Decitabine Plus Cytarabine for Induction of Remission in Newly Diagnosed Elderly Acute Myeloid Leukemia (AML) and Advanced Myelodysplastic Syndrome (MDS)
Phase: NA
Conditions: Chronic Myelomonocytic Leukemia-2, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Untreated Adult Acute Myeloid Leukemia
Sponsor: University of Washington

9019 
1 
 
 
 
 
 
)UHG+XWFKLQVRQ&DQFHU5HVHDUFK&HQWHU
8QLYHUVLW\RI:DVKLQJWRQ
6HDWWOH&DQFHU&DUH$OOLDQFH
 
 
 
 
 
'HFLWDELQHSOXVF\WDUDELQHIRU,QGXFWLRQRI5HPLVVLRQLQ1HZO\
'LDJQRVHG(OGHUO\$FXWH0\HORLG/HXNHPLD$0/DQG$GYDQFHG
0\HORG\VSODVWLF6\QGURPH0'6
 
Current Version: 10.03.16 
Previous Version: 
07.31.15 
 
Principal Investigator: 
Pamela S. Becker, MD, PhD 
Professor of Medicine, UW 
Associate Member, FHCRC 
University of Washington 
850  Republican St. N415 
Seattle, WA 98109  
Email: pbecker@uw.edu 
 
Sub-Investigators: 
 
 
Elihu Estey, MD 
Professor of Medicine, UW 
Member FHCRC 
825 Eastlake Ave E, Seattle, WA 98109 
Tel: 206-288-7176 
Email: eestey@seattlecca.org 
 
 
Megan Othus, PhD 
Assistant Member, Biostatistics and 
Biomathematics Program, PHS Fred 
Hutchinson Cancer Research Center 
Tel: 206-667-5749 
Email: mothus@fredhutch.org 

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
2 
 
 
 
 
Seattle Cancer Care Alliance Network Investigators 
 
 
Sub Investigators 
Jack Hensold, MD 
Bozeman Deaconess Cancer Center 
(406) 585-5070; 888-389-1000 
(406) 585-5000 for after hours calls 
Thomas Rado, MD 
Columbia Basin Hematology and Oncology 
(509) 783-0144 
Aimee Kohn, MD 
Evergreen Hospital Medical Center 
(425) 899-3953 
(425) 899-3181 for after hours calls 
Eric Chen, MD 
Group Health Cooperative 
Bellevue clinic: (425) 502-3690; Bellevue 
Urgent Care: (425) 502-4120; Seattle clinic: 
(206) 326-3111; Seattle Urgent Care (206) 326- 
3000 or (206) 326-3341 for paging operator 
after hours 
John Keech, MD 
MultiCare Health System 
(253) 403-1677 
(253) 530-8060 
Thomas Kummet, MD 
Olympic Medical Center 
(360) 683-9895 
Kiarash Kojouri, MD 
Skagit Valley Hospital 
(360) 428-2146 
Mitchell Garrison, MD 
Wenatchee Valley Medical Center 
(509) 663-8711 

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
3 
 
 
 
 
 
Table of Contents 
1. Study Objective ............................................................................................................................. 4 
2. Rationale ....................................................................................................................................... 4 
3. Patient Eligibility ............................................................................................................................ 6 
4. Pre-Treatment Evaluation ............................................................................................................. 7 
5. Treatment Plan .............................................................................................................................. 7 
6. Post Treatment Testing ................................................................................................................. 8 
7. Criteria for Removal from Study ................................................................................................... 8 
8. Statistical Considerations .............................................................................................................. 8 
a. Statistical objective .......................................................................................................... 8 
b. Study design ..................................................................................................................... 9 
9. Stopping Rules ............................................................................................................................... 9 
10.Regulatory Reporting Requirements ........................................................................................... 11 
a. Adverse Event reporting ................................................................................................ 11 
b. Grade 3-4 toxicity expectations ..................................................................................... 12 
11.Data and Safety Monitoring Plan ................................................................................................ 12 
12.Data Management/Confidentiality ............................................................................................. 12 
13.References ................................................................................................................................... 13 
14. Appendix: Treatment-Related Mortality (TRM) Score……………………………………………………….18 

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
4 
 
 
 
 
 
 
 
 
2EMHFWLYHV
D([DPLQHZKHWKHUDFRPELQDWLRQRIGHFLWDELQHJLYHQIRUGD\VGD\V
UDWKHUWKDQWKHXVXDOGD\VSOXV³VWDQGDUGGRVH DUD&PJPGDLO\GD\V
PLJKWLPSURYHPRQWKVXUYLYDOSUREDELOLW\IURPWKHKLVWRULFDOWRLQ
SDWLHQWVDJHtZLWKQHZO\GLDJQRVHG$0/
 
E7HVWZKHWKHUWKLVFRPELQDWLRQPLJKWPDLQWDLQ&5UDWHDWRXUKLVWRULFLQ
WKHVHSDWLHQWV
 
F6WXG\IDFWRUVWKDWOHDGSK\VLFLDQVWRHVFDODWHRUPDLQWDLQDUD&GRVHVLQWKRVH
SDWLHQWVZKRKDYHKDGDQ³LQWHUPHGLDWHUHVSRQVH´VKRUWRI&5WRWKHILUVWF\FOHV
RIWKHFRPELQDWLRQ
 
G:KLOHPDLQWDLQLQJDZDUHQHVVRIFRQIRXQGLQJFRYDULDWHVH[DPLQHWKHHIIHFWRI
VXFKGRVHHVFDODWLRQRQ&5UDWH
 
5DWLRQDOH
,WLVJHQHUDOO\UHFRJQL]HGWKDWPRVWSDWLHQWVDJHtZLWKQHZO\GLDJQRVHG$0/OLYH
OHVVWKDQPRQWKVZLWKWKHUDSLHVVXFKDVGD\VRIGDXQRUXELFLQRULGDUXELFLQDQG
RIDUD&³´ORZGRVHDUD&/'$& DQGPRUHUHFHQWO\D]DFLWGLQHRUGHFLWDELQH
7KHSULQFLSDOFDXVHRIGHDWKLVQRWWUHDWPHQWUHODWHGPRUWDOLW\UDWHVRIZKLFK
DSSHDUWREHGHFOLQLQJVKDUSO\HYHQDIWHU5DWKHUIDLOXUHLVJHQHUDOO\GXHWR
³UHVLVWDQFH´LHIDLOXUHWRHQWHU&5GHVSLWHOLYLQJORQJHQRXJKWRGRVRRUUHODSVHIURP
&53ULQFLSDOFRYDULDWHVDVVRFLDWHGZLWKUHVLVWDQFHDUHF\WRJHQHWLFVIRUIDLOXUH
WRHQWHU&5DQGIRUUHODSVHF\WRJHQHWLFVVORZFRXQWUHFRYHU\PROHFXODUPDUNHUV
DEHUUDWLRQVLQ130&(%3$$6;/'107DW\SHRIUHVSRQVH&5YV&5SRU
&5LDQGPLQLPDOUHVLGXDOGLVHDVHDW&5
 
*LYHQWKHLUSRRUSUHGLFWHGRXWFRPHZLWKVWDQGDUGWKHUDS\ROGHUSDWLHQWVDUHW\SLFDOO\
FDQGLGDWHVIRU³FOLQLFDOWULDOV´+RZHYHUDVHDUFKRIWKH1&,ZHEVLWHFOLQLFDOWULDOVJRY
LQGLFDWHV!WULDOVIRUROGHUSDWLHQWVZLWKQHZO\GLDJQRVHG$0/7KLVFDQRQO\LQGLFDWH
WKDWSUHFOLQLFDOUDWLRQDOHVDUHLQVXIILFLHQWWRLQGLFDWHZKLFKWULDOLVEHVW7KHIDLOXUHRI
PRVWQHZDJHQWVWRVXEVWDQWLDOO\LPSURYHRXWFRPHGHVSLWHWKHLUVHHPLQJO\FRPSHOOLQJ
UDWLRQDOHVOHQGVIXUWKHUVXSSRUWWRWKLVVXSSRVLWLRQ 7KXVHPSLULFLVPVWLOOUXOHV
GHYHORSPHQWRIWKHUDS\IRU$0/ $VDFRUROODU\WKHUHLVFXUUHQWO\DQHPSKDVLVRQWULDOV
WKDWHQUROODUHODWLYHO\VPDOOQXPEHURISDWLHQWVDOORZLQJPRUHGUXJVWREHWHVWHG

 
2XUPRVWUHFHQWHIIRUWLQWKHVHSDWLHQWVLQYROYHGWRVHGRVWDWDQDPLQRSHSWLGDVHLQKLELWRU
FRPELQHGZLWKHLWKHUDUD&RUGHFLWDELQHDVGHFLGHGE\UDQGRPL]DWLRQSURWRFRO
+RZHYHUDFDVHRIP\RFDUGLWLVLQDSDWLHQWJLYHQVLQJOHDJHQWWRVHGRVWDWDWDQRWKHU
KRVSLWDOSURPSWHGWKH)'$WRLQWHUGLFWXVHRIWRVHGRVWDWLQDOOVWXGLHV1RQHWKHOHVV
DOWKRXJKIRUPDOVWRSSLQJFULWHULDKDGQRWEHHQPHWLWDSSHDUHGXQOLNHO\WKDWHLWKHUDUPRI

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
5 
 
 
 
 
RXUVWXG\ZRXOGOHDGWRDPDMRULPSURYHPHQWLQVXUYLYDO26RU&5DOWKRXJKERWKDUPV
KDGUHODWLYHO\OLWWOHWR[LFLW\DOORZLQJSDWLHQWVWRVSHQGWKHPDMRULW\RIWKHLUWLPHDV
RXWSDWLHQWV*LYHQWKDWZHKDYHSODFHGSDWLHQWVRQWKHWRVHGRVWDWGHFLWDELQHRUDUD&
PRQWKO\IRUPRQWKVWKDWWKHOHQJWKRIWKH)'$KROGLVXQFHUWDLQDQGWKDWWKH
OLNHOLKRRGRIPDMRUVXFFHVVZLWKWKHVHFRPELQDWLRQVVHHPHGVPDOOZHKDYHGHFLGHGZH
QHHGDUHSODFHPHQWVWXG\
 
:KLOHUHFRJQL]LQJWKDWWKHUHDUHPDQ\FDQGLGDWHVIRUVXFKDVWXG\ZHKDYHFKRVHQD
FRPELQDWLRQRIGHFLWDELQHDQGF\WDUDELQH5HDVRQVDUHDVIROORZV
D'DWDVXJJHVWLQJGD\VRIGHFLWDELQHSURGXFHVKLJKHUUHVSRQVHUDWHVWKDQWKH
XVXDOGD\V
E'HFLWDELQHIROORZHGE\VWDQGDUGFKHPRWKHUDS\DSSHDUHGWREHSURPLVLQJLQ
DSXEOLVKHGSKDVH,VWXG\7KHUDWLRQDOHIRUGHFLWDELQHLQROGHUSDWLHQWVLVWKDW
WKHUHLVDEQRUPDO'1$PHWK\ODWLRQLQ$0/DQGK\SRPHWK\ODWLRQDJHQWVKDYH
KDGHIILFDF\LQP\HORG\VSODVWLFV\QGURPHDQGWRDOHVVHUH[WHQW$0/7KH
WKHRU\LVWKDWK\SRPHWK\ODWLQJDJHQWVPD\DFWE\³SULPLQJ´FHOOVWRVXVFHSWLELOLW\
WRVXEVHTXHQWFKHPRWKHUDS\ 7RZDUGWKHJRDORIVWXG\LQJWKLVSULQFLSOHRXU
FHQWHUFXUUHQWO\KDVDQRQJRLQJWULDORIGHFLWDELQHIROORZHGE\0(&
PLWR[DQWURQHHWRSRVLGHF\WDUDELQHFKHPRWKHUDS\IRUUHODSVHGSDWLHQWVSURWRFRO
1&7
F$OWKRXJKDUD&KDV\HWWREHFRPELQHGZLWKGD\VRIGHFLWDELQHWKHDEVHQFH
RIWR[LFLW\ZLWKWRVHGRVWDWPXFKKLJKHUGRVHVRIDUD&WKDQSURSRVHGKHUH
JPYV JPVXJJHVWVH[FHVVWR[LFLW\ZLOOQRWEHDQLVVXHJLYHQWKDWWKH
SDWLHQWVWREHWUHDWHGDUHYHU\VLPLODUWRWKRVHWUHDWHGLQWKHWRVHGRVWDWWULDOLQDQ\
HYHQWVWRSSLQJUXOHVDUHLQSODFHIRUVKRUWVXUYLYDO
G7ZRVWXGLHVZHUHSUHVHQWHGLQDEVWUDFWIRUPGHVFULELQJFRPELQDWLRQVRI
FRQFXUUHQWGHFLWDELQHDQGF\WDUDELQHDGPLQLVWUDWLRQLQSDWLHQWV 2QHSLORWVWXG\
FRPELQHGGHFLWDELQHPJPGD\;GD\VDQGF\WDUDELQHPJPGD\;
GD\VZLWK*&6)SULPLQJLQSDWLHQWVZLWK0'6RU$0/1&7
*UDGHDQGWR[LFLWLHVLQFOXGHGPXFRVLWLVDQGSXOPRQDU\LQILOWUDWHVLQIHFWLRQ
2QHRISDWLHQWVDFKLHYHG&5WZRKDGSURJUHVVLYHGLVHDVHDQGZHUHQRW
HYDOXDEOH 7KHRWKHUVWXG\FRPELQHG DUD&DQGGHFLWDELQHDWKLJKHUGRVHVWKDQ
SURSRVHGKHUHPJPGRVHIRUDUD&DQGPJPGRVHIRUGHFLWDELQH
IRUGD\VIROORZHGE\6&7ZLWKDKLJKHU&5UDWHDQGZLWKRXW LQFUHDVHLQ
HLWKHUVHYHUHLQIHFWLRQUDWHRU HDUO\PRUWDOLW\RYHUGHFLWDELQHDORQHLQ0'6
1&77KHUHLVDUGVWXG\OLVWHGRQFOLQLFDOWULDOVJRYHQWLWOHG
³3KDVH,,6WXG\RI'HFLWDELQHDQG&\WDUDELQHIRU2OGHU3DWLHQWVZLWK1HZO\
'LDJQRVHG$FXWH0\HORJHQRXV/HXNHPLD$0/1&7WKDWLVRSHQ
IRUHQUROOPHQW
H7KHUHZDVDSUHFOLQLFDOVWXG\LQ[HQRJUDIWPLFHZKHUHGLIIHUHQWVFKHGXOHVRI
GHFLWDELQHDQGF\WDUDELQHZHUHDGPLQLVWHUHGHLWKHUFRQFXUUHQWRUVHTXHQWLDOZLWK
QRGLIIHUHQFHREVHUYHGLQWKHUHGXFWLRQRIOHXNHPLDEXUGHQDOWKRXJKWKHUHZHUH
GLIIHUHQFHVLQPHWK\ODWLRQ
I7KHDEVHQFHRISKDUPDFHXWLFDOFRPSDQ\VSRQVRUVKLSZLOOSHUPLWIOH[LELOLW\WKXV
DOORZLQJXVWRH[DPLQHKRZSK\VLFLDQVXVHGDWDWRGHFLGHRQGRVHHVFDODWLRQ,Q
SDUWLFXODUDIWHUUHFHLSWRIFRXUVHVRIWKHUDS\SDWLHQWVZLOOEHFODVVLILHGDVEHLQJ

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
6 
 
 
 
 
LQ&5PDUURZEODVWVE\PRUSKRORJ\QHXWURSKLOFRXQW!SODWHOHW
FRXQW!RUQRW3DWLHQWVQRWLQ&5ZLOOEHIXUWKHUFODVVLILHGDVKDYLQJD
PDUURZEODVWVE\PRUSKRORJ\EXWZLWKFRXQWVQRWPHHWLQJWKHDERYH
FULWHULDIRU&5EtPDUURZEODVWVE\PRUSKRORJ\RUFPDUURZ
EODVWVE\PRUSKRORJ\3DWLHQWVLQDZLOOUHFHLYHDUGF\FOHDWWKHVDPHGRVHVDQG
SDWLHQWVLQEZLOOUHFHLYHDQHVFDODWHGGRVHRIDUD&JPGDLO\GD\VDVLQ
WKHDUD&DUPRIWKHWRVHGRVWDWVWXG\)RUSDWLHQWVLQJURXSFSK\VLFLDQVZLOO
GHFLGHZKHWKHUWRNHHSWKHDUD&GRVHDWJPGDLO\GD\VRUWRHVFDODWHLW
WRWKHJPGDLO\;GRVHQRWHGLQEDERYH:HZLOOIRUPDOO\HOLFLWWKHFULWHULD
XVHGWRDUULYHDWWKLVGHFLVLRQ7KHVHPLJKWLQFOXGHPDUURZFHOOXODULW\GHFUHDVHLQ
EODVWVRUFHOOXODULW\RUWKHLUSURGXFWFRPSDUHGWRSUHWUHDWPHQWWR[LFLW\
DOWKRXJKGRVHHVFDODWLRQZLOOQRWEHDOORZHGLIJUDGHtQRQKHPDWRSRLHWLF
WR[LFLW\RFFXUUHGRQWKHILUVWFRXUVHVSDWLHQWDJHRUZLVKHVHWF,WLVQRW
DSSDUHQWWKDWWKHGHFLVLRQPDNLQJSURFHVVIRUGRVHHVFDODWLRQKDVEHHQ
LQYHVWLJDWHGEHIRUH7KDWWKLVLVDWRSLFRILQWHUHVWKRZHYHUVHHPVFOHDUIURPRXU
REVHUYDWLRQVWKDWZKLOHJHQHUDOO\WKHKLJKHUWKHEODVWFRXQWWKHPRUHOLNHO\WKDW
SK\VLFLDQVDUHWREHJLQDQGFRXUVHZLWKLQZHHNRIDGD\PDUURZWKHUHLV
FRQVLGHUDEOHRYHUODSZLWKVRPHSDWLHQWVZLWKKLJKPDUURZEODVWFRXQWVQRW
UHFHLYLQJDQGFRXUVHDQGYLFHYHUVDDQGZLWKWKHUHDVRQVIRUWKHVHGHFLVLRQV
TXLWHRSDTXH
J,QWXUQWKHVFKHPDRXWOLQHGLQZLOOSHUPLWXVWRFRPSDUHRXWFRPHVLQSDWLHQWV
LQWKHLQWHUPHGLDWHEODVWJURXSDFFRUGLQJWRZKHWKHUWKH\UHFHLYHGWKH
VDPHRUDQHVFDODWHGGRVHRQFRXUVH2IFRXUVHWKHHIIHFWRIDGRVHLQFUHDVH
ZRXOGOLNHO\EHFRQIRXQGHGE\WKHHIIHFWRIUHDVRQVWKHSDWLHQWGLGRUGLGQRW
UHFHLYHDQHVFDODWHGGRVH+RZHYHUZHZLOODEOHWRH[DPLQHRXWFRPHRQFRXUVH
DFFRUGLQJWRWKHUHDVRQVIRUJLYLQJQRWJLYLQJDQHVFDODWHGGRVH
 
3DWLHQW(OLJLELOLW\
D 1HZO\GLDJQRVHG$0/E\:+2FULWHULDP\HORLGEODVWVE\PRUSKRORJ\
LQHLWKHUEORRGRUPDUURZ
E +LJKULVN0'6RU031LQFOXGLQJ&00/DVGHILQHGE\P\HORLG
EODVWVLQHLWKHUEORRGRUPDUURZ
F $JH
G3DWLHQWVPD\KDYHUHFHLYHGD]DFLWLGLQHGHFLWDELQHRUOHQDOLGRPLGHEXWQR
³F\WRWR[LFWKHUDS\´VXFKDVDUD&RUDQWKUDF\FOLQHV'DWDVXJJHVWWKDWIDLOXUHWR
UHVSRQGWRD]DFLWLGLQHUHGXFHVSUREDELOLW\RIUHVSRQVHWR+HQFHLQWKH
LQWHUHVWRIKDYLQJDUHODWLYHO\KRPRJHQHRXVSRSXODWLRQZKLOHSDWLHQWVZKRKDYH
UHFHLYHGDQGIDLOHGD]DFLWLGLQHRUGHFLWDELQHZLOOEHHOLJLEOHIRUWKLVVWXG\WKH\
ZLOOEHDQDO\]HGVHSDUDWHO\IURPSDWLHQWVZKRKDYHQRWUHFHLYHGWKHVHGUXJV
H 7UHDWPHQWUHODWHGPRUWDOLW\750VFRUH 3DWLHQWVZLWK750
VFRUHV!LQZKRPWKHULVNRIGHDWKZLWKLQGD\VRIEHJLQQLQJLQGXFWLRQ
WKHUDS\KDVDYHUDJHGZLOOSUHIHUHQWLDOO\EHSODFHGRQSURWRFRO
I3URYLVLRQRIZULWWHQLQIRUPHGFRQVHQW
J1RWHXQOLNHSKDUPDFHXWLFDOFRPSDQ\VSRQVRUHGSURWRFROVHOLJLELOLW\LVQRW
FRQGLWLRQHGRQELOLUXELQFUHDWLQLQHRUDEVHQFHRIRWKHUPDOLJQDQF\ZLWKLQWKH
SDVW\HDUV7KH750VFRUHLQFRUSRUDWHVFUHDWLQLQHDQGWKXVDKLJKFUHDWLQLQH

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
7 
 
 
 
 
FDQLQSULQFLSOHEHRIIVHWE\IDYRUDEOHYDOXHVIRUWKHRWKHUFRYDULDWHVLQWKH750
VFRUH%LOLUXELQZDVQRWDFRYDULDWHLQWKH750)XUWKHUPRUHLQWKHGRVHV
ZHDUHXVLQJGRVHDGMXVWPHQWRIGHFLWDELQHRUDUD&LVQRWLQGLFDWHGLQWKH
SUHVHQFHRIUHQDORUKHSDWLFDEQRUPDOLWLHV 2XUEURDGHOLJLELOLW\FULWHULDPD\
LQFUHDVHWKHOLNHOLKRRGWKDWRXUUHVXOWVZLOOEHJHQHUDOL]DEOH7KHLQDELOLW\WR
UHSURGXFHUHVXOWVRIHDUO\SKDVH$0/VWXGLHVKDVEHHQDSUREOHPLQWKHSDVW
 
 
 
 
 3UHWUHDWPHQW(YDOXDWLRQ
7KHIROORZLQJLVDUHFRPPHQGDWLRQDQGZLOOEHFROOHFWHGIURPVWDQGDUGRIFDUHHYDOXDWLRQV
PLVVLQJLWHPVZLOOQRWEHFRQVLGHUHGDSURWRFROGHYLDWLRQ
D &%&GLIIHUHQWLDOSODWHOHWFRXQW
E&KHPLVWU\WRLQFOXGHELOLUXELQ$/7$67DOEXPLQ%81FUHDWLQLQH
HOHFWURO\WHVLQFOXGLQJFDOFLXPDQGPDJQHVLXP
F ,IQRWGRQHZLWKLQWKHSUHYLRXVGD\VERQHPDUURZIRUPRUSKRORJ\IORZ
F\WRJHQHWLFV),6+DQGZLWKLQVXUDQFHDSSURYDO21&23/(;
 
7UHDWPHQW3ODQ
7KHIROORZLQJLVDUHFRPPHQGDWLRQDQGZLOOEHFROOHFWHGIURPVWDQGDUGRIFDUHHYDOXDWLRQV
YDULDWLRQVWRWKHVFKHGXOHZLOOEHGRQHZLWKSK\VLFLDQGLVFUHWLRQDQGZLOOQRWEHFRQVLGHUHG
DSURWRFROGHYLDWLRQ
D'HFLWDELQHPJPGDLO\,9GD\VWKURXJK
E$UD&PJPRQFHGDLO\E\,9EROXVGD\VWKURXJK
F 3DWLHQWVZLOOUHFHLYHVXFKFRXUVHVJLYHQGD\VDSDUWUHJDUGOHVVRIEORRG
FRXQWV
G2QFRXUVHK\GUR[\XUHDZLOOEHJLYHQLIWKHEODVWFRXQW:%&;EODVWV
HLWKHUUHPDLQV!IRUGD\VDIWHUEHJLQQLQJGHFLWDELQHDUD&RUUHDFKHV
WKLVOHYHODIWHUWKHUDS\LVEHJXQ3DWLHQWVZLOOEHUHPRYHGIURPVWXG\LI
K\GUR[\XUHDLVVWLOOUHTXLUHGPRUHWKDQZHHNVDIWHUWKHUDS\LVEHJXQ
H%RQHPDUURZZLOOEHH[DPLQHGZHHNVDIWHULQLWLDWLRQRIFRXUVHZLWK
GHFLVLRQVEDVHGRQWKHUHVXOWRIWKLVPDUURZDQGRQDVVHVVPHQWRIQRQ
KHPDWRORJLFWR[LFLW\RQFRXUVHVDQG
I3DWLHQWVZLOOEHUHHYDOXDWHGDIWHUDQ\UGFRXUVH
 
 
 
0DUURZUHVSRQVHDIWHU
FRXUVH
1RQKHPDWRORJLF
WR[LFLW\
3ODQ
EODVWV
IORZ
JUDGH
&RXUVHDWVDPH
GRVHV GHF
PJPGD\V
DUD&PJP
GD\V
!EODVWV
IORZ
JUDGH
&RXUVHDWVDPH
GRVHGHFLWDELQHEXW
DUD&DWJP
GDLO\;GD\V

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
8 
 
 
EODVWV
IORZ
JUDGH
'RFWRUGHFLGHV
EHWZHHQWKH DUD
&GRVHVUHDVRQVIRU
GHFLVLRQHOLFLWHG

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
9 
 
 
 
 
EODVWV
IORZ
!JUDGH
&RXUVHDWVDPH
GRVHVDVFRXUVHV
DQGEXWGXUDWLRQ
VKRUWHQHGWR
GHFLWDELQHGD\V
DQGDUD& GD\V
!EODVWV
IORZ
!JUDGH
2IIVWXG\
 
5HVSRQVHDIWHU
FRXUVH
1RQKHPDWRORJLF
WR[LFLW\
3ODQ
&5&5S&5L
JUDGH
!JUDGH
PRUHFRXUVHVDWVDPH
GRVHDVFRXUVH
PRUHFRXUVHVDW
GRVHGHFUHDVHV
1RQHRIDERYH
1$
2IIVWXG\
 
&5 PDUURZEODVWVE\PRUSKRORJ\$1&!SODWHOHWFRXQW!
&5S DVIRU&5EXWZLWKSODWHOHWFRXQW
&5L PDUURZEODVWVE\PRUSKRORJ\DQGHLWKHUDPDUURZFHOOXODULW\EDW
OHDVWFHOOVFRXQWHGRUF$1&
 
3RVWWUHDWPHQW7HVWLQJ
7KHIROORZLQJLVDUHFRPPHQGDWLRQDQGZLOOEHFROOHFWHGIRUPVWDQGDUGRIFDUHHYDOXDWLRQV
PLVVLQJLWHPVZLOOQRWEHFRQVLGHUHGDSURWRFROGHYLDWLRQ
D &%&GLIIHUHQWLDOSODWHOHWVDWOHDVWWZLFHZHHNO\
E(OHFWURO\WHV%81FUHDWLQLQHDWOHDVWZHHNO\
F %RQHPDUURZH[DPDIWHUF\FOHVRIWKHUDS\DVGHVFULEHGDERYH
G ,ISDWLHQWKDVEODVWVE\IORZQRWHUHDVRQVIRUGHFLVLRQWRNHHSDUD&GRVH
DVRQFRXUVHVRUWRLQFUHDVHLWVHHIURPEHORZ
 
&ULWHULD)RU5HPRYDO)URP6WXG\
D 5HTXLUHPHQWIRUK\GUR[\XUHDWRNHHS:%&PRUHWKDQZHHNVDIWHU
EHJLQQLQJWUHDWPHQWVHH(DERYH
E!JUDGHQRQKHPDWRORJLFWR[LFLW\DQG!EODVWVE\IORZDIWHUFRXUVH
F 1R&5&5S&5LDIWHUFRXUVH
G3K\VLFLDQ¶VRUSDWLHQW¶VGHFLVLRQ
 
 
,IDVXEMHFWSUHIHUVWREHWUHDWHGE\DORFDOSURYLGHUDIWHUHQUROOLQJLQWKLVVWXG\WKDWZLOO
EHFRQVLGHUHGHQGRIWUHDWPHQWSHUWKLVSURWRFRODQGORQJWHUPSRVWWUHDWPHQWIROORZ
XSZLOOEHJLQ7KLVIROORZXSZLOOEHREWDLQHGIRUDOOVXEMHFWVXSWRPRQWKVDIWHUWKH
ODVWGRVHRIVWXG\PHGLFDWLRQ/RQJWHUPIROORZXSLQIRUPDWLRQZLOOEHJDWKHUHGYLD
WHOHSKRQHRUHPDLOZLWKWKHVXEMHFW¶VUHIHUULQJSK\VLFLDQRIILFHV7KLVGDWDZLOOEH
FROOHFWHGLQWKHVRXUFHGRFXPHQWVHJVXEMHFWPHGLFDOUHFRUGDQGWUDQVFULEHGLQWRWKH
DSSURSULDWH&5)
 
 
 

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
10 
 
 
6WDWLVWLFDO&RQVLGHUDWLRQV
 
D3ULPDU\REMHFWLYHV
7KHSURWRFRO¶VSULPDU\REMHFWLYHLVWRHYDOXDWHZKHWKHULWLVSODXVLEOHDVGHILQHGE\
SRVWHULRUSUREDELOLWLHVGHVFULEHGEHORZLQVHFWLRQFWKDWWKHFRPELQDWLRQRIGHFLWDELQH
DUD&DGPLQLVWHUHGDVLQVHFWLRQZLOOLQFUHDVHWKHSURSRUWLRQRISDWLHQWVDOLYHDW
PRQWKVDIWHUHQUROOPHQWRQWKHSURWRFRO26ZKLOHQRWGHFUHDVLQJWKHSURSRUWLRQWKDW
DFKLHYH&5FRPSDUHGWRKLVWRULFDOUDWHV

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
11 
 
 
 
 
E+LVWRULFDOGDWDIRU26DQG&5
 
+LVWRULFDOGDWDIRU26DUHGHULYHGIURPDFRPSOHWHG6:2*WULDORID]DFLWLGLQH
JHPWX]XPDER]RJDPLFLQLQSDWLHQWVZKRVHHOLJLELOLW\UHTXLUHPHQWVZHUHVLPLODUWRWKRVH
KHUH,QWKDWVWXG\RISDWLHQWVPRQWKRYHUDOOVXUYLYDO26ZDV02WKXV
SHUVRQDOFRPPXQLFDWLRQ+LVWRULFDOGDWDIRU&5UDWHDUHGHULYHGIURPRXUUHFHQWFORVHG
WRVHGRVWDWVWXG\)+&5&SURWRFROLQZKLFKRISDWLHQWVDFKLHYHG&526
GDWDDUHQRW\HWPDWXUHHQRXJKIURPWKLVVWXG\KHQFHRXUXVHRIGDWDIURPWKH6:2*
VWXG\
 
F6WXG\GHVLJQ
7KHVWXG\LVSRZHUHGIRUDLPSURYHPHQWLQ26IURPQXOOK\SRWKHVLVEDVHG
RQKLVWRULFDOGDWDWRDOWHUQDWLYHK\SRWKHVLV,QDGGLWLRQZHZDQWWRPDLQWDLQD
KLJKSUREDELOLW\WKDWWKH&5UDWHLVQRWGHFUHDVHGEHORZWKHKLVWRULFDOUDWHRI
 
0DNLQJWKHGHVLJQDGDSWLYHLVGLIILFXOWJLYHQWKHDFFUXDOUDWHDQGWKHPRQWKVQHHGHGWR
REVHUYHVXUYLYDO$UHODWLYHO\VPDOOFRKRUWVL]HIRUH[DPSOHZRXOGPDNHWKHVWXG\
ORJLVWLFDOO\LPSRVVLEOHZKLOHDUHODWLYHO\ODUJHFRKRUWVL]HIRUH[DPSOHPLJKWPDNH
WKHWULDOXQVDIH$VDEDODQFHZHZLOOHYDOXDWHVWRSSLQJUXOHVEDVHGRQWKHILUVWDQG
ILUVWSDWLHQWV $FFUXDOZLOOEHKHOGZKLOHWKHILUVWDQGSDWLHQWVDUHEHLQJ
FROOHFWHG7KHPD[LPXPVDPSOHVL]HLV
 
6WRSSLQJ5XOHVDFFUXDOZRXOGVWRSVKRXOGHLWKHURIWKHUXOHVEHORZEHPHW
 
 
 
L 267KHWULDOZLOOVWRSLIWKHQXPEHURISDWLHQWVDOLYHDWPRQWKVLVRU
 
LL &5±7KHWULDOZLOOVWRSDFFUXDOLIWKHQXPEHURISDWLHQWVZKRDFKLHYH&5LV
 RU
 
,IWKHVWXG\FRPSOHWHVIXOODFFUXDOZHZLOOGHFODUHWKLVUHJLPHQQRWRIIXUWKHULQWHUHVWLI
HLWKHUWKH26UDWHLVRULI  DFKLHYH&5
 
7KHPD[LPXPVDPSOHVL]HZLOOEH:HVHHDSSUR[LPDWHO\SDWLHQWVROGHUWKDQ
ZLWKQHZO\GLDJQRVHG$0/DQQXDOO\7KLVWULDOZLOOUHSODFHSURWRFRO:KLOHWKHUH
ZLOOEHFRPSHWLQJWULDOVDFFUXHGSDWLHQWVLQ\HDUDQGZHDQWLFLSDWHWKDWWKLV
VWXG\ZLOOKDYHVLPLODUDFFUXDO(QUROOPHQWZRXOGEHJLQRQFH,5%DSSURYDOLVVHFXUHG
:HEHOLHYHLWLPSRUWDQWWRPRQLWRUERWKVXUYLYDODQG&5$OWKRXJKKLVWRULFDOO\LWKDV
EHHQWKRXJKWWKDWWKHUHZDVDWLJKWOLQNEHWZHHQVXUYLYDODQG&5PRUHUHFHQWHYLGHQFH
GRHVQRWVXSSRUWWKLVDVVXPSWLRQ,QSDUWLFXODUVWXGLHVE\WKH05&1&5,JURXSLQWKH
8.LQGLFDWHWKDW&5UDWHVFDQLQFUHDVHZLWKRXWHIIHFWRQRYHUDOOVXUYLYDO26ZLWK26
WKHPRVWLPSRUWDQWRXWFRPHIRUWKHSDWLHQW+HQFHZHGRQRWUHTXLUHDQLPSURYHPHQWLQ
&5UDWH+RZHYHUGDWDIURP6:2*DQG0'$QGHUVRQLQGLFDWHWKDWZLWKWKHUDS\VLPLODU
WRZKDWZHDUHWHVWLQJLQWKLVSURWRFROWKHJUHDWPDMRULW\RIORQJWHUPVXUYLYRUVDOLYHIRU
!\HDUVDIWHUVWDUWLQJWKHUDS\DFKLHYH&5*LYHQWKLVEDFNJURXQGZHDUHXQZLOOLQJWR
DFFHSWDGHFOLQHLQ&5UDWH
 
G3HUIRUPDQFHRIWKHGHVLJQXQGHUYDULRXVFOLQLFDOVFHQDULRV

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
12 
 
 
 
 
$VVXPLQJLQGHSHQGHQFHEHWZHHQ26DQG&5ZHVLPXODWHGWKHRSHUDWLQJ
FKDUDFWHULVWLFVRIWKHGHVLJQDQGVXPPDUL]HUHVXOWVLQWKHWDEOHEHORZ,QUHDOLW\26
DQG&5PD\QRWEHLQGHSHQGHQWEXWZHEHOLHYHWKLVLVDFRQVHUYDWLYHDVVXPSWLRQIRU
HYDOXDWLQJSURSHUWLHVRIWKHGHVLJQ
 
7KHGHVLJQ¶VRSHUDWLQJFKDUDFWHULVWLFVLQDUHVKRZQEHORZ
 
 
 
 
6FHQDULR
3UREDELOLW\
VWRSDIWHU
SDWLHQWV
3UREDELOLW\
VWRSDIWHU
SDWLHQWV
3UREDELOLW\
VWRSHDUO\
3UREDELOLW\
SRVLWLYHWULDO
$OWHUQDWLYH
QRGHFUHDVH
LQ&5
26 
&5 




$OWHUQDWLYH
ZLWK
LPSURYHG
&5
26 
&5 




1XOO
GHFUHDVHLQ
&5
26 
&5 




1XOOQR
GHFUHDVHLQ
&5
26 





,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
13 
 
 
 
 
&5 
7RRWR[LF
ZRUVH26
DQGQR
GHFUHDVHLQ
&5
26 
&5 




 
 
,I26LVLPSURYHGDQGWKH&5UDWHLVWKHVDPHDVWKHKLVWRULFDOUDWHWKLVGHVLJQKDV
SRZHU,IERWK26DQGWKH&5UDWHVDUHLPSURYHGWKLVGHVLJQKDVSRZHU,I26LV
QRWLPSURYHGDQGWKH&5UDWHLVZRUVHWKDQWKHKLVWRULFDOUDWHWKHSUREDELOLW\RI
LQFRUUHFWO\FRQFOXGLQJWKHWULDOLVSRVLWLYHDQGWKHUHJLPHQZDUUDQWVIXUWKHUVWXG\LV
,I26LVQRWLPSURYHGDQGWKH&5UDWHLVWKHVDPHDVWKHKLVWRULFDOUDWHWKHSUREDELOLW\
RILQFRUUHFWO\FRQFOXGLQJWKHWULDOLVSRVLWLYHDQGWKHUHJLPHQZDUUDQWVIXUWKHUVWXG\LV
 ,IWKH26LVZRUVHWKDQWKHKLVWRULFDOUDWHDQGWKH&5UDWHLVWKHVDPHDVWKH
KLVWRULFDOUDWHWKHSUREDELOLW\WULDOLQFRUUHFWO\KDVDSRVLWLYHUHVXOWLVDQGWKH
SUREDELOLW\RIVWRSSLQJDFFUXDOHDUO\LV
5HJXODWRU\DQG5HSRUWLQJ5HTXLUHPHQWV
$GYHUVH(YHQW5HSRUWLQJ
0DQ\LIQRWPRVWRIWKHSDWLHQWVWREHWUHDWHGKHUHZRXOGSUHVXPDEO\UHFHLYH
DQWKUDF\FOLQHDUD&IRUH[DPSOHDVLQ³´([SHFWDWLRQVIRUJUDGHRUJDQWR[LFLW\
ZLWKLGDUXELFLQDUD&KDYHEHHQUHSRUWHGVHH7DEOHEHORZ:HZLOOXVHWKHVHDV
DFRQWUROIRURXUGD\GHFLWDELQHGD\DUD&UHJLPHQ
 
Grade ≥3 adverse events other than hematologic toxicities will be recorded, graded, and reported as 
appropriate.  AEs will be collected for the duration that the patients remain on protocol.  AEs that do 
not meet the requirement for expedited reporting will be reported to the IRB as part of the annual 
renewal of the protocol.  Myelosuppression and associated complications are expected events during 
leukemia therapy; therefore, myelosuppression and associated simple complications such as fever, 
infections, bleeding, and related hospitalizations will not be reported as individual AEs but will be 
summarized in the annual report to the IRB. 
7R[LFLWLHVZLOOEHJUDGHGXVLQJWKH&7&$(1&,&RPPRQ7HUPLQRORJ\&ULWHULDIRU
$GYHUVH(YHQWV9HUVLRQ,QIRUPDWLRQRQWKHVHFULWHULDFDQEHGRZQORDGHGIURPWKH
&7(3ZHEVLWHKWWSFWHSFDQFHUJRYUHSRUWLQJFWFKWPO

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
14 
 
 
 
 
*UDGHWR[LFLW\H[SHFWDWLRQV
7DEOH3HUFHQW*UDGHWR[LFLW\H[SHFWDWLRQVZLWK,GDUXELFLQ&\WDUDELQH 
7R[LFLW\3HUFHQWRI3DWLHQWV$IIHFWHG
$QHPLD
7KURPERF\WRSHQLD
1HXWURSHQLD
)HYHURI8QNQRZQ2ULJLQ
'RFXPHQWHG,QIHFWLRQ
+RVSLWDOL]DWLRQ
5HQDO
+HSDWLF
&DUGLDF
'LDO\VLV
,QWHQVLYH&DUH8QLW$GPLVVLRQ
0HFKDQLFDO9HQWLODWLRQ
+\SRQDWUHPLD
+\SRNDOHPLD
 
'DWDDQG6DIHW\0RQLWRULQJ3ODQ
2QJRLQJWULDORYHUVLJKWLVFDUULHGRXWE\WKH3ULQFLSDO,QYHVWLJDWRUDQGWKHUHVHDUFKVWDII
7KH\ZLOOPHHWIUHTXHQWO\WRUHYLHZUHFHQWO\DFTXLUHGGDWDDQGDGYHUVHHYHQWV7KHGDWD
UHFRUGHGZLWKLQWKHUHVHDUFKFKDUWVDQGSURWRFROGDWDEDVHZLOOEHFRPSDUHGZLWKWKHGDWD
WKDWLVDYDLODEOHIURPWKHPHGLFDOUHFRUGDQGRUFOLQLFDOKLVWRULHV$OOLQYHVWLJDWRUVRQWKH
SURWRFROKDYHUHFHLYHGIRUPDOWUDLQLQJLQWKHHWKLFDOFRQGXFWRIKXPDQUHVHDUFK7KH
3ULQFLSDO,QYHVWLJDWRUZLOOUHFHLYHPRQLWRULQJVXSSRUWDVGHVFULEHGEHORZ,QVWLWXWLRQDO
VXSSRUWRIWULDOPRQLWRULQJLVSURYLGHGLQDFFRUGDQFHZLWKWKH)+&5&8QLYHUVLW\RI
:DVKLQJWRQ&DQFHU&RQVRUWLXP,QVWLWXWLRQDO'DWDDQG6DIHW\0RQLWRULQJ3ODQ8QGHU
WKHSURYLVLRQVRIWKLVSODQ)+&5&&OLQLFDO5HVHDUFK6XSSRUWFRRUGLQDWHVGDWDDQG
FRPSOLDQFHPRQLWRULQJFRQGXFWHGE\FRQVXOWDQWVFRQWUDFWUHVHDUFKRUJDQL]DWLRQVRU)+&5&
HPSOR\HHVXQDIILOLDWHGZLWKWKHFRQGXFWRIWKHVWXG\,QGHSHQGHQWPRQLWRULQJYLVLWVRFFXUDW
VSHFLILHGLQWHUYDOVGHWHUPLQHGE\WKHDVVHVVHGULVNOHYHORIWKHVWXG\DQGWKHILQGLQJVRI
SUHYLRXVYLVLWVSHUWKHLQVWLWXWLRQDO'603,QDGGLWLRQSURWRFROVDUHUHYLHZHGDWOHDVW
DQQXDOO\DQGDVQHHGHGE\WKH&RQVRUWLXP'DWDDQG6DIHW\0RQLWRULQJ&RPPLWWHH'60&
)+&5&6FLHQWLILF5HYLHZ&RPPLWWHH65&DQGWKH)+&5&8QLYHUVLW\RI:DVKLQJWRQ
&DQFHU&RQVRUWLXP,QVWLWXWLRQDO5HYLHZ%RDUG,5%7KHUHYLHZFRPPLWWHHVHYDOXDWH
DFFUXDODGYHUVHHYHQWVVWRSSLQJUXOHVDQGDGKHUHQFHWRWKHDSSOLFDEOHGDWDDQGVDIHW\
PRQLWRULQJSODQIRUVWXGLHVDFWLYHO\HQUROOLQJRUWUHDWLQJSDWLHQWV7KH,5%UHYLHZVWKHVWXG\
SURJUHVVDQGVDIHW\LQIRUPDWLRQWRDVVHVFRQWLQXHGDFFHSWDELOLW\RIWKHULVNEHQHILWUDWLRIRU
KXPDQVXEMHFWV$SSURYDORIFRPPLWWHHVDVDSSOLFDEOHLVQHFHVVDU\WRFRQWLQXHWKHVWXG\
7KHWULDOZLOOFRPSO\ZLWKWKHVWDQGDUGJXLGHOLQHVVHWIRUWKE\WKHVHUHJXODWRU\FRPPLWWHHVDQG
RWKHULQVWLWXWLRQDOVWDWHDQGIHGHUDOJXLGHOLQHV
 
 
 
'DWD0DQDJHPHQW&RQILGHQWLDOLW\
7KHLQYHVWLJDWRUZLOOHQVXUHWKDWGDWDFROOHFWHGFRQIRUPWRDOOHVWDEOLVKHGJXLGHOLQHV
(DFKSDWLHQWLVDVVLJQHGDXQLTXHSDWLHQWQXPEHUWRDVVXUHFRQILGHQWLDOLW\3DWLHQWVZLOO
QRWEHUHIHUUHGWRE\WKLVQXPEHUE\QDPHRUE\DQ\RWKHULGHQWLILHULQDQ\SXEOLFDWLRQ
RUH[WHUQDOSUHVHQWDWLRQ7KHOLFHQVHGPHGLFDOUHFRUGVGHSDUWPHQWDIILOLDWHGZLWKWKH

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
15 
 
 
LQVWLWXWLRQZKHUHWKHSDWLHQWUHFHLYHGPHGLFDOFDUHPDLQWDLQVDOORULJLQDOLQSDWLHQWDQG
RXWSDWLHQWFKDUWGRFXPHQWV3DWLHQWUHVHDUFKILOHVDUHVFDQQHGDQGVWRUHGLQDVHFXUH
GDWDEDVH$FFHVVLVUHVWULFWHGWRSHUVRQQHODXWKRUL]HGE\WKH'LYLVLRQRI&OLQLFDO
5HVHDUFK

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
16 
 
 
 
 
 
 
 
 
5()(5(1&(6
 

'RKQHU+(VWH\(+$PDGRUL6$SSHOEDXP)5%XFKQHU7%XUQHWW$.HWDO
'LDJQRVLVDQGPDQDJHPHQWRIDFXWHP\HORLGOHXNHPLDLQDGXOWV
UHFRPPHQGDWLRQVIURPDQLQWHUQDWLRQDOH[SHUWSDQHORQEHKDOIRIWKH(XURSHDQ
/HXNHPLD1HW%ORRG-DQ

(VWH\(+(SLJHQHWLFVLQ&OLQLFDO3UDFWLFH7KHH[DPSOHVRID]DFLWLGLQHDQGGHFLWDELQHLQ
P\HORG\VSODVLDDQGDFXWHP\HORLGOHXNHPLD/HXNHPLD6HS
GRLOHX(SXE-XQ

2WKXV0.DQWDUMLDQ+03HWHUVGRUI65DYDQGL)&RUWHV-(3LHUFH6$HWDO'HFOLQLQJ
UDWHVRIWUHDWPHQWUHODWHGPRUWDOLW\LQSDWLHQWVZLWKQHZO\GLDJQRVHGDFXWH
P\HORLGOHXNHPLDDPOJLYHQLQWHQVLYHLQGXFWLRQUHJLPHQVDUHSRUWIURPWKH
6RXWKZHVW2QFRORJ\*URXS6:2*DQG0'$QGHUVRQ&DQFHU&HQWHU0'$
/HXNHPLD(SXE-XQGRLOHX

$SSHOEDXP)5*XQGDFNHU++HDG'56ORYDN0/:LOOPDQ&/*RGZLQ-(HWDO
$JHDQGDFXWHP\HORLGOHXNHPLD%ORRG

<DQDGD0*0*%RUWKDNXU*5DYDQDGL).DQWDUMLDQ+(VWH\( 5HODSVHDQGGHDWK
GXULQJILUVWUHPLVVLRQLQDFXWHP\HORLGOHXNHPLD+DHPDWRORJLFD


(VWH\(+6KHQ<7KDOO3)(IIHFWRIWLPHWRFRPSOHWHUHPLVVLRQRQVXEVHTXHQWVXUYLYDO
DQGGLVHDVHIUHHVXUYLYDOWLPHLQ$0/5$(%WDQG5$(%%ORRG


3DWHO-30LWKDW*)LJXHURD0()HUQDQGH]+6XQ=5DFHYVNLV-HWDO3URJQRVWLF
UHOHYDQFHRILQWHJUDWHGJHQHWLFSURILOLQJLQDFXWHP\HORLGOHXNHPLD1HZ(QJODQG
-RXUQDORI0HGLFLQH

:DOWHU5%.DQWDUMLDQ+0+XDQJ;3LHUFH6$6XQ=*XQGDFNHU+0HWDO(IIHFWRI
FRPSOHWHUHPLVVLRQDQGUHVSRQVHVOHVVWKDQFRPSOHWHUHPLVVLRQRQVXUYLYDOLQ
DFXWHP\HORLGOHXNHPLD$&RPELQHG(DVWHUQ&RRSHUDWLYH2QFRORJ\*URXS
6RXWKZHVW2QFRORJ\*URXSDQG0'$QGHUVRQ&DQFHU&HQWHU6WXG\-&OLQ
2QFRO

:DOWHU5%*RROH\7$:RRG%/0LODQR))DQJ06RUURU0/HWDO,PSDFWRI
SUHWUDQVSODQWDWLRQPLQLPDOUHVLGXDOGLVHDVHDVGHWHFWHGE\PXOWLSDUDPHWULFIORZ
F\WRPHWU\RQRXWFRPHRIP\HORDEODWLYHKHPDWRSRLHWLFFHOOWUDQVSODQWDWLRQIRU
DFXWHP\HORLGOHXNHPLD-&OLQ2QFRO

(VWH\(+7KDOO3)1HZGHVLJQVIRUSKDVHFOLQLFDOWULDOV%ORRG

+LOOV5.%XUQHWW$.$SSOLFDELOLW\RID3LFND:LQQHUWULDOGHVLJQWRDFXWHP\HORLG
OHXNHPLD%ORRG

,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
17 
 
 
 
 

%OXP:*DU]RQ5.OLVRYLF5%6FKZLQG6:DONHU$*H\HU6HWDO&OLQLFDOUHVSRQVH
DQGPL5ESUHGLFWLYHVLJQLILFDQFHLQROGHU$0/SDWLHQWVWUHDWHGZLWKDGD\
VFKHGXOHRIGHFLWDELQH3URFHHGLQJVRIWKH1DWLRQDO$FDGHP\RI6FLHQFHV


5LWFKLH(.)HOGPDQ(-&KULVWRV3-5RKDQ6'/DJDVVD&%,SSROLWL&HWDO
'HFLWDELQHLQSDWLHQWVZLWKQHZO\GLDJQRVHGDQGUHODSVHGDFXWHP\HORLG
OHXNHPLD/HXN/\PSKRPD

6FDQGXUD-05RER]*-0RK00RUDZD(%UHQHW)%RVH-5HWDO3KDVHVWXG\RI
HSLJHQHWLFSULPLQJZLWKGHFLWDELQHSULRUWRVWDQGDUGLQGXFWLRQFKHPRWKHUDS\IRU
SDWLHQWVZLWK$0/%ORRG
15. 
Butera J, Winer E, Wang C, Castillo JJ, et al. A phase II study with decitabine, low-dose 
cytarabine and G-CSF priming in high-risk myelodysplastic syndromes, 
refractory/relapsed acute myelogenous leukemia or acute myeloid leukemia 
in patients with significant comorbidities. 2011 ASCO Annual Meeting. J Clin 
Oncol 29: 2011 (suppl; abstr 6537). 

+XLVKHQJ$L.DL[XQ+X4L\XQ6XQ;LDR/LHWDO0LFURWUDQVSODQWDWLRQZLWK
'HFLWDELQHDQG&\WDUDELQH,PSURYHV3DWLHQW2XWFRPHVLQ0\HORG\VSODVWLF
6\QGURPHV$6+$QQXDO0HHWLQJ3RVWHU$EVWUDFWV6HVVLRQ

/HRQDUG603HUU\7:RRGPDQ&%.HDUQV36HTXHQWLDOWUHDWPHQWZLWKF\WDUDELQHDQG
GHFLWDELQHKDVDQLQFUHDVHGDQWLOHXNHPLDHIIHFWFRPSDUHGWRF\WDUDELQHDORQHLQ
[HQRJUDIWPRGHOVRIFKLOGKRRGDFXWHP\HORLGOHXNHPLD3/262QHH


8HGD0;LH+6DQGKX5.:DOWHU5%3DJHO-0%HFNHU36HWDO7KH8VHRI'D\
%RQH0DUURZ&KDUDFWHULVWLFVLQWKH'HFLVLRQWR3XUVXHD6HFRQG&RXUVHRI
,QGXFWLRQ&KHPRWKHUDS\LQWKH7UHDWPHQWRI$FXWH0\HORLG/HXNHPLD$6+
$QQXDO0HHWLQJ$EVWUDFWV

-DEERXU(*DUFLD0DQHUR*%DWW\16KDQ-2¶%ULHQ6&RUWHV-HWDO2XWFRPHRI
SDWLHQWVZLWKP\HORG\VSODVWLFV\QGURPHVDIWHUIDLOXUHRIGHFLWDELQHWKHUDS\
&DQFHU

:DOWHU5%2WKXV0%RUWKDNXU*5DYDQGL)&RUWHV-(3LHUFH6$$SSHOEDXP)5
.DQWDUMLDQ+$(VWH\(+3UHGLFWLRQRIHDUO\GHDWKDIWHULQGXFWLRQWKHUDS\IRU
QHZO\GLDJQRVHGDFXWHP\HORLGOHXNHPLDZLWKSUHWUHDWPHQWULVNVFRUHVDQRYHO
SDUDGLJPIRUWUHDWPHQWDVVLJQPHQW-&OLQ2QFRO

:DOWHU5%$SSHOEDXP)57DOOPDQ06:HLVV16/DUVRQ5$(VWH\(+
6KRUWFRPLQJVLQWKHFOLQLFDOHYDOXDWLRQRIQHZGUXJVDFXWHP\HORLGOHXNHPLDDV
SDUDGLJP%ORRG

$WDOODK(&RUWHV-2
%ULHQ63LHUFH65LRV0%(VWH\(HWDO(VWDEOLVKPHQWRI
EDVHOLQHWR[LFLW\H[SHFWDWLRQVZLWKVWDQGDUGIURQWOLQHFKHPRWKHUDS\LQDFXWH
P\HORJHQRXVOHXNHPLD%ORRG










,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018

9019 
18 
 
 


$33(1',;7UHDWPHQW5HODWHG0RUWDOLW\7506FRUH

&DOFXODWLRQRI6LPSOLILHG7UHDWPHQW5HODWHG0RUWDOLW\7506FRUH
,QFOXGHVFRYDULDWHVSHUIRUPDQFHVWDWXV36DJHSODWHOHWFRXQWDOEXPLQVHFRQGDU\$0/
ZKLWHEORRGFHOOFRXQW:%&SHULSKHUDOEORRGEODVWSHUFHQWDJHDQGFUHDWLQLQH

6FRUH H[ZLWK[ 36DJH±SODWHOHWFRXQW±
DOEXPLQKDYHVHFRQGDU\$0/:%&SHULSKHUDOEORRGEODVW
SHUFHQWDJHFUHDWLQLQH


3UREDELOLW\RI750$ERYHDQG%HORZ9DULRXV6LPSOLILHG7506FRUH&XWRIIV

7506FRUH
,QWHUYDO
3DWLHQWVEHORZ
ZLWKLQDERYH750
6FRUH,QWHUYDO
7503UREDELOLW\LI
EHORZ7506FRUH
,QWHUYDO
750
3UREDELOLW\LI
ZLWKLQ750
6FRUH,QWHUYDO

750
3UREDELOLW\LI
DERYH750
6FRUH,QWHUYDO

±




±




±




±




±




±




±





)URP:DOWHU5%2WKXV0%RUWKDNXU*5DYDQGL)&RUWHV-(3LHUFH6$$3SHOEDXP)5
.DQWDUMLDQ+0(VWH\(+3UHGLFWLRQRIHDUO\GHDWKDIWHULQGXFWLRQWKHUDS\IRUQHZO\
GLDJQRVHGDFXWHP\HORLGOHXNHPLDZLWKSUHWUHDWPHQWULVNVRFUHVDQRYHOSDUDGLJPIRU
WUHDWPHQWDVVLJQPHQW-&OLQ2QFRO


,5%$SSURYHG
'RFXPHQW5HOHDVH'DWH
Printed on 2/8/2018