effusion9/355 (2.5%) 96/354 (1.7%) 6
Pneumonitis23/355 (6.5%) 3333/354 (9.3%) 40
Pneumothorax1/355 (0.3%) 10/354 (0%) 0
Pulmonary fibrosis0/355 (0%) 01/354 (0.3%) 1
Respiratory disorder17/355 (4.8%) 2321/354 (5.9%) 31
Voice alteration3/355 (0.8%) 41/354 (0.3%) 1
Skin and subcutaneous tissue disorders
Alopecia8/355 (2.3%) 106/354 (1.7%) 9
Decubitus ulcer0/355 (0%) 01/354 (0.3%) 1
Dry skin11/355 (3.1%) 139/354 (2.5%) 12
Erythema multiforme0/355 (0%) 01/354 (0.3%) 1
Hand-and-foot syndrome8/355 (2.3%) 99/354 (2.5%) 11
Nail disorder1/355 (0.3%) 30/354 (0%) 0
Pain of skin3/355 (0.8%) 32/354 (0.6%) 2
Petechiae67/355 (18.9%) 8951/354 (14.4%) 68
Photosensitivity3/355 (0.8%) 50/354 (0%) 0
Pruritus25/355 (7%) 3131/354 (8.8%) 41
Rash acneiform2/355 (0.6%) 22/354 (0.6%) 2
Rash desquamating201/355 (56.6%) 358200/354 (56.5%) 317
Skin disorder44/355 (12.4%) 6742/354 (11.9%) 58
Skin hyperpigmentation1/355 (0.3%) 33/354 (0.8%) 4
Skin induration0/355 (0%) 01/354 (0.3%) 2
Skin striae1/355 (0.3%) 10/354 (0%) 0
Skin ulceration5/355 (1.4%) 66/354 (1.7%) 8
Sweating30/355 (8.5%) 5019/354 (5.4%) 32
Urticaria6/355 (1.7%) 75/354 (1.4%) 5
Vascular disorders
Flushing0/355 (0%) 02/354 (0.6%) 3
Hematoma32/355 (9%) 4034/354 (9.6%) 39
Hemorrhage15/355 (4.2%) 2231/354 (8.8%) 33
Hot flashes2/355 (0.6%) 44/354 (1.1%) 4
Hypertension15/355 (4.2%) 2113/354 (3.7%) 25
Hypotension32/355 (9%) 3732/354 (9%) 36
Lymphedema0/355 (0%) 01/354 (0.3%) 1
Lymphocele0/355 (0%) 01/354 (0.3%) 1
Phlebitis13/355 (3.7%) 1915/354 (4.2%) 17
Thrombosis6/355 (1.7%) 63/354 (0.8%) 3
Vascular disorder0/355 (0%) 04/354 (1.1%) 4
Vasculitis2/355 (0.6%) 20/354 (0%) 0
Visceral arterial ischemia0/355 (0%) 01/354 (0.3%) 1

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/TitleRichard Stone, MD
OrganizationDana Farber Cancer Institute
Phone
Emailrstone@partners.org
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00651261
Other Study ID Numbers:
  • CALGB-10603
  • CALGB-10603
  • EUDRACT-2006-006852-37
  • CDR0000590404
First Posted:
Apr 2, 2008
Last Update Posted:
Aug 18, 2021
Last Verified:
Aug 1, 2021