A Multi-center, Randomized, Phase 3 Study of Sequential Pralatrexate Versus Observation in Patients Previously Undiagnosed Peripheral T-cell Lymphoma Who Achieved an Objective Response After Initial Treatment With CHOP-based Chemotherapy
Phase: PHASE3
Conditions: Peripheral T-cell Lymphoma
Sponsor: Spectrum Pharmaceuticals, Inc

Offici al Titl e:  
A  M ulti -c e nt er, R a n d o miz e d, P h as e 3 St u d y of S e q u e nti al 
Pr al atr e x at e V ers us O bs er v ati o n i n P ati e nts wit h Pr e vi o usl y  
U n di a g n os e d P eri p h er al T -c ell L y m p h o m a W h o H a v e Ac hi e v e d a n 
O bj ecti v e R es p o ns e F oll o wi n g I niti al Tr e at m e nt wit h C H O P -b as e d  
C h e m ot h er a p y  
N C T 0 1 4 2 0 6 7 9  
N C T  Nu m b er: 
D oc u m e nt  D at e : 
Pr ot oc ol V ersi o n 2 . 1: 3 1 Oct o b er 2 0 1 1  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 of 9 5 
Cli ni c al St u d y Pr ot o c ol 
St u d y Title: 
A M ulti-ce nter, Ra n d o mize d, P hase 3 St u d y of Se q ue ntial 
Pralatre xate Vers us O bser vati o n i n Patie nts wit h Pre vi o usl y 
U n dia g n ose d Peri p heral T-cell L y m p h o ma W h o Ha ve Ac hie ve d a n 
O bjecti ve Res p o nse F oll o wi n g I nitial Treat me nt wit h C H O P- base d 
C he m ot hera p y 
St u d y N u m ber: 
P D X- 0 1 7 
St u d y P h ase: 
3 
St u d y Dr u g: 
Pralatre xate I njecti o n 
I N D N u m ber: 
5 2, 6 0 4 
E u dr a C T N u m ber: 
2 0 1 0- 0 2 2 2 3 0- 8 1 
S p o ns or: 
All os T hera pe utics, I nc. 
S p o ns or C o nt act: 
, M D 
 
 U S A 
P h o ne: 
 
Fa x: 
 
 
Pr ot oc ol Versi o n/ D ate: 
2. 1/ 3 1 Oct 2 0 1 1 
 
T his st u d y will be c o n d ucte d acc or di n g t o G o o d Cli nical Practice ( G C P) as descri be d b y t he 
G C P Directi ve a n d E ur o pea n U ni o n ( E U) Dire cti ve ( 2 0 0 1/ 2 0/ E C) a n d ot her a p plica ble G C P 
re q uire me nts of t he re gi o ns w here t he st u d y is c o n d ucte d.  All esse ntial d oc u me nts will be 
arc hi ve d. 
C o nfi de nti alit y St ate me nt 
T he i nf or mati o n c o ntai ne d i n t his d oc u me nt, par tic ularl y u n p u blis he d data, is t he pr o pert y or 
u n der c o ntr ol of All os T hera pe u tics, I nc., a n d is pr o vi de d t o y o u i n c o nfi de nce as a n 
i n vesti gat or, p ote ntial i n vesti gat or, or c o ns ulta nt, f or revie w b y y o u, y o ur staff, a n d a n 
a p plica ble I nstit uti o nal Re vie w B oar d, Et hics C o m mittee, or Researc h Et hics B oar d.  T he 
i nf or mati o n is o nl y t o be use d b y y o u i n c o n necti o n wit h a ut h orize d cli nical st u dies of t he 
i n vesti gati o nal dr u g descri be d i n t he pr ot oc ol.  Y o u will n ot discl ose a n y of t he i nf or mati o n 
t o ot hers wit h o ut writte n a uth orizati o n fr o m All os T hera pe uti cs, I nc., e xce pt t o t he e xte nt 
necessar y t o o btai n i nf or me d c o nse nt fr o m t h ose pers o ns t o w h o m t he dr u g ma y be 
a d mi nistere d.  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 of 9 5 
S Y N O P SI S 
St u d y Title: 
A M ulti-ce nter, Ra n d o mize d, P hase 3 St u d y of Se q ue ntial Pralatre xate Vers us O bser vati o n i n 
Patie nts wit h Pre vi o usl y U n dia g n ose d Peri p he ral T-cell L y m p h o ma W h o Ha ve Ac hie ve d a n 
O bjecti ve Res p o nse F oll o wi n g I nitial Trea t me nt wit h C H O P- base d C he m ot hera p y  
St u d y N u m ber: 
P D X- 0 1 7 
St u d y P h ase: 3 
St u d y Ce nters Pl a n ne d: T his will be a n i nter nati o nal, m ulti-ce nter st u d y.  
O bjecti ves: 
Pri mar y  
• 
Deter mi ne t he efficac y of pralatre xate c o m p are d t o o bser vati o n w he n a d mi nistere d t o 
patie nts wit h pre vi o usl y u n dia g n ose d peri p heral T-cell l y m p h o ma ( P T C L) w h o ha ve 
ac hie ve d a n o bjecti ve res p o nse after c o m pleti n g at least 6 c ycles of c ycl o p h os p ha mi de, 
d o x or u bici n, vi ncristi ne, a n d pre d nis o ne ( C H O P)- base d treat me nt. 
Sec o n dar y  
• 
Deter mi ne t he safet y of pralatre xate w h e n a d mi nistere d f oll o wi n g a c o urse of 
C H O P- base d treat me nt t o patie nts wit h pre vi o usl y u n dia g n ose d P T C L. 
Effic ac y E n d p oi nts: 
Pri mar y  
• 
Pr o gressi o n-free s ur vi val ( P F S) a n d o verall s ur vi val ( O S) 
Sec o n dar y  
• 
O bjecti ve res p o nse (c o m plete re s p o nse [ C R] or partial resp o nse [ P R]) t o pralatre xate 
vers us o bser vati o n 
Tre at me nt Pl a n: 
T his is a n i nter nati o nal, m ulti-ce nter, ra n d o mize d, P hase 3, o pe n-la bel st u d y of se q ue ntial 
pralatre xate vers us o bser vati o n i n patie nts wit h pre vi o usl y u n dia g n ose d P T C L w h o ha ve 
ac hie ve d a n o bjecti ve res p o nse f o ll o wi n g i nitial treat me nt wit h C H O P- base d c he m ot hera p y.  
U p o n d oc u me ntati o n of c o m pleti o n of a n o bjecti v e res p o nse f oll o wi n g at least 6 c ycles of a 
desi g nate d C H O P- base d c he m ot hera p y c o nf ir mati o n of hist o pat h ol o g y b y i n de pe n de nt 
re vie w, a n d c o nfir mati o n t hat all eli gi bilit y criteria are met, patie nts will be ra n d o mize d i n a 
2: 1 rati o t o eit her pralatre xate or o bser va ti o n, acc or di n g t o a per m ute d bl oc k desi g n wit h 
stratificati o n fact or of: 
• 
Res p o nse per i n vesti gat or at c o m pleti o n of  C H O P- base d t hera p y (c o m plete res p o nse 
[ C R] vs partial res p o nse [ P R]) 
Patie nts ra n d o mize d t o t he Pralatre xate Ar m will recei ve pralatre xate as a n i ntra ve n o us (I V) 
p us h a d mi nistere d o ver a mi ni m u m of 3 0 sec o n ds  u p t o a ma xi m u m of 5 mi n utes via a pate nt 
free-fl o wi n g I V li ne c o ntai ni n g n or mal sali ne ( 0. 9 % s o di u m c hl ori de [ Na Cl]) wee kl y f or 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
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3 wee ks ( ± 1 da y at eac h ti me p oi nt) of a 4- wee k c ycle.  T he i nitial d ose of pralatre xate will 
be 3 0 m g/ m 2, w hic h base d o n pr ot oc ol- defi ne d criteria, ma y be re d uce d t o 2 0 m g/ m2 wit h 
p ote ntial f urt her re d ucti o ns t o 1 5 a n d 1 0 m g/ m 2.  Pralatre xate will c o nti n ue t o be 
a d mi nistere d u ntil a criteri o n f or st u d y treat me nt disc o nti n uati o n is met or u p t o a ma xi m u m 
of 2 years. 
Patie nts ra n d o mize d t o t he O bser vati o n Ar m will re mai n u n der o bser vati o n, atte n d cli nic 
visits e ver y 4 wee ks, a n d be c o ntacte d b y a h ealt hcare pr ofessi o nal d uri n g wee k 2 of e ver y 
4- wee k peri o d u ntil a criteri o n f or st u d y treat me nt disc o nti n uati o n is met.   
All patie nts will recei ve vita mi n s u p pl e me ntati o n, c o nsisti n g of vita mi n B 1 2 1 m g 
i ntra m usc ular (I M) e ver y 8- 1 0 wee ks a n d f olic aci d 1- 1. 2 5 m g b y m o ut h ( p o) o nce a da y 
( q d).  Vita mi n s u p ple me ntati o n will be gi n at least 7 da ys pri or t o t he pr ojecte d i nitiati o n of 
pralatre xate/ o bser vati o n a n d c o nti n ue t hr o u g h o u t t he st u d y u ntil t he I nitial F oll o w- u p Visit. 
N u m ber of P atie nts Pl a n ne d:  
 A t otal of 5 4 9 patie nts will be ra n d o mize d 2: 1 t o pralatre xate or o bser vati o n.   
T ar get P o p ul ati o n:  
A d ult patie nts wit h pre vi o us l y u n dia g n ose d P T C L w h o ha ve ac hie ve d a n o bjecti ve res p o nse 
after c o m pleti o n of i nitial treat me nt of at leas t 6 c ycles of o ne of t he f oll o wi n g C H O P- base d 
t hera p y re gi me ns: 
a. C H O P 2 1 
b.  C H O P 1 4 
c. C H O E P 
d.  Ot her C H O P varia nts 
D ur ati o n of Tre at me nt:  
Patie nts will recei ve st u d y treat me nt ( pralatre x ate or o bser vati o n) u ntil o ne of t he f oll o wi n g 
criteria f or st u d y treat me nt  disc o nti n uati o n a p plies: 
• 
De vel o p me nt of pr o gres si ve disease ( P D) 
• 
I nitiati o n of ra diati o n t hera p y ( R T) or s yste mic c he m o/ bi ol o gical t hera p y f or treat me nt of 
P T C L 
• 
Recei pt of s yste mic ster oi ds > 1 0 da ys, wit h t he e xce pti o n of t h ose as state d i n e xcl usi o n 
criteri o n # 5 
• 
De vel o p me nt of a n a d verse e ve nt ( A E) t hat i nterferes wit h t he patie nt’s partici pati o n 
• 
L ost t o f oll o w- u p 
• 
Patie nt decisi o n 
• 
I n vesti gat or decisi o n 
• 
S p o ns or decisi o n 
I n a d diti o n, f or patie nts ra n d o mize d t o t he Pralatre xate Ar m, t he f oll o wi n g treat me nt 
disc o nti n uati o n criteria a p pl y: 
• 
3 or m ore c o nsec uti ve d oses of pralatre xate o mitte d or m ore t ha n 2 8 da ys bet wee n d oses 
of pralatre xate 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
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• 
Treat me nt wit h pralatre xate f or 2 years 
St u d y D ur ati o n: 
All patie nts w h o recei ve at le ast 1 d ose of pralatre xate will be f oll o we d f or safet y t hr o u g h 
3 5 ( ± 5) da ys after t heir last d ose of pralatre xate or u ntil all treat me nt-relate d A Es ha ve 
res ol ve d or ret ur ne d t o baseli ne/ Gra de 1, w hic hever is l o n ger, or u ntil it is deter mi ne d t hat 
t he o utc o me will n ot c ha n ge wit h f urt her f oll o w- u p. 
Patie nts w h o are ra n d o mize d t o t he O bser v ati o n Ar m w h o d o n ot disc o nti n ue t he st u d y 
wit hi n 3 da ys of ra n d o mi zati o n will be f oll o we d f or safet y u ntil 3 5 ( ± 5) da ys after t he st u d y 
treat me nt disc o nti n uati o n criteria are met.  
All patie nts w h o are ra n d o mize d will ha ve  f oll o w- u p u ntil o bjecti vel y d oc u me nte d P D; 
t hereafter, patie nts are f oll o we d f or s ur vi val.  T he ti mi n g of f oll o w- u p will be at 8 wee ks 
( ± 1 wee k) t he n e ver y 1 2 wee ks ( ± 1 wee k) t hr o u g h 3 years p ost-ran d o mizati o n, a n d t he n 
e ver y 2 4 wee ks ( ± 4 wee ks) t hereafter t hr o u g h 7 years p ost-ra n d o mizati o n.  P D will be 
c o nfir me d b y ce ntral re vie w u ntil t he firs t P F S a nal ysis ( descri be d bel o w), a n d per 
i n vesti gat or assess me nt t hereafter. 
All s u bse q ue nt t hera pies f or P T C L will be c o llecte d f or u p t o 7 years fr o m ra n d o mizati o n; 
t he best res p o nse t o t he first s u bse q ue nt t hera p y will be c ollecte d.  S ur vi val f oll o w- u p will 
c o nti n ue f or u p t o 7 years fr o m ra n d o mizati o n. 
As disc usse d i n t he statistical met h o ds secti o n, a n a nal ysis will be perf or me d w he n b ot h 
2 8 0 P F S e ve nts a n d 1 2 8 O S e ve nts ha ve occ urre d.  If t he P F S a nal ysis is n ot si g nifica nt at 
t he 0. 0 5 le vel, t he st u d y will be st o p pe d. 
Eli gi bilit y Criteri a 
I ncl usi o n Criteria 
1.  Patie nt’s P T C L hist ol o g y has bee n c o nfir me d as o ne of t he f oll o wi n g b y a n i n de pe n de nt 
pat h ol o g y re vie wer, usi n g t he Re vise d E ur o pea n A merica n  L y m p h o ma ( R E A L) W orl d 
Healt h Or ga nizati o n ( W H O) disease classificati o n: 
a. T/ nat ural killer ( N K)- cell le u ke mia/l y m p h o ma 
b.  A d ult T-cell l y m p h o ma/l e u ke mia ( h u m a n T-cell le u ke mia vir us [ H T L V] 1 +) 
c. A n gi oi m m u n o blastic T-cell l y m p h o ma  
d.  A na plastic lar ge cell l y m p h o ma ( A L C L), pri m ar y s yste mic t y pe, e xcl u di n g a na plastic 
l y m p h o ma ki nase p ositi ve ( AL K +) wit h I nter nati o nal Pr o g n ostic I n de x (I PI) sc ore 
< 2 at i nitial dia g n osis a n d C R afte r c o m pleti o n of C H O P- base d t hera p y 
e. P T C L- u ns pecifie d 
f. E nter o pat h y-t y pe i ntesti nal l y m p h o ma 
g.  He pat os ple nic T-cell l y m p h o ma 
h.  S u bc uta ne o us pa n nic uli tis T-cell l y m p h o ma 
i. Tra nsf or me d m yc osis f u n g oi des 
j. E xtra n o dal T/ N K-cell l y m p h o ma  nasal or nasal t y pe 
k.  Pri mar y c uta ne o us ga m ma- delta T-cell l y m p h o ma 
l. Pri mar y c uta ne o us C D 8 + a g gressi ve e pi der mic c yt ot o xic T-cell l y m p h o ma 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 5 of 9 5 
2.  D oc u me ntati o n t hat t he patie nt has c o m plete d  at least 6 c y cles of C H O P- base d t hera p y, 
i ncl u di n g: 
a. C H O P 2 1  
b.  C H O P 1 4 
c. C H O E P 
d.  Ot her C H O P varia nts: i ncl u des all 4 c o m p o ne nts of C H O P re prese nte d, wit h 
s u bstit uti o n all o we d f or a n y 1 c o m p o ne nt wit h a dr u g of t he sa me mec ha nis m of 
acti o n (e g, varia nt a nt hrac ycli nes).  A d diti o nal c o m p o ne nts t o C H O P are all o we d, 
wit h t he e xce pti o n of ale mt uz u ma b; r it u xi ma b ma y be c o m bi ne d wit h C H O P 
pr o vi de d t hat it is n ot gi ve n wit h i n 3 c ycles of ra n d o mizati o n. 
3.  Patie nt has ac hie ve d a C R or P R per i n ve sti gat or’s assess me nt f oll o wi n g c o m pleti o n of 
C H O P- base d t hera p y a n d has ha d a ra di ol o g ical assess me nt wit hi n 2 1 da ys pri or t o 
ra n d o mizati o n. 
4.  ≥ 1 8 years of a ge. 
5.  Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) perf or ma nce stat us ≤ 2. 
6.  A de q uate he mat ol o gical, he patic, a n d re nal f u ncti o n as defi ne d b y: 
a. A bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1 0 0 0/ µ L 
b.  Platelet c o u nt ≥ 1 0 0, 0 0 0/ µ L 
c. T otal bilir u bi n ≤ 1. 5 m g/ d L 
d.  As partate a mi n otra nsferase ( A S T) a n d ala ni ne a mi n otra nsferase ( A L T) ≤ 2. 5 ×  u p per 
li mit of n or mal ( U L N), ( A S T/ A L T < 5 ×  U L N if d oc u me nte d he patic i n v ol ve me nt 
wit h l y m p h o ma).  All patie nts wit h he pa titis B vir us ( H B V)-p ositi ve ser ol o g y m ust 
ha ve li ver f u ncti o n tests w it hi n t he a b o ve para meters. 
e. Creati ni ne ≤ 1. 5 m g/ d L (if t he patie nt’s creati ni ne is > 1. 5 m g/ d L, t he n t he calc ulate d 
creati ni ne cleara nce m ust be ≥ 5 0 m L/ mi n). 
7.  Fe males of c hil d beari n g p ote nti al (ie, e xcl u di n g patie nts w h o are p ost me n o pa usal f or at 
least 1 year [ > 1 2 m o nt hs since last me nses] or are s ur gicall y sterilize d) m ust: 
a. Ha ve a ne gati ve ser u m pre g na nc y test w it hi n 1 4 da ys pri or t o ra n d o mizati o n a n d 
b.  A gree t o practice a me dicall y acce pta ble c o ntrace pti ve re gi me n fr o m st u d y treat me nt 
i nitiati o n u ntil at least 3 0 da ys after t he last a d mi nistrati o n of pralatre xate. 
8.  Males w h o are se x uall y acti ve, i ncl u di n g t h ose wit h a pre g na nt part ner, m ust a gree t o 
practice a me dicall y acce pta ble barrier met h o d c o ntrace pti ve re gi me n (e g, c o n d o ms) 
w hile recei vi n g pralatre xate a n d f or 9 0 da ys af ter t he last a d mi nistrati o n of pralatre xate. 
9.  Patie nt has gi ve n writte n i nf or me d c o nse nt (I C). 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
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E xcl usi o n Criteria  
1.  Patie nt has:  
a. Prec urs or T/ N K ne o plas ms  
b.  A L C L ( A L K +)  wit h I PI sc ore < 2 at i ni tial dia g n osis a n d C R after c o m pleti o n of 
C H O P- base d t hera p y 
c. T-cell pr ol y m p h oc ytic le u ke mia ( T- P L L) 
d.  T-cell lar ge gra n ular l y m p h oc ytic le u ke mia 
e. M yc osis f u n g oi des, ot her t ha n tra nsf or me d m yc osis f u n g oi des  
f. Sézar y s y n dr o me 
g.  Pri mar y c uta ne o us C D 3 0 + dis or ders:  A L C L a n d l y m p h o mat oi d pa p ul osis 
2.  If t here is a hist or y of pri or mali g na ncies other t ha n t h ose e xce pti o ns liste d bel o w, t he 
patie nt m ust be disease-free f or ≥ 5 years.  Patie nts wit h t he f oll o wi n g pri or mali g na ncies 
less t ha n 5 years bef ore st u d y e ntr y ma y still be e nr olle d if t he y ha ve recei ve d treat me nt 
res ulti n g i n c o m plete res ol uti o n of t he ca ncer a n d c urre ntl y ha ve n o cli nical, ra di ol o gic, 
or la b orat or y e vi de nce of acti ve or rec urre nt disease. 
a. N o n- mela n o ma s ki n ca ncer  
b.  Carci n o ma i n sit u of t he cer vi x 
c. L ocalize d pr ostate ca ncer 
d.  L ocalize d t h yr oi d ca ncer 
3.  Patie nt has recei ve d pri or treat me nt (c he m ot hera p y or ra diati o n) f or P T C L, ot her t ha n a 
si n gle all o we d C H O P re gi men, wit h t he e xce pti o n of: 
a. Patie nts wit h nasal N K l y m p h o ma are per mitte d t o ha ve recei ve d l ocal ra diati o n 
t hera p y n o less t ha n 4 wee ks pri or t o ra n d o mizati o n. 
b.  Patie nts wit h tra nsf or me d m yc osis f u n g oi des are per mitte d t o ha ve recei ve d 1 
s yste mic si n gle-a ge nt c he m ot hera p y ( ot her t ha n met h otre xate) pri or t o tra nsf or mati o n 
of t heir disease. 
4.  Pri or e x p os ure t o pralatre xate. 
5.  Recei pt of s yste mic c ortic oster oi ds wit hi n 3 wee ks of st u d y treat me nt, u nless patie nt has 
bee n ta ki n g a c o nti n u o us d ose of ≤ 1 0 m g/ da y of oral pre d nis o ne or e q ui vale nt f or at least 
4 wee ks or as part of a C H O P pre d nis o ne ta per.   
6.  Pla n ne d use of a n y treat me nt f or P T C L d uri n g t he c o urse of t he st u d y. 
7.  Patie nt has: 
a. H u ma n i m m u n o deficie nc y vir us ( HI V)- p osit i ve dia g n osis wit h a C D 4 c o u nt of 
< 1 0 0 m m 3 or detecta ble viral l oa d wit hi n past 3 m o nt hs a n d is recei vi n g 
a nti-retr o viral t hera p y. 
b.  H B V- p ositi ve ser ol o g y a n d is recei vi n g i nterf er o n t hera p y or has li ver f u ncti o n test 
res ults o utsi de t he para meters of st u d y i ncl usi o n criteria.  Patie nts are per mitte d t o 
recei ve ot her a nti viral t hera pies if t he t hera p y has bee n a d mi nistere d at a sta ble d ose 
f or ≥ 4 wee ks.  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 of 9 5 
c. He patitis C vir us ( H C V) wit h detecta ble viral l oa d or i m m u n o l o gical e vi de nce of 
c hr o nic acti ve disease or recei v i n g/re q uiri n g a nti viral t hera p y. 
d.  S y m pt o matic ce ntral ner v o us s yste m ( C N S) me tastases or lesi o ns f or w hic h treat me nt 
is re q uire d. 
e. U nc o ntr olle d h y perte nsi o n or c o n gesti ve hear t fail ure Class III/I V acc or di n g t o t he 
Ne w Y or k Heart Ass ociati o n’s He art Fail ure G ui deli nes (see 
htt p:// w w w.a merica n heart. or g/ pr ese nter.j ht ml?i de ntifier = 3 0 6 5 0 8 0). 
f. Acti ve u nc o ntr olle d i nfecti o n, u n derl yi n g me dical c o n diti o n i ncl u di n g u nsta ble 
car diac disease, or ot her seri o us ill ness t hat w o ul d i m pair t he a bilit y of t he patie nt t o 
recei ve pr ot oc ol treat me nt.   
8.  Patie nt has ha d maj or s ur ger y wit hi n 2 wee k s pri or t o st u d y e ntr y; ot her t ha n f or li ne 
place me nt or bi o ps y pr oce d ure.  
Test Pr o d uct, D ose, a n d M o de of A d mi nistr ati o n:  
Pralatre xate will be a d mi nistere d via I V  p us h o ver a mi ni m u m of 3 0 sec o n ds u p t o a 
ma xi m u m of 5 mi n utes.  O ne c ycle is 4 wee ks i n d urati o n c o nsisti n g of wee kl y d osi n g at a 
starti n g d ose of pralatre xate 3 0 m g/ m 2 f or 3 wee ks, f oll o we d b y 1 wee k of rest.  D ose 
re d ucti o n t o 2 0 m g/ m2 wit h f urt her re d ucti o ns t o 1 5 a n d 1 0 m g/ m2 will be all o we d f or 
defi ne d t o xicit y.   
Pralatre xate will be a d mi nistere d i nt o a pate nt free-fl o wi n g I V li ne c o ntai ni n g n or mal sali ne 
( 0. 9 % s o di u m c hl ori de [ Na Cl]). 
Effic ac y Assess me nts: 
T he pri mar y efficac y set, als o referre d t o as t he i nte nt-t o-treat p o p ulati o n, i ncl u des all 
ra n d o mize d patie nts.  Eac h patie nt will be i ncl u de d i n t he treat me nt gr o u p assi g ne d at 
ra n d o mizati o n, re gar dless of t he treat me nt recei ve d.  T his a nal ysis set will be use d f or t he 
pri mar y a nal yses of all efficac y e n d p oi nts. 
T u m or Res p o nse Assess me nts  
Meas ure d fr o m ra n d o mi zati o n, res p o nse e val uati o ns  are t o occ ur at 8 wee ks ( ± 1 wee k) t he n 
e ver y 1 2 wee ks ( ± 1 wee k) t hr o u g h 3 years p ost-ra n d o mizati o n, t he n e ver y 2 4 wee ks 
( ± 4 wee ks) t hr o u g h 7 years p ost-ra n d o mizati o n.  T u m or res p o nse will be deter mi ne d b y 
ce ntral re vie w at least u ntil t he a nal ysis of P F S.  If P F S a nal ys is is n ot si g nifica nt at t he 0. 0 5 
le vel at t hat a nal ysis, t he st u d y will be st o p pe d.   
Pr o gressi o n-free S ur vi val  
P F S ti me is calc ulate d as t he n u m ber of da ys fr o m ra n d o mizati o n t o t he date of o bjecti ve 
d oc u me ntati o n of P D or deat h, re gar dless of ca use ( date of P D or deat h - date of 
ra n d o mizati o n + 1).  Patie nts w h o are ali ve wit h o ut a disease res p o nse assess me nt of P D will 
be ce ns ore d at t heir last disease assess me nt da te or t he date of ra n d o mizati o n, w hic he ver is 
later.  Date of pr o gressi o n will n ot be i m p ute d f or patie nts wit h missi n g t u m or assess me nt(s) 
bef ore  a n assess me nt of P D.  Patie nts w h o wit h dr a w fr o m treat me nt pri or t o P D will be 
f oll o we d f or disease stat us w he ne ver p ossi ble, e ve n if s u bse q ue nt t hera p y, i ncl u di n g 
tra ns pla nt, has bee n i nitiate d pri or t o d oc u me nte d P D per ce ntral re vie w at least u ntil t he P F S 
a nal ysis.  Patie nts w h o ha ve n o res p o nse assess me nts after baseli ne will be ce ns ore d at 
ra n d o mizati o n.   

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 8 of 9 5 
O verall S ur vi val  
O verall s ur vi val ti me is  calc ulate d as t he n u m ber of da ys fr o m ra n d o mizati o n t o t he date of 
deat h, re gar dless of ca use ( date of deat h - date of ra n d o mizati o n + 1).  S ur vi val f oll o w- u p 
will c o nti n ue f or u p t o 7 years fr o m ra n d o mizati o n. 
S afet y Assess me nts:  
All patie nts w h o are ra n d o mize d t o t he Pral atre xate Ar m w h o recei ve at least 1 d ose of 
pralatre xate pl us all patie nts ra n d o mize d t o t he O bser vati o n Ar m w h o d o n ot disc o nti n ue t he 
st u d y wit hi n 3 da ys of ra n d o mizati o n will be e valua ble f or safet y.  Safet y will be e val uate d 
b y assess me nt of p h ysical e xa mi nati o ns, cli nical  la b orat or y val ues, treat me nt-e mer ge nt A Es 
(all gra des), S A Es, a n d disc o nti n uati o ns d ue t o treat me nt-relate d A Es.  Safet y will be 
assesse d acc or di n g t o t he Nati o nal Ca ncer I n stit ute ( N CI) C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E ve nts ( C T C A E) scale, Versi o n 4. 0.  
P h ar m ac o ki netic Assess me nts: 
T here will be s parse sa m pli n g f or p o p ulati o n p har mac o ki netics ( P O P P K).  A p pr o xi matel y 
t w o-t hir ds of t he patie nts ra n d o mize d t o t he Pralatre xate Ar m ( n ≈ 2 4 5) w h o c o nse nt t o 
plas ma sa m pli n g will ha ve sa m pli n g perf or me d at c ycle 1, d ose 1 ( pre-i njecti o n, e n d of 
i njecti o n, a n d 8 a n d 2 4 h o urs p ost-i njecti o n).  Of t hese 2 4 5 patie nts, 2 0 patie nts at select sites 
will als o ha ve plas ma sa m pli n g perf or me d at c ycle 2, d ose 3 ( pre-i njecti o n, e n d of i njecti o n, 
a n d 8 a n d 2 4 h o urs p ost-i njecti o n). 
St atistic al Met h o ds: 
T he sa m ple size is base d o n c o m pari n g t he tr eat me nt gr o u ps wit h res pect t o t he pri mar y 
efficac y e n d p oi nts of P F S a n d O S.  T here will be 1 fi nal a nal ysis of P F S, a n d 2 i nteri m a n d 
1 fi nal a nal ysis of O S.  T he first i nteri m a nal ys is of O S will be perf or me d at t he sa me ti me as 
t he P F S a nal ysis.  T he first a nal ysis will be perf or me d w he n b ot h 2 8 0 P F S e ve nts a n d 
1 2 8 O S e ve nts ha ve occ urre d.  T he o nl y a nal ys is f or P F S will be perf or me d at t his first 
a nal ysis p oi nt, a n d will be asse sse d at t he 0. 0 5 le vel of si g nifica nce.  If P F S is si g nifica nt at 
t he 0. 0 5 le vel, t he first i nteri m a nal ysis will be c o n d ucte d o n s ur vi val at t his ti me.  If t he P F S 
a nal ysis is n ot si g nifica nt at t he 0. 0 5 le vel, t h e st u d y will be st o p pe d.  T he sec o n d i nteri m a n d 
fi nal a nal yses f or O S will be perf or me d w he n t w o-t hir ds ( 2 5 6) a n d all 3 8 5 O S e ve nts ha ve 
occ urre d, res pecti vel y.  
T he stratifie d l o g-ra n k test w ill be t he pri mar y met h o d use d t o test t he h y p ot hesis t hat 
pralatre xate e xte n ds P F S a n d O S relati ve t o o bser vati o n.  I n a d diti o n, t he stratifie d C o x 
re gressi o n m o del will be use d t o calc ulate t he P F S a n d s ur vi val hazar d rati o ( H R), al o n g wit h 
t heir 9 5 % c o nfi de nce i nter val ( CIs).  Res ults of t he u nstratifie d C o x re gressi o n m o del (a n d 
l o g-ra n k test) will als o be prese nte d.  T he pro p orti o nal hazar ds ass u m pti o n of t he C o x m o del 
will be assesse d.   
A D M C will peri o dicall y re vie w safet y data at re g ularl y sc he d ule d meeti n gs a n d at t he sa me 
ti me as eac h a nal ysis of efficac y.  T he first f or mal safet y re vie w will occ ur w he n 
a p pr o xi matel y 1 0 0 patie nts ha ve bee n ra n d o m ize d a n d c o m pl ete d at least 8 wee ks p ost-
ra n d o mizati o n pralatre xate/ o bservati o n or ha ve disc o nti n ue d. 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 9 of 9 5 
At eac h i nteri m a nal ysis f or s ur vi val, t he st u d y ma y be st o p pe d f or o ver w hel mi n g e vi de nce 
of f utilit y or s u peri orit y acc or di n g t o s pecifie d b o u n daries.  T he D M C ma y als o ma ke 
rec o m me n dati o ns re gar di n g a dj ust me nts t o t he sa m ple size, if t he y are warra nte d. 
D ate of Pr ot oc ol:  3 1 Oct 2 0 1 1 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 0 of 9 5 
T A B L E O F C O N T E N T S 
S Y N O P SI S ...................................................................................................................... ........... 2 
T A B L E O F C O N T E N T S ......................................................................................................... 1 0  
LI S T O F I N- T E X T T A B L E S .................................................................................................. 1 4  
LI S T O F I N- T E X T FI G U R E S................................................................................................. 1 4  
LI S T O F A P P E N DI C E S .......................................................................................................... 1 4  
LI S T O F A B B R E VI A TI O N S .................................................................................................. 1 6  
1  
I N V E S TI G A T O R S A N D S T U D Y A D MI NI S T R A TI V E S T R U C T U R E ...................... 2 2  
2  
I N T R O D U C TI O N ...........................................................................................................2 3  
2. 1  
Bac k gr o u n d I nf or mati o n o n N o n- H o d g ki n’s L y m p h o mas .................................... 2 3  
2. 2  
Classificati o n of T-cell L y m p h o mas ...................................................................... 2 3  
2. 3  
Pr o g n osis of T-cell L y m p h o mas ............................................................................ 2 4  
2. 3. 1  
C urre nt First-li ne T hera p y f or Peri p heral T-ce ll L y m p h o ma ......................2 7  
3  
P R A L A T R E X A T E .......................................................................................................... 3 0  
3. 1  
P h ysical, C he mical, P har mace utical Pr o perties ..................................................... 3 0  
3. 2  
N o ncli nical St u dies wi t h Pralatre xate .................................................................... 3 1 
3. 2. 1  
N o ncli nical P har mac ol o g y ........................................................................... 3 1  
3. 2. 1. 1  
Xe n o graft St u dies i n L y m p h o ma M o dels............................................ 3 2  
3. 2. 2  
N o ncli nical T o xic ol o g y ............................................................................... 3 5  
4  
O N C O L O G Y S T U DI E S WI T H P R A L A T R E X A T E ...................................................... 3 6  
4. 1  
St u dies i n Patie nts wit h L y m p h o pr oliferati ve Mali g na ncies ................................. 3 6  
4. 1. 1  
Si n gle- A ge nt St u dies ................................................................................... 3 6  
4. 1. 2  
C o m bi nati o n St u dies .................................................................................... 3 7  
4. 2  
St u dies i n Patie nts wit h S oli d T u m ors ................................................................... 3 8  
4. 2. 1  
All os Si n gle-a ge nt St u dies ........................................................................... 3 8  
4. 2. 2  
M S K C C St u dies i n Patie nts wit h S oli d T u m ors .......................................... 3 9  
4. 3  
Safet y O ver vie w of O nc ol o g y Patie nts Recei vi n g Pralatre xate ............................ 4 0  
4. 3. 1  
Preca uti o ns ................................................................................................... 4 0  
4. 4  
Cli nical P har mac ol o g y ........................................................................................... 4 1  
4. 4. 1  
P har mac o ki netics ......................................................................................... 4 1  
5  
R A TI O N A L E F O R T H E C U R R E N T S T U D Y ............................................................... 4 2  
6  
S T U D Y O BJ E C TI V E S .................................................................................................... 4 3  
7  
I N V E S TI G A TI O N A L P L A N ..........................................................................................4 4  
7. 1  
Vita mi n A d mi nistrati o n ......................................................................................... 4 4  
7. 2  
Pralatre xate A d mi nistrati o n ................................................................................... 4 4  
7. 3  
St u d y D urati o n ....................................................................................................... 4 4  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 1 of 9 5 
7. 4  
Treat me nt M o dificati o ns of Pralatre xate ............................................................... 4 5  
7. 4. 1  
He mat ol o gical A d verse E ve nts .................................................................... 4 6  
7. 4. 2  
N o n- he mat ol o gical A d verse E ve nts ............................................................ 4 6  
8  
P A TI E N T P O P U L A TI O N ............................................................................................... 4 8  
8. 1  
N u m ber of Patie nts a n d Patie nt Selecti o n .............................................................. 4 8  
8. 2  
I ncl usi o n of Fe males a n d Mi n orities ......................................................................4 8  
8. 3  
I ncl usi o n Criteria ................................................................................................... 4 8 
8. 4  
E xcl usi o n Criteria .................................................................................................. 4 9  
9  
S T U D Y D R U G A N D P H A R M A C E U TI C A L I N F O R M A TI O N ................................... 5 2  
9. 1  
Pralatre xate I njecti o n ............................................................................................. 5 2  
9. 1. 1  
Pralatre xate I njecti o n F or m ulati o n .............................................................. 5 2  
9. 1. 2  
Pralatre xate I njecti o n St ora ge a n d Ha n dli n g ............................................... 5 2  
9. 1. 3  
Pac ka gi n g/ La beli n g...................................................................................... 5 2  
9. 1. 4  
Pralatre xate I njecti o n D o sa ge a n d A d mi nistrati o n ......................................5 2  
9. 1. 4. 1  
Pre parati o n a n d Pralatre xate I njecti o n D ose Calc ulati o n..................... 52  
9. 1. 5  
A d mi nistrati o n of Pral atre xate I njecti o n ...................................................... 5 3  
9. 2  
Dr u g Acc o u nta bilit y............................................................................................... 5 3  
1 0  S T U D Y P R O C E D U R E S ................................................................................................. 5 4  
1 0. 1  
Scree ni n g................................................................................................................ 5 4  
1 0. 2  
Patie nt Ra n d o mizati o n ........................................................................................... 5 5  
1 0. 3  
Pralatre xate Treat me nt/ O bser vati o n I nitiati o n ....................................................... 5 5  
1 0. 3. 1  
Pralatre xate A d mi nistrati o n ......................................................................... 5 5  
1 0. 4  
Pralatre xate Ar m Pr oce d ures ................................................................................. 5 6  
1 0. 4. 1  
Pralatre xate C ycle 1, D ose 1 ........................................................................ 5 6  
1 0. 4. 2  
Pralatre xate Ar m: C ycle 1, D oses 2- 3 .......................................................... 5 6  
1 0. 4. 3  
Pr oce d ures f or S u bse q ue nt C ycles, D oses 1- 3 f or a Ma xi m u m of 2 
Years ............................................................................................................ 5 7  
1 0. 5  
O bser vati o n Ar m Pr oce d ures ................................................................................. 5 7  
1 0. 5. 1  
O bser vati o n Ar m: Baseli ne Visit ................................................................. 5 7  
1 0. 5. 2  
O bser vati o n Ar m: Wee k 2 of E ver y 4- wee k Peri o d f or a Ma xi m u m of 2 
Years ............................................................................................................ 5 7  
1 0. 5. 3  
O bser vati o n Ar m:  E ver y 2 8 da ys ( ± 3 da ys) f or a Ma xi m u m of 2 Years ... 5 8  
1 0. 6  
Res p o nse E val uati o n .............................................................................................. 5 8  
1 0. 7  
I nitial F oll o w- u p Visit............................................................................................5 9  
1 0. 7. 1  
Pralatre xate Ar m .......................................................................................... 5 9  
1 0. 7. 2  
O bser vati o n Ar m .......................................................................................... 5 9  
1 0. 8  
F oll o w- u p Visits..................................................................................................... 6 0  
1 0. 9  
L o n g-ter m F oll o w- u p ............................................................................................. 6 0  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 2 of 9 5 
1 1  D U R A TI O N O F T R E A T M E N T ..................................................................................... 6 0  
1 1. 1  
Criteria f or St u d y Treat me nt Disc o nti n uati o n ....................................................... 6 0  
1 2  L A B O R A T O R Y T E S T S ................................................................................................. 6 1  
1 2. 1  
L ocal La b orat or y Tests .......................................................................................... 6 1  
1 2. 1. 1  
He mat ol o g y .................................................................................................. 6 1  
1 2. 1. 2  
C he mistr y ..................................................................................................... 6 1  
1 2. 2  
Ce ntral La b orat or y ................................................................................................. 6 2  
1 2. 2. 1  
Plas ma P har mac o ki netics ............................................................................. 6 2  
1 2. 2. 2  
I n de pe n de nt Pat h ol o g y Re vie w ...................................................................6 2  
1 2. 2. 3  
Me dical P h ot o gra p h y ................................................................................... 6 2  
1 2. 2. 4  
Ce ntral Ra di ol o g y I ma gi n g .......................................................................... 6 2  
1 3  C O N C O MI T A N T M E DI C A TI O N S ............................................................................... 6 3  
1 3. 1  
A ntie metic T hera p y ............................................................................................... 6 3  
1 3. 2  
He mat o p oietic Gr o wt h Fact ors .............................................................................. 6 3  
1 3. 3  
M uc ositis Ma na ge me nt .......................................................................................... 6 3  
1 3. 4  
C ortic oster oi d Use ................................................................................................. 6 3  
1 3. 5  
Pr o p h ylactic A nti-i nfecti ve A ge nts ........................................................................ 6 4  
1 3. 6  
Pai n Ma na ge me nt................................................................................................... 6 4  
1 3. 7  
Bl o o d Pr o d ucts ....................................................................................................... 6 4  
1 3. 8  
Ot her S u p p orti ve Care Me dicati o ns....................................................................... 6 4  
1 3. 9  
Ra di ot hera p y, C yt ot o xic T hera p y, Bi ol o gic T hera p y, or I m m u ne Res p o nse 
M o difiers ................................................................................................................ 6 4  
1 4  A D V E R S E E V E N T S ....................................................................................................... 6 5  
1 4. 1  
Defi niti o n ............................................................................................................... 6 5  
1 4. 2  
G ui deli nes f or Rec or di n g a n d Attri b uti o n Sc ori n g of A d verse E ve nts ................. 6 6  
1 4. 3  
Rec or di n g of A d verse E ve nts ................................................................................ 6 6  
1 4. 3. 1  
Rec or di n g of A d verse E ve nts ...................................................................... 6 6  
1 4. 3. 2  
Gra di n g of A d verse E ve nts .......................................................................... 6 6  
1 4. 4  
F oll o w- u p of A d verse E ve nts ................................................................................ 6 6  
1 4. 5  
Relati o ns hi p ........................................................................................................... 6 6  
1 4. 6  
Seri o us A d verse E ve nts ......................................................................................... 6 7  
1 4. 6. 1  
Defi niti o n ..................................................................................................... 6 7  
1 4. 6. 2  
Seri o us A d verse E ve nt Re p orti n g ................................................................ 6 7  
1 4. 6. 3  
E xcl usi o ns t o Seri o us A d vers e E ve nt Re p orti n g Re q uire me nts .................. 6 8  
1 4. 7  
Re pr o d ucti ve Ris ks ................................................................................................ 6 9  
1 4. 7. 1  
Pre g na nc y N otificati o n ................................................................................ 6 9  
1 5  S T A TI S TI C A L P L A N ..................................................................................................... 7 0  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 3 of 9 5 
1 5. 1  
O bjecti ves .............................................................................................................. 7 0  
1 5. 2  
E n d p oi nts ............................................................................................................... 7 0  
1 5. 2. 1  
Efficac y E n d p oi nts ....................................................................................... 7 0  
1 5. 2. 2  
Safet y E n d p oi nts .......................................................................................... 7 0  
1 5. 3  
A nal ysis P o p ulati o n ............................................................................................... 7 0  
1 5. 3. 1  
Pri mar y A nal ysis Set/I nte nt -t o-treat A nal ysis Set .......................................7 0  
1 5. 3. 2  
Safet y A nal ysis Set ...................................................................................... 7 1  
1 5. 3. 3  
I nteri m A nal yses Sets .................................................................................. 7 1 
1 5. 4  
Sa m ple Size ............................................................................................................ 7 1  
1 5. 5  
Stratificati o n ........................................................................................................... 7 2  
1 5. 6  
A nal ysis Pla ns ........................................................................................................ 7 2  
1 5. 6. 1  
I nteri m A nal yses of O S ................................................................................ 7 2 
1 5. 6. 2  
Fi nal A nal yses of Efficac y E n d p oi nts .......................................................... 7 3  
1 5. 7  
Efficac y E n d p oi nts ................................................................................................. 7 4  
1 5. 7. 1  
Pr o gressi o n-free S ur vi val............................................................................. 7 4  
1 5. 7. 2  
O verall S ur vi val ........................................................................................... 7 4  
1 5. 7. 3  
O bjecti ve Res p o nse Rate ............................................................................. 7 5  
1 5. 8  
Safet y A nal ysis ...................................................................................................... 7 5  
1 5. 8. 1  
A d verse E ve nts ............................................................................................ 7 5  
1 5. 8. 2  
A d verse E ve nts Gr o u pe d b y Si milar Preferre d Ter m .................................. 7 6  
1 5. 8. 3  
La b orat or y Para meters ................................................................................. 7 6  
1 6  S T U D Y M A N A G E M E N T .............................................................................................. 7 7  
1 6. 1  
I n vesti gat or Res p o nsi bilities ..................................................................................7 7  
1 6. 1. 1  
G o o d Cli nical Practice ................................................................................. 7 7  
1 6. 1. 2  
I R B/ E C/ R E B A p pr o val ................................................................................7 7  
1 6. 1. 3  
I nf or me d C o nse nt.........................................................................................7 7  
1 6. 1. 4  
St u d y Files a n d Rete nti o n of Rec or ds .......................................................... 7 7  
1 6. 2  
Rec or di n g a n d C ollecti n g of Data .......................................................................... 7 8  
1 6. 2. 1  
Case Re p ort F or ms ....................................................................................... 7 8  
1 6. 2. 2  
Data Clarificati o n F or ms.............................................................................. 7 8  
1 6. 2. 3  
Self-e vi de nt C orrecti o ns .............................................................................. 7 9  
1 6. 2. 4  
Dr u g Acc o u nta bilit y..................................................................................... 7 9  
1 6. 3  
Pr ot oc ol C o m plia nce .............................................................................................. 8 0  
1 6. 4  
S p o ns or Res p o nsi bilities ........................................................................................ 8 0  
1 6. 4. 1  
A me n d me nts t o t he Pr ot oc ol ........................................................................ 8 0  
1 6. 4. 2  
Safet y M o nit ori n g ........................................................................................ 8 0  
1 6. 5  
J oi nt I n vesti gat or/ S p o ns or Res p o nsi bilities ........................................................... 8 1 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 4 of 9 5 
1 6. 5. 1  
Access t o I nf or mati o n f or M o nit ori n g a n d A u diti n g ................................... 8 1  
1 6. 5. 2  
Ter mi nati o n of t he St u d y ............................................................................. 8 1  
1 6. 5. 3  
P u blicati o n P olic y ........................................................................................ 8 1  
1 6. 6  
C o nfi de ntialit y ....................................................................................................... 8 1  
1 7  R E F E R E N C E S ................................................................................................................ 8 2  
 
LI S T O F I N- T E X T T A B L E S 
Ta ble 2. 1  
W H O T-cell L y m p h o ma  Classificati o n8 ......................................................2 4  
Ta ble 2. 2  
L y m p h o ma-i n de pe n de nt Pr o g n ostic Ris k  Fact ors per t he I nter nati o nal 
Pr o g n ostic I n de x .......................................................................................................... 2 5  
Ta ble 2. 3  
C o m paris o n of C o m plete Res p o nse Rate  a n d 5- Year O verall S ur vi val i n 
B- a n d T-cell Ne o plas ms 1 0 ...........................................................................................2 7  
Ta ble 3. 1.  
I n Vitr o C o m paris o n of Met h otre xate A nal o gs ........................................... 3 2  
Ta ble 3. 2.  
C o m paris o n of Gr o wt h I n hi biti o n b y Pralatre xate a n d Met h otre xate 
A gai nst H u ma n L y m p h o ma Cell Li nes ....................................................................... 3 3  
Ta ble 3. 3.  
Treat me nt of H u ma n H T ( Diff use Lar ge B Cell) N o n- H o d g ki n's 
L y m p h o ma Xe n o grafts i n N O D/ S CI D Mice ............................................................... 3 3  
Ta ble 3. 4.  
Treat me nt of H u ma n R L ( Tra nsf o r me d F ollic ular) N o n- H o d g ki n's 
L y m p h o ma Xe n o grafts i n N O D/ S CI D Mice ............................................................... 3 4  
Ta ble 3. 5.  
Treat me nt of H u ma n S KI- D L B C L- 1 ( De N o v o Diff use Lar ge B- Cell) 
N o n- H o d g ki n's L y m p h o ma Xe n o gr afts i n N O D/ S CI D Mice ...................................... 3 4  
Ta ble 7. 1.  
Pralatre xate Treat me nt M o dificat i o ns f or He mat ol o gical A Es ................... 4 6 
Ta ble 7. 2.  
Pralatre xate Treat me nt M o di ficati o ns f or M uc ositis ...................................4 7  
Ta ble 7. 3.  
Pralatre xate Treat me nt M o difi cati o ns f or Treat me nt-relate d 
Car di o vasc ular, Der mat ol o gical, He patic, Ne ur ol o gic, Re nal, or  Res pirat or y A Es ....4 7  
 
LI S T O F I N- T E X T FI G U R E S 
Fi g ure 2. 1.  
5- year O verall S ur vi val b y Hist ol o gic T y pe 1 ...............................................2 6  
Fi g ure 2. 2.  
O verall S ur vi val b y Hist ol o gic T y pe 1 ..........................................................2 8  
Fi g ure 3. 1.  
I n Vi v o S CI D Bei ge Xe n o graft M o del of S KI- D L B C L- 1 ...........................3 5  
 
LI S T O F A P P E N DI C E S 
A p pe n di x 1  
Sc he d ule of St u d y Pr oce d ures / E val uati o ns Ta ble f or 
Pralatre xate Treat me nt ................................................................................................. 8 6  
A p pe n di x 2  
Sc he d ule of St u d y Pr oce d ures/ E val u ati o ns Ta ble f or O bser vati o n ..... 8 7  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 5 of 9 5 
A p pe n di x 3  
E C O G Perf or ma nce Scale .................................................................... 8 8  
A p pe n di x 4  
T he I nter nati o nal W or ks h o p Criteria 4 3 ................................................8 9  
A p pe n di x 5  
S p o ns or Si g nat ure ................................................................................ 9 4  
A p pe n di x 6  
I n vesti gat or Si g nat ure ..........................................................................9 5  
 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 6 of 9 5 
LI S T O F A B B R E VI A TI O N S 
A E 
a d verse e ve nt 
AI D S 
ac q uire d i m m u n o de ficie nc y s y n dr o me 
A L C L 
a na plastic lar ge cell l y m p h o ma 
A L K 
a na plastic l y m p h o ma ki nase 
A L T 
ala ni ne a mi n otra nsferase 
A N C 
a bs ol ute ne utr o p hil c o u nt 
Ara- C 
c ytara bi ne or c yt osi ne ara bi n osi de 
A S T 
as partate a mi n otra nsferase 
A T C 
A nat o mical T hera pe utic C he mical 
A U C 
area u n der t he c ur ve 
A U C ∞ 
area u n der t he c ur ve t o i nfi nit y 
β - h C G 
β - h u ma n c h ori o nic g o na d otr o pi n 
B S A 
b o d y s urface area 
° C 
de grees Celsi us 
C A S 
C he mical A bstracts Ser vice 
C F R 
C o de of Fe deral Re g ulati o ns 
C H O P 
c ycl o p h os p ha mi de, d o x or u bici n, vi ncristi ne, a n d pre d nis o ne 
C H O P 1 4  
C H O P gi ve n e ver y 2 wee ks or 1 4 da ys 
C H O P 2 1  
C H O P gi ve n e ver y 3 wee ks or 2 1 da ys 
CI 
c o nfi de nce i nter val 
c m 
ce nti meter 
C ma x  
ma xi m u m c o nce ntrati o n 
C N S 
ce ntral ner v o us s yste m 
C R 
c o m plete res p o nse 
C R A 
cli nical researc h ass ociate 
C R F 
case re p ort f or m 
C R O 
cli nical researc h or ga nizati o n  
C R u 
u nc o nfir me d C R 
C T 
c o m p ute d t o m o gra p h y 
C T A 
cli nical trial a gree me nt 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 7 of 9 5 
C T C A E 
C o m m o n Ter mi n ol o g y Crit eria f or A d verse E ve nts 
C T C L 
c uta ne o us T-cell l y m p h o ma 
C T E P 
Ca ncer T hera p y E val uati o n Pr o gra m 
D C F 
Data Clarificati o n F or ms 
D H F R 
di h y dr of olate re d uctase 
d L 
deciliter 
D L B C L 
diff use lar ge B-cell 
D L T 
d ose-li miti n g t o xicit y 
D M C 
Data M o nit ori n g C o m mittee 
E B V 
E pstei n Barr vir us 
E C 
Et hics C o m mittee 
E C G 
electr ocar di o gra m 
E C O G 
Easter n C o o perati ve O nc ol o g y Gr o u p 
E D C 
electr o nic data ca pt ure 
E S H A P 
et o p osi de, met h yl pre d nis ol o ne, c ytara bi ne, a n d cis plati n 
E U 
E ur o pea n U ni o n 
° F 
de grees Fa hre n heit 
F D A 
F o o d a n d Dr u g A d mi nistrati o n 
F D G 
fl u or o de o x y gl uc ose 
F F S 
fail ure-free s ur vi val 
F P G S 
f ol yl p ol y gl uta m yl s y nt hetase 
G C P 
g o o d cli nical practice 
G- C S F 
gra n ul oc yte c ol o n y-sti m ulati n g fact or 
Ge m 
ge mcita bi ne 
G F R 
gl o mer ular filtrati o n rate 
G L P 
g o o d la b orat or y practice 
G M- C S F  
gra n ul oc yte- macr o p ha ge  c ol o n y-sti m ulati n g fact or 
H B V 
he patitis B vir us 
Hct 
he mat ocrit 
H C V 
he patitis C vir us 
H g b 
he m o gl o bi n 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 8 of 9 5 
HI V 
h u ma n i m m u n o deficie nc y vir us 
H R 
hazar d rati o 
H T L V 
h u ma n T-cell le u ke mia vir us 
I B 
I n vesti gat or’s Br oc h ure 
I C 
i nf or me d c o nse nt 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I C5 0 
half ma xi m u m i n hi bit or y c o nce ntrati o n 
I L S G 
I nter nati o nal L y m p h o ma St u d y Gr o u p 
I M 
i ntra m usc ular 
I N D 
i n vesti gati o nal ne w dr u g 
I N N 
i nter nati o nal n o n pr o prietar y na me 
I P 
i ntra perit o neal 
I PI 
I nter nati o nal Pr o g n ostic I n de x 
I R B 
I nstit uti o nal Re vie w B oar d 
I R T 
i nteracti ve res p o nse tec h n ol o g y 
I V 
i ntra ve n o us 
I V R S 
i nteracti ve v oice res p o nse s yste m 
I W C 
I nter nati o nal W or ks h o p Criteria 
k g 
kil o gra m 
K i 
i n hi biti o n c o nsta nt 
K m  
bi n di n g c o nsta nt 
L 
liter 
L D H 
lactic de h y dr o ge nase 
m 2 
s q uare meter 
M A L T 
m uc osa-ass ociate d l y m p hatic tiss ue l y m p h o mas 
M C 
ma ntle cell 
Me d D R A
®   
me dical dicti o nar y f or re g ulat or y acti vities 
m g 
milli gra m 
mi n 
mi n ute 
m L 
milliliter 
m m 
milli meter 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 1 9 of 9 5 
m Os m ol 
milli os m ole 
M RI 
ma g netic res o na nce i ma gi n g 
M S K C C  
Me m orial Sl oa n- Ke tteri n g Ca ncer Ce nter 
M T D 
ma xi m u m t olerate d d ose 
M T X 
met h otre xate 
Na Cl 
s o di u m c hl ori de 
N C C N 
Nati o nal C o m pre he nsi ve Ca ncer Net w or k 
N CI 
Nati o nal Ca ncer I nstit ute 
N D A 
Ne w Dr u g A p plicati o n 
N H L 
n o n- H o d g ki n’s l y m p h o ma 
N K 
nat ural killer  
N, n, or n o.  
n u m ber 
N O D/ S CI D  
n o n- o bese, dia betic/se vere c o m bi ne d i m m u n o deficie nt 
N O S 
n ot ot her wise s pecifie d 
N S AI D 
n o n-ster oi dal a nti-i nfla m mat or y dr u g 
N S C L C 
n o n-s mall cell l u n g ca ncer 
n M 
na n o m olar 
n m ol 
na n o m ole 
O R R 
o verall res p o nse rate 
O S 
o verall s ur vi val 
P B S C T 
peri p heral bl o o d ste m cell tra ns pla nt 
P D 
pr o gressi ve disease 
P D X 
pralatre xate, ( R S )- 1 0- pr o par g yl- 1 0- deazaa mi n o pteri n 
P E T 
p ositr o n e missi o n t o m o gra p h y 
P F S 
pr o gressi o n-free s ur vi val 
P K 
p har mac o ki netics 
p M 
pic o m olar 
p o 
oral 
P O P P K 
p o p ulati o n P K 
P R 
partial res p o nse 
P T C L 
peri p heral T-cell l y m p h o ma 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 0 of 9 5 
P T C L- U  
P T C L- u ns pecifie d 
q 
e ver y 
q d 
o nce a da y 
R E A L 
Re vise d E ur o pea n A merica n L y m p h o ma 
R E B 
Researc h Et hics B oar d 
R F C- 1 
re d uce d f olate carrier- 1 
R S 
rect us si nister; a race mic mi xt ure of a c hiral c o m p o u n d 
R T 
ra diati o n t hera p y 
S A E 
seri o us a d verse e ve nt 
S A E R 
seri o us a d verse e ve nt re p ort 
S D 
sta ble disease 
S E 
sta n dar d err or 
S N 
site n otificati o n 
S O C 
s yste m or ga n class 
S P D 
s u m of t he pr o d uct of t he dia meters 
S RI 
S o ut her n Researc h I nstit ute 
S RI I nter nati o nal  
Sta nf or d Researc h I nstit ute I nter nati o nal 
t1/ 2 
half-life 
T C C 
tra nsiti o nal cell carci n o ma 
T E N 
t o xic e pi der mal necr ol ysis 
T- L B 
prec urs or T-l y m p h o blastic l y m p h o ma 
T- P L L 
T-cell pr ol y m p h oc ytic le u ke mia 
U L N 
u p per li mit of n or mal 
U S 
U nite d States 
U S A N 
U nite d States A d o pte d Na me 
U S P 
U nite d States P har mac o peia 
µ g 
micr o gra m 
μ L 
micr oliter 
μ M 
micr o m olar 
µ m ol 
micr o m ole 
V ma x  
ma xi m u m rate c o nsta nt 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 1 of 9 5 
W B C 
w hite bl o o d cells 
W H O 
W orl d Healt h Or ga nizati o n 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 2 of 9 5 
1 
I N V E S TI G A T O R S A N D S T U D Y A DMI NI S T R A TI V E S T R U C T U R E 
Pri or t o st u d y i nitiati o n, t he i n vesti gat or at eac h site m ust pr o vi de t o All os T hera pe utics, I nc. 
( All os) a si g ne d pr ot oc ol si g nat ure pa ge, a f ull y e xec ute d a n d si g ne d U nite d States ( U S) 
F or m F o o d a n d Dr u g A d mi nistrati o n ( F D A) 1 5 7 2, a n d a Fi na ncial Discl os ure F or m.  
Fi na ncial Discl os ure F or ms m ust als o be c o m p lete d f or all s u bi n vesti gat ors liste d o n t he U S 
F or m F D A 1 5 7 2 w h o will be directl y i n v ol ve d i n  t he treat me nt or e val uati o n of researc h 
patie nts i n t his st u d y. 
T he st u d y will be a d mi nistere d a n d m o nit ore d b y e m pl o yees or re prese ntati ves of All os.  
Cli nical researc h ass ociates ( C R As) will m o n it or eac h site o n a peri o dic basis a n d perf or m 
verificati o n of s o urce d oc u me ntati o n f or eac h patie nt.  T he Cli nical Dr u g Safet y a n d 
P har mac o vi gila nce De part me nt at All os will be  res p o nsi ble f or e ns uri n g ti mel y re p orti n g of 
e x pe dite d seri o us a d verse e ve nt re p orts ( S A E Rs) t o re g ulat or y a ge ncies a n d i n vesti gat ors. 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 3 of 9 5 
2 
I N T R O D U C TI O N 
2. 1 
B a c k gr o u n d I nf or m ati o n o n N o n- H o d g ki n’ s L y m p h o m a s 
I ncl u de d u n der t he cate g or y of l y m p h o ma are s o me of t he fastest gr o wi n g a n d m ost 
a g gressi ve ca ncers ( B ur kitt’s l y m p h o ma, l y m p h o blastic l y m p h o ma/le u ke mia), as well as 
s o me of t he m ost i n d ole nt (s mall l y m p h oc ytic l y m p h o ma, f ollic ular l ym p h o ma, a n d mar gi nal 
z o ne l y m p h o ma), ma ki n g l y m p h o ma o ne of t he m o st heter o ge ne o us gr o u ps of mali g na ncies.  
It is t his c o nsi dera ble bi ol o gical di versit y t hat i m p oses si g nifica nt c halle n ges i n 
u n dersta n di n g t he cell of ori gi n a n d differe ntiati n g t he s o meti mes s u btle disti ncti o ns bet wee n 
t he relate d s u bt y pes of disease, as well as i n i de ntif yi n g t he best treat me nts f or eac h.  T-cell 
l y m p h o mas re prese nt a heter o ge ne o us arra y of a g gressi ve n o n- H o d g ki n’s l y m p h o ma ( N H Ls) 
a n d acc o u nt f or a p pr o xi matel y 1 0- 1 5 % of all ne wl y dia g n ose d cases of N H L i n t he U S. 1- 3 
W hile t he eti ol o g y of t he l y m p h o ma diseas es re mai ns lar gel y u n k n o w n, it is clear t hat 
be gi n ni n g pri or t o 1 9 5 0, a n e pi de mic of N H L, b ut n ot ot her he mat o p oietic ne o plas ms, was 
d oc u me nte d i n ma n y p o p ulati o ns, wit h a n es ti mate d 5 0 % i ncrease i n t he a ge-a dj uste d 
i nci de nce fr o m 1 9 7 0- 1 9 9 0 i n t he U S.4- 6  W hile re p orts s u g gest t hat t he stee p rise i n i nci de nce 
ma y ha ve sl o we d i n rece nt years, ca uti o n n ee ds t o be e xercise d i n i nter preti n g t hese 
i nci de nce rates gi ve n t he i n n u mera ble fact ors t hat ca n i nfl ue nce t hese statistics, li ke ac q uire d 
i m m u n o defi cie nc y s y n dr o me ( AI D S), ne w dia g n ostic tec h ni q ues, a n d ot her eti ol o gic fact ors, 
s uc h as i nfecti o ns.  I nteresti n gl y, i n d ustrialize d nati o ns e x perie nce a hi g her i nci de nce of 
N H L t ha n d o de vel o pi n g c o u ntries, wit h t he hi g h est i nci de nce rate i n t he w orl d occ urri n g i n 
t he U S a n d Ca na da.7  T hese statistics ra n k N H L as t he si xt h m ost c o m m o n ca ncer a n d t he 
si xt h m ost c o m m o n ca use of ca ncer deat h, acc o u ntin g f or 4 % of all ca ncers a n d 4 % of ca ncer 
deat hs.  W hile t he y are c o nsi dere d bi ol o gicall y di verse diseases wit h re s pect t o t heir cell of 
ori gi n, all are t h o u g ht t o be  deri ve d fr o m l y m p h oc ytes. 
2. 2 
Cl a s sifi c ati o n of T- c ell L y m p h o m a s 
As me nti o ne d, T-cell l y m p h o ma s acc o u nt f or a p pr o xi matel y 1 0-1 5 % of all ne wl y dia g n ose d 
cases of N H L i n t he U S.  Acc or di n g t o t he W orl d Healt h Or ga nizati o n ( W H O) classificati o n, 
T-cell l y m p h o mas are di vi de d i nt o a vari et y of s u bt y pes, as s h o w n bel o w i n Ta ble 2. 1 . 
Acc or di n g t o t his classificati o n, t here are c o nsi d ere d t o be at least 1 6 disti nct s u bt y pes of 
T-cell l y m p h o ma. 8 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 4 of 9 5 
T a bl e 2. 1  
W H O T- c ell L y m p h o m a Cl a s sifi c ati o n 8  
M at ure T- a n d N K-cell Ne o pl as ms 
 
T-cell pr ol y m p h oc ytic le u ke mia 
T-cell lar ge gra n ular l y m p h oc ytic le u ke mia 
C hr o nic l y m p h o pr oliferati ve dis or der of N K-cells 
A g gressi ve N K-cell le u ke mia 
E B V + T-cell l y m p h o pr oliferati ve dis or der of c hil d h o o d 
A d ult T-cell l y m p h o ma/le u ke mia 
E xtra n o dal T-cell/ N K-cell l y m p h o ma, nasal t y pe 
E nter o pat h y-ass ociate d T-cell l y m p h o ma 
He pat os ple nic T-cell l y m p h o ma 
S u bc uta ne o us pa n nic ulitis -li ke T-cell l y m p h o ma 
M yc osis f u n g oi des 
Sézar y s y n dr o me 
Pri mar y c uta ne o us C D 3 0 + T-cell l y m p h o pr oliferati ve dis or ders 
Pri mar y c uta ne o us ga m ma- delta T-cell l y m p h o mas 
Peri p heral T-cell l y m p h o ma, N O S 
A n gi oi m m u n o blastic T-cell l y m p h o ma 
A na plastic lar ge cell l y m p h o ma, A L K + t y pe 
A na plastic lar ge cell l y m p h o ma, A L K- t y pe 
 
N K = nat ural killer  
E B V = E pstei n Barr vir us 
N O S = n ot ot her wise s pecifie d 
A L K = a na plastic l y m p h o ma ki nase 
2. 3 
Pr o g n o si s of T- c ell L y m p h o m a s 
Al m ost all T/ nat ural killer ( N K)-cell l y m p h o ma s are a g gressi ve diseases re q uiri n g s yste mic 
c he m ot hera p y.  T here are select T-cell s u bsets of  disease t hat are c o nsi dere d m ore i n d ole nt, 
i ncl u di n g T-cell lar ge gra n ular l y m p h oc ytic le u ke mia, pr i mar y c uta ne o us C D 3 0 + dis or ders 
(i ncl u di n g a na plastic lar ge cell l y m p h o ma [ A L CL] a n d l y m p h o mat oi d pa p ul osis), or m yc osis 
f u n g oi des/ Sézar y s y n dr o me. 
I n ge neral, T/ N K-cell diseases are ass ociate d wit h a w orse pr o g n osis c o m pare d wit h t heir 
B-cell c o u nter parts.  It is n ot  e ntirel y clear w h y T-cell l y mp h o mas ha ve a w orse pr o g n osis; 
h o we ver, se veral t he ories ha ve bee n a d va nce d  ar o u n d t he f u n da me ntal bi ol o gical differe nces 
bet wee n B- a n d T-cell l y m p h o mas wit h re gar d  t o t heir i ntri nsic c he m ose nsiti vit y.  T he 
o bser vati o n has als o bee n ma de t hat patie nts wit h T-cell l y mp h o mas ge nerall y prese nt wit h 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 5 of 9 5 
m ore hi g h-ris k disease, at least base d o n t he I nter nati o nal Pr o g n ostic I n de x (I PI). 9  T he I PI 
all o ws f or t he ris k stratificati o n of patie nts wi t h all t y pes of l y m p h o ma, a n d has bee n a p plie d 
t o patie nts wit h b ot h i n d olent a n d a g gressi ve l y m p h o mas. 9  T his i n de x is base d u p o n 
5 i m p orta nt pr o g n ostic fact ors: a ge, East er n C o o perati ve O nc ol o g y Gr o u p ( E C O G) 
Perf or ma nce Stat us, a b n or mal le vels of l actic de h y dr o ge nase ( L D H), n u m ber of e xtra n o dal 
sites, a n d sta ge, wit h hi g her sc ores i n dicati n g w orse o utc o me. 9  Ta ble 2. 2 pr o vi des 
i nf or mati o n o n t he relati ve ris k of deat h ass ociate d wit h eac h of t hese pr o g n ostic fact ors. 
T a bl e 2. 2  
L y m p h o m a-i n d e p e n d e nt Pr o g n o sti c Ri s k F a ct or s p er t h e 
I nt er n ati o n al Pr o g n o sti c I n d e x 
F act or  
Rel ati ve Ris k 
of De at h 
A ge ( ≤ 6 0 vers us > 6 0) 
1. 9 6 
Ser u m L D H ( ≤ 1 x n or mal vers us > 1 x n or mal) 
1. 8 5 
E C O G Perf or ma nce Stat us ( 0 or 1 vers us 2- 4) 
1. 8 0 
Sta ge of Disease (I or II vers us III or I V) 
1. 4 7 
E xtra n o dal Site  I n v ol ve me nt (≤ 1 site vers us > 1 site) 
1. 4 8 
T he I PI is calc ulate d b y a d di n g t he n u m ber of ris k fact ors i de ntifie d a b o ve, res ulti n g i n t he classificati o n of 
patie nts wit h l o w (a n y 1 ris k fact or), l o w-i nter me diate  (a n y 2 ris k fact ors), hi g h-i nter me diate (a n y 3 ris k 
fact ors), a n d hi g h ( 4- 5 ris k fact ors) ris k disease. 
Assess me nt of t hese pr o g n ostic fact ors i n a lar ge c o h ort of B-cell a n d T-cell l y m p h o mas 
s u g geste d t hat T-cell p he n ot y pe ap pears t o be a n i n de pe n de nt a d verse pr o g n ostic fact or i n 
a d diti o n t o t he I PI sc ore. 1 0  Of n ote, a p pr o xi matel y 8 0 % of patie nts wit h peri p heral T-cell 
l y m p h o ma ( P T C L) ha ve a n I PI of 2 or hi g her at dia g n osis c o m pare d wit h 6 9 % of patie nts 
wit h diff use lar ge B-cell l y m p h o ma.
1  Fi g ure 2. 1  dis pla ys t he 5- year s ur vi val b y hist ol o gical 
s u bt y pe. 1 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 6 of 9 5 
Fi g ur e 2. 1.  5- y e ar O v er all S ur vi v al b y Hi st ol o gi c T y p e 1 
0
 
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
A n a pl a sti c l ar g e T/ n ull- c ell
M ar gi n al z o n e B- c ell, M A L T
F olli c ul ar, all gr a d e s
L y m p h o pl a s m a c yt oi d
M ar gi n al z o n e B- c ell, n o d al
S m all l y m p h o c yti c ( C L L)
Pri m ar y m e di a sti n al l ar g e B- c ell
Hi g h- gr a d e B- c ell, B ur kitt-li k e
D L B C L
B ur kitt' s
M a ntl e c ell
Pr e c ur s or T-l y m p h o bl a sti c
P T C L, all t y p e s
5- yr o v er all s ur vi v al, %
 
W hile ne ver f ull y esta blis he d i n a n y pr os pecti v e ra n d o mize d cli nical st u d y, it is reas o na bl y 
well acce pte d t hat T-cell l y m p h o mas are m ore c halle n gi n g t o effecti vel y treat t ha n B-cell 
l y m p h o mas.  Ta ble 2. 3  prese nts s o me of t hese data.1 0  F or e xa m ple, i n t he pre vi o usl y 
me nti o ne d st u d y, t he 5- year s ur vi val rate f or patie nts wit h 1, 2, or 3 ris k fact ors wit h 
B- vers us T-cell l y m p h o ma was 6 3 % vers us  6 0 %, 5 3 % vers us 3 6 %, a n d 3 5 % vers us 2 3 %, 
res pecti vel y.  Si milar tre n ds were als o o bser ve d f or t he rate of c o m plete res p o nses ( C R). 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 7 of 9 5 
T a bl e 2. 3  
C o m p ari s o n of C o m pl et e R e s p o n s e R at e a n d 5- Y e ar O v er all 
S ur vi v al i n B- a n d T- c ell N e o pl a s m s 1 0  
I PI F act ors  
Li ne a ge Assi g n me nt 
C o m plete Re missi o n 
R ate ( %) 
5- Ye ar O ver all 
S ur vi v al ( %) 
O verall 
B- 
T- 
6 3 % 
5 4 % 
5 3 % 
4 1 % 
0 
B- 
T- 
8 1 % 
8 2 % 
8 4 % 
7 7 % 
1 
B- 
T- 
7 1 % 
7 3 % 
6 3 % 
6 0 % 
2 
B- 
T- 
6 3 % 
5 8 % 
5 3 % 
3 6 % 
3 
B- 
T- 
5 2 % 
3 5 % 
3 5 % 
2 3 % 
T hese data are c orr o b orate d t o s o me e xte nt b y t he cate g orizati o n of differe nt o verall s ur vi val 
( O S) rates b y hist ol o gical s u bt y pe usi n g t he I nter nati o nal L y m p h o ma St u d y Gr o u p (I L S G) 
classificati o n, w hic h s u b- di vi de d t he l y m p h o mas i nt o 4 br oa d gr o u pi n gs, i ncl u di n g: ( 1) t h ose 
wit h 5- year o verall s ur vi val rate of great er t ha n 7 0 % i ncl u di n g f ollic ular l y m p h o ma, 
mar gi nal z o ne B-cell l y m p h o ma of m uc osa-ass ociate d l y m p hatic tiss ue l y m p h o mas 
( M A L T t y pe), a n d a na plastic l y m p h o ma ki nase ( A L K) p ositi ve a na plastic lar ge T-cell 
l y m p h o ma; ( 2) t h ose hist ol o gical s u bt y pes wit h 5- year s ur vi val rates of 5 0 %- 7 0 %, i ncl u di n g 
s mall l y m p h oc ytic, l y m p h o plas mac yt oi d, a n d n o dal mar gi nal z o ne B-cell l y m p h o mas; 
( 3) t h ose l y m p h o mas wit h 5- year o verall s ur vi val rates of 3 0 %- 4 9 %, i ncl u di n g diff use lar ge 
B-cell l y m p h o ma, pri mar y me diasti nal lar ge B- cell l y m p h o ma, a n d t he hi g h- gra de, B-cell, 
B ur kitt-li ke a n d B ur kitt l y m p h o mas; a n d fi na ll y, ( 4) t h ose hist ol o gical s u bt y pes wit h t he 
w orse o verall pr o g n osis a n d 5- year s ur vi val rate s less t ha n 3 0 %, i ncl u di n g P T C L, prec urs or 
T-l y m p h o blastic l y m p h o ma, a n d ma ntle cell l y m p h o ma. 1 1  T hese res ults ha ve bee n m ore 
rece ntl y c o nfir me d b y ot hers s h o wi n g t hat patie nts wit h P T C L ha ve a n es peciall y p o or 
o utc o me wit h a 5- year o verall s ur vi val rate of o nl y 2 6 % f oll owi n g treat me nt wit h sta n dar d 
d o x or u bici n-c o ntai ni n g re gi me ns. 1 2 
T hese o bser vati o ns str o n gl y s u g gest t hat patie nt s wit h T-cell l y m p h o ma are i n nee d of ne w 
treat me nt o pti o ns. 
2. 3. 1 
C urr e nt Fir st-li n e T h er a p y f or P eri p h er al T- c ell L y m p h o m a 
T here are c urre ntl y n o a p pr o ve d a ge nts f or firs t-li ne treat me nt of P T C L.  Patie nts wit h t he 
m ost a g gressi ve T-cell l y m p h o ma  s u bt y pes recei ve ver y little c li nical be nefit fr o m sta n dar d 
t hera pies1 3, 1 4 , 1 5, a n d ne w treat me nt c o m bi nati o ns are nee de d t o i m pr o ve b ot h pr o gressi o n-free 
s ur vi val ( P F S) a n d O S i n t he patie nt p o p ulati o n u n der st u d y i n t his pr ot oc ol. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 8 of 9 5 
T he di verse nat ure a n d rarit y of T-cell l y m p h o mas p ose a c hal le n ge t o t he s yste matic st u d y 
of t hese mali g na ncies a n d t he i d e ntificati o n of “sta n dar d” t her a pe utic strate gies.  Rece nt 
re vie ws ha ve atte m pte d t o c haracterize treat me nt a p pr oac hes t o P T C L, as well as t o descri be 
ne w a ge nts t hat ha ve p ote ntial acti vit y a gai nst a variet y of t hese diseases. 1 3, 1 4  First-li ne 
treat me nt of patie nts wit h P T C L ge nerall y co nsists of c o m bi nati o n c he m ot hera p y, pri maril y 
wit h c ycl o p h os p ha mi de, d o x or u bici n, vi ncristi ne, a n d pre d nis o ne ( C H O P), b ut res p o nse is 
ac hie ve d i n a p pr o xi matel y half t he patie nts a n d is ge nerall y of s h ort d urati o n. 1 2 , 1 6  T he 
me dia n s ur vi val f or P T C L, i ncl u di n g all s u bt y pes, is 1- 3 years.
1,  1 7 ,1 5  Fi g ure 2. 2 dis pla ys t he 
O S of P T C L, as well as t hat f or prec urs or  T-l y m p h o blastic l y m p h oma a n d t he B-cell N H L 
wit h t he l o west O S, ma ntle cell.  I n a st u d y e val uati n g 4 differe nt c he m ot hera p y re gi me ns i n 
2 8 8 patie nts wit h P T C L a n d 1 5 9 5 patie nts wit h B-cell l y m p h o ma, t he 5- year e ve nt-free 
s ur vi val rate was 3 2 % f or P T C L patie nts. 1 0  F or t he m ost c o m m o n hist ol o gic s u bt y pe of 
P T C L, P T C L- u ns pecifie d ( P T C L- U), w hic h c o m pri se a p pr o xi matel y 3 4 % of all cases see n i n 
N ort h A merica, t he 5- year fail u re-free s ur vi val ( F F S) is 2 0 %.1 8  
Fi g ur e 2. 2.  O v er all S ur v i v al b y Hi st ol o gi c T y p e1 
 
T- L B = prec urs or T-l y m p h o blastic l y m p h o ma 
P T C L = peri p heral T-cell l y m p h o ma 
M C = ma ntle cell 
O utc o me data f or patie nts wit h T-cell l y m p h o ma w h o recei ve first-li ne C H O P are li mite d.  
A retr os pecti ve st u d y of t he I nte r nati o nal T- Cell L ym p h o ma Pr oject de m o nstrate d a 5- year 
O S rate of 3 2 % a n d a 5- year F F S rate of 2 0 % f or patie nts wit h P T C L- U, wit h wi del y var yi n g 
res ults f or ot her s u bt y pes, m ost of w h o m recei ve d a n a nt hrac ycli ne-c o ntai ni n g re gi me n.1 8  I n 
a retr os pecti ve e val uati o n of 9 6 patie nts di a g n ose d wit hi n t he No n- H o d g ki n’s L y m p h o ma 
Classificati o n Pr oject, R u di ger et  al re p ort a si milar fi n di n g, wit h 5- year O S a n d F F S rates of 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 2 9 of 9 5 
2 6 % a n d 2 0 %, res pecti vel y, f or P T C L pa tie nts treate d wit h a d o x or u bici n-c o ntai ni n g 
re gi me n.1 2  T he esti mate d me dia n F F S i n t hese patie nts is a p pr o xi matel y 6 m o nt hs. 
T he first-li ne res p o nse rates t o a nt hrac ycli ne-c o ntai ni n g re gi me ns, i ncl u di n g C H O P 
c he m ot hera p y, f or patie nts wit h P T C L ha ve b ee n re p orte d t o ra n ge bet wee n 5 0 % a n d 7 0 %, 
yet t he l o n g-ter m s ur vi val of t hese patie nts re mai ns dis mal.1 8  A variet y of ot her 
a nt hrac ycli ne- base d c o m bi nati o n t hera pies ha ve als o s h o w n acti vit y, i ncl u di n g i nf usi o nal 
treat me nt pr o gra ms, s uc h as C H O P pl us et o p osi de.1 9  N o n-al k ylat or base d treat me nt 
pr o gra ms e x pl oiti n g n ucle osi de a nal o gs li ke de o x yc of or m yci n, fl u dara bi ne, ge mcita bi ne, a n d 
cla dri bi ne, as well as m o n ocl o nal a nti b o di es/i m m u n ot o xi ns, a n d hi g h- d ose c he m ot hera p y 
f oll o we d b y peri p heral bl o o d ste m cell tra ns pla nt ( P B S C T) ha ve als o bee n use d i n patie nts 
wit h T-cell l y m p h o mas wit h var yi n g de grees of s uccess. 2 0  W hile earl y data s u g gest t hat 
t hese strate gies ma y be m ore effecti ve at i n d uci n g mea ni n gf ul d ura ble C Rs, ma n y patie nts 
ne ver ac hie ve t he re missi o ns necessar y t o ma ke  P B S C T feasi ble a n d t here are n o ra n d o mize d 
data a vaila ble t hat all o w a deter mi nati o n t hat P B S C T is s u peri or t o ot her f or ms of u p-fr o nt 
c o n ve nti o nal c o m bi nati o n c he m ot hera p y pr o gra ms. 2 1 
T he esse ntial t hera pe utic g oal wit h t his P T C L patie nt p o p ulati o n is t o c o ntr ol disease 
pr o gressi o n i n or der t o pr ol o n g t he cli nical be nefit ac hie ve d fr o m i nte nsi ve c he m ot hera p y 
re gi me ns s uc h as C H O P a n d C H O P- base d t hera p y a n d s o e xte n d s ur vi val. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 0 of 9 5 
3 
P R A L A T R E X A T E 
3. 1 
P h y si c al, C h e mi c al, P h ar m a c e uti c al Pr o p erti e s 
Na me of Dr u g Pr o d uct 
Pralatre xate I njecti o n ( Pralatre xate S ol uti o n f or I nf usi o n 
i n t he E ur o pea n U ni o n [ E U]) 
Na me of Acti ve P har ma ce utical 
I n gre die nt 
Pralatre xate 
U nite d States A d o pte d Na me 
( U S A N) C o u ncil C he mical Na me
( 2S )- 2-[[ 4-[( 1R S )- 1-[( 2, 4- dia mi n o pteri di n- 6- yl) 
met h yl] b ut- 3- y n yl] be nz o yl ]a mi n o] pe nta ne di oic aci d 
Ot her C he mical Na mes 
(R S )- 1 0- pr o par g yl- 1 0- deazaa mi n o pteri n 
I nter nati o nal n o n pr o prietar y na me (I N N) C he mical 
Na me: N - { 4-[ 1-( 2, 4- dia mi n o pteri di n- 6- yl) pe nt- 4- y n- 2-
yl] be nz o yl }- L - gl uta mic aci d  
C he mical A bstracts Ser vi ce ( C A S) Na me: L- gl uta mic 
aci d, N-[ 4-[ 1-[( 2, 4- dia mi n o- 6- pteri di n yl) met h yl]- 3-
b ut y n- 1- yl] be nz o yl] 
U S A N a n d I N N N o n pr o prietar y 
Na me 
Pralatre xate 
Tra de Na me 
F O L O T Y N ®  
P har mac ol o gical Class 
A nti ne o plastic a ge nt/a nti meta b olite/f olic aci d a nal o g 
( A nat o mical T hera pe utic C he mical [ A T C] c o de L 0 1 
B A 0 5) 
E m pirical F or m ula 
C 2 3H 2 3N 7O 5 
M olec ular Wei g ht 
4 7 7. 5 
C he mistr y A bstract Re gistr y 
N u m ber 
1 4 6 4 6 4- 9 5- 1 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 1 of 9 5 
Str uct ural F or m ula 
N
N
N
N
N
H
C O 2 H
H
N H 2
H 2 N
O
H
*
a n d e pi m er at C *
C O 2 H
C H
 
F or detaile d i nf or mati o n a b o ut t he ge nera l p har mac ol o g y, p har mac o ki netics ( P K), a n d 
n o ncli nical t o xic ol o g y a n d efficac y st u dies of pralatre xate, refer t o t he c urre nt pralatre xate 
I n vesti gat or’s Br oc h ure (I B) su p plie d b y All os.  T his d oc u me nt m ust be re vie we d pri or t o 
i nitiati n g t he st u d y. 
3. 2 
N o n cli ni c al St u di e s wit h Pr al atr e x at e 
3. 2. 1 
N o n cli ni c al P h ar m a c ol o g y 
Pralatre xate, a met h otre xate a nal o g, was i nitia ll y de vel o pe d b y Me m orial Sl oa n- Ketteri n g 
Ca ncer Ce nter ( M S K C C) i n c olla b orati o n wit h  S o ut her n Researc h I nstit ute ( S RI) a n d 
Sta nf or d Researc h I nstit ute I nter nati o nal ( S RI I nter nati o nal).  Pralatre xate is a s y nt hetic 
1 0- deazaa mi n o pteri n a ntif olate.  T he 1 0- deazaa mi n o pteri ns are a class of rati o nall y desi g ne d 
a ntif olates de m o nstrati n g greater a ntit u m or e ffects t ha n met h otre xate i n i n vitr o t u m or 
m o dels a n d h u ma n t u m or xe n o grafts i n mice. 2 2- 2 4 
Pralatre xate is a f olate a nal o g meta b olic i n hi bit or t hat c o m petiti vel y i n hi bits t he e nz y me 
di h y dr of olate re d uctase ( D H F R).  I n i n vitr o st u dies, pralatre xate s h o we d i m pr o ve d c yt ot o xic 
acti vit y a gai nst a pa nel of ca ncer cell li nes c o m pare d wit h met h otre xate.  T he i m pr o ve d 
c yt ot o xic acti vit y is li kel y d ue t o pralatre xate  bei n g a m ore efficie nt per mea nt f or re d uce d 
f olate tra ns p ort a n d it bei n g m ore efficie ntl y p ol y gl uta m ylate d b y t he e nz y me 
f ol yl p ol y gl uta m yl sy nt hetase ( F P G S). 2 3,  2 5  Si milar t o w hat has bee n re p orte d f or 
met h otre xate, cell ular u pta ke of pralatre xate  is t h o u g ht t o occ ur via t he re d uce d f olate 
carrier- 1 ( R F C- 1) me m bra ne pr otei n.  T his pr otei n has e v ol ve d t o efficie ntl y tra ns p ort 
re d uce d nat ural f olates i nt o hi g hly pr oliferati ve cells, i n or der t o meet t he de ma n ds f or p uri ne 
a n d p yri mi di ne n ucle oti des d uri n g cell re plica ti o n.  I nsi de t he cell, pralatre xate is 
p ol y gl uta m ylate d b y F P G S, a n e nz y me i n v ol ve d i n p ol y gl uta m ylati o n of re d uce d nat ural 
f olates.  T heref ore, pralatre xate ma y act as a c o m petiti ve i n hi bit or f o r p ol y gl uta m ylati o n of 
nat ural f olates.  F urt her, it is belie ve d t hat t h e a d diti o n of gl uta mate resi d ues t o pralatre xate 
lea ds t o i ncrease d i ntracell ular half-life, t h us all o wi n g f or pr ol o n ge d dr u g acti o n i n mali g na nt 
cells.  T he relati ve i ncrease i n cell ular u pta ke a n d differe nces i n p ol y gl uta mate f or mati o n i n 
n or mal vers us mali g na nt cells ma y acc o u nt f or t h e e n ha nce d acti vit y of pralatre xate.     
Pralatre xate de m o nstrate d a 1 0-f ol d greater  rate of p ol y gl uta m ylati o n b y F P G S t ha n 
met h otre xate ( Ta ble 3. 1 ).  I n a c yt ot o xicit y assa y usi n g a n u m ber of h u ma n n o n-s mall cell 
l u n g ca ncer ( N S C L C) a n d breast ca ncer cell li nes, pralatre xate was f o u n d t o be s u peri or t o 
b ot h met h otre xate ( 1 3- t o 4 0-f ol d l o wer I C 5 0 [ half ma xi m u m i n hi bit or y c o nce ntrati o n]) a n d 
a n ot her met h otre xate a nal o g, e dat re xate ( 2- t o 4-f ol d l o wer I C5 0). 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 2 of 9 5 
T a bl e 3. 1.  
I n Vitr o C o m p ar i s o n of M et h otr e x at e A n al o g s 
 
Pr al atre x ate  
E d atre x ate  
Met h otre x ate  
D H F R I n hi biti o n, K i ( p M) 
1 3. 4 
5. 8 
4. 9 
F P G S Acti vit y, V ma x / Km  
2 3. 2 
1 0. 3 
2. 2 
I n vitr o Acti vit y 
I C5 0 C o nce ntrati o n (μ M): 
 
 
 
  M D A- 4 6 8 ( breast) 
0. 1 1 
0. 3 9 
4. 5 
  S K- B R III ( breast) 
0. 2 8 
0. 9 9 
4. 2 
  Z R- 7 5- 1 ( breast) 
0. 2 6 
0. 8 6 
3. 5 
  S K- L C 8 ( N S C L C) 
0. 4 2 
1. 2 4 
1 0. 3 
  S K- L C 1 6 ( N S C L C) 
0. 1 1 
0. 2 6 
2. 1 
D H F R = di h y dr of olate re d uctase; K i = i n hi biti o n c o nsta nt; p M = pic o m olar; F P G S = f ol yl p ol y gl uta m yl 
s y nt hetase; V ma x  = ma xi m u m rate c o nsta nt; Km  = bi n di n g c o nsta nt; I C5 0 = half ma xi m u m i n hi bit or y 
c o nce ntrati o n; μ M = micr o m olar; N S C L C = n o n-s mall cell l u n g ca ncer
 
Scree ni n g of pralatre xate i n t he Nati o nal Ca ncer I nstit ute ( N CI) 6 0- Cell Scree n s u g gest 
p ote nt c yt ot o xic acti vit y acr oss a br oa d s pect r u m of t u m or t y pes, i ncl u di n g le u ke mia, 
N S C L C, c ol o n ca ncer, ce ntral ner v o us s yste m  ca ncer, mela n o ma, o varia n ca ncer, re nal 
ca ncer, a n d breast ca ncer. 
Pralatre xate was e val uate d f o r gr o wt h i n hi bit or y acti vit y a gai nst h u ma n t u m or cell li nes 
re prese nti n g hea d a n d nec k ca ncer ( H LaC), breast ca ncer ( M D A- M B- 2 3 1, M D A- M B- 4 3 5), 
a n d N S C L C ( A 5 4 9, M V 5 2 2).  U n der t he e x peri me nt al c o n diti o ns, pralatre xate, teste d as a 
si n gle a ge nt, was m ost acti ve i n t he M V 5 2 2 l u n g a n d M D A- M B - 2 3 1 breast cell li nes wit h 
I C5 0 val ues of 1 2. 8 n M ( M V 5 2 2) a n d 1 8. 0 n M ( M D A-M B- 2 3 1).  C yt ot o xicit y of pralatre xate 
was c o m par a ble i n H La C a n d M D A- M B- 4 3 5 wit h I C 5 0 val ues of 2 5. 8 n M a n d 2 4. 1 n M.  T he 
A 5 4 9 l u n g a de n ocarci n o ma li ne was l east se nsiti ve t o pralatre xate (I C 5 0 = 6 5. 1 n M).  I n a 
hea d-t o- hea d c o m paris o n wit h c o n ve nti o nal t her a pe utics, pralatre xate was m ore c yt ot o xic 
t ha n cis plati n i n e ver y ca ncer cell li ne teste d a n d s u peri or t o  paclita xel i n t he M D A- M B- 2 3 1 
breast a n d b ot h l u n g li nes.  Pral atre xate als o de m o nstrate d s u pe ri or acti vit y vers us d oceta xel 
i n t he M V 5 2 2 l u n g li ne.   
O verall, t he N CI- 6 0 cell li ne res ults, as well as i n vitr o testi n g i n a d diti o nal h u ma n t u m or cell 
t y pes, i n dicates t hat pralatre xate e x hi bits si g nifica nt c yt ot o xic acti vit y acr oss a n u m ber of 
s oli d a n d l y m p h o pr oliferati ve t u m or t y pes. 
3. 2. 1. 1 
X e n o gr aft St u di e s i n L y m p h o m a M o d el s 
Beca use met h otre xate is acti ve i n t he trea t me nt of a g gressi ve N H L, t he efficac y of 
pralatre xate a n d met h otre xate were c o m parati vel y e val uate d a gai nst 5 l y m p h o ma cell li nes: 
R L (tra nsf or me d f ollic ular l y m p h o ma), H T, S K I- D L B C L- 1 ( diff use lar ge B-cell l y m p h o ma), 
Raji ( B ur kitt’s), a n d Hs 4 4 5 ( H o d g ki n’s disease).  After 5 da ys  of c o nti n u o us i n vitr o 
e x p os ure, pralatre xate de m o nstrat e d 8- t o 2 0-f ol d gr eater c yt ot o xicit y t h a n met h otre xate i n 
all cell li nes (Ta ble 3. 2 ). 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 3 of 9 5 
T a bl e 3. 2.  
C o m p ari s o n of Gr o wt h  I n hi biti o n b y Pr al atr e x at e a n d 
M et h otr e x at e A g ai n st H u m a n L y m p h o m a C ell Li n e s 
Cell li ne  
L y m p h o m a t y pe 
I C5 0 Pr al atre x ate 
( n M) 
I C5 0 Met h otre x ate 
( n M) 
P  v al ue 
Hs 4 4 5 
H o d g ki n’s disease  
1. 6 ± 0. 8 
3 2 ± 2. 2  
0. 0 4 5 5 
H T 
Diff use lar ge B-cell  
3. 0 ± 0. 4 
3 5 ± 5. 0  
0. 0 2 3 6 
Raji 
B ur kitt’s 
2. 0 ± 0. 3 
1 6 ± 0. 8  
0. 0 0 3 4 
R L 
Tra nsf or me d f ollic ular  
2 3 ± 2. 0 
2 1 0 ± 4 0  
0. 0 4 2 9 
S KI- D L B C L- 1  
Diff use lar ge B-cell  
5. 1 ± 0. 1 
4 8 ± 2. 5  
0. 0 0 3 5 
I C5 0 = half ma xi m u m i n hi bit or y c o nce ntrati o n, n M = na n o m olar 
Ne xt, pralatre xate a n d met h otre xate were e val uate d i n t u m or xe n o graft m o dels of 3 h u ma n 
N H L cell li nes.  T u m or- beari n g n o n- o bese, dia betic/se vere c o m bi ne d i m m u n o deficie nt 
( N O D/ S CI D) mice were treate d wit h sali ne (co ntr ol) or t he ma xi m u m t olerate d d oses 
( M T Ds) of met h otre xate ( 4 0 m g/ k g) or pralatre xate ( 6 0 m g/k g) via a n i ntra perit o neal (I P) 
r o ute t wice wee kl y f or 2 wee ks.  Al m ost 9 0 % of H T l y m p h o mas treate d  wit h pralatre xate 
c o m pletel y re gresse d, w hereas t h ose treate d w it h met h otre xate s h o we d o nl y m o dest gr o wt h 
dela ys ( Ta ble 3. 3). 
T a bl e 3. 3.  
Tr e at m e nt of H u m a n H T ( D iff u s e L ar g e B C ell) N o n- H o d g ki n' s 
L y m p h o m a X e n o gr aft s i n N O D/ S CI D Mi c e 
A ge nt 
D ose 
( m g/ k g) 
Wei g ht
c h a n ge
( %) 
T u m or 
di a meter 
( m m ± S E) 
T u m or 
v ol u me 
( m m3 ± S E) 
A ver a ge t u m or 
re gressi o n ( %) 
C o m plete 
re gressi o ns 
( n o./t ot al) 
C o ntr ol  
—  
+ 1 3. 3  
1 1. 2 ± 1. 3  
+ 6 4 1 ± 2 5 2  
— 
0/ 8 
Met h otre xate  
4 0  
- 9. 8  
8. 7 ± 2. 0  
+ 3 0 0 ± 2 2 5  
— 
0/ 7 
Pralatre xate  
6 0  
- 8. 9  
0. 5 ± 0. 3  
- 9 5 ± 0. 8  
9 9 
8/ 9 
N O D/ S CI D = n o n- o bese, dia betic/se vere c o m bi ne d i m m u n o deficie nt; m g = milli gra m; k g = kil o gra m; 
m m = milli meter; n o. = n u m ber; S E = sta n dar d err or  
I n 2 ot her m o dels, c o m plete t u m or re gressi o n rates of 5 6 % ( R L, Ta ble 3. 4 ) a n d 
3 0 % ( S KI- D L B C L- 1, Ta ble 3. 5 ) were o bser ve d after pralatre xate treat me nt.  N o t u m or 
re gressi o ns a n d o nl y mi n or gr o wt h i n hi biti o n was n ote d i n t he met h otre xate-treate d a ni mals. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 4 of 9 5 
T a bl e 3. 4.  
Tr e at m e nt of H u m a n R L ( T r a n sf or m e d F olli c ul ar) N o n- H o d g ki n' s 
L y m p h o m a X e n o gr aft s i n N O D/ S CI D Mi c e 
A ge nt 
D ose 
( m g/ k g) 
Wei g ht 
c h a n ge 
( %) 
T u m or di a meter
( m m ± S E) 
C h a n ge i n 
t u m or v ol u me
( m m3 ± S E) 
T u m or 
re gressi o n 
( %) 
C o m plete 
re gressi o ns 
( n o./t ot al) 
C o ntr ol  
—  
+ 1 5. 9  
1 2. 5 ± 1. 3  
+ 1 2 2 8 ± 2 3 8  
— 
0/ 7 
Met h otre xate  
4 0  
- 1 4. 8  
1 0. 9 ± 0. 5  
+ 6 1 8 ± 1 0 8  
— 
0/ 1 2 
Pralatre xate  
6 0  
- 1 1. 1  
2. 7 ± 1. 1  
- 4 6 ± 3 4  
5 7 
5/ 9 
N O D/ S CI D = n o n- o bese, dia betic/se vere c o m bi ne d i m m u n o deficie nt; m g = milli gra m; k g = kil o gra m; 
n o. = n u m ber; S E = sta n dar d err or  
T a bl e 3. 5.  
Tr e at m e nt of H u m a n S KI- D L B C L- 1 ( D e N o v o Diff u s e L ar g e B- C ell) 
N o n- H o d g ki n' s L y m p h o m a X e n o gr aft s i n N O D/ S CI D Mi c e 
A ge nt 
D ose 
( m g/ k g) 
Wei g ht 
c h a n ge 
( %) 
T u m or di a meter  
( m m ± S E) 
C h a n ge i n 
t u m or v ol u me
( m m3 ± S E) 
T u m or 
re gressi o n 
( %) 
C o m plete 
re gressi o ns 
( n o./t ot al) 
C o ntr ol  
—  
+ 4. 9  
1 2 ± 0. 3  
+ 7 8 6 ± 6 4 6  
—  
0/ 8 
Met h otre xate  
4 0  
+ 1. 9  
9. 5 ± 0. 4  
+ 2 9 9 ± 5 8  
—  
0/ 1 0 
Pralatre xate  
6 0  
- 1. 2  
3. 5 ± 0. 7  
- 8 1 ± 1 6 
5 4  
3/ 1 0 
N O D/ S CI D = n o n- o bese, dia betic/se vere c o m bi ne d i m m u n o deficie nt; m g = milli gra m; k g = kil o gra m; 
n o. = n u m ber; S E = sta n dar d err or  
T hese res ults de m o nstrate t hat pralatre xate has t he p ote ntial t o e x hi bit greater acti vit y a gai nst 
h u ma n N H L t ha n met h otre xate. 
A ntif olates a n d c yti di ne a nal o gs ha ve ha d a r ole i n t he treat me nt of ma n y ki n ds of 
l y m p h o pr oliferati ve mali g na ncies.  Met h otre xate is k n o w n t o s y ner gize wit h c ytara bi ne i n a 
sc he d ule- de pe n de nt ma n ner.  T he c o m bi nati o n of pralatre xate a n d t he c yti di ne a nal o g 
ge mcita bi ne ( 2’, 2’- difl u or o de oz yc yti di ne) wa s st u die d.  T he acti vit y of t he sta n dar d 
c o m bi nati o n of met h otre xate/c ytara bi ne was c o m p are d wit h t hat of pralatre xate/ ge mcita bi ne. 
A xe n o graft e x peri me nt i n t he S KI- D L B C L- 1 m o del was c o n d ucte d at o ne- q uarter of t he 
M T D of pralatre xate a n d ge mcita bi ne ( 1 5 m g/ k g eac h).  A si milar d ose re d ucti o n f or 
met h otre xate a n d c ytara bi ne was n ot perf or me d gi ve n t he lac k of acti vit y see n at t he M T D i n 
a n e x pl orat or y st u d y.  C o ntr ol gr o u ps ha d t o be  e ut ha nize d earl y d ue t o e xcessi ve t u m or 
gr o wt h, as di d a ni mals recei vi n g met h otre xate ( 6 0 m g/ k g) al o ne, c ytara bi ne ( 3 0 0 m g/ k g) 
al o ne, or b ot h dr u gs i n c o m bi na ti o n.  I n c o ntrast, treat me nt wit h pralatre xate, ge mcita bi ne, or 
c o m bi nati o ns of t hese 2 at 2 5 % of t he M T D was mar ke dl y m ore efficaci o us.  C o m plete 
t u m or re gressi o ns were o nl y o bser ve d i n t h ose a ni mals recei vi n g pralatre xate f oll o we d b y 
ge mcita bi ne ( Fi g ure 3. 1 ).  T hese i n vi v o e x peri me nts clearl y esta blis h a mar ke d s u peri orit y 
of pralatre xate a n d ge mcita bi ne w he n gi ve n i n  a se q ue ntial fas hi o n.  T hese res ults raise t he 
p ossi bilit y t hat pralatre xate, wit h or wit h o ut t he sc he d ule d a d mi nistrati o n of ge m cita bi ne, 
ma y pr o vi de a ne w treat me nt m o dalit y f or select l y m p h o pr oliferati ve mali g na ncies. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 5 of 9 5 
Fi g ur e 3. 1.  I n Vi v o S CI D B ei g e X e n o gr aft M o d el of S KI- D L B C L- 1 
 
 
S CI D = se vere c o m bi ne d i m m u n o deficie nt; M T X = met h otre xate; Ara- C = c ytara bi ne; P D X or P = pralatre xate; 
Ge m or G = ge mcita bi ne; C R = c o m plete re missi o n/res p o nse 
 
3. 2. 2 
N o n cli ni c al T o xi c ol o g y 
A c o m pre he nsi ve ac ute a n d s u bac ute t o xic ol o g y e val uati o n pr o gra m has bee n perf or me d t o 
g o o d la b orat or y practices ( G L P) c o m plia nce a n d per I nter nati o nal C o nfere nce o n 
Har m o nisati o n (I C H) g ui da nce t o e m ulate t he r o ute, d ose, a n d sc he d ul e of pralatre xate 
a d mi nistrati o n use d i n cli nical de vel o p me nt,  i ncl u di n g: car di o vasc ular a n d ne ur ol o gical 
safet y assess me nts; si n gle a n d re peat- d ose t o xic olo g y st u dies i n rats a n d d o gs; i n vitr o a n d i n 
vi v o ge n ot o xicit y st u dies t o deter mi ne m uta ge nic p ote ntial of pralatre xate; e m br y ofetal 
de vel o p me nt a n d mater nal t o xicit y st u dies i n rats; a n d l ocal t olera nce st u dies i n rats.  
Pralatre xate di d n ot s h o w e vi d e nce of car di o vasc ular or ne ur ol o gic t o xicit y.  T o xic ol o gical 
assess me nts i n rats a n d d o gs re veale d t he a ntici pate d d ose-li miti n g t o xicities ( D L Ts) of t he 
gastr oi ntesti nal a n d he mat ol o gical s yste ms.  Pralatre xate was f o u n d t o ha ve l o w m uta ge nic 
p ote ntial i n a pa nel of ge n ot o xi cit y assa ys.  Si milar t o ot he r a ntif olates, pralatre xate was 
f o u n d t o be t o xic t o de vel o pi n g e m br y os i n e mbr y ofetal de vel o p me nt st u dies i n rats a n d 
ra b bits.  Pralatre xate was n ot t o xic i n l ocal t olera nce st u dies i n rats.  Refer t o t he pralatre xate 
I B f or f urt her i nf or mati o n o n n o ncli nical t o xic ol o g y st u dies c o n d ucte d wit h pralatre xate. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 6 of 9 5 
4 
O N C O L O G Y S T U DI E S WI T H P R A L A T R E X A T E 
O ver 6 0 0 a d ult ca ncer patie nts ha ve recei ve d pralatre xate i n 1 5 o n g oi n g or c o m plete d 
P hase 1 or 2 cli nical o nc ol o g y st u dies.   
F or detaile d i nf or mati o n a b o ut t he o nc ol o g y st u d ies of pralatre xate, refer t o t he c urre nt 
pralatre xate I B. 
4. 1 
St u di e s i n P ati e nt s wit h L y m p h o pr olif er ati v e M ali g n a n ci e s  
4. 1. 1 
Si n gl e- A g e nt St u di e s 
St u d y P D X- 0 2- 0 7 8 is a P hase 1/ 2 st u d y i n patie nts wit h rela pse d or refract or y a g gressi ve 
N H L or H o d g ki n’s disease.  After i nitial assess me nt of a n e ver y ot her wee k sc he d ule, a 
wee kl y sc he d ule wit h vita mi n B 1 2 a n d f olic aci d s u p ple me ntati o n was i nitiate d.  I n t he i nitial 
versi o n of t he st u d y, t h e starti n g d ose of pral atre xate was 1 3 5 m g/ m 2 a d mi nistere d e ver y 
ot her wee k wit h i ntra patie nt d ose escalati o n.  W he n D L Ts occ urre d at t he d ose of 4 5 m g/ m2  
f or 6 wee ks of a 7- wee k c ycle, t he M T D was deter mi ne d t o be 3 0 m g/ m2/ wee k f or 6 wee ks 
o n a 7- wee k c ycle.   
Data fr o m P D X- 0 2- 0 7 8, were p u blis he d o n 4 8 pa tie nts e val ua ble f or res p o nse i n t he st u d y.2 6  
Res p o nses were o bser ve d i n 1 5 of 4 8 e val ua ble patie nts, f or a n o verall res p o nse rate ( O R R) 
of 3 1 %.  F o urtee n of 2 6 ( 5 4 %) e val ua ble patie nts wit h T-cell l y m p h o ma res p o n de d t o 
pralatre xate treat me nt ( 8 wit h C Rs a n d 6 wit h partial res p o nses [ P Rs]).  A m o n g t he 
2 0 e val ua ble patie nts wit h B-cell l y m p h o ma, 1 patie nt ac hie ve d a P R. 
D ue i n part t o t he res p o nses see n i n t he P D X 0 2- 0 7 8 st u d y, it was deci de d t o e x pl ore 
pralatre xate as a si n gle a ge n t i n rela pse d/refract or y P T C L i n st u d y P D X- 0 0 8.  P D X- 0 0 8 is a 
P hase 2, si n gle-ar m, n o n-ra n d o mize d, o pe n-la bel,  i nter nati o nal, m ulti-ce nter, re gistrati o n-
directe d st u d y desi g ne d t o e val uate t he safet y a n d efficac y of pralatre xate w he n a d mi nistere d 
c o nc urre ntl y wit h vita mi n B 1 2 a n d f olic aci d s u p ple me ntati o n t o patie nts wit h rela pse d or 
refract or y P T C L.  T he st u d y c o m plete d e nr oll ment of 1 1 5 patie nts i n A pr 2 0 0 8; 1 1 1 patie nts 
recei ve d at least 1 d ose of pralatre xate a n d were c o nsi d ere d e val ua ble f or safet y.  
T he o bjecti ves of t he st u d y were t o deter m i ne t he efficac y, safet y, a n d P K pr ofile of 
pralatre xate wit h c o nc urre nt vita mi n B 1 2 a n d f olic aci d s u p ple me ntati o n w he n a d mi nistere d 
t o patie nts wit h rela pse d or refract or y P T C L.  T he pri mar y efficac y e n d p oi nt of t he st u d y was 
res p o nse rate a n d sec o n dar y efficac y e n d p oi nts were d urati o n of res p o nse, P F S, a n d O S.  
Data fr o m P D X- 0 0 8 were prese nte d i n t he cli n ical st u d y re p ort, w hic h was s u b mitte d i n Ne w 
Dr u g A p plicati o n ( N D A) t o t he U S F D A.  I n Se p 2 0 0 9, t he F D A gra nte d accelerate d 
a p pr o val f or pralatre xate i n t he treat me nt of patie nts wit h rela pse d or refract or y P T C L.  
Pralatre xate is mar kete d  i n t he U S as F O L O T Y N®  ( Pralatre xate I njecti on) at a c o nce ntrati o n 
of 2 0 m g/ m L f or use i n t his patie nt p o p ulati o n. 
I n P D X- 0 0 8, pralatre xate was a d ministere d at a d ose of 3 0 m g/ m 2/ wee k f or 6 wee ks i n a 
7- wee k c ycle.  T he pr ot oc ol al l o we d f or d ose re d ucti o n t o 2 0 m g/ m2/ wee k if a patie nt 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 7 of 9 5 
e x perie nce d pr ot oc ol- defi ne d a d verse e ve nts ( A Es).  A patie nt was c o nsi dere d e val ua ble if 
he/s he recei ve d at least 1 d ose of pralatre xate a n d met t he maj or i ncl usi o n criteri o n 
# 1, ie, t he dia g n osis of eli gi ble P T C L hist o pat h ol o gical s u bt y pe c o nfir me d b y ce ntral 
pat h ol o g y re vie w.  I n t he P D X- 0 0 8 st u d y, 1 0 9 pa tie nts were c o nsi dere d e val ua ble f or 
efficac y.  T we nt y- ni ne perce nt ( n  = 3 2) of e val ua ble patie nts e x perie nce d eit her a C R, a n 
u nc o nfir me d C R ( C R u), or a P R, as assesse d b y ce ntral i n de pe n de nt o nc ol o g y re vie w.  
T hirt y- ni ne perce nt of patie nts ( n = 4 3) e x perie nce d eit her a C R/ C R u or P R, as assesse d b y 
t he st u d y i n vesti gat ors.2 7  T he res p o nses o bser ve d were d ura ble as assesse d b y i n de pe n de nt 
ce ntral re vie w, wit h a me dia n d urati o n of 1 0. 1 m o nt hs a n d a Ka pla n- Meier esti mate of 
6 0 % f or t he pr o ba bilit y of ac hie vi n g a d urati o n of res p o nse ≥ 6 m o nt hs.  T he me dia n P F S 
a n d O S f or t he 1 0 9 patie nts as esti mate d b y t he Ka pla n- Meier met h o d were 3. 5 m o nt hs 
(ra n ge 1 da y - 2 3. 9 m o nt hs) a n d 1 4. 5 m o nt hs (ra n ge 1. 0- 2 4. 1 m o nt hs), res pecti vel y. 
St u d y P D X- 0 1 0 is a P hase 1, o pe n-la bel, m ulti- ce nter st u d y desi g ne d t o deter mi ne a n 
effecti ve a n d well-t olerate d d ose a n d sc he d ule of pralatre xate as a si n gle a ge nt w he n 
a d mi nistere d c o nc urre ntl y wit h vita mi n B 1 2 a n d f olic aci d s u p ple me ntati o n t o patie nts wit h 
rela pse d or refract or y c uta ne o us T-cell l y m p h oma ( C T C L).  F oll o wi n g preli mi nar y re vie w of 
safet y a n d res p o nse data fr o m t he d osin g re gi me ns e x pl ore d t h us far, 1 5 m g/ m 2 f or 3/ 4 wee ks 
was deter mi ne d t o be t he d ose utilize d i n t he d ose e x pa nsi o n p hase of  t he st u d y, i n w hic h a n 
a d diti o nal 2 0 patie nts will be e val uate d.    
I nteri m efficac y data were prese nte d at t he 1 5t h C o n gress of t he E ur o pea n He mat ol o g y 
Ass ociati o n o n t he P D X- 0 1 0 st u d y i n patie nts wit h C T C L. 2 8  I n vesti gat or-assesse d res p o nses 
were o bser ve d i n 1 9 of 4 7 e val ua ble patie nts ( 4 0 %), i ncl u di n g 2 C Rs a n d 1 7 P Rs.  Fi nal 
efficac y data will be a nal yze d at t he c o m pleti o n of t he st u d y. 
St u d y P D X- 0 1 5 is a P hase 2, si n gle-ar m, n o n -ra n d o mize d, o pe n-la bel, m ulti-ce nter st u d y 
desi g ne d t o e val uate t he efficac y a n d safet y/t ole ra bilit y of pralatre xate w he n a d mi nistere d 
c o nc urre ntl y wit h vita mi n B 1 2 a n d f olic aci d s u p ple me ntati o n t o patie nts wit h rela pse d or 
refract or y B-cell N H L. T his st u d y is o n g oi n g a n d n o data are c urre ntl y a vaila ble. 
4. 1. 2 
C o m bi n ati o n St u di e s 
Pralatre xate is bei n g st u die d as c o m b i nati o n treat me nt wit h ge mcita bi ne i n 
rela pse d/refract or y l y m p h o pr oliferati ve mali g na ncies ( P D X- 0 0 9).  St u d y P D X- 0 0 9 is a 
P hase 1/ 2a, o pe n-la bel, m ulti-ce nter st u d y of pr alatre xate a n d ge mcita bi ne a d mi nistere d o n 
se q ue ntial da ys, or t he sa me da y de pe n di n g o n c o h ort, wit h vita mi n B 1 2 a n d f olic aci d 
s u p ple me ntati o n t o patie nts wit h rela pse d or refract or y l y m p h o pr oliferati ve mali g na ncies.  
T he P hase 1 p orti o n of t he st u d y was n o nra n d o mize d, w hile t he P hase 2 p orti o n is 
ra n d o mize d bet wee n sa me da y d osi n g or se q ue ntial da y d osi n g.  T he o bjecti ves of t he st u d y 
are: 1) t o deter mi ne t he M T D a n d rec o m me n de d P hase 2 d ose of t he c o m bi nati o n of 
pralatre xate a n d ge mcita bi ne ( P hase  1); 2) t o e val uate t he safet y a n d t olera bilit y of escalati n g 
d oses of pralatre xate a n d ge mcita bi ne ( P hase 1); 3) t o deter mi ne t h e P K pr ofile of t he 
c o m bi nati o n of pralatre xate a n d ge mcita bi ne ( P ha se 1 a n d 2a); a n d 4) t o c o nfir m t olera bilit y 
a n d assess preli mi nar y efficac y i n patie nts wit h  rela pse d or refract or y H o d g ki n’s l y m p h o ma, 
P T C L, a n d B-cell l y m p h o ma ( P hase 2a). 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 8 of 9 5 
I nteri m efficac y data were prese nte d i n a p oster prese ntati o n at t he 5 1st A n n ual A merica n 
S ociet y of He mat ol o g y Meeti n g o n t he 3 3 patie nts  e nr olle d i n t his st u d y w h o were e val ua ble 
f or res p o nse.2 9  F o ur of 7 patie nts wit h H o d g ki n’s l y m p h o ma, 2 of 1 1 patie nts wit h P T C L, 
a n d 2 of 1 5 patie nts wit h diff use lar ge B-cel l l y m p h o ma ( 1 of w h o m als o ha d P T C L) 
ac hie ve d a P R.  Fi nal efficac y data will be a nal yze d at t he c o m pleti o n of t he st u d y. 
4. 2 
St u di e s i n P ati e nt s wit h S oli d T u m or s  
4. 2. 1 
All o s Si n gl e- a g e nt St u di e s 
I n t he P hase 1 st u d y, P D X- 0 0 7, i n vesti gati n g pralatre xate as a si n gle a ge nt wit h vita mi n 
s u p ple me ntati o n i n patie nts wit h relapse d N S C L C, d osi n g starte d at 1 5 0 m g/ m 2 e ver y 
2 wee ks a n d i nitiall y escalate d i n 4 0 m g/ m 2 i ncre me nts t o 2 7 0 m g/ m2 e ver y ( q) 2 wee ks.  
Base d o n t he D L Ts e x perie nce d i n t he 3 2 5 m g/ m 2 c o h ort of Treat me nt Gr o u p A, t he M T D 
f or Treat me nt Gr o u p A was deter mi ne d t o be 2 7 0 m g/ m2.  C o h orts i n Treat me nt Gr o u p B 
were i nitiate d at d ose le vels  bel o w t he M T D deter mi ne d f or Treat me nt Gr o u p A t o f urt her 
assess t he safet y a n d t olera bi lit y of pralatre xate.  T he starti n g d ose f or Treat me nt Gr o u p B 
was 2 3 0 m g/ m 2.  Alt h o u g h D L Ts were o bser ve d at t he 1 9 0 m g/ m2 d ose gi ve n e ver y 2 of 
4 wee ks, t hese D L Ts were of l o wer gra de ( 2  patie nts b ot h wit h Gra de 2 m uc ositis) t ha n 
D L Ts o bser ve d i n a n y ot her c o h ort, a n d t h eref ore, t his d ose is t he rec o m me n de d 
P hase 2 d ose.  
St u d y P D X- 0 1 1 is a P hase 2, o pe n-la bel, m u lti-ce nter st u d y of pralatre xate w he n 
a d mi nistere d c o nc urre ntl y wit h vita mi n B 1 2 a n d f olic aci d s u p ple me ntati o n i n patie nts wit h 
a d va nce d or metastatic rela pse d tra nsiti o nal cell carci n o ma ( T C C) of t he uri nar y bla d der.  
T he o bjecti ves of t his st u d y ar e: 1) t o deter mi ne t he o bjec ti ve res p o nse rate ( C R + P R); 
2) t o deter mi ne t he d urati o n of res p o nse, cl i nical be nefit rate, P F S, a n d O S; a n d 3) t o 
e val uate t he safet y a n d t olera bilit y of pralatre xate wit h c o nc urre nt vita mi n B 1 2 a n d f olic aci d 
s u p ple me ntati o n i n patie nts wit h a d va nce d or metastatic rela pse d T C C of t he uri nar y bla d der.   
St u d y P D X- 0 1 2 is a ra n d o mize d, o pe n-la bel,  m ulti-ce nter P hase 2 b st u d y c o m pari n g 
pralatre xate a n d erl oti ni b i n patie nts wit h  Sta ge III B/I V N S C L C w h o are or ha ve bee n 
ci garette s m o kers.  T he o bjecti ves of t he st u d y are: 1) t o esti mate t he efficac y of pralatre xate 
as assesse d b y o verall s ur vi val c o m pare d t o t hat  of erl oti ni b; 2) t o esti mate t he efficac y of 
pralatre xate as assesse d b y res p o nse rate c o m pare d t o t hat of erl oti ni b; 3) t o esti mate t he 
efficac y of pralatre xate as asse sse d b y P F S c o m pare d t o t hat of erl oti ni b; a n d 4) t o e val uate 
t he safet y a n d t olera bilit y of q 2 wee ks a d mi nistrati o n of pralatre xate i n patie nts wit h Sta ge 
III B/I V N S C L C.   
St u d y P D X- 0 1 4 is a n o pe n la bel, m ulti-ce nter, P hase 2 st u d y of pralatre xate i n fe male 
patie nts wit h Pre vi o usl y-treate d a d va nce d or metastatic breast ca ncer w h o ha ve faile d pri or 
treat me nt(s).   
St u d y P D X- 0 1 6 is a P hase 1, n o nra n d o mize d, o pe n- la bel, si n gle-ar m, c o m bi ne d cli nical 
p har mac ol o g y a n d cli nical st u d y t o e val uate t he e xcreti o n a n d meta b olic pr ofile of 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 3 9 of 9 5 
pralatre xate a n d t o relate t hese fi n di n gs t o c o nc urre nt P K assess me nts i n patie nts wit h 
a d va nce d ca ncer.   
4. 2. 2 
M S K C C St u di e s i n P ati e nt s wit h S oli d T u m or s 
St u d y P D X- 9 7- 0 0 6 was a P hase 1, si n gle-ce nter , d ose-escalati o n st u d y t o deter mi ne t he 
M T D a n d sc he d ule ( wee kl y or bi wee kl y) of si n gle-a ge nt pralatre xate.  T he st u d y was 
c o n d ucte d e xcl usi vel y i n patie nts wit h N S C L C,  w h o ha d bee n pre vio usl y treate d wit h a 
me dia n of 2 pri or c he m ot hera p y re gi me ns. 3 0  T hirt y-fi ve patie nts were e nr olle d a n d 3 3 were 
treate d.  I nitiall y, pralatre xate was a d mi nistere d at a d ose of 3 0 m g/ m 2 wee kl y f or 3 of 4 
wee ks.  T he pr ot oc ol was a me n de d t o a q 2 wee ks treat me nt o n a 4- w ee k c ycle, wit h d ose 
escalati o n fr o m 1 5 - 1 7 0 m g/ m 2.  T he wee kl y treat me nt wit h pralatre xate f or 3 wee ks i n a 
4- wee k c ycle was d ose li miti n g at 3 0 m g/ m 2.  Alteri n g t he treat me nt sc he d ule, h o we ver, t o q 
2 wee ks (i n a 4- wee k c ycle) all o we d m uc h hi g her d oses t o be a d mi nistere d.  T he M T D a n d 
rec o m me n de d P hase 2 d ose was 1 5 0 m g/ m2.  O ne patie nt i n St u d y P D X- 9 7- 0 0 6, w h o 
recei ve d t he M T D of 1 5 0 m g/ m2, ac hie ve d a P R, a n d 6 patie nts ac hie ve d sta ble disease ( S D). 
St u d y P D X- 9 9- 0 5 3 was a P hase 2, o pe n-la bel, si n gl e-ce nter st u d y e val ua ti n g t he efficac y of 
si n gle-a ge nt pralatre xate i n patie nts wit h Sta ge III B or Sta ge I V N S C L C. 3 1  T hirt y- ni ne 
patie nts were e nr olle d a n d treate d.  Patie nts recei ve d pralatre xate q 2 wee ks o n a 4- wee k 
c ycle.  T we nt y- ni ne patie nts were treate d i n t he 1 5 0 m g/ m 2 d ose gr o u p.  T o decrease t he 
i nci de nce of st o matitis, t he last 1 0 patie nts e nr olle d were treate d wit h 1 3 5 m g/ m2 of 
pralatre xate.  I n st u d y P D X- 9 9- 0 5 3, t he me dia n d urati o n of s ur vi val f or all patie nts was 
1 3 m o nt hs ( mea n = 1 6 m o nt hs), wit h me dia n  d urati o ns of 1 6 m o nt hs f or t he 1 5 0 m g/ m2 
gr o u p a n d 7. 5 m o nt hs f or t he 1 3 5 m g/ m 2 gr o u p. 
St u d y P D X 9 9- 0 8 3 was a P hase 1, o pe n-la bel, si n gle-ce nter, d ose-esca lati o n st u d y e val uati n g 
t he c o m bi nati o n of pralatre xate wit h a ta xa ne ( paclita xel or d oceta xel) i n a d ult patie nts wit h 
a d va nce d s oli d t u m ors. 3 2  F ort y-ei g ht patie nts were e nr olle d a n d treate d.  F ort y-si x of t h ose 
patie nts ha d N S C L C.  T he i nitial star ti n g d ose of pralatre xate was 1 1 0 m g/ m2 c o m bi ne d wit h 
1 7 5 m g/ m 2 of paclita xel a d mi nistere d o n t he sa me da y q 2 wee ks i n a 4- wee k c ycle, h o we ver, 
D L Ts pre ve nte d deter mi nati o n of a t olera bl e d ose wit h t his c o m bi nati o n.  T he M T D a n d 
rec o m me n de d P hase 2 d ose of t he pralatre xate- d oceta xel c o m bi nati o n wit h vita mi ns was 
1 2 0 m g/ m 2 of pralatre xate wit h 3 5 m g/ m2 d oceta xel a d mi nistere d o n t he sa me da y o nce 
q 2 wee ks.  O ne patie nt i n P D X- 9 9- 0 8 3 treate d bel o w t he M T D (treate d wit h pralatre xate 
9 0 m g/ m 2 + paclita xel 1 7 5 m g/ m2, wit h o ut vita mi n s u p ple me ntati o n) ac hie ve d a P R a n d 
3 2 patie nts ha d S D, 1 0 of w h o m were treate d wit h o ut vita mi ns a n d 2 2 of w h o m recei ve d 
vita mi ns. 
St u d y P D X 0 1- 0 1 4 was a P hase 1, o pe n-la bel, si n gle-ce nter, d ose-escalati o n st u d y t o 
deter mi ne t he M T D f or pralatre xate a n d pr o be neci d gi ve n i n c o m bi nati o n q 2 wee ks i n 
patie nts wit h s oli d t u m ors. 1 3  Se ve ntee n patie nts were e nr olle d.  T he pralatre xate d ose was 
ke pt at 4 0 m g/ m 2; t he d ose escalati o n of pr o be neci d pr ocee de d fr o m 7 0 t o 2 3 3 m g/ m 2.  
Treat me nt wit h pralatre xate i n c o m bi nati o n wit h pr o be neci d q 2 wee ks o n a 4- wee k c ycle 
e xcee de d t he M T D at 4 0 m g/ m 2 pralatre xate a n d 2 3 3 m g/ m2 pr o be neci d d ue t o st o matitis.  
T he M T D a n d rec o m me n de d P hase 2 d ose of t h e pralatre xate a n d pr o be neci d c o m bi nati o n 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 0 of 9 5 
was 4 0 m g/ m 2 of pralatre xate a d mi nistere d wit h 1 4 0 m g/ m2 pr o be neci d q 2 wee ks.  N o 
patie nt ac hie ve d a C R or P R, b ut 5 patie nts e x peri e nce d S D.  T he c o m bi nati o n of pralatre xate 
wit h pr o be neci d di d n ot de m o nstrate e n ha nce d t h era pe utic acti vit y a n d t he d ose le vels t hat 
were t olerate d were li mite d.   
St u d y P D X 0 1- 0 7 6 was a P hase 2, o pe n-la bel, si n gle-ce nter st u d y i n patie nts wit h 
u nresecta ble mali g na nt ple ural mes ot heli o ma. 3 3  Se ve ntee n patie nts were e nr olle d a n d 
1 6 patie nts were treate d.  T he d os e of pralatre xate was 1 3 5 m g/ m 2 i ntra ve n o us (I V) 
q 2 wee ks o n a 4- wee k c ycle.  N o patie nt i n t he st u d y ac hie ve d a C R or a P R; h o we ver, 
1 0 patie nts ha d S D ( d urati o n ra n ge: 2 + t o 4 7 m o nt hs).  T he me dia n ti me t o pr o gressi ve 
disease ( P D) f or all 1 6 patie nts treate d i n t he st u d y was 3 m o nt hs.  T he me dia n d urati o n of 
s ur vi val f or all 1 6 patie nts was 5. 5 m o nt hs. 
4. 3 
S af et y O v er vi e w of O n c ol o g y P a ti e nt s R e c ei vi n g Pr al atr e x at e 
4. 3. 1  
Pr e c a uti o n s 
B o ne m arr o w s u p pressi o n : Pralatre xate ma y s u p press b o ne marr o w f u ncti o n, ma nifeste d b y 
ne utr o pe nia, t hr o m b oc yt o pe nia, a n d a ne mia .  D ose m o dificati o ns are descri be d i n 
Secti o n 7. 4 ( Ta ble 7. 1 ) base d o n a bs ol ute ne utr o p hil co u nt ( A N C) a n d platelet c o u nts pri or t o 
eac h d ose. 
M uc ositis : Treat me nt wit h pralatre xate ma y ca use m uc ositis.  If ≥ Gra de 2 m uc ositis is 
o bser ve d, t he d ose s h o ul d be m o difie d acc or di n g t o Secti o n 7. 4, Ta ble 7. 2 . 
Der m at ol o gic re acti o ns : Pralatre xate has bee n ass ociate d wit h se vere der mat ol o gic reacti o ns, 
w hic h ma y res ult i n deat h.  T hese der mat ol o gic reacti o ns ha ve bee n re p orte d i n cli nical 
st u dies ( 1 4/ 6 6 3 patie nts [ 2. 1 %]) a n d p ost mar keti n g e x perie nce, a n d ha ve i ncl u de d s ki n 
e xf oliati o n, ulcerati o n, a n d t o xic e pi der mal necr ol ysis ( T E N).  T hese reacti o ns ma y be 
pr o gressi ve a n d i ncrease i n se verit y wit h f urt her treat me n t, a n d ma y i n v ol ve s ki n a n d 
s u bc uta ne o us sites of k n o w n l y m p h o ma.  Patie nts wit h s ki n reacti o ns m ust  be m o nit ore d 
cl osel y, a n d if s ki n reacti o ns are se vere, st u d y treat me nt ma y be m o difie d or disc o nti n ue d 
(see Secti o n 7. 4, Ta ble 7. 3 ). 
T u m or lysis sy n dr o me :  T u m or l ysis s y n dr o me has bee n re p orte d i n patie nts wit h l y m p h o ma 
recei vi n g pralatre xate.  Patie nts recei vi n g pralatre xate s h o ul d be m o nit ore d cl osel y a n d 
treate d f or c o m plicati o ns. 
F olic aci d a n d vit a mi n B 1 2 s u p ple me nt ati o n:  Patie nts m ust be i nstr ucte d t o ta ke f olic aci d 
a n d vita mi n B 1 2 t o p ote ntiall y re d uce treat me nt-relate d he mat ol o gical t o xicit y a n d m uc ositis 
(see Secti o n 7. 1 ). 
Pre g n a ncy a n d bre astfee di n g :  Pralatre xate ma y ca use fetal har m w he n a d mi nistere d t o a 
pre g na nt w o ma n.  Pralatre xate was e m br y ot o xic a n d fet ot o xic i n rats a n d ra b bits.  It is n ot 
k n o w n w het her pralatre xate is e xcrete d i n h u ma n  mil k.  Ma n y dr u gs are e xcrete d i n h u ma n 
m il k a n d t here is t he p ote ntial f or seri o us a d verse reacti o ns i n n ursi n g i n fa nts fr o m t his dr u g.  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 1 of 9 5 
St u d y treat me nt m ust n ot be a d mi nistere d d uri n g pre g na nc y or w he n  breastfee di n g (see 
Secti o n 1 4. 7 ). 
Re n al i m p air me nt :  Pralatre xate has n ot bee n f or mall y teste d i n patie nts wit h m o derate a n d 
se vere re nal i m pair me nt.  Patie nts m ust ha ve a de q uate re nal f u ncti o n t o be eli gi ble f or 
i ncl usi o n i n t his st u d y, as defi ne d i n Secti o n 8. 3 . 
He p atic i m p air me nt :  Pralatre xate has n ot bee n f or mall y teste d i n patie nts wit h he patic 
i m pair me nt.  Patie nts m ust ha ve a de q uate he patic f u ncti o n t o be eli gi ble for i ncl usi o n i n t his 
st u d y, as defi ne d i n Secti o n 8. 3.  Li ver f u ncti o n test a b n or malities ha ve bee n o bser ve d after 
pralatre xate a d mi nistrati o n, b ut  are us uall y n ot ca use f or m o dificati o n of pralatre xate 
treat me nt.  H o we ver, persistent li ver f u ncti o n test a b n or malit ies ma y be i n dicat ors of li ver 
t o xicit y a n d ma y re q uire d ose m o difi cati o n (see Ta ble 7. 3 ). 
Patie nts recei vi n g pralatre xate s h o ul d be m o nit ore d cl osel y beca use A Es ma y occ ur at a n y 
ti me d uri n g t hera p y.  F or detaile d i nf or mati o n a b o ut t he safet y pr ofile of pralatre xate, refer t o 
t he c urre nt pralatre xate I B. 
4. 4 
Cli ni c al P h ar m a c ol o g y 
4. 4. 1 
P h ar m a c o ki n eti c s 
Pralatre xate R a n d S diastere o mers f oll o w a p pare nt firs t- or der P K wit h t he area u n der t he 
c ur ve t o i nfi nit y ( A U C ∞) i ncreasi n g i n a near li near ma n ner wit h d ose.  T otal, re nal, a n d n o n-
re nal cleara nces as well as v ol u me of distrib uti o n were c o nsta nt w it hi n ( n o mi nal) d oses 
ra n gi n g fr o m 3 0 m g/ m2 t o 3 2 5 m g/ m2.  C o m pari n g t he 2 diastere o mers, plas ma e x p os ures of 
t he R diastere o mer e xcee d t h ose of t he S diastere o mer b y a p pr o xi matel y 2-f ol d; t he reas o n 
f or t his is u nclear at t his p oi nt.  F or a m ore detaile d descri pti o n of pralatre xate P K a n d 
p o p ulati o n P K ( P O P P K), see t he pralatre xate I B. 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 2 of 9 5 
5 
R A TI O N A L E F O R T H E C U R R E N T S T U D Y 
Patie nts wit h P T C L are i n nee d of a d diti o nal treat me nt o pti o ns.  Pralatre xate e x hi bite d 
e nc o ura gi n g acti vit y i n n o ncli nical i n vitr o a n d i n vi v o m o dels of l y m p h o ma.  T his acti vit y 
was e val uate d cli nicall y i n a P hase 1/ 2 st u d y ( P D X- 0 2- 0 7 8) i n patie nts wit h l y m p h o ma i n 
w hic h a res p o nse rate of 5 4 % was o bser ve d i n patie nts wit h T-cell l y m p h o ma. 2 6  Efficac y 
a nal yses fr o m t he P hase 2 st u d y P D X- 0 0 8, w hic h wa s c o n d ucte d i n patie nts wit h rela pse d or 
refract or y P T C L, i n dicates t hat pralatre xate ex hi bite d cli nicall y si g nifica nt acti vit y i n t he 
patie nts u n der st u d y, de m o nstrati n g a n o verall res p o nse rate of 2 9 % a n d me dia n d urati o n of 
res p o nse of 1 0. 1 m o nt hs. 
C H O P a n d C H O P- base d treat me nts are t he m o st c o m m o nl y use d t hera pe utic re gi me ns f or 
patie nts wit h ne wl y dia g n ose d P T C L.  H o we ver, as a maj orit y of t hese patie nts pr o gress or 
rela pse f oll o wi n g C H O P, t he P F S o utc o me f or patients res p o n di n g t o C H O P re mai ns dis mal.  
I n t he P D X- 0 0 8 st u d y, 1 5 e val ua ble patie nts recei ve d pralatre xate as t heir sec o n d-li ne 
treat me nt after C H O P, 7 of w h o m ( 4 7 %) res p o n de d t o pralat re xate b y ce ntral re vie w.  Base d 
o n t he res p o nses o bser ve d i n t he P D X- 0 0 8 st u d y, t he c urre nt pr ot oc ol will deter mi ne f or 
t h ose patie nts w h o res p o n d t o CH O P t hera p y w het her pralatre xate  a d mi nistere d directl y after 
c o m pleti o n of a C H O P re gi me n ca n i m pr o ve P F S  a n d O S relati ve t o o bser vati o n directl y 
after c o m pleti o n of a C H O P re gi me n.   
As descri be d i n Secti o n 4. 1. 1 , pralatre xate a d mi nistere d at 3 0 m g/ m2 has bee n t olerate d a n d 
de m o nstrate d t o ha ve a t hera pe utic effect  i n patie nts wit h l y m p h o ma i n st u dies 
P D X- 0 2- 0 7 8 a n d P D X- 0 0 8.  T he pr o p ose d d osi n g re gi me n f or t his st u d y i ncl u des wee kl y 
d osi n g f or 3 wee ks f oll o we d b y 1 wee k of rest.  T his differs sli g htl y fr o m P D X- 0 0 8, w hic h 
utilize d a d osi n g re gi me n of wee kl y a d mi nistra ti o n f or 6 wee ks f oll o we d b y 1 wee k of rest.  
A n a nal ysis of t he P D X- 0 0 8 res ults re veale d t h at of t he 5 7 treate d patie nts w h o recei ve d t he 
first 3 d oses wit h o ut a d ose m o dificati o n, 2 4 patie nts ( 4 2 %) re q uire d a d ose m o dificati o n, 
i ncl u di n g p ossi bl y treat me nt disc o nti n uati o n, pri or t o t he rest week, ie, at eit her d oses 4, 5, or 
6.  T h us, all o wi n g a brea k after 3 d oses ma y i ncr ease t he l o n g-ter m t olera bilit y t o f ull- d ose 
pralatre xate.  T heref ore, t he i nitial d ose a n d fre q ue nc y of pralatre xate i n P D X- 0 1 7 will be 
3 0 m g/ m 2 a d mi nistere d I V wee kl y f or 3 wee ks, wit h 1 wee k rest ( 4- wee k c ycle), wit h 
s u bse q ue nt d ose re d ucti o n(s) base d o n t o xicit y.  All patie nts will recei ve vita mi n 
s u p ple me ntati o n c o nsisti n g of vita mi n B 1 2 a n d f olic aci d. 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 3 of 9 5 
6 
S T U D Y O B J E C TI V E S 
T he pri mar y o bjecti ve of t his st u d y is: 
• 
Deter mi ne t he efficac y of pralatre xate c o m p are d t o o bser vati o n w he n a d mi nistere d t o 
patie nts wit h pre vi o usl y u n dia g n ose d P T C L  w h o ha ve ac hie ve d a n o bjecti ve res p o nse 
after c o m pleti n g at least 6 c ycl es of C H O P- base d treat me nt. 
T he sec o n dar y o bjecti ve of t his st u d y is: 
• 
Deter mi ne t he safet y of pralatre xate w h e n a d mi nistere d f oll o wi n g a c o urse of 
C H O P- base d treat me nt t o patie nts wit h pre vi o usl y u n dia g n ose d P T C L. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 4 of 9 5 
7 
I N V E S TI G A TI O N A L P L A N 
T his is a n i nter nati o nal, m ulti-ce nter, ra n d o mize d, P hase 3, o pe n-la bel st u d y of se q ue ntial 
pralatre xate vers us o bser va ti o n i n patie nts w h o ha ve ac hie ve d a n o bjecti ve res p o nse 
f oll o wi n g i nitial treat me nt wit h C H O P- base d c he m ot hera p y i n patie nts wit h pre vi o usl y 
u n dia g n ose d P T C L.  Patie nts will be ra n d o mize d 2: 1 t o eit her pralatre xate or o bser vati o n.  
Patie nts will be stratifie d b y: 
• 
Res p o nse per i n vesti gat or at c o m pleti o n of C H O P- base d t hera p y ( C R vs P R) 
7. 1 
Vit a mi n A d mi ni str ati o n  
Vita mi n s u p ple me ntati o n f or patie nts i n b ot h ar ms of t he st u d y will c o nsist of vita mi n B 1 2 
1 m g i ntra m usc ular (I M) e ver y 8- 1 0 wee ks a n d f olic aci d 1- 1 . 2 5 m g orall y ( p o) o nce a da y 
( q d).  Vita mi n s u p ple me ntati o n will be gi n at least 7 da ys pri or t o t he pr ojecte d i nitiati o n of 
pralatre xate/ o bser vati o n a n d c o nti n ue t hr o u g h o u t t he st u d y u ntil t he I nitial F oll o w- u p Visit 
(Secti o n 1 0. 7 ). 
7. 2 
Pr al atr e x at e A d mi ni str ati o n 
O ne c ycle of pralatre xate t hera p y is 4 wee ks i n  d urati o n a n d c o nsists of 3 wee kl y d oses of 
pralatre xate I V p us h o ver 3 0 sec o n ds a n d u p t o 5 mi n utes, wit h 1 wee k of rest .  T he i nitial 
d ose of pralatre xate will be 3 0 m g/ m 2/ wee k.  F or patie nts wit h a b o d y s urface area ( B S A) 
> 2 m 2, t he a d mi nistere d d ose will be calc ulate d usi n g a ca p pe d B S A val ue of 2 m2.  
Pralatre xate d ose re d ucti o n t o 2 0 m g/ m 2 wit h f urt her re d ucti o n t o 1 5 a n d 1 0 m g/ m2 will be 
all o we d f or defi ne d t o xicities (see Secti o n 7. 4 ).  Pralatre xate will c o nti n ue t o be a d mi nistere d 
u ntil a criteri o n f or st u d y treat me nt disc o nti n uati o n is met ( Secti o n 7. 3 ) or u p t o a ma xi m u m 
of 2 years. 
7. 3 
St u d y D ur ati o n  
Patie nts will recei ve st u d y treat me nt ( pralatre xat e or o bser vati o n) u ntil o ne of t he criteria 
liste d bel o w f or st u d y treat me nt disc o nti n uati o n a p plies: 
• 
De vel o p me nt of P D 
• 
I nitiati o n of ra diati o n t hera p y ( R T) or s yste mic c he m o/ bi ol o gical t hera p y f or treat me nt of 
P T C L 
• 
Recei pt of s yste mic ster oi ds f or > 1 0 da ys , wit h t he e xce pti o n of t h ose as state d i n 
e xcl usi o n criteri o n # 5 (see Secti o n 8. 4 ) 
• 
De vel o p me nt of a n A E t hat i nterferes wit h t he patie nt’s partici pati o n 
• 
L ost t o f oll o w- u p 
• 
Patie nt decisi o n 
• 
I n vesti gat or decisi o n 
• 
S p o ns or decisi o n 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 5 of 9 5 
I n a d diti o n, f or t h ose patie nts ra n d o mize d t o t he Pralatre xate Ar m, a d diti o nal pralatre xate 
treat me nt disc o nti n uati o n criteria are: 
• 
3 or m ore c o nsec uti ve d oses of pralatre xate o mitte d or m ore t ha n 2 8 da ys bet wee n d oses 
of pralatre xate  
• 
Treat me nt wit h pralatre xate f or 2 years 
All patie nts w h o recei ve at le ast 1 d ose of pralatre xate will be f oll o we d f or safet y t hr o u g h 
3 5 ( ± 5) da ys after t heir last d ose of pralatre xate or u ntil all treat me nt-relate d A Es ha ve 
res ol ve d or ret ur ne d t o baseli ne/ Gra de 1, w hic hever is l o n ger, or u ntil it is deter mi ne d t hat 
t he o utc o me will n ot c ha n ge wit h f urt her f oll o w- u p. 
Patie nts w h o are ra n d o mize d t o t he O bser v ati o n Ar m w h o d o n ot disc o nti n ue t he st u d y 
wit hi n 3 da ys of ra n d o mi zati o n will be f oll o we d f or safet y u ntil 3 5 ( ± 5) da ys after st u d y 
treat me nt disc o nti n uati o n criteria are met. 
All patie nts w h o are ra n d o mize d will be f o ll o we d u ntil o bjecti vel y d oc u me nte d P D f or u p t o 
7 years fr o m ra n d o mizati o n.  T he details of re s p o nse f oll o w- u p are pr o vi de d i n Secti o n 1 0. 8 .  
P D will be c o nfir me d b y ce ntral re vie w  u ntil t he first P F S a nal ysis, see Secti o n 1 5. 6. 1 , a n d 
per i n vesti gat or assess me nt t hereafter.  S u bse q ue nt t hera pies f or P T C L will be c ollecte d f or 
u p t o 7 years fr o m ra n d o mizati o n; t he best res p o n se t o t he first s u bse q ue nt t hera p y will be 
c ollecte d.  S ur vi val f oll o w- u p will c o nti n ue f or u p t o 7 years fr o m ra n d o mizati o n. 
As disc usse d i n Secti o n 1 5. 6. 1, a n a nal ysis will be perf or me d w he n b ot h 2 8 0 P F S e ve nts a n d 
1 2 8 O S e ve nts ha ve occ urre d.  If t he P F S a nal ys is is n ot si g nifica nt at t he 0. 0 5 le vel, t he 
st u d y will be st o p pe d. 
7. 4 
Tr e at m e nt M o difi c ati o n s of Pr al atr e x at e 
Pralatre xate d ose m o difi cati o ns will be all o we d acc or di n g t o t he criteria o utli ne d bel o w i n 
Ta ble 7. 1 , Ta ble 7. 2 , a n d Ta ble 7. 3 .  D ose re d ucti o n t o 2 0 m g/ m2 wit h f urt her re d ucti o ns t o 
1 5 m g/ m 2 a n d 1 0 m g/ m2 will be all o we d f or t he t o xicities defi ne d i n t he ta bles bel o w.  If a n 
A E occ urs t hat pre ve nts t he a d mi nistrati o n of pralatre xate o n t he sc he d ule d d osi n g da y 
(±  1 da y), t he d ose will be o mitte d t hat wee k an d t he patie nt will be reassesse d t he f oll o wi n g 
wee k t o pr ocee d t o t he ne xt d ose of t he c ycle.   

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 6 of 9 5 
7. 4. 1 
H e m at ol o gi c al A d v er s e E v e nt s 
Treat me nt m o dificati o n f or he m at ol o gic al  A Es occ urri n g o n t he pla n ne d d osi n g da y will be 
ma de as o utli ne d i n Ta ble 7. 1. 
T a bl e 7. 1.  
Pr al atr e x at e Tr e at m e nt M o difi c ati o n s f or H e m at ol o gi c al A E s 
He m at ol o gic al P ar a meter o n Pl a n ne d 
D osi n g D a y 
Acti o n 
A N C ≥ 1 0 0 0/μ L ( ≤ Gra de 2)  
or  
platelets ≥ 5 0, 0 0 0/μ L ( ≤ Gra de 2)  
•  
N o c ha n ge i n pralatre xate d ose. 
A N C ≥ 5 0 0/μ L a n d < 1, 0 0 0/ μ L ( Gra de 3) 
wit h o ut fe ver 
•  
A d mi nister c yt o ki ne pr o p h yla xis a n d/ or treat me nt per 
A S C O g ui deli nes. 3 4 . 
•  
D o n ot a d mi nister pralatre xate u ntil rec o ver y t o 
≤ Gra de 2 (≥ 1 0 0 0/μ L).  U p o n rec o ver y t o ≤ Gra de 2, 
a d mi nister pralatre xate wit h o ut a c ha n ge i n d ose. 
A N C ≥ 5 0 0/μ L a n d < 1, 0 0 0/ μ L ( Gra de 3) 
ass ociate d wit h si n g le oral te m perat ure 
≥ 3 8. 1°C re q uiri n g pare nteral a nti bi otics  
or  
A N C < 5 0 0/ μ L ( Gra de 4)  
•  
A d mi nister c yt o ki ne pr o p h yla xis a n d/ or treat me nt per 
A S C O g ui deli nes. 3 4  
•  
D o n ot a d mi nister pralatre xate u ntil rec o ver y t o 
≤ Gra de 2 (≥ 1 0 0 0/μ L).  U p o n rec o ver y t o ≤ Gra de 2, 
a d mi nister pralatre xate wit h o ut a c ha n ge i n d ose.   
•  
If re occ urre nce wit hi n 2 8 da ys, re d uce t he pralatre xate 
d ose t o t he ne xt l o wer d ose le vel.   
•  
Disc o nti n ue pralatre xate if e ve nt re occ urs at 1 0 m g/ m 2 
des pite c yt o ki ne s u p p ort. 
Platelets < 5 0, 0 0 0/ μ L ( ≥ Gra de 3)  
•  
D o n ot a d mi nister pralatre xate u ntil rec o ver y t o 
≤ Gra de 2 (≥ 5 0, 0 0 0/μ L).  U p o n rec o ver y t o ≤ Gra de 2, 
a d mi nister pralatre xate wit h o ut a c ha n ge i n d ose.  
•  
If a platelet c o u nt of Gra de 4 ( < 2 5, 0 0 0/μ L) re occ urs 
wit hi n 2 8 da ys, re d uce t he pralatre xate d ose t o t he ne xt 
l o wer d ose le vel. 
•  
Disc o nti n ue pralatre xate if a platelet c o u nt of Gra de 4 
( < 2 5, 0 0 0/μ L) occ urs t wice wit hi n 2 8 da ys at 
1 0 m g/ m 2. 
A N C – a bs ol ute ne utr o p hil c o u nt 
°C – de grees Celsi us 
7. 4. 2 
N o n- h e m at ol o gi c al A d v er s e E v e nt s 
F or all i nsta nces of m uc ositis occ urri n g o n t he pla n ne d d osi n g da y, treat me nt m o dificati o ns 
will be ma de as o utli ne d i n Ta ble 7. 2 .  F or tre at me nt-rel ate d c ar di o v asc ul ar, 
der m at ol o gic al, he p atic, ne ur ol o gic,  re n al, or res pir at or y A Es, treat m e nt m o dificati o ns 
will be ma de as o utli ne d i n Ta ble 7. 3 .  F or all ot her n o n- hemat ol o gical treat me nt-relate d 
A Es, treat me nt m o dificati o ns s h o ul d be ma de at t he i n vesti gat or’s discreti o n. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 7 of 9 5 
T a bl e 7. 2.  
Pr al atr e x at e Tr e at m e nt  M o difi c ati o n s f or M u c o siti s 
M uc ositis Gr a de o n 
Pl a n ne d D osi n g 
D a y  
Acti o n 
0 or 1 
•  
N o c ha n ge i n pralatre xate d ose. 
2 
•  
O mit t his wee k’s d ose of pralatre xate. A d mi nister wit h n o c ha n ge i n 
pralatre xate d ose if res ol uti o n t o Gra de 0- 1. 
•  
If re occ urre nce, o mit t his wee k’s d ose, u p o n res ol uti o n t o Gra de 0- 1, 
re d uce t he d ose t o ne xt l o wer d ose le vel.. 
3  
D o n ot a d mi nister pralatre xate u ntil rec o ver y t o Gra de 0- 1.  
•  
U p o n rec o ver y t o Gra de 0- 1, re d uce t o ne xt l o wer d ose le vel  
•  
Disc o nti n ue pralatre xate if ≥ Gra de 3 m uc ositis persists f or 
≥ 2 c o nsec uti ve wee ks or re occ urs wit hi n 2 8 da ys if o n 1 0 m g/ m2 
4 
•  
Disc o nti n ue pralatre xate. 
 
T a bl e 7. 3.  
Pr al atr e x at e Tr e at m e nt M o difi c ati o n s f or Tr e at m e nt-r el at e d 
C ar di o v a s c ul ar, D er m at ol o gi c al, H e p ati c, N e ur ol o gi c, R e n al, or 
R e s pir at or y A E s 
E ve nt Gr a de  
Acti o n 
0- 2 
•  
N o c ha n ge i n pralatre xate d ose. 
3 
D o n ot a d mi nister pralatre xate u ntil rec o ver y t o ≤ Gra de 2. 
•  
U p o n rec o ver y t o ≤ Gra de 2 a d mi nister pralatre xate wit h o ut a c ha n ge 
i n d ose. 
•  
If t he patie nt e x perie nces t he sa me Gra de 3 treat me nt-relate d A E d o 
n ot a d mi nister u ntil rec o ver y t o ≤ Gra de 2 a n d a d mi nister wit h a 
re d ucti o n t o t he ne xt l o wer d ose le vel. 
•  
Disc o nti n ue pralatre xate if t he sa me Gra de 3 treat me nt-relate d A E 
rec urs wit hi n 2 8 da ys at 1 0 m g/ m2. 
4 
•  
Disc o nti n ue pralatre xate.  
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 8 of 9 5 
8 
P A TI E N T P O P U L A TI O N  
8. 1 
N u m b er of P ati e nt s a n d P ati e nt S el e cti o n 
T he tar get patie nt p o p ulati o n is a d ult patie nts  wit h pre vi o usl y u n dia g n ose d P T C L w h o ha ve 
ac hie ve d a n o bjecti ve res p o nse afte r pre-st u d y first-li ne treat me nt wit h at least 6 c ycles of 
o ne of t he f oll o wi n g C H O P- base d treat me nts: 
a. C H O P 2 1  
b.  C H O P 1 4 
c. C H O E P 
d.  Ot her C H O P varia nts 
A t otal of 5 4 9 patie nts will be ra n d o mize d  2: 1 t o pralatre xate or o bser vati o n. 
8. 2 
I n cl u si o n of F e m al e s a n d Mi n oriti e s 
E ntr y i nt o t his st u d y is o pe n t o males a n d fe ma les of a n y et h nic ori gi n.  Race a n d ge n der are 
n ot k n o w n t o affect s ur vi val o u tc o me i n t his disease, n or are t he y k n o w n t o be ass ociate d 
wit h differe ntial s ur vi val b y treat me nt.  Fe males a n d mi n orities will be acti vel y recr uite d f or 
t his pr ot oc ol.   
8. 3 
I n cl u si o n Crit eri a  
A patie nt will be eli gi ble f or i ncl usi o n o nl y if all of t he f oll o wi n g criteria a p pl y: 
1.  Patie nt’s P T C L hist ol o g y has bee n c o nfir me d as o ne of t he f oll o wi n g b y a n i n de pe n de nt 
pat h ol o g y re vie wer, usi n g t he Re vise d E ur o pea n A meri ca n L y m p h o ma ( R E A L) W H O 
disease classificati o n 
a. T/ N K-cell le u ke mia/l y m p h o ma 
b.  A d ult T-cell l y m p h o ma/l e u ke mia ( h u m a n T-cell le u ke mia vir us [ H T L V] 1 +) 
c. A n gi oi m m u n o blastic T-cell l y m p h o ma  
d.  A L C L, pri mar y s yste mic t y pe, e xcl u di n g A L K +  wit h I PI sc ore < 2 at i nitial dia g n osis 
a n d C R after c o m pleti o n of C H O P- base d t hera p y 
e. P T C L- u ns pecifie d 
f. E nter o pat h y-t y pe i ntesti nal l y m p h o ma 
g.  He pat os ple nic T-cell l y m p h o ma 
h.  S u bc uta ne o us pa n nic uli tis T-cell l y m p h o ma 
i. Tra nsf or me d m yc osis f u n g oi des 
j. E xtra n o dal T/ N K-cell l y m p h o ma  nasal or nasal t y pe 
k.  Pri mar y c uta ne o us ga m ma- delta T-cell l y m p h o ma 
l. Pri mar y c uta ne o us C D 8 + a g gressi ve e pi der mic c yt ot o xic T-cell l y m p h o ma 
2.  D oc u me ntati o n t hat t he patie nt  has c o m plete d at least 6 c ycles of C H O P- base d t hera p y, 
i ncl u di n g: 
• 
C H O P 2 1  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 4 9 of 9 5 
• 
C H O P 1 4 
• 
C H O E P 
• 
Ot her C H O P varia nts: i ncl u des all 4 c o m p o ne nts of C H O P re prese nte d, wit h 
s u bstit uti o n all o we d f or a n y 1 c o m p o ne nt wit h a dr u g of t he sa me mec ha nis m of 
acti o n (e g, varia nt a nt hrac ycli nes).  A d diti o nal c o m p o ne nts t o C H O P are all o we d, 
wit h t he e xce pti o n of ale mt uz u ma b; r it u xi ma b ma y be c o m bi ne d wit h C H O P 
pr o vi de d t hat it is n ot gi ve n wit h i n 3 c ycles of ra n d o mizati o n.  
3.  Patie nt has ac hie ve d a C R or P R per i n ve sti gat or’s assess me nt f oll o wi n g c o m pleti o n of 
C H O P- base d t hera p y a n d has ha d a ra di ol o g ical assess me nt wit hi n 2 1 da ys pri or t o 
ra n d o mizati o n. 
4.  ≥ 1 8 years of a ge. 
5.  E C O G perf or ma nce stat us ≤ 2. 
6.  A de q uate he mat ol o gical, he patic, a n d re nal f u ncti o n as defi ne d b y: 
a. A bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1 0 0 0/ µ L 
b.  Platelet c o u nt ≥ 1 0 0, 0 0 0/ µ L 
c. T otal bilir u bi n ≤ 1. 5 m g/ d L 
d.  As partate a mi n otra nsferase ( A S T) a n d ala ni ne a mi n otra nsferase ( A L T) ≤ 2. 5 ×  u p per 
li mit of n or mal ( U L N), ( A S T/ A L T < 5 ×  U L N if d oc u me nte d he patic i n v ol ve me nt 
wit h l y m p h o ma).  All patie nts wit h he pa titis B vir us ( H B V)-p ositi ve ser ol o g y m ust 
ha ve li ver f u ncti o n tests w it hi n t he a b o ve para meters. 
e. Creati ni ne ≤ 1. 5 m g/ d L (if t he patie nt’s creati ni ne is > 1. 5 m g/ d L, t he n t he calc ulate d 
creati ni ne cleara nce m ust be ≥ 5 0 m L/ mi n). 
7.  Fe males of c hil d beari n g p ote nti al (ie, e xcl u di n g patie nts w h o are p ost me n o pa usal f or at 
least 1 year [ > 1 2 m o nt hs since last me nses] or are s ur gicall y sterilize d) m ust: 
a. Ha ve a ne gati ve ser u m pre g na nc y test w it hi n 1 4 da ys pri or t o ra n d o mizati o n a n d 
b.  A gree t o practice a me dicall y acce pta ble c o ntrace pti ve re gi me n fr o m st u d y treat me nt 
i nitiati o n u ntil at least 3 0 da ys after t he last a d mi nistrati o n of pralatre xate. 
8.  Males w h o are se x uall y acti ve, i ncl u di n g t h ose wit h a pre g na nt part ner, m ust a gree t o 
practice a me dicall y acce pta ble barrier met h o d c o ntrace pti ve re gi me n (e g, c o n d o ms) 
w hile recei vi n g pralatre xate a n d f or 9 0 da ys af ter t he last a d mi nistrati o n of pralatre xate. 
9.  Patie nt has gi ve n writte n i nf or me d c o nse nt (I C). 
8. 4 
E x cl u si o n Crit eri a 
A patie nt will n ot be eli gi ble f or i ncl usi o n if a n y of t he f oll o wi n g criteria a p pl y: 
1.  Patie nt has:  
a. Prec urs or T/ N K ne o plas ms 
b.  A L C L ( A L K +) wit h I PI sc ore < 2 at i ni tial dia g n osis a n d C R after c o m pleti o n of 
C H O P- base d t hera p y 
c. T-cell pr ol y m p h oc ytic le u ke mia ( T- P L L) 

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d.  T-cell lar ge gra n ular l y m p h oc ytic le u ke mia 
e. M yc osis f u n g oi des, ot her t ha n tra nsf or me d m yc osis f u n g oi des  
f. Sézar y s y n dr o me 
g.  Pri mar y c uta ne o us C D 3 0 + dis or ders:  A L C L a n d l y m p h o mat oi d pa p ul osis 
2.  If t here is a hist or y of pri or mali g na ncies other t ha n t h ose e xce pti o ns liste d bel o w, t he 
patie nt m ust be disease-free f or ≥ 5 years.  Patie nts wit h t he f oll o wi n g pri or mali g na ncies 
less t ha n 5 years bef ore st u d y e ntr y ma y still be e nr olle d if t he y ha ve recei ve d treat me nt 
res ulti n g i n c o m plete res ol uti o n of t he ca ncer a n d c urre ntl y ha ve n o cli nical, ra di ol o gic, 
or la b orat or y e vi de nce of acti ve or rec urre nt disease. 
a. N o n- mela n o ma s ki n ca ncer  
b.  Carci n o ma i n sit u of t he cer vi x 
c. L ocalize d pr ostate ca ncer 
d.  L ocalize d t h yr oi d ca ncer 
3.  Patie nt has recei ve d pri or treat me nt (c he m ot hera p y or ra diati o n) f or P T C L, ot her t ha n a 
si n gle all o we d C H O P re gi men, wit h t he e xce pti o n of: 
a. Patie nts wit h nasal N K l y m p h o ma are per mitte d t o ha ve recei ve d l ocal ra diati o n 
t hera p y n o less t ha n 4 wee ks pri or t o ra n d o mizati o n. 
b.  Patie nts wit h tra nsf or me d m yc osis f u n g oi des are per mitte d t o ha ve recei ve d 
1 s yste mic si n gle-a ge nt c he m ot hera p y ( o t her t ha n met h otre xate) pri or t o 
tra nsf or mati o n of t heir disease. 
4.  Pri or e x p os ure t o pralatre xate. 
5.  Recei pt of s yste mic c ortic oster oi ds wit hi n 3 wee ks of st u d y treat me nt, u nless patie nt has 
bee n ta ki n g a c o nti n u o us d ose of ≤ 1 0 m g/ da y of oral pre d nis o ne or e q ui vale nt f or at least 
4 wee ks or as part of a C H O P pre d nis o ne ta per. 
6.  Pla n ne d use of a n y treat me nt f or P T C L d uri n g t he c o urse of t he st u d y. 
7.  Patie nt has:  
a. H u ma n i m m u n o deficie nc y vir us ( HI V)- p osit i ve dia g n osis wit h a C D 4 c o u nt of 
< 1 0 0 m m 3 or detecta ble viral l oa d wit hi n past 3 m o nt hs a n d is recei vi n g 
a nti-retr o viral t hera p y. 
b.  H B V- p ositi ve ser ol o g y a n d is recei vi n g i nterf er o n t hera p y or has li ver f u ncti o n test 
res ults o utsi de t he para meters of st u d y i ncl usi o n criteria.  Patie nts are per mitte d t o 
recei ve ot her a nti viral t hera pies if t he t hera p y has bee n a d mi nistere d at a sta ble d ose 
f or ≥ 4 wee ks.  
c. He patitis C vir us ( H C V) wit h detecta ble viral l oa d or i m m u n o l o gical e vi de nce of 
c hr o nic acti ve disease or recei v i n g/re q uiri n g a nti viral t hera p y. 
d.  S y m pt o matic ce ntral ner v o us s yste m ( C N S) me tastases or lesi o ns f or w hic h treat me nt 
is re q uire d. 
e. U nc o ntr olle d h y perte nsi o n or c o n gesti ve hear t fail ure Class III/I V acc or di n g t o t he 
Ne w Y or k Heart Ass ociati o n’s He art Fail ure G ui deli nes (see 
htt p:// w w w.a merica n heart. or g/ pr ese nter.j ht ml?i de ntifier = 3 0 6 5 0 8 0). 

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f. Acti ve u nc o ntr olle d i nfecti o n, u n derl yi n g me dical c o n diti o n i ncl u di n g u nsta ble 
car diac disease, or ot her seri o us ill ness t hat w o ul d i m pair t he a bilit y of t he patie nt t o 
recei ve pr ot oc ol treat me nt.   
8.  Patie nt has ha d maj or s ur ger y wit hi n 2 wee k s pri or t o st u d y e ntr y; ot her t ha n f or li ne 
place me nt or bi o ps y pr oce d ure.  
 

Pralatre xate I njecti o n 
 
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Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
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9 
S T U D Y D R U G A N D P H A R M A C E U TI C A L I N F O R M A TI O N  
9. 1 
Pr al atr e x at e I nj e cti o n 
9. 1. 1 
Pr al atr e x at e I nj e cti o n F or m ul ati o n 
Pralatre xate I njecti o n ( Pralatr e xate S ol uti o n f or I nf usi o n i n t he E U) will be s u p plie d b y All os 
a n d will ha ve bee n teste d a n d release d acc or di n g t o esta blis he d s pecificati o ns.  Pralatre xate 
I njecti o n is f or m ulate d as a sterile s ol uti o n f or i njecti o n a n d will be s u p plie d i n si n gle- use 
glass vials c o ntai ni n g a n is ot o nic pare nteral s ol uti o n at a c o nce ntrati o n of 2 0 m g/ m L of 
pralatre xate.  T he os m ol alit y of Pralatre xate I njecti o n is ~ 3 0 0 m Os m ol/ k g.  T he f or m ulati o n 
is a clear yell o w s ol uti o n. 
9. 1. 2 
Pr al atr e x at e I nj e cti o n St or a g e a n d H a n dli n g 
Pralatre xate I njecti o n is a c yt ot o xic a ntica n cer a ge nt.  Ca uti o n s h o ul d be e xercise d i n 
ha n dli n g, pre pari n g, a n d a d mi nisteri n g of t h e s ol uti o n.  T he use of gl o ves a n d ot her 
pr otecti ve cl ot hi n g is rec o m me n de d.  If Pralatre xate I njecti o n c o mes i n c o ntact wit h t he s ki n, 
i m me diatel y a n d t h or o u g hl y was h wit h s oa p a n d water.  If Pralatre xa te I njecti o n c o mes i n 
c o ntact wit h m uc o us me m bra nes, fl us h t h or o u g hl y wit h water.   
T he i nstit uti o nal, l ocal, a n d all a p plica ble p olicies a n d pr oce d ures m ust be f oll o we d f or 
pr o per ha n dli n g a n d dis p osal of c he m ot hera p y dr u gs. 
Pralatre xate I njecti o n m ust be  st ore d refri gerate d at 2- 8°C ( 3 6- 4 6° F) (see U nite d States 
P har mac o peia [ U S P] C o ntr olle d C ol d Te m perat ure) u ntil use.  Pralatre xate I njecti o n vials 
s h o ul d be st ore d i n ori gi nal cart o n t o pr otect fr o m li g ht u ntil use.  Pralatre xate I njecti o n vials 
c o ntai n n o preser vati ves a n d are i n te n de d f or si n gle use o nl y.  Vials of Pralatre xate I njecti o n 
m ust be st ore d u n der sec ure d c o n diti o ns wit h  access li mite d t o a ut h orize d st u d y pers o n nel 
o nl y.  After wit h dra wal of d ose, discar d vial i ncl u di n g a n y u n use d p orti o n.   
9. 1. 3 
P a c k a gi n g/ L a b eli n g 
T he c o nte nts of t he la bel will be i n acc or da nce wit h all a p plica ble re g ulat or y re q uire me nts. 
9. 1. 4 
Pr al atr e x at e I nj e cti o n D o s a g e a n d A d mi ni str ati o n 
9. 1. 4. 1 
Pr e p ar ati o n a n d Pr al atr e x at e I nj e cti o n D o s e C al c ul ati o n  
A p pr o priate mas k, pr otecti ve cl ot hi n g, e ye pr otecti o n, gl o ve s, a n d Class II vertical 
la mi nar-airfl o w safet y ca bi nets are re q uire d d uri n g pre parati o n a n d ha n dli n g.  Please refer t o 
t he St u d y I nstr ucti o ns pr o vi de d b y All os/ desi g nee f or detaile d g ui da nce re gar di n g 
dis pe nsi n g, dis p osal, a n d acc o u nta bi lit y of Pralatre xate I njecti o n. 
Pralatre xate I njecti o n m ust be i nf use d as t he v ol u me of a d mi nistrati o n base d o n t he ori gi nal 
c o nce ntrati o n of 2 0 m g/ m L.   

Pralatre xate I njecti o n 
 
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Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
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T he B S A will be calc ulate d base d o n t he patie nt’ s act ual wei g ht o btai ne d wit hi n 2 da ys pri or 
t o t he first Pralatre xate I njecti o n d ose of eac h c ycle, u nless ot her wise n ote d i n  Secti o n 1 0. 4 .  
T he patie nt will recei ve t he sa me Pralatre xate I njecti o n d ose ( base d o n t he B S A calc ulate d at 
c ycle 1) t hr o u g h o ut treat me nt u nless t he patie nt’s act ual wei g ht c ha n ges b y ≥ 1 0 %.  T he 
v ol u m e t o be i nf use d will be base d o n t he f oll o wi n g calc ulati o n: 
V ol u me ( m L) = ( Patie nt B S A [ m 2]) x ( pralatre xate d ose [ m g/ m2]) 
2 0 m g/ m L ( pralatre xate c o nce ntrati o n) 
Patie nts wit h a B S A > 2 m 2 will be ca p pe d at 2 m2. 
9. 1. 5 
A d mi ni str ati o n of Pr al atr e x at e I nj e cti o n  
Pralatre xate I njecti o n is a clear, yell o w s ol uti o n.  Pare nteral dr u g pr o d ucts s h o ul d be 
i ns pecte d vis uall y f or partic ulate matter a n d disc ol orati o n pri or t o a d mi nistrati o n, w he ne ver 
s ol uti o n a n d c o ntai ner per mit.  D o n ot use a n y vials e x hi biti n g partic ulate matter or 
disc ol orati o n.   
T he calc ulate d d ose of Pralatre xate I njecti o n s h o ul d be ase pticall y wit h dra w n i nt o a s yri n ge 
f or i m me diate use.  D o n ot dil ute Pralatre xate I njecti o n. 
A p pr o priate pr oce d ures f or c yt ot o xic a ge nts  m ust be f oll o we d f or a d mi nistrati o n of 
Pralatre xate I njecti o n. 
Pralatre xate I njecti o n will be  a d mi nistere d as a n I V p us h o ver a mi ni m u m of 3 0 sec o n ds u p 
t o a ma xi m u m of 5 mi n utes i nt o a pate nt I V li ne c o ntai ni n g n or mal sali ne ( 0. 9 % s o di u m 
c hl ori de [ Na Cl] at a n i nitial d ose of 3 0 m g/ m 2.  If t he I V p us h of pralatre xate is i nterr u pte d or 
dela ye d, t he a d mi nistrati o n s h o ul d be  restarte d as s o o n as p ossi ble. 
T he p har macist/ desi g nee ma y dis pe nse Pralatre xate I njecti o n t o t he researc h tea m i n t he vial 
or i n a pre-fille d s yri n ge acc or di n g t o t he i nstit uti o nal practice.  Pralatre xate I njecti o n vials 
will be dis p ose d of i m me diatel y after use.  T he vial a n d re mai ni n g v ol u me of Pralatre xate 
I njecti o n s h o ul d be discar de d acc or di n g t o t he i nstit uti o n’s p olic y f or dis p osal of c yt ot o xic 
a ge nts. 
9. 2 
Dr u g A c c o u nt a bilit y 
All os re q uires t hat dr u g acc o u nta bilit y l o gs be mai ntai ne d.  T hese l o gs m ust rec or d q ua ntities 
of Pralatre xate I njecti o n recei ve d fr o m All o s a n d q ua ntities dis pe nsed t o patie nts, i ncl u di n g 
l ot/ batc h n u m ber, date dis pe nse d, patie nt i de ntifier n u m ber, patie nt i nitials, pr ot oc ol n u m ber, 
d ose, bala nce f or war d, a n d t he i nitials of  t he pers o n dis pe nsi n g t he me dicati o n. 

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1 0 S T U D Y P R O C E D U R E S 
St u d y pr oce d ures are s u m marize d i n A p pe n di x 1  a n d A p pe n di x 2 , Sc he d ule of St u d y 
Pr oce d ures/ E val uati o ns Ta bles. 
1 0. 1 
S cr e e ni n g  
T he pr oce d ures a n d e val uati o ns re q uire d f o r ra n d o mizati o n are s u m marize d bel o w.  
Ra n d o mizati o n of eli gi ble patie nts m ust occ ur wit hi n 6 wee ks of da y 1 of t he last pla n ne d 
c ycle of C H O P- base d c he m ot hera p y.     
1.  Re vie w eli gi bilit y criteria. 
2.  O btai n writte n I C f or pat h ol o g y re vie w pri or t o se n di n g pat h ol o g y s peci me n(s) t o 
i n de pe n de nt path ol o g y re vie wer. 
3.  Se n d t he pat h ol o g y s peci me n(s) t o i n de pe n de nt pat h ol o g y re vie wer (see Secti o n 1 2. 2. 2 ).  
I n de pe n de nt pat h ol o g y re vie w of t u m or tiss ue s peci me ns a n d c o nfir mati o n of dia g n osis 
m ust occ ur pri or t o ra n d o m izati o n a n d ca n occ ur a n y ti me after t he i nitial P T C L 
dia g n osis, pr o vi de d t hat t he patie nt has c o nse nte d t o t he pat h ol o g y re vie w.   
U nless ot her wise s pecifie d, t he f oll o wi n g pr o ce d ures a n d e val uati o ns will be perf or me d 
wit hi n 2 1 da ys pri or t o ra n d o mizati o n: 
1.  O btai n writte n I C f or partici pati o n i n t his  st u d y pri or t o i nitiatin g a n y st u d y pr oce d ure 
t hat is n ot c o nsi dere d sta n dar d of care. 
2.  Re vie w eli gi bilit y criteria. 
3.  Re vie w me dical c hart a n d rec o r d me dical/s ur gical hist or y. 
4.  D oc u me nt hist o pat h ol o g y fr o m l ocal pat h ol o g y re p ort. 
5.  D oc u me nt I PI sc ore at i nitial dia g n osis. 
6.  Rec or d baseli ne/c urre nt me dical stat us, i ncl u di n g B s y m pt o ms relate d t o P T C L. 
7.  D oc u me nt dates of C H O P- base d c he m ot hera p y.   
8.  D oc u me nt t he i n vesti gat or’s assess me nt of  res p o nse after recei pt of C H O P- base d 
c he m ot hera p y. 
9.  D oc u me nt k n o w n meas ura ble disease para mete rs b y o btai ni n g t he f oll o wi n g ra di o gra p hic 
i ma gi n g:    
•  
C o m p ute d t o m o gra p h y ( C T) of c hest, nec k, a b d o me n, a n d pel vis ( ma g netic res o na nce 
i ma gi n g [ M RI] all o we d if t he patie nt ca n n ot t olerate t he I V c o ntrast). 
•  
Ot her i ma gi n g tec h ni q ues d oc u me nti n g diseas e site ot her t ha n c hest, nec k, a b d o me n, 
a n d pel vis, if a p plica ble. 
1 0.  Perf or m w h ole b o d y p ositr o n e missi o n t o m o gra p h y ( P E T) ( base of s k ull t o mi d-t hi g h) if 
l ocal sta n dar d of care. 
1 1.  D oc u me nt c uta ne o us disease wit h me dical p h ot o gra p h y of u p t o 5 tar get lesi o ns, w hic h 
will be c h ose n b y t he i n vesti gat or (refer t o St u d y I nstr ucti o ns). 

Pralatre xate I njecti o n 
 
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Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
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1 0. 4 
Pr al atr e x at e Ar m Pr o c e d ur e s 
1 0. 4. 1 
Pr al atr e x at e C y cl e 1, D o s e 1 
T he f oll o wi n g e val uati o ns a n d pr oce d ures m u st ta ke place wit hi n 3 da ys f oll o wi n g 
ra n d o mizati o n a n d pri or t o treat me nt i nitiati o n ( pralatre xate c ycle 1, d ose 1), u nless 
ot her wise n ote d bel o w: 
1.  Rec or d c urre nt me dicati o ns i ncl u di n g c o m plia nce wit h vita mi n s u p ple me ntati o n 
a d mi nistere d fr o m 7 da ys pri or t o ra n d o mizati o n (see Secti o n 1 3 ). 
2.  Assess a n d rec or d B s y m pt o ms . 
3.  Rec or d st u d y- pr oce d ure-re late d A Es a n d attri b uti o n 
(see htt p://cte p.ca ncer. g ov/re p orti n g/ctc. ht ml). 
4.  Rec or d wei g ht i n kil o gra ms ( k g), hei g ht i n  ce nti meters (c m) a n d calc ulate B S A.  T he 
patie nt’s wei g ht a n d B S A, t o calc ulate t h e v ol u me of t he pralatre xate d ose ma y be 
assesse d u p t o 7 da ys pri or t o c ycle 1, d ose 1. 
5.  L ocal la b orat or y: C ollect pre-i njec ti o n bl o o d f or he mat ol o g y a n d c he mistr y 
(i ncl u di n g baseli ne L D H) (see Secti o n 1 2. 1 ).  If a n y of t he la b orat or y eli gi bilit y criteria 
are n o l o n ger met at t his ti me, dela y treat me nt f or u p t o 1 wee k u ntil t hese val ues ret ur n  
t o t he s pecifie d para meters, as f oll o ws: A N C ≥ 1 0 0 0/ µ L, platelet c o u nt ≥ 1 0 0, 0 0 0/ µ L, 
t otal bilir u bi n ≤ 1. 5 m g/ d L, A S T a n d A L T ≤ 2. 5 ×  U L N ( A S T/ A L T <  5 ×  U L N if 
d oc u me nte d he patic i n v ol ve me nt wit h l y m p h o ma), creati ni ne ≤ 1. 5 m g/ d L or calc ulate d 
creati ni ne cleara nce ≥ 5 0 m L/ mi n. 
6.  C ollect pre-i njecti o n bl o o d sa m ple f or P K (see Secti o n 1 2. 2. 1 ).  P K sa m pli n g will be 
perf or me d at c ycle 1, d ose 1 u ntil sa m ples ha ve bee n o btai ne d o n 2 4 5 patie nts.  O btai n 
sa m ples u ntil n otifie d b y All os or desi g nee.   
7.  A d mi nister pralatre xate I V  p us h o ver a mi ni m um of 3 0 sec o n ds u p t o a ma xi m u m of 
5 mi n utes. 
8.  C ollect bl o o d sa m ples f or P K at t he e n d of i njecti o n a n d at 8 an d 2 4 h o urs p ost-i njecti o n 
(see Secti o n 1 2. 2. 1).  P K sa m pli n g will be perf or me d at c ycle 1, d ose 1 u ntil sa m ples 
ha ve bee n o btai ne d o n 2 4 5 patie nts.  O btai n  sa m ples u ntil n otifie d b y All os or desi g nee. 
1 0. 4. 2 
Pr al atr e x at e Ar m: C y cl e 1, D o s e s 2- 3 
1.  Rec or d A Es a n d attri b uti o n (see htt p://cte p.ca ncer. g o v/re p orti n g/ctc. ht ml).  Refer t o 
Secti o n 7. 4  f or t he pralatre xate d ose m o dificati o n criteria. 
2.  Rec or d c urre nt me dicati o ns i ncl u di n g c o m plia nce wit h vita mi n s u p ple me ntati o n. 
3.  Re vie w date of pre vi o us vita mi n B 1 2 i njecti o n.  A d mi nister vita mi n B1 2 1 m g I M 
q 8- 1 0 wee ks. 
4.  L ocal la b orat or y: C ollect bl o o d f or he mat ol o g y a n d c he mistries wit hi n 1 da y pri or t o 
eac h pralatre xate d ose.  
5.  If t he patie nt is n ot e x perie nci n g a n y A Es t hat warra nt treat me nt m o dificati o n or 
disc o nti n uati o n, a d mi nister pralatre xate I V  p us h o ver a mi ni m u m of 3 0 sec o n ds u p t o a 
ma xi m u m of 5 mi n utes.   

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 5 7 of 9 5 
1 0. 4. 3 
Pr o c e d ur e s f or S u b s e q u e nt C y cl e s, D o s e s 1- 3 f or a M a xi m u m of 2 Y e ar s 
Patie nts ma y c o nti n ue t o recei ve pralatre xate u n less t he patie nt e x perie nces a n y of t he criteria 
n ote d i n pr ot oc ol Secti o n 1 1. 1 . 
1.  Pri or t o eac h ne w c ycle: rec or d wei g ht i n k g a n d calc ulate B S A.  T he patie nt’s wei g ht 
a n d B S A ma y be assesse d u p t o 2 da ys pri or t o t he start of eac h c ycle. 
2.  Pri or t o eac h ne w c ycle: Assess a n d rec or d B s y m pt o ms u p t o 2 da ys pri or t o t he start of 
eac h c ycle. 
3.  Rec or d A Es a n d attri b uti o n (see htt p://cte p.ca ncer. g o v/re p orti n g/ctc. ht ml).  Refer t o 
Secti o n 7. 4  f or t he pralatre xate d ose m o dificati o n criteria. 
4.  Rec or d c urre nt me dicati o ns i ncl u di n g c o m plia nce wit h vita mi n s u p ple me ntati o n. 
5.  Re vie w date of pre vi o us vita mi n B 1 2 i njecti o n.  A d mi nister vita mi n B1 2 1 m g I M 
q 8- 1 0 wee ks. 
6.  L ocal la b orat or y: C ollect bl o o d f or he mat ol o g y a n d c he mistries (i ncl u di n g L D H d uri n g 
wee k 1) wit hi n 1 da y pri or t o ea c h pralatre xate d ose (see Secti o n 1 2. 1 ).  
7.  At c ycle 2, d ose 3, c ollect pre-i njecti o n bl o o d sa m ple f or P K i n 2 0 patie nts at select sites 
(see Secti o n 1 2. 2. 1 ). 
8.  If t he patie nt is n ot e x perie nci n g a n y A Es t hat warra nt treat me nt m o dificati o n or 
disc o nti n uati o n, a d mi nister pralatre xate I V  p us h o ver a mi ni m u m of 3 0 sec o n ds u p t o a 
ma xi m u m of 5 mi n utes. 
9.  At c ycle 2, d ose 3, c ollect bl o o d sa m ples f or P K i n 2 0 patie nts at select sites 
pre-i njecti o n, e n d of i njecti o n, a n d 8 a n d 2 4 h o urs p ost-i nje cti o n (see Secti o n 1 2. 2. 1). 
1 0. 5 
O b s er v ati o n Ar m Pr o c e d ur e s 
1 0. 5. 1 
O b s er v ati o n Ar m: B a s eli n e Vi sit  
T he f oll o wi n g e val uati o ns a n d pr oce d ures m u st ta ke place wit hi n 3 da ys f oll o wi n g 
ra n d o mizati o n, u nless ot her wise n ote d bel o w: 
1.  Rec or d c urre nt me dicati o ns i ncl u di n g c o m plia nce wit h vita mi n s u p ple me ntati o n 
a d mi nistere d fr o m 7 da ys pri or t o ra n d o mizati o n (see Secti o n 1 3 ). 
2.  Assess a n d rec or d B s y m pt o ms. 
3.  Rec or d st u d y- pr oce d ure-relate d A Es a n d attri b uti o n (see 
htt p://cte p.ca ncer. g o v/r e p orti n g/ctc. ht ml). 
4.  Rec or d wei g ht i n k g a n d hei g ht i n c m u p t o 7 da ys pri or t o baseli ne visit. 
5.  L ocal la b orat or y: C ollect bl o o d f or he mat ol o g y a n d c he mistr y (i ncl u di n g baseli ne L D H) 
(see Secti o n 1 2. 1).  
1 0. 5. 2 
O b s er v ati o n Ar m: W e e k 2 of E v er y 4- w e e k P eri o d f or a M a xi m u m of 2 
Y e ar s 
T he patie nt will be c o ntacte d (e g, p h o ne call or c li nic visit) wee k 2 of e ver y 4- wee k peri o d.  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 5 8 of 9 5 
1.  Rec or d A Es a n d attri b uti o n (see htt p ://cte p.ca ncer. g o v/re p orti n g/ctc. ht ml). 
1 0. 5. 3 
O b s er v ati o n Ar m:  E v er y 2 8 d a y s ( ± 3 d a y s) f or a M a xi m u m of 2 Y e ar s 
1.  Rec or d A Es a n d attri b uti o n (see htt p ://cte p.ca ncer. g o v/re p orti n g/ctc. ht ml). 
2.  Assess a n d rec or d B s y m pt o ms. 
3.  Rec or d c urre nt me dicati o ns i ncl u di n g c o m plia nce wit h vita mi n s u p ple me ntati o n. 
4.  Re vie w date of pre vi o us vita mi n B 1 2 i njecti o n.  A d mi nister vita mi n B1 2 1 m g I M 
q 8- 1 0 wee ks. 
5.  L ocal la b orat or y: C ollect bl o o d f or he mat ol o g y a n d c he mistries (i ncl u di n g L D H) (see 
Secti o n 1 2. 1 ). 
1 0. 6 
R e s p o n s e E v al u ati o n  
Res p o nse a n d pr o gressi o n of disease will be e val uate d b y usi n g t he I nter nati o nal W or ks h o p 
Criteria (I W C, A p pe n di x 4 ).  All res p o nses will be e val uate d b y a desi g nate d, i n de pe n de nt 
ce ntral re vie w at least u ntil t he P F S a nal ysis (see Secti o n 1 5. 6. 1 ).  T he i n vesti gat or’s 
assess me nt of res p o nse will als o be c ollecte d.  All necessar y d oc u me ntati o n t o deter mi ne 
res p o nse will be c ollecte d at t he i n vesti gati o nal sites a n d se nt t o t he ce ntral re vie wer.  T he 
first res p o nse e val uati o n is t o occ ur 8 wee ks ( ± 1 wee k) after ra n d o mizati o n.  S u bse q ue nt 
res p o nse e val uati o ns are t o occ ur e ver y 1 2 wee ks ( ± 1 wee k) ti me d fr o m ra n d o mizati o n 
t hr o u g h 3 years p ost-ra n d o mizati o n, t he n e ver y 2 4 wee ks ( ± 4 wee ks) t hr o u g h 7 years p ost-
ra n d o mizati o n.  U nsc he d ule d res p o nse assess me nts will als o be se nt t o  t he ce ntral re vie wer 
f or e val uati o n.  Res p o nse assess me nts will occ ur u ntil P D per ce ntral re vie w, at least u ntil t he 
P F S a nal ysis.   
T he f oll o wi n g pr oce d ures/tests are t o be  perf or me d f or eac h res p o nse e val uati o n: 
1.  Ra di o gra p hic i ma gi n g ( use sa me i ma gi n g t ec h ni q ue as pre- pralatre xate/ o bser vati o n 
scree ni n g):  
•  
C T of c hest, nec k, a b d o me n, a n d pel vis ( M RI all o we d if t he patie nt ca n n ot t olerate 
t he I V c o ntrast) 
•  
W h ole b o d y P E T ( base of s k ull t o mi d-t hi g h) if perf or me d as per l ocal sta n dar d of 
care  
•  
Ot her i ma gi n g tec h ni q ues d oc u me nti n g dise ase site(s) ot her t ha n c hest, nec k, 
a b d o me n, a n d pel vis, if a p plica ble. 
2.  If a p plica ble, assess c uta ne o us disease usi n g me dical p h ot o gra p h y (refer t o St u d y 
I nstr ucti o ns).  
3.  D oc u me nt disease-relate d fi n di n gs per p h ysical e xa mi nati o n. 
4.  If t he patie nt has a C R b y i ma gi n g, a b o ne marr o w bi o ps y/as pirate assess me nt 
(i ncl u di n g i m m u n o hist oc he mistr y) m ust be perf or me d t o c o nfir m C R if b o ne marr o w 
bi o ps y/as pirate res ults were  p ositi ve or i n deter mi nate pri or t o ra n d o mizati o n t o 
pralatre xate/ o bser vati o n.  O nce a patie nt’ s b o ne marr o w is ne gati ve f or l y m p h o ma, t he 
b o ne marr o w bi o ps y/as pirate will be re peate d o nl y w he n cli nicall y i n dicate d u nless it is 
t he patie nt’s o nl y site of disease. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 5 9 of 9 5 
5.  A t u m or bi o ps y ma y be perf or me d if nee de d  t o c o nfir m a res p o nse e val uati o n as per 
i n vesti gat or discreti o n. 
6.  D oc u me nt i n vesti gat or’s assess me nt of res p o nse. 
1 0. 7 
I niti al F oll o w- u p Vi sit  
1 0. 7. 1 
Pr al atr e x at e Ar m 
All patie nts w h o recei ve at leas t 1 d ose of pralatre xate will atte n d t he I nitial F oll o w- u p Visit 
3 5 ( ±  5) da ys after t he last d ose of pralatre xate.   
I n t he e ve nt t he patie nt wit h dra ws c o nse nt t o a n y f urt her st u d y partici pati o n a n d ref uses t o 
atte n d t he I nitial F oll o w- u p Visit, t he f oll o wi n g pr oce d ures a n d e val uati o ns m ust be 
perf or me d a t t he ti me t he patie nt wit h dra ws c o nse nt. 
1.  Rec or d c o nc o mita nt me dicati o ns t hr o u g h 3 0 da ys after t he last pralatre xate d ose. 
2.  Rec or d all A Es a n d attri b uti o n t hr o u g h 3 0 da ys after t he last pralatre xate d ose.  Fr o m 
3 1 da ys after t he last pralatre xate d ose,  o nl y rec or d pralatre xate-relate d A Es a n d 
attri b uti o n (see htt p://cte p.ca n cer. g o v/re p orti n g/ctc. ht ml).  
3.  Assess a n d rec or d B s y m pt o ms. 
4.  Perf or m p h ysical e xa mi nati o n.  D oc u me nt a n y ne w or w orse ne d fi n di n gs as A Es. 
5.  Assess a n d rec or d E C O G perf or ma nce stat us (see A p pe n di x 3 ). 
6.  L ocal la b orat or y: c ollect bl o o d f or he mat ol o g y a n d ser u m c he mistr y (i ncl u di n g L D H, 
see Secti o n 1 2. 1 ).  
7.  Re vie w d osi n g of f olic aci d a n d d oc u me nt c o m plia nce.  
8.  I nstr uct patie nt t o disc o ntin ue f olic aci d a n d vita mi n B 1 2. 
9.  Rec or d reas o n f or disc o nti n uati o n of pralatre xate ( Secti o n 1 1. 1 ). 
1 0.  Rec or d first s u bse q ue nt t hera p y f or P T C L, if a p plica ble.   
 
1 0. 7. 2 
O b s er v ati o n Ar m 
Patie nts w h o are ra n d o mize d t o t he O bser vati o n Ar m will atte n d t he I nitial F oll o w- u p Visit 
3 5 da ys ( ± 5 da ys) after st u d y treat me nt disc o nti n uati o n criteria are m et.   
I n t he e ve nt t he patie nt wit h dra ws c o nse nt t o a n y f urt her st u d y partici pati o n a n d ref uses t o 
atte n d t he I nitial F oll o w- u p Visit, t he f oll owi n g pr oce d ures a n d e val uati o ns m ust be 
perf or me d at t he ti me t he pa tie nt wit h dra ws c o nse nt. 
1.  Rec or d c o nc o mita nt me dicati o ns t hr o u g h 3 0 da ys after st u d y treat me nt disc o nti n uati o n 
criteria ( Secti o n 1 1. 1) are met.  
2.  Rec or d all A Es a n d attri b uti o n (see htt p://cte p.ca ncer. g o v/ re p orti n g/ctc. ht ml) t hr o u g h 
3 0 da ys after st u d y treat me nt disc o nti n uati o n criteria ( Secti o n 1 1. 1) are met.  
3.  Assess a n d rec or d B s y m pt o ms. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 0 of 9 5 
4.  Perf or m p h ysical e xa mi nati o n.  D oc u me nt a n y ne w or w orse ne d fi n di n gs as A Es.  
5.  Assess a n d rec or d E C O G perf or ma nce stat us (see A p pe n di x 3 ). 
6.  L ocal la b orat or y: c ollect bl o o d f or he mat ol o g y a n d ser u m c he mistr y (i ncl u di n g L D H, 
see Secti o n 1 2. 1 )  
7.  Re vie w d osi n g of f olic aci d a n d d oc u me nt c o m plia nce. 
8.  I nstr uct patie nt t o disc o nti n ue f olic aci d a n d vita mi n B 1 2. 
9.  Rec or d reas o n f or disc o nti n uati o n of o bser vati o n ( Secti o n 1 1. 1 ). 
1 0.  Rec or d first s u bse q ue nt t hera p y f or P T C L, if  a p plica ble.  First s u bse q ue nt t hera p y f or 
P T C L is at t he i n vesti gat or’s disc reti o n a n d ca n i ncl u de pralatre xate. 
1 0. 8 
F oll o w- u p Vi sit s 
All patie nts w h o are ra n d o mize d are t o ha ve  f oll o w- u p as o utli ne d bel o w u ntil o bjecti vel y 
d oc u me nte d P D; t hereafter, patie nts are f oll o we d f or s ur vi val.  T he ti mi n g of f oll o w- u p will 
be at 8 wee ks ( ± 1 wee k), t he n e ver y 1 2 wee ks ( ± 1 wee k) t hr o u g h 3 years p ost-
ra n d o mizati o n, a n d t he n e ver y 2 4 wee ks (± 4 wee ks) t hereafter t hr o u g h 7 years p ost-
ra n d o mizati o n.  P D will be c o nfir me d b y ce ntral re vie w u ntil t he fi rst P F S a nal ysis, see 
Secti o n 1 5. 6. 1 , a n d per i n vesti gat or assess me nt t hereafter. 
T he f oll o wi n g pr oce d ures/e val uati o ns m ust be perf or me d at eac h f oll o w- u p ti me p oi nt. 
1.  Rec or d st u d y-treat me nt-relate d A Es (see htt p://cte p.ca ncer. g o v/re p orti n g/ctc. ht ml). 
2.  E val uati o n of res p o nse (see Secti o n 1 0. 6  f or tests a n d pr oce d ures). 
3.  Rec or d s u bse q ue nt t hera pies f or P T C L a n d d oc u me nt t he best res p o nse t o t he first 
s u bse q ue nt t hera p y.  
1 0. 9 
L o n g-t er m F oll o w- u p  
All s u bse q ue nt t hera pies f or P T C L will be c o llecte d f or u p t o 7 years fr o m ra n d o mizati o n 
a n d t he best res p o nse t o t he first s u bse q ue nt t hera p y will be d oc u me nte d.  O nce patie nts ha ve 
d oc u me nte d P D, s ur vi val stat us a n d s u bse q ue nt t hera pies will be c ollecte d o n all patie nts 
a p pr o xi matel y e ver y 6 m o nt hs t hr o u g h 7 years fr o m ra n d o mizati o n.   
1 1 D U R A TI O N O F T R E A T M E N T 
All patie nts are free t o wit h dra w  fr o m partici pati o n i n t his st u d y at a n y ti me, f or a n y reas o ns, 
s pecifie d or u ns pecifie d, a n d wit h o ut prej u dice.  T he reas o n f or t he patie nt disc o nti n ui n g 
pralatre xate/ o bser vati o n or ter mi nati n g fr o m t he st u d y m ust be rec or de d o n t he case re p ort 
f or m ( C R F).  Pralatre xate will c o nti n ue t o be a d mi nistere d u ntil a criteri o n f or st u d y 
treat me nt disc o nti n uati o n is met (Secti o n 7. 3 ) or u p t o a ma xi m u m of 2 years. 
1 1. 1 
Crit eri a f or St u d y Tr e a t m e nt Di s c o nti n u ati o n  
Patie nts will recei ve st u d y treat me nt ( pralatre x ate or o bser vati o n) u ntil o ne of t he f oll o wi n g 
criteria f or st u d y treat me nt  disc o nti n uati o n a p plies: 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 1 of 9 5 
• 
De vel o p me nt of P D  
• 
I nitiati o n of R T or s yste mic c he m o/ biol o gical t hera p y f or treat me nt of P T C L 
• 
Recei pt of s yste mic ster oi ds > 1 0 da ys, wit h t he e xce pti o n of t h ose as state d i n e xcl usi o n 
criteri o n # 5 (see Secti o n 8. 4 ) 
• 
De vel o p me nt of a n A E t hat i nterferes wit h t he patie nt’s partici pati o n 
• 
L ost t o f oll o w- u p 
• 
Patie nt decisi o n 
• 
I n vesti gat or decisi o n 
• 
S p o ns or decisi o n 
I n a d diti o n, f or t h ose patie nts ra n d o mize d t o t he Pralatre xate Ar m, a d diti o nal pralatre xate 
treat me nt disc o nti n uati o n criteria are: 
• 
3 or m ore c o nsec uti ve d oses of pralatre xate o mitte d or m ore t ha n 2 8 da ys bet wee n d oses 
of pralatre xate  
• 
Treat me nt wit h pralatre xate f or 2 years 
Patie nts will be see n f or t he I nitial F o ll o w- u p Visits as o utli ne d i n Secti o n 1 0. 7 . 
If a n i n vesti gat or feels t hat a patie nt w o ul d c o nti n ue t o be nefit fr o m pralatre xate t hera p y after 
c o m pleti o n of 2 years’ t hera p y, t he y s h o ul d di sc uss wit h t he s p o ns or’s me dical c o ntact a n d 
a gree w het her or n ot it is a p pr o priate t o c o nti n ue treat me nt. 
1 2 L A B O R A T O R Y T E S T S 
1 2. 1 
L o c al L a b or at or y T e st s 
T he f oll o wi n g pa nels will be d o ne l ocall y wit h t he desi g nate d tests.  C o pies of c urre nt 
la b orat or y certificati o ns a n d n or mal ra n ges will be pr o vi de d t o All os at st u d y start a n d u p o n 
e ver y re ne wal t hr o u g h o ut t he d urati o n of pr alatre xate or o bser vati o n f or t he l o n gest 
partici pati n g patie nt at t he site. 
1 2. 1. 1 
H e m at ol o g y 
Tests t o be c o n d ucte d are w hite bl o o d cell ( W B C) c o u nt, he m o gl o bi n ( H g b) c o nce ntrati o n, 
he mat ocrit ( Hct), platelet c o u nt, a n d A N C. 
1 2. 1. 2 
C h e mi str y 
Tests t o be c o n d ucte d are creati n i ne, t otal bilir u bi n, A S T, A L T, L D H, t otal pr otei n, al b u mi n, 
a n d β - h C G pre g na nc y test at scree ni n g (if a p plica ble). 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 2 of 9 5 
1 2. 2 
C e ntr al L a b or at or y 
1 2. 2. 1 
Pl a s m a P h ar m a c o ki n eti c s 
At sites partici pati n g i n plas ma sa m pli n g f or P K a nal ysis, a p pr o xi matel y 2 4 5 patie nts 
ra n d o mize d t o t he Pralatre xate Ar m (t w o-t hir ds of t he pla n ne d t otal) w h o c o nse nt t o plas ma 
sa mpli n g will ha ve sa m pli n g perf or me d at c ycl e 1, d ose 1 ( pre-i njecti o n, e n d of i njecti o n, 
a n d 8 a n d 2 4 h o urs p ost-i njecti o n).  Of t hese 2 4 5 pa tie nts, 2 0 patie nts at select sites will als o 
ha ve plas ma sa m pli n g perf or me d at c ycle 2, d os e 3 ( pre-i njecti o n, e n d of  i njecti o n, a n d 8 a n d 
2 4 h o urs p ost- i njecti o n). 
Plas ma sa m ples will be s plit i n 2 e q ual ali q u ots a n d fr oze n i n se parate t u bes f or a nal ysis of 
pralatre xate c o nce ntrati o n.  T he c o nce ntrati o ns  of pralatre xate at eac h ti me- p oi nt will be 
deter mi ne d usi n g vali date d bi oa nal ytical met h o ds at M PI Researc h.  See St u d y I nstr ucti o ns 
pr o vi de d b y All os/ desi g nee f or detaile d g ui da n ce re gar di n g t he c ollect i o n, pr ocessi n g, a n d 
s hi p me nt of sa m ples. 
Sta n dar d P K para meters will be esti mate d fr o m t he li mite d plas ma sa m pli n g (e g, area u n der 
t he c ur ve [ A U C], ma xi m u m c o nce ntrati o n [ Cma x ], a n d half-life [t1/ 2]), a n d P O P P K a nal yses 
will be c o n d ucte d via n o nli near mi xe d-effects m o deli n g t o esti mate P O P P K para meters f or 
pralatre xate. 
1 2. 2. 2 
I n d e p e n d e nt P at h ol o g y R e vi e w 
C o nfir mati o n of P T C L hist o pat h ol o g y s u bt y pe will be perf or me d b y a n i n de pe n de nt 
pat h ol o g y re vie wer.  Pat h ol o g y s peci me ns fr o m t he patie nt’s i nitial dia g n osis will be se nt t o 
i n de pe n de nt pat h ol o g y re vie w.  C o nfir mati o n of a n eli gi ble  P T C L hist o pat h ol o g y s u bt y pe 
m ust be d oc u m e nte d b y t he i n de pe n de nt pat h ol o g y re vie wer pri or t o  ra n d o mizati o n.  See 
St u d y I nstr ucti o ns pr o vi de d b y All os/ desi g n ee f or detaile d g ui da nce re gar di n g sa m ple 
re q uire me nts a n d t he pre parati o n a n d s hi p me nt of sli des.  
1 2. 2. 3 
M e di c al P h ot o gr a p h y 
D oc u me ntati o n of c uta ne o us disease wit h me di cal p h ot o gra p h y will be perf or me d b y t he site 
at scree ni n g a n d at eac h res p o nse assess me nt, if a p plica ble.   Up t o 5 tar get lesi o ns will be 
c h ose n b y t he i n vesti gat or a n d p h ot o gra p he d.   See St u d y I nstr ucti o ns pr o vi de d b y t he ce ntral 
me dical p h ot o gra p h y la b orat or y ( C a nfiel d Scie ntific, I nc.) f or detaile d g ui da nce re gar di n g 
p h ot o gra p h re q uire me nts a n d tra nsfer. 
1 2. 2. 4 
C e ntr al R a di ol o g y I m a gi n g 
Ra di ol o gic i ma gi n g of eac h pati e nt will be c o m plete d at scree ni n g a n d at eac h res p o nse 
assess me nt as descri be d i n Secti o ns 1 0. 1  a n d 1 0. 6 .  All sca ns will be se nt t o a desi g nate d, 
i n de pe n de nt ce ntral re vie wer u ntil at least t he first i nteri m a nal ysis.   See St u d y I nstr ucti o ns 
pr o vi de d b y t he ce ntral re vie wer ( C ore La b Part ners) f or detaile d g ui da nce re gar di n g i ma gi n g 
re q uire me nts a n d tra nsfer. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 3 of 9 5 
1 3 C O N C O MI T A N T M E DI C A TI O N S 
All me dicati o ns a d mi nistere d fr o m 7 da ys pr i or t o ra n d o mizati o n t hro u g h 3 0 da ys after t he 
last pralatre xate a d mi nistratio n, or t hr o u g h 3 0 da ys after treat m e nt disc o nti n uati o n criteria are 
met f or patie nts i n t he O bser vati o n Ar m, will be  rec or de d o n t he C R F.  A d diti o ns, deleti o ns, 
or c ha n ges of d osa ge of me dicati o ns will als o be n ote d. 
1 3. 1 
A nti e m eti c T h er a p y 
T here is n o e vi de nce t o e x pect dr u g- dr u g i ntera cti o ns bet wee n pralatre xate a n d sta n dar d 
a ntie metic t hera p y a n d n o s pecific a ntie metic t hera p y has yet bee n pr o ve n t o be s u peri or o ver 
ot hers i n t he setti n g of pralat re xate a d mi nistrati o n.  T heref ore, pr o p h yla xis a n d treat me nt of 
na usea a n d v o miti n g ca n be a d mi nistere d acc or d i n g t o t he sta n dar d of care wit hi n t he 
i nstit uti o n; h o we ver, a d mi nistrati o n is n ot rec o m me n de d pri or t o t he first d ose beca use of t he 
l o w e met o ge nicit y of pralatre xate.   
Ster oi ds are n ot all o we d f or pr o p h yla xis or treat me nt of na usea/ v o miti n g. 
1 3. 2 
H e m at o p oi eti c Gr o wt h F a ct or s 
He mat o p oietic gr o wt h fact ors ma y be a d mi nistere d i n acc or da nce wit h t he i nstr ucti o ns f or 
treat me nt m o dificati o n f or he mat ol o gical e ve nts i n Ta ble 7. 1 .  Er yt hr o p oieti n will be all o we d 
if it is j u d ge d b y t he i n vesti gat or t o be i n t he best i nterest of t he patie nt (e g, f or patie nts wit h 
u n derl yi n g a ne mia or u nacce pta ble he mat ol o gic t o xicit y).  Ot her he mat o p oietic gr o wt h 
fact ors (e g, gra n ul oc yte c ol o n y-sti m ulati n g fact or [ G- C S F], gra n ul oc yte- macr o p ha ge c ol o n y-
sti m ulati n g fact or [ GM- C S F]), wit h t he e xce pti o n of pe gfil grasti m ( Ne ulasta
® , A m ge n), are 
t o be a d mi nistere d per pac ka ge i nsert.   
1 3. 3 
M u c o siti s M a n a g e m e nt 
Patie nts recei vi n g pralatre xate s h o ul d be assesse d f or ris k of  m uc ositis pri or t o start of 
treat me nt wit h c o nti n ue d assess me nt f or s y m pt oms pri or t o eac h d ose.  Me dicati o ns a n d 
m o ut h was hes, i ncl u di n g salt a n d s o da m o ut h was hes, use d f or pro p h yla xis a n d/ or treat me nt of 
m uc ositis m ust be rec or de d as c o nc o mita nt me dicati o ns.  D ose m o dificati o ns f or m uc ositis 
are f o u n d i n Ta ble 7. 2 ; h o we ver, i n vesti gat ors s h o uld refer t o t he Nati o nal C o m pre he nsi ve 
Ca ncer Net w or k ( N C C N) Tas k F orce Re p ort f or t he Pre ve nti o n a n d Ma na ge me nt of 
M uc ositis i n Ca ncer Care f or assista n ce wit h ris k assess me nt a n d gra di n g of m uc ositis, 
g ui da nce o n s y m pt o m ma na ge me nt, a n d patie n t e d ucati o n t o ols o n effecti ve oral care 
re gi me ns a n d re p orti n g of m uc ositis s y m pt o ms.3 5 
1 3. 4 
C orti c o st er oi d U s e 
Patie nts are all o we d t o be gi n st u d y treat me nt w hile recei vi n g s yste m ic c ortic oster oi ds 
pr o vi de d t he patie nt has bee n  ta ki n g a c o nti n u o us d ose of ≤ 1 0 m g/ da y of oral pre d nis o ne or 
e q ui vale nt f or at least 4 wee ks or as part of a C H O P pre d nis o ne ta per.  Ot her c o nc o mita nt 
s yste mic c ortic oster oi d t herap y d uri n g t he pralatre xate treat m e nt/ o bser vati o n p hase of t his 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 4 of 9 5 
st u d y is pr o hi bite d ( wit h e xce pti o n of c orticoster oi ds a d mi nistere d  f or a n o n-l y m p h o ma 
c o n diti o n, e g, br o nc hitis, f or ≤ 1 0 da ys).  I n hale d or t o pical ster oi ds (a d mi nistere d f or reas o ns 
ot her t ha n t o treat c uta ne o us disease) are all o we d. 
1 3. 5 
Pr o p h yl a cti c A nti-i nf e cti v e A g e nt s 
Use of pr o p h ylactic a nti bi otics/a nti virals/a ntif u n gals is  all o we d a n d ma y be a d mi nistere d at 
t he discreti o n of t he i n vesti gator.  If a nti bi otic pr o p h yla xis is i n dicate d, alter nati ves t o 
s ulfa met h o xaz ole/tri met h o pri m m ust be c o nsi dere d as it has a ntif olate acti vit y.  D ue t o t he 
p ossi bilit y of a d diti ve t o xicit y (i ncl u di n g m yel os u p pressi o n) w he n use d i n c o m bi nati o n wit h 
pralatre xate, c o nc urre nt use of t he 2 dr u gs s h o ul d be a v oi de d. 
1 3. 6 
P ai n M a n a g e m e nt 
Pai n ma na ge me nt s h o ul d be a d dresse d pr o m ptl y b y t he atte n di n g p h ysicia n ma na gi n g t he 
patie nt.  D ue t o t he c o ntri b uti o n of re nal e xcreti o n (a p pr o xi matel y 3 4 %) t o t he o verall 
cleara nce of pralatre xate, c o nc o mita nt a d mi nistrati o n of n o n- ster oi dal a nti-i nfla m mat or y 
dr u gs ( N S AI Ds) a n d pr o be neci d ma y res ult i n de la ye d cleara nce of pralatre xate.  T hese dr u gs 
s h o ul d be use d wit h ca uti o n w hile patie nts are e nr olle d i n t his st u d y; alter nati ves t o N S AI Ds 
a n d pr o be neci d s h o ul d be c o nsi dere d w he n p ossi ble. 
1 3. 7 
Bl o o d Pr o d u ct s 
Bl o o d pr o d uct tra nsf usi o ns are all o we d pe r t he discreti o n of t he i n vesti gat or. 
1 3. 8 
Ot h er S u p p orti v e C ar e M e di c ati o n s 
T he a d mi nistrati o n of a p petite -sti m ulati n g h or m o nes (e g, me gestr ol acetate) is all o we d t o 
c o ntr ol a n ore xia a n d cac he xia. 
1 3. 9 
R a di ot h er a p y, C yt ot o xi c T h er a p y,  Bi ol o gi c T h er a p y, or I m m u n e 
R e s p o n s e M o difi er s 
N o R T, ot her c yt ot o xic a ge nts, bi ol o gic t her a p y, i m m u ne res p o nse m o difiers, or ste m cell 
tra ns pla nt are t o be a d mi nistere d t o patie nts u ntil pralatre xate/ o bser vati o n has bee n 
disc o nti n ue d.   

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 5 of 9 5 
1 4 A D V E R S E E V E N T S 
1 4. 1 
D efi niti o n 
A n A E is defi ne d as a n y u nt o war d me dical occ u rre nce i n a patie nt or cli nical i n vesti gati o n 
patie nt, te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her or n ot c o nsi dere d 
relate d t o t he me dici nal pr o d uct.  T heref ore, a n A E ca n be a n y u nfa v ora ble a n d u ni nte n de d 
si g n (i ncl u di n g a n a b n or mal la b orat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of a me dicinal pr o d uct.  T his defi niti o n of a n A E will be 
e xte n de d i n t his st u d y t o i ncl u de  a n y u nt o war d me dical occ urre nce i n patie nts partici pati n g i n 
t he O bser vati o n Ar m of t he st u d y, as well. 
T he ter m “t o xicit y” is n ot clearl y defi ne d b y re g ulat or y or ga nizati o ns a n d is c urre ntl y use d 
o nl y f or hist orical reas o ns b y t he N CI.  T her ef ore, t he ter m “a d verse e ve nt” is use d 
t hr o u g h o ut t his d oc u me nt t o refer t o a n y u nfav ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), s y m pt o m, or diseas e te m p orall y ass ociate d wit h t he st u d y dr u g, 
as well as a n y ot her st u d y-treat me nt-relate d t o xicities.  H o we ver, si nce t his is a n 
i n vesti gati o nal st u d y, all t o xicities are c o nsi dere d A Es a n d m ust be re p orte d. 
E xa m ples of a n A E i ncl u de: 
• 
E xacer bati o n of a c hr o nic or i nter mitte nt pre-e xisti n g c o n diti o n i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n. 
• 
Ne w c o n diti o ns detecte d or dia g n ose d after i n vesti gati o nal pr o d uct a d mi nistrati o n, e ve n 
t h o u g h it ma y ha ve bee n prese nt pri or t o t he start of t he st u d y. 
• 
Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g i nteracti o n. 
• 
Si g ns, s y m pt o ms, or t he cli nical se q uel ae of a s us pecte d o ver d ose of eit her 
i n vesti gati o nal pr o d uct or a c o nc urre nt me dicati o n. 
• 
A Es ma y i ncl u de pre-treat me nt or p ost-treat me nt e ve nts t hat occ ur as a res ult of pr ot oc ol-
ma n date d pr oce d ures (ie, i n vasi ve pr oce d ures, m o dificati o n of patie nt’s pre vi o us 
t hera pe utic re gi me n). 
E xa m ples of a n A E d o n ot i ncl u de  a/a n: 
• 
Me dical or s ur gical pr oce d ures (e g, e n d os c o p y, a p pe n dect o m y); t he c o n diti o n t hat lea ds 
t o t he pr oce d ure is a n A E. 
• 
Sit uati o ns w here a n u nt o war d me dical o cc urre nce d oes n ot occ ur (e g, s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital). 
• 
A ntici pate d da y-t o- da y fl uct uati o ns of pre-e x isti n g disease(s) or co n diti o n(s) prese nt or 
detecte d at t he start of t he st u d y t hat d o n ot w orse n. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 6 of 9 5 
1 4. 2 
G ui d eli n e s f or R e c or di n g a n d A ttri b uti o n S c ori n g of A d v er s e 
E v e nt s 
Ti mel y a n d c o m plete re p orti n g of A Es is esse ntial.  M o nit ori n g a n d d oc u me ntati o n of all 
A Es all o ws f or i de ntificati o n of p ote ntial st u d y - dr u g or d ose-relate d A Es, a n d f or a d here nce 
t o re g ulat or y re q uire me nts.  Please refer t o t he C R F C o m pleti o n G ui deli nes l ocate d i n t he 
st u d y bi n der f or detaile d i nstr ucti o ns. 
1 4. 3 
R e c or di n g of A d v er s e E v e nt s 
1 4. 3. 1 
R e c or di n g of A d v er s e E v e nt s  
A n y A E t hat occ urs fr o m t he ti me t he st u d y I C  is o btai ne d u ntil ra n d o mizati o n nee ds t o be 
rec or de d o n t he A E C R F pa ge(s), o nl y  if t he e ve nt was relate d t o a st u d y pr oce d ure.  All 
ot her A Es/fi n di n gs pri or t o ra n d o mizati o n m ust  be rec or de d as baseli ne fi n di n gs o n t he 
a p plica ble C R F pa ge(s). 
A n y A E t hat occ urs fr o m ra n d o mizati o n t hr o u g h 3 0 da ys after t he last d ose of pralatre xate or 
t hr o u g h 3 0 da ys after treat me nt disc o nti n uatio n criteria are met f or t he O bser vati o n Ar m 
m ust be rec or de d o n t he A E C R F.  Fr o m 3 1 da ys  after t he last d ose of pralatre xate, o nl y A Es 
t hat are relate d t o pralatre xate nee d t o be ca pt ure d o n t he A E C R F.  
1 4. 3. 2 
Gr a di n g of A d v er s e E v e nt s 
T his st u d y will utilize t he N C I C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E) 
Scale, Versi o n 4. 0 f or A E gra di n g ( htt p ://cte p.ca ncer. g o v/re p orti n g/ctc. ht ml). 
1 4. 4 
F oll o w- u p of A d v er s e E v e nt s 
All A Es a n d si g nifica nt a b n or mal la b orat or y val ues m ust be f oll o we d u p i n acc or da nce wit h 
t he I C H G o o d Cli nical Practice ( G C P) g ui deli nes, a n d ot her a p plica ble re g ulat or y 
re q uire me nts (e g, U S C o de of Fe deral Re g ulati o ns [ C F R]). 
1 4. 5 
R el ati o n s hi p 
T he relati o ns hi p of t he e ve nt t o pralatre xate wi ll be assesse d usi n g t he f oll o wi n g defi niti o ns: 
N ot Rel ate d : 
E vi de nce e xists t hat t he A E ha s a n eti ol o g y ot her t ha n pralatre xate (s uc h as, pre-e xisti n g 
c o n diti o n, u n derl yi n g disease, i nterc urre nt ill ness, or c o nc o mita nt me dicati o ns). 
Rel ate d : 
A te m p oral relati o ns hi p e xists bet wee n t he e ve n t o nset ( or w orse ni n g) a n d t he a d mi nistrati o n 
of pralatre xate.  It ca n n ot be rea dil y e x plai ne d b y t he patie nt’s cli nical state,  i nterc urre nt 
ill ness, or c o nc o mita nt me dicati o ns.  I n case of cessati o n or re d ucti o n of t he d ose, t he e ve nt 
a bates or res ol ves, a n d it rea p pears u p o n c halle n ge. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 7 of 9 5 
It s h o ul d be e m p hasize d t hat i neffecti ve treat me nt s h o ul d n ot be c o nsi dere d as ca usall y 
relate d i n t he c o nte xt of A E re p orti n g. 
T hese criteria, i n a d diti o n t o g o o d cli nical j u d g me nt, s h o ul d be use d as a g ui de f or 
deter mi ni n g t he ca usal assess me nt. 
1 4. 6 
S eri o u s A d v er s e E v e nt s 
I n t he i nterest of patie nt care a n d t o all o w All os t o f ulfill all re g ulat or y re q uire me nts, a n y 
seri o us a d verse e ve nt ( S A E), re gar dless of ca usal relati o ns hi p t o pralatre xate, m ust be 
re p orte d t o All os wit hi n 2 4 h o urs of k n o wle d ge of t he e ve nt. 
1 4. 6. 1 
D efi niti o n 
S A Es are defi ne d ( C F R 3 1 2. 3 2, I C H of Tec h nical Re q uire me nts f or Re gistrati o n of 
P har mace uticals f or H u ma n Use E 2 A G ui deli ne) as  t h ose A Es t hat meet a n y of t he f oll o wi n g 
criteria: 
• 
Res ults i n deat h. 
• 
Is life-t hreate ni n g: ie, a n y e ve nt t hat, i n t he o pi ni o n of t he i n vesti gat or, p oses a n 
i m me diate ris k of deat h fr o m t hat e ve nt. 
• 
Re q uires i n patie nt h os pitaliza ti o n or pr ol o n gati o n of e xistin g h os pitalizati o n (e xcl u di n g 
h os pitalizati o ns f or st u d y t hera p y, disease- relate d pr oce d ures, or place me nt of a n 
i n d welli n g cat heter, u nless ass ociate d wit h ot her S A Es). 
• 
Res ults i n a persiste nt or si g nifica nt disa bilit y/i nca pacit y. 
• 
Res ults i n a c o n ge nital a n o mal y/ birt h defect. 
• 
I ncl u des i m p orta nt me dical e ve nts t hat ma y n ot be i m me diatel y life-t hreate ni n g or res ult 
i n deat h or h os pitalizati o n b ut ma y je o par dize t he patie nt or ma y req uire i nter ve nti o n t o 
pre ve nt 1 of t he o utc o mes lis te d i n t his defi niti o n. 
1 4. 6. 2 
S eri o u s A d v er s e E v e nt R e p orti n g 
• 
A n y S A E t hat occ urs fr o m t he ti me t he st u d y I C is o btai ne d u ntil ra n d o mizati o n nee ds t o 
be re p orte d o nl y if t he e ve nt was relate d t o a st u d y pr oce d ure. 
• 
A n y S A E t hat occ urs fr o m ra n d o mizati o n t h r o u g h 3 0 da ys after t he last d ose of 
pralatre xate or t hr o u g h 3 0 da ys after treat me nt disc o nti n ua ti o n criteria are met f or t he 
O bser vati o n Ar m m ust be re p orte d t o All os wit hi n 2 4 h o urs of k n o wle d ge of t he e ve nt.  
Fr o m 3 1 da ys after t he last d ose of pralatre xate, patie nts will c o nti n ue t o be assesse d f or 
S A Es t hat are relate d t o pralatre xate. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 8 of 9 5 
• 
S A Es (re gar dless of ca usalit y) m ust  be re p orte d a n d t he S A E R fa xe d wit hi n 2 4 h o urs of 
k n o wle d ge of t he e ve nt t o : 
All os T hera pe utics, I nc. 
Pri mar y C o ntact: Cli nical Dr u g Safet y a n d 
P har mac o vi gila nce De part me nt 
P h o ne: 
 
Fa x: 
 or 
 
E mail: all os dr u gsafet y @all os.c o m 
All os ma y re q uest a d diti o nal i nf or mati o n fr o m  t he i n vesti gat or t o e ns ure t he ti mel y 
c o m pleti o n of acc urate safet y re p orts.  Safet y data  t hat are critical t o t he re p orta bilit y of a n 
S A E, s uc h as ca usalit y assess me n t a n d seri o us criteria, s h o ul d be i ncl u de d i n t he i nitial fa x 
f or S A E R.  If o mitte d, a ti mel y res p o nse t o dr u g safet y data q ueries recei ve d fr o m All os or 
a n All os desi g nee is e x pecte d. 
T he i n vesti gat or m ust ta ke all t hera pe utic m eas ures necessar y f or res ol uti o n of t he S A E.  
A n y me dicati o ns necessar y f or tr eat me nt of t he S A E m ust be r ec or de d o nt o t he c o nc o mita nt 
me dicati o n secti o n of t he patie nt’s C R F. 
S A Es t hat are pralatre xate-relate d will be  f oll o we d u ntil res ol uti o n or ret ur ne d t o 
baseli ne/ Gra de 1, w hic he ver is l o n ger, or u ntil  it is deter mi ne d t hat t he o utc o me will n ot 
c ha n ge wit h f urt her f oll o w- u p. 
A d diti o nall y, t he S A E m ust be  e ntere d o n t he A E pa ge(s) of t he C R F.  F oll o w- u p S A E Rs 
nee d t o be s u b mitte d t o All os as s o o n as a d diti o nal i nf or mati o n re gar di n g t he e ve nt bec o mes 
a vaila ble (e g, dia g n osis is ma de, la b orat or y or test res ults, e ve nt c o urse, o utc o me, etc).  T he 
All os C R A or desi g nee will c ollect t h e ori gi nal S A E R fr o m t he site. 
All os/ desi g nee will be res p o nsi ble f or re p orti n g S A Es t o t he re g ulat or y a ut h orities i n 
acc or da nce wit h a p plica ble e x pe dite d re p orti n g re g ulat or y g ui deli nes.  T he i n vesti gat or is 
res p o nsi ble f or s u b mitti n g S A Es t o his/ her I nstit uti o nal Re vie w B oar d (I R B)/ Et hics 
C o m mittee ( E C)/ Researc h Et hics B oar d ( R E B). 
1 4. 6. 3 
E x cl u si o n s t o S eri o u s A d v er s e E v e nt R e p orti n g R e q uir e m e nt s 
T he f oll o wi n g are n ot c o nsi dere d S A Es: 
• 
Sit uati o ns w here a n u nt o war d me dical occ urre nce di d n ot occ ur (e g, s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital). 
• 
A ntici pate d da y-t o- da y fl uct uati o ns of pre-e x isti n g disease(s) or co n diti o n(s) prese nt or 
detecte d pri or t o ra n d o mizati o n t hat d o n ot w orse n. 
• 
Electi ve h os pitalizati o ns s olel y f or t he i nitia ti o n of s u bse q ue nt t hera p y f or t he disease 
bei n g st u die d. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 6 9 of 9 5 
1 4. 7 
R e pr o d u cti v e Ri s k s 
Pralatre xate m ust n ot be use d  d uri n g pre g na nc y or breastfee din g.  Pre- me n o pa usal fe males of 
c hil d beari n g p ote ntial will f oll o w a n a p pr o ve d, me dicall y acce pte d birt h c o ntr ol re gi me n 
(e g, birt h c o ntr ol pills, i ntra uteri ne de vice, c o n d o ms, i m pla nts) or a gree t o a bstai n fr o m 
heter ose x ual i nterc o urse w hile partici pati n g i n  t he st u d y a n d f or 3 0 da ys f oll o wi n g t he last 
d ose of pralatre xate.   
Males w h o are se x uall y acti ve m ust a gree t o practice a me dicall y acce pta ble barrier met h o d 
c o ntrace pti ve re gi me n (e g, c o n d o ms) or a gree t o  a bstai n fr o m heter ose x ual i nterc o urse w hile 
recei vi n g pralatre xate a n d f or 9 0 da ys after t he last a d mi nistrati o n of pralatre xate. 
1 4. 7. 1 
Pr e g n a n c y N otifi c ati o n 
Pre g na ncies i n v ol vi n g a st u d y patie n t or a patie nt’s part ner t hat occ ur fr o m t he first d ose of 
pralatre xate t hr o u g h 3 0 da ys afte r t he last d ose of pralatre xate m ust be br o u g ht t o t he 
atte nti o n of t he treati n g p h ysicia n i m me diatel y a n d re p orte d t o All os w it hi n 2 4 h o urs after t he 
i n vesti gat or has gai ne d k n o wle d ge of t he e ve nt, usi n g t he Pre g na nc y N otificati o n F or m.  T he 
i n vesti gat or m ust re p ort a n y s uc h e ve nt t o All os wit hi n 2 4 h o urs via tele p h o ne a n d via fa x 
(see c o ntact i nf or mati o n i n Secti o n 1 4. 6. 2 ).  F oll o w- u p i nf or mati o n re gar di n g t he o utc o me of 
t he pre g na nc y will be re q ueste d b y t he All os Cli nical Dr u g Safet y a n d P har mac o vi gila nce 
De part me nt.  
Treat me nt will be disc o n ti n ue d f or all patie nts w h o bec o me pre g na nt d uri n g partici pati o n i n 
t his st u d y. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 0 of 9 5 
1 5 S T A TI S TI C A L P L A N  
1 5. 1 
O bj e cti v e s 
Pri mar y  
• 
Deter mi ne t he efficac y of pralatre xate c o m p are d t o o bser vati o n w he n a d mi nistere d t o 
patie nts wit h pre vi o usl y u n dia g n ose d P T C L  w h o ha ve ac hie ve d a n o bjecti ve res p o nse 
after c o m pleti n g at least 6 c ycl es of C H O P- base d treat me nt. 
Sec o n dar y  
• 
Deter mi ne t he safet y of pralatre xate w h e n a d mi nistere d f oll o wi n g a c o urse of 
C H O P- base d treat me nt t o patie nts wit h pre vi o usl y u n dia g n ose d P T C L. 
1 5. 2 
E n d p oi nt s 
1 5. 2. 1 
Effi c a c y E n d p oi nt s 
Pri mar y  
• 
P F S a n d O S. 
Sec o n dar y  
• 
O bjecti ve res p o nse ( C R or P R) t o pralatre xate vers us o bser vati o n. 
T he pri mar y a nal yses of P F S a n d res p o nse will us e t he ce ntral re vie w t u m or assess me nts per 
I W C wit h o ut usi n g P E T.  A d diti o nal a nal yses of P F S a n d res p o nse will use I W C, i ncl u di n g 
P E T, a n d i n vesti gat ors’ assess me nt of res p o nse. 
1 5. 2. 2 
S af et y E n d p oi nt s 
T he safet y e n d p oi nts i ncl u de: 
• 
I nci de nce a n d se verit y of treat me nt-e mer ge nt A Es. 
• 
C ha n ges i n la b orat or y val ues. 
1 5. 3 
A n al y si s P o p ul ati o n 
1 5. 3. 1 
Pri m ar y A n al y si s S et/I nt e nt-t o-tr e at A n al y si s S et 
T he pri mar y efficac y set, als o referre d t o as t he i nte nt-t o-treat p o p ulati o n, i ncl u des all 
ra n d o mize d patie nts.  Eac h patie nt will be i ncl u de d i n t he treat me nt gr o u p assi g ne d at 
ra n d o mizati o n, re gar dless of t he treat me nt recei ve d.  T his a nal ysis set will be use d f or t he 
pri mar y a nal yses of all efficac y e n d p oi nts. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 1 of 9 5 
1 5. 3. 2 
S af et y A n al y si s S et 
T he safet y a nal ysis set c o nsists of all patie nts ra n d o mize d t o t he Pralatre xate Ar m w h o 
recei ve at least 1 d ose of pralatre xate pl us all patie nts ra n d o mize d t o t he O bser vati o n Ar m 
w h o d o n ot disc o nti n ue t he st u d y wit hi n 3 da ys of ra n d o mizati o n.  T his a nal ysis set will be 
use d f or t he pri mar y a nal yses  of all safet y e n d p oi nts. 
1 5. 3. 3 
I nt eri m A n al y s e s S et s 
O ne a nal ysis of P F S, a n d 2 f or mal i nteri m a n al yses a n d a fi nal a nal ysis of O S will be 
perf or me d.  T he first a nal ysis will be pe rf or me d w he n b ot h 2 8 0 P F S e ve nts a n d 1 2 8 O S 
e ve nts ha ve occ urre d.  T he o nl y a nal ysis f or P F S will be perf or me d at t his first a nal ysis, a n d 
will be assesse d at t he 0. 0 5 le vel of si g nifica n ce.  If P F S is si g nifica nt at t he 0. 0 5 le vel, a n 
a nal ysis will be c o n d ucte d o n O S at t his ti me.  If P F S is n ot si g nifica nt at t he 0. 0 5 le vel, t he 
st u d y will be st o p pe d.  T w o a d diti o nal a nal yses of s ur vi val will be perf or me d w he n 
a p pr o xi matel y t w o-t hir ds of 3 8 5 deat hs, a n d a ll 3 8 5 deat hs ha ve occ urre d, res pecti vel y. 
1 5. 4 
S a m pl e Si z e 
A t otal of 5 4 9 ra n d o mize d patie nt s are pla n ne d f or t his st u d y.   
O utc o me data f or patie nts wit h T-cell l y m p h o ma w h o recei ve first-li ne C H O P is li mite d.  A 
retr os pecti ve st u d y of t he I nter nati o nal T- Cell L y m p h o ma Pr oject de m o nstrate d a 5- year O S 
rate of 3 2 % a n d a 5- year F F S rate of 2 0 % f or patie nts wit h P T C L- N O S , wit h wi del y var yi n g 
res ults f or ot her s u bt y pes.1 8  Me dia n O S f or t hese patie nts di d n ot see m t o be a f u ncti o n of 
w het her t he patie nt recei ve d a n a nt hrac ycli ne- base d i n d ucti o n t hera p y.  I n a retr os pecti ve 
e val uati o n of 9 6 patie nts dia g n ose d wit hi n t he N o n- H o d g ki n’s L y mp h o ma Classificati o n 
Pr oject, R u di ger et al re p ort  a si milar fi n di n g, wit h 5- year O S a n d F F S rates of 2 6 % a n d 
2 0 %, res pecti vel y, f or P T C L patie nts trea te d wit h a d o x or u bici n-c o ntai ni n g re gi me n.1 2  
Per Fi g ure 1 of t he R u di ger p u blicati o n, t he esti mate d me dia n F F S i n t hese patie nts is 
a p pr o xi matel y 6 m o nt hs.   
Re p orts of res p o nse rate t o firs t-li ne C H O P- base d re gi me ns i n patie nts wit h P T C L are als o 
a vaila ble.  Galla mi ni, et al  ( 2 0 0 7) c o n d ucte d a s mall st u d y ( n = 2 4 e val ua ble) e val uati n g 
C H O P pl us ale mt uz u ma b a d mi nistere d e ver y 4 wee ks f or a t otal of 2 8 wee ks. 1 6  T he y 
o bser ve d a n o verall res p o nse rate of 7 5 % ( 7 1 % C R, 4 % P R).  I n  a se parate re p ort, Galla mi ni, 
et al perf or me d a retr os pecti v e a nal ysis of 3 8 5 patie nts wit h P T C L- U, wit h t he maj orit y 
( 7 8 %) recei vi n g c he m ot hera p y c o ntai ni n g a nt hrac ycli ne.3 6  T he y re p orte d a n o verall 
res p o nse rate of 7 4 % ( 5 3 % C R, 2 1 % P R) i n t he 3 7 2 e val ua ble patie nts.  Merca dal a n d 
c ollea g ues re p orte d o n a series of 4 1 patie nts ≤ 6 5 years ol d w h o were pla n ne d t o recei ve 
6 c ycles of i nte nsi ve c he m ot hera p y ( hi g h- d ose C H O P alter nati n g wit h et o p osi de, 
met h yl pre d nis ol o ne, c ytara bi ne, a n d cis plati n  [ E S H A P]) f oll o we d b y a ut ol o g o us ste m cell 
tra ns pla ntati o n, if i n res p o nse.3 7  T we nt y-ei g ht patie nts ( 6 8 %) recei ve d t he pla n ne d 6 c o urses 
of t hera p y, 6 ( 1 5 %) patie nts recei ve d 5 c o urse s of t hera p y, a n d 7 ( 1 7 %) recei ve d less t ha n 
5 c o urses.  F oll o wi n g t he c he m ot hera p y p hase, t he C R rate was 4 9 % a n d t he P R rate was 
1 0 %.  Ki m a n d c olla b orat ors a d mi nistere d C H O P  pl us et o p osi de a n d ge mcita bi ne t o a c o h ort 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 2 of 9 5 
of 2 6 first-li ne P T C L patie nts. 3 8  T he me dia n n u m ber of c ycles a d mi nistere d was 4, a n d t he 
o verall res p o nse rate was 7 7 % ( 6 2 % C R, 1 5 % P R).  A b o u ya bis a n d c o llea g ues perf or me d a 
meta-a nal ysis of n o n- A L C L P T C L patie nts r ecei vi n g a nt hrac ycli ne- base d c he m ot hera p y i n 
t he first-li ne setti n g.3 9  A t otal of 3 1 st u dies were i de ntified i n v ol vi n g a t otal of 1 9 9 6 patie nts.  
T he o verall C R rate was 5 5 % a n d t he 5- year O S rate was 3 7 %. 
Acr oss all of t hese re p orte d st u dies, a p pr o xi matel y  5 0 % of patie nts ac hie ve a C R t o first-li ne 
C H O P, wit h a n a d diti o nal 1 0- 2 0 % ac hie vi n g a P R.  F urt her m ore, t he 5- year P F S is 
a p pr o xi matel y 2 0 %, wit h a me dia n P F S of a p pr o xi matel y 9 m o nt hs i n all patie nts.  F or t he 
P D X- 0 1 7 st u d y, we ass u me o ne-t hir d of patie nts will ha ve disease refract or y t o C H O P, a n d 
t hat t he me dia n P F S i n t hese patie nts will be 3 m o nt hs.  C o u ple d wit h a n o verall me dia n P F S 
of 9 m o nt hs, a n d ass u mi n g e x p o ne ntiall y distri b ute d P F S, t his i m plies t he me dia n P F S i n 
patie nts w h o res p o n d t o C H O P is a p pr o xi matel y  1 6 m o nt hs.  S u btracti n g o ut 6 m o nt hs f or 
C H O P a d mi nistrati o n a n d was h o ut  pri or t o ra n d o mizati o n res ults i n a n esti mate d 1 0 m o nt h 
me dia n P F S f or t he O bser vati o n Ar m patie nts i n t his st u d y. 
T he sa m ple size is base d o n c o m pari n g t he tr eat me nt gr o u ps wit h res pect t o t he pri mar y 
efficac y e n d p oi nts of P F S a n d O S.  Ass u mi n g pr o p orti o nal hazar ds, a tr ue  hazar d rati o ( H R) 
o n O S of 0. 7 3, a n d a 2: 1 ra n d o mizati o n (treat me nt: o bser vati o n) wit h a t otal of 5 4 9 patie nts 
( 3 6 6 i n t he treat me nt gr o u p vs 1 8 3 i n t he o bser vati o n gr o u p), a t otal of 3 8 5 O S e ve nts 
( deat hs) will pr o vi de at least 8 0 % p o wer t o s h o w H R < 1. 0 0 usi n g a 2-si de d stratifie d 
l o g-ra n k test at a 0. 0 5 si g nifica nce le vel (al p ha = 0. 0 5), ass u mi n g a n accr ual peri o d of 
5 4 m o nt hs a n d a f oll o w u p peri o d of 3 0 m o nt hs.  F or a H R o n P F S of 0. 6 7, a n d a 
2: 1 ra n d o mizati o n (treat me nt: o bser vati o n), a t otal of 2 8 0 P F S e ve nts ( P D + deat hs) will 
pr o vi de at least 8 0 % p o wer t o s h o w H R < 1. 0 0 usi n g a 2-si de d stratifie d l o g-ra n k test at a 
0. 0 5 si g nifica nce le vel (al p ha = 0. 0 5).   
1 5. 5 
Str atifi c ati o n  
Patie nts meeti n g ra n d o mizati o n eli g i bilit y criteria will be ra n d o mize d 2: 1 t o t he Pralatre xate 
Ar m or t he O bser vati o n Ar m acc or di n g t o a pe r m ute d bl oc k desi g n, bala nci n g wit hi n t he 
f oll o wi n g strat u m. 
• 
Res p o nse per i n vesti gat or at c o m pleti o n of C H O P- base d t hera p y ( C R vs P R) 
1 5. 6 
A n al y si s Pl a n s 
1 5. 6. 1 
I nt eri m A n al y s e s of O S 
T w o f or mal i nteri m a nal yses a n d a fi nal a nal ysis  of O S will be perfor me d.  T he first i nteri m 
a nal ysis will be perf or me d w he n b ot h 2 8 0 P F S e ve nts a n d 1 2 8 O S e ve nts ha ve occ urre d.  
T he o nl y a nal ysis f or P F S will be perf or me d at t his ti me, a n d will be assesse d at t he 
0. 0 5 le vel of si g nifica nce.  If P F S is si g nifica nt at  t he 0. 0 5 le vel, a n i nteri m a nal ysis will be 
c o n d ucte d o n s ur vi val at t his ti me.  If t here ar e 1 2 8 O S e ve nts, or 1/ 3 of t he i nf or mati o n of 
3 8 5 deat hs, i ncl u de d i n t he first i nteri m a nal ys is of O S, t he le vel of si g nifica nce (al p ha) 
w o ul d be 0. 0 0 0 2, acc or di n g t o O’ Brie n a n d Fle mi n g. 4 0  If P F S is si g nifica nt, a test f or f utilit y 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 3 of 9 5 
of O S will n ot be c o n d ucte d at t he first i nteri m a n al ysis si nce s uc h a res ult c o ul d n ot occ ur.  
T he sec o n d i nteri m a nal ysis f or O S will be perf or me d w he n t w o-t hir ds ( 2 5 6) of t he s ur vi val 
e ve nts ha ve occ urre d, at t he 0. 0 1 3 le vel of si g nifica nce.  T he H R st o p pi n g b o u n d f or f utilit y 
at t his i nteri m a nal ysis will be 1. 0 5 ( 9 5 % c o nf i de nce i nter val [ CI]: 0. 8 0, 1. 2 9).  If t he H R f or 
O S is greater t ha n 1. 0 5, t he st u d y will be st o p pe d .  T he fi nal a nal ysis f or s ur vi val will be 
perf or me d w he n 3 8 5 O S e ve nts ha ve occ urr e d, at t he 0. 0 4 6 le vel of si g nifica nce.   
A D M C will peri o dicall y re vie w safet y data at re g ularl y sc he d ule d meeti n gs a n d at t he sa me 
ti me as eac h i nteri m a nal ysis of efficac y.  T he first f or mal safet y re vie w will occ ur w he n 
a p pr o xi matel y 1 0 0 patie nts ha ve bee n ra n d o m ize d a n d c o m pl ete d at least 8 wee ks p ost-
ra n d o mizati o n pralatre xate/ o bservati o n or ha ve disc o nti n ue d. 
 
At eac h i nteri m a nal ysis f or s ur vi val, t he st u d y ma y be st o p pe d f or o ver w hel mi n g e vi de nce 
of f utilit y or s u peri orit y acc or di n g t o s pecifie d b o u n daries.  T he D M C ma y als o ma ke 
rec o m me n dati o ns re gar di n g a dj ust me nts t o t he sa m ple size, if t he y are warra nte d. 
1 5. 6. 2 
Fi n al A n al y s e s of Effi c a c y E n d p oi nt s 
T he pri mar y efficac y a nal ysis o n P F S will be perf or me d w he n a p pr o xi matel y 2 8 0 P F S e ve nts 
a n d 1 2 8 O S e ve nts ha ve occ urre d.  T his is es ti mate d t o occ ur a p pr o xi matel y 4 8 m o nt hs after 
t he first patie nt is ra n d o mize d.  All os will set a data c ut- off date f or t he pri mar y efficac y 
a nal yses i n a ntici pati o n of 2 8 0 t h P F S e ve nt a n d 1 2 8t h O S e ve nt.  T he pri mar y efficac y 
a nal ysis o n O S will be perf or me d w he n a p pr o xi matel y 3 8 5 O S e ve nts ha ve occ urre d. 
A ste p- d o w n pr oce d ure will be use d f or a nal yzi n g t he c o- pri mar y e n d p oi nts of P F S a n d O S.  
If t he P F S e n d p oi nt is si g nifica nt at t he 0. 0 5 le vel t he O S e n d p oi nt will be teste d at a n o verall 
si g nifica nce le vel of 0. 0 5.  H o we ver, if t he P F S e n d p oi nt fails t o s h o w si g nifica nce, t he st u d y 
will be st o p pe d a n d O S will n ot be teste d.  T he st u d y will meet its pri mar y o bjecti ve if b ot h 
t he P F S a n d O S e n d p oi nts are si g nifica nt.  T he i nteri m a nal ysis f or O S will be i m ple me nte d 
usi n g t he err or-s pe n di n g a p pr oac h of La n a n d De Mets acc or di n g t o t he u nifie d fa mil y 
a p pr oac h wit h b o u n dar y relati o ns hi ps of O’ Brie n a n d Fle mi n g f or earl y st o p pi n g t o reject t he 
n ull h y p ot hesis (s u peri orit y). 4 1  T he b o u n daries f or earl y st o p pin g d ue t o fail ure t o reject t he 
n ull h y p ot hesis (f utilit y) will be deter mi ne d acc o r di n g t o t he u nifie d fa mil y a p pr oac h wit h 
b o u n dar y s ha pe para meters o n t he sa m ple mea n scale t hat res ult fr o m c h o osi n g 
P  = 2. 0 (all R a n d A para meters i n t he u nifie d fa mil y a p pr oac h set e q ual t o zer o) 4 2. 
T he pri mar y a nal yses of P F S a n d o bjecti ve res p o nse will use t he ce ntral re vie w t u m or 
assess me nts per I W C wit h o ut usi n g P E T.  A d diti o nal a nal yses of P F S a n d res p o nse will use 
I W C, i ncl u di n g P E T, a n d i n vesti gat ors’ assess me nt of res p o nse.  A d ditio nal details re gar di n g 
ce ntral re vie w will be pr o vi de d i n t he re vie wer’s c harter.  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 4 of 9 5 
1 5. 7 
Effi c a c y E n d p oi nt s  
1 5. 7. 1 
Pr o gr e s si o n-fr e e S ur vi v al 
P F S ti me is calc ulate d as t he n u m ber of da ys fr o m ra n d o mizati o n t o t he date of o bjecti ve 
d oc u me ntati o n of P D or deat h, re gar dless of ca use ( date of P D or deat h - date of 
ra n d o mizati o n + 1).  Patie nts w h o are ali ve wit h o ut a disease res p o nse assess me nt of P D will 
be ce ns ore d at t heir last disease assess me nt da te or t he date of ra n d o mizati o n w hic he ver is 
later.  Date of pr o gressi o n will n ot be i m p ute d f or patie nts wit h missi n g t u m or assess me nt(s) 
bef ore  a n assess me nt of P D.  Patie nts w h o wit h dra w fr o m treat me nt pri or t o P D wit h o ut 
wit h dra wi n g c o nse nt will be f oll o we d f or di sease stat us w he ne ver p ossi ble, e ve n if 
s u bse q ue nt t hera p y, i ncl u di n g tra ns pla nt, has bee n i nitiate d pri or t o d oc u me nte d P D per 
ce ntral re vie w at least u ntil t he P F S a nal ysis.  Patie nts w h o ha ve n o res p o nse assess me nts 
after baseli ne will be ce ns o re d at ra n d o mizati o n.   
Strata use d i n t he a nal yses will be t h ose use d f or st u d y ra n d o mizati o n (as rec or de d o n t he 
I R T).  Wit h t his tec h ni q ue, t he H R ca n be c o nsiste ntl y esti mate d (ass u mi n g t he pr o p orti o nal 
hazar ds m o del is c orrect), as t he p ote ntial bias d ue t o t he as y m metric visits is re m o ve d.  It 
als o c orrects f or t he T y pe I err or i nflati o n a n d retai ns t he n o mi nal st u d y p o wer.   
T he pri mar y a nal ysis of P F S will be base d o n P D as deter mi ne d b y i n de pe n de nt ce ntral 
re vie w bli n de d t o treat me nt gr o u p assi g n me nt.  A se parate c harter will detail s pecifics a b o ut 
ce ntral re vie w o perati o n a n d res p o nse/ P D defi ni ti o n details.  A d diti o nal a nal yses will use t he 
i n vesti gat ors’ assess me nt of res p o nse. 
T he stratifie d l o g-ra n k test w ill be t he pri mar y met h o d use d t o test t he h y p ot hesis t hat 
pralatre xate e xte n ds P F S relati ve t o o bser vati o n.  I n a d diti o n, t he stra tifie d C o x re gressi o n 
m o del will be use d t o calc ulate t he P F S ( H R), al o n g wit h t he 9 5 % c o nfi de nce i nter val ( CI).  
Res ults of t he u nstratifie d C o x re gressi o n m o del (a n d l o g-ra n k test) will als o be prese nte d.  
T he pr o p orti o nal hazar ds ass u m pti o n of  t he C o x m o del will be assesse d. 
1 5. 7. 2 
O v er all S ur vi v al 
O S ti me is calc ulate d as t he n u m ber of da ys  fr o m ra n d o mizati o n t o t he date of deat h, 
re gar dless of ca use ( date of deat h - date of ra n d o mizati o n + 1).  S ur vi val f oll o w- u p will 
c o nti n ue f or u p t o 7 years fr o m ra n d o mizati o n. 
T he stratifie d l o g-ra n k test w ill be t he pri mar y met h o d use d t o test t he h y p ot hesis t hat 
pralatre xate e xte n ds O S relati ve t o o bser vati o n.  I n a d diti o n, t he O S H R, al o n g wit h 9 5 % CIs, 
will be esti mate d via t he stratifie d C o x m o del.  Strata use d i n t hese a nal yses will be t h ose 
use d f or st u d y ra n d o mizati o n (as rec or de d usi n g t he I R T).  Res ults of  t he u nstratifie d C o x 
re gressi o n m o del (a n d l o g-ra n k test) will als o be prese nte d.  T he pr o p orti o nal hazar ds 
ass u m pti o n of t he C o x m o del will be assesse d.   

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 5 of 9 5 
1 5. 7. 3 
O bj e cti v e R e s p o n s e R at e 
T he n u m ber a n d perce nta ge of patie nts wit h a n  o bjecti ve res p o nse of C R or P R will be 
s u m marize d.  T he perce nta ge will be calc ulate d b y di vi di n g t he n u m ber of patie nts wit hi n 
eac h cate g or y of res p o nse b y t he n u m ber of patie n ts wit h meas ura ble disease at baseli ne.  
Eac h patie nt will be c o u nte d wit hi n o nl y 1 re s p o nse gr o u p, wit h t he o verall best res p o nse 
d uri n g t he st u d y as t he classificati o n gr o u p.  T h e treat me nt gr o u ps will be c o m pare d wit h 
res pect t o o bjecti ve res p o nse rate ( C R + P R) usi n g t he stratifie d C oc hra n- Ma ntel- Hae nszel 
test.  A 2-si de d 9 5 % e xact CI will be calc ulate d f or t he differe nce i n o bjecti ve res p o nse rates 
bet wee n t he 2 treat me nt gr o u ps.  Descri pti ve statistics will be pr o vi de d f or best t u m or 
res p o nse f or eac h treat me nt gr o u p.   
1 5. 8 
S af et y A n al y si s 
A nal ysis of safet y will be perf or me d o n t he safe t y a nal ysis set.  St u d y data will be m o nit ore d 
o n a n o n g oi n g basis b y t he cli nical st u d y tea m t o e ns ure patie nts’ safet y. 
1 5. 8. 1 
A d v er s e E v e nt s 
T he Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) will be use d t o c o de all A Es t o 
a s yste m or ga n class ( S O C) a n d a preferre d ter m .  Patie nt i nci de nce of A Es will be ta b ulate d 
b y S O C, preferre d ter m, a n d se verit y gra de f o r all A Es, S A Es, treat me nt-relate d A Es, a n d 
treat me nt-relate d S A Es.  Eac h of t hese o ut p uts will i ncl u de ta b ulati o n b y ma xi m u m se verit y 
f or eac h S O C a n d preferre d ter m as re p orte d b y t he i n vesti gat or base d o n C T C A E, 
Versi o n 4. 0.  If a n A E ca n n ot be gra de d ba se d o n C T C A E, t he i n vesti gat or will assi g n a 
se verit y base d o n 1 = mil d, 2 = m o derate, 3 = se vere, 4 = life t hreate ni n g, a n d 5 = deat h 
relate d t o A E.  S u m maries of A Es, S A Es, treatme nt-relate d A Es, a n d treat me nt-relate d S A Es 
occ urri n g i n at least 5 % of t he patie nts will be pr o vi de d i n desce n di n g or der of fre q ue nc y b y 
S O C a n d preferre d ter m. 
A d diti o nal ta bles s u m marizi n g patie nt i nci de nce ( b y preferre d ter m) of t he f oll o wi n g will be 
ge nerate d: 
• 
All A Es 
• 
S A Es 
• 
Treat me nt-relate d A Es 
• 
Treat me nt-relate d S A Es 
• 
Gra de 3 or hi g her A Es 
• 
A Es lea di n g t o t he disc o nti n uati o n of pralat re xate or o bser vati o n or re m o val fr o m st u d y 
• 
A Es lea di n g t o d ose re d ucti o ns of t he st u d y dr u g 
• 
A Es wit h i nci de nce ≥ 5 % 
• 
Deat hs 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 6 of 9 5 
1 5. 8. 2 
A d v er s e E v e nt s Gr o u p e d b y Si mil ar Pr ef err e d T er m 
S u m mar y ta bles of treat me nt e mer ge nt, treat me nt-relate d, seri o us, a n d seri o us treat me nt-
relate d A Es gr o u pe d b y si milar preferre d ter m will be prese nte d.  F or t his prese ntati o n, 
certai n si milar preferre d ter ms ha ve bee n i de ntifie d a n d will be c o de d t o t he sa me preferre d 
ter m i n or der t o prese nt t he e ve nt i n a u nif or m ma n ner.  T hese ter ms are prese nte d i n t he 
statistical a nal ysis pla n (a d diti o nal preferre d ter ms ma y be i de ntifie d wit hi n eac h cate g or y 
d uri n g data re vie w a n d a d de d t o t his list).  
Se parate o ut p uts will be pr o vi de d f or s u b gr o u ps defi ne d b y a ge gr o u p ( < 6 5, ≥ 6 5), ge n der, 
a n d race (if feasi ble).   
Detaile d listi n gs f or all A Es a n d listi n gs a n d/ or narrati ves will be pr o vi de d f or seri o us a n d 
si g nifica nt A Es, a n d deat hs ( wit h ‘ o n st u d y’ deat hs [ deat hs t hat occ ur bef ore t he e n d of safet y 
f oll o w u p peri o d] i de ntifie d). 
1 5. 8. 3 
L a b or at or y P ar a m et er s 
La b orat or y para meters f or he mat ol o g y a n d bl o o d c he mistr y will be s u m marize d at baseli ne 
a n d last o bser ve d val ue.  A d diti o nall y, t he ma xi m u m a n d mi ni m u m o bser ve d p ost baseli ne 
val ues will be s u m marize d al o n g wit h t he c h a n ge fr o m baseli ne t o t he ma xi m u m o bser ve d 
val ue, mi ni m u m o bser ve d val ue, a n d last o bser ve d val ue.  Ta bles of s hifts i n se verit y 
( C T C A E Versi o n 4. 0) fr o m baseli ne f or selecte d la b orat or y para meters a n d selecte d 
ti me- p oi nts ma y als o be pr o vi de d.  A listi n g of all la b orat or y assess me nts ma y be pr o vi de d. 
I nci de nce of la b orat or y a b n or malities a n d s u bject i nci de nce of Gra de 3 or 4 la b orat or y 
t o xicities will be prese nte d.  S u m maries of he mat ol o g y a n d ser u m c he mistr y para meters 
al o n g wit h gra de s hifts fr o m baseli ne will be prese nte d. 
Sta n dar d P K para meters will be esti mate d fr o m t he li mite d plas ma sa m pli n g (e g, A U C, C ma x , 
a n d t 1/ 2). 
P O P P K a nal yses will be c o n d ucte d via n o nli near  mi xe d-effects m o deli n g t o esti mate P O P P K 
para meters f or pralatre xate, i n cl u di n g t y pical val ues, i nter-i n di vi d ual variati o n, a n d resi d ual 
varia bilit y after a d mi nistrati o n of  pralatre xate i n t he patie nt p o p ulati o n, a n d t o esti mate t he 
effects of i n di vi d ual-s pecific c o variate fact ors (e g, de m o gra p hics, disease state, etc) t hat ma y 
be pre dicti ve of t he u ne x plai ne d ra n d o m varia b ilit y i n pralatre xate P K.  I n a d diti o n, t he 
relati o ns hi p bet wee n t he P K of pralatre xate a n d res p o nse (safet y a n d efficac y) will be 
e x pl ore d. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 7 of 9 5 
1 6 S T U D Y M A N A G E M E N T 
1 6. 1 
I n v e sti g at or R e s p o n si biliti e s  
1 6. 1. 1 
G o o d Cli ni c al Pr a cti c e  
T he i n vesti gat or will e ns ure t hat t his st u d y is c o n d ucte d i n f ull c o m plia nce wit h t he 
pri nci ples of t he “ Declarati o n of Helsi n ki ” (as a me n de d i n T o k y o, Ve nice, H o n g K o n g, a n d 
S o ut h Africa), I C H g ui deli nes, or wit h t he la ws a n d re g ulati o ns of t he c o u ntr y i n w hic h t he 
researc h is c o n d ucte d.  B y si g ni n g t he U S F or m F D A 1 5 7 2, “ State me nt of I n vesti gat or”, t he 
i n vesti gat or c o m mits t o a d here t o a p plica ble secti o ns of t he U S C F R parts 5 0 “ Pr otecti o n of 
H u ma n S u bj ects”, 5 4 “ Fi na ncial Discl os ure b y Cli nical I n vesti gat or s”, 5 6 "I nstit uti o nal 
Re vie w B oar ds”, a n d 3 1 2 s u b part D “ Res p o nsi bi lities of S p o ns ors a n d I n vesti gat ors”.  All 
i n vesti gat ors will e ns ure a d here nce t o I C H g uideli nes f or G C P a n d Cli nical Safet y Data 
Ma na ge me nt. 
1 6. 1. 2 
I R B/ E C/ R E B A p pr o v al 
T he i nstit uti o n’s I R B/ E C/ R E B, or ot her c o m m ittee f u ncti o ni n g i n a si milar ca pacit y, will 
re vie w a n d a p pr o ve t he pr ot oc ol, i nitial a n d re vise d I C d oc u me nts, pr ot oc ol a me n d me nts, 
a n d safet y ite ms.  After a p pr o val b y t he IR B/ E C/ R E B, d oc u me ntati o n of a p pr o val a n d t he 
a p pr o ve d I C d oc u me nt will be se nt t o All os/ desi g n ee bef ore a n y patie nt is e nr olle d i nt o t his 
st u d y. 
1 6. 1. 3 
I nf or m e d C o n s e nt  
T he i n vesti gat or is res p o nsi ble f or pre pari n g t he writte n I C d oc ume nt f or t his st u d y.  All os or 
its desi g nee will pr o vi de t he i n vesti gat or wit h te m plates f or a n I C d oc u me nt.  T he 
i n vesti gat or ma y rearra n ge or re w or d t he c o nte nts of t hese te m plates, or ma y a d d ot her 
ele me nts or la n g ua ge, pr o vi de d t he mea ni n g a n d c o nte nt are n ot c ha n ge d or  delete d.  All os or 
desi g nee m ust re vie w a n d a p pr o ve t he I C d oc u me n t t hat is use d b y t he i n vesti gat or f or t his 
st u d y pri or t o I R B/ E C/ R E B s u b missi o n. 
Writte n I C will be o btai ne d fr o m all patie nts pa rtici pati n g i n t his st u d y, i n acc or da nce wit h 
I C H G C P a n d c urre nt re g ulat or y re q uire me nts.  T he case hist or y f or eac h patie nt m ust 
d oc u me nt t hat t he I C pr ocess wa s o btai ne d pri or t o partici patio n i n t he st u d y.  T he ori gi nal 
I C d oc u me nt will be ke pt i n t he patie nt’s rec or d, a n d a c o p y will be pr o vi de d t o t he patie nt. 
1 6. 1. 4 
St u d y Fil e s a n d R et e nti o n of R e c or d s 
T he i n vesti gat or m ust retai n all st u d y rec or ds u ntil at least 2 years after t he last a p pr o val of a 
mar keti n g a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o pe n di n g or c o nte m plate d 
mar keti n g a p plicati o ns i n a n I C H re gi o n or at  least 2 years ha ve ela pse d si nce t he f or mal 
disc o nti n uati o n of cli nical de vel o p me nt of t he i n vesti gati o nal pr o d uct as per 2 1 C F R 3 1 2. 6 2 
a n d I C H G C P E 6 4. 9. 5 a n d 5. 5. 1 2.  T hese d oc u me nts m ust be retai ne d f or a l o n ger peri o d, 
h o we ver, if re q uire d b y t he a p plica ble re g ulat or y re q uire me nts or b y a n a gree me nt wit h 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 8 of 9 5 
All os.  It is t he res p o nsi bilit y of t he s p o ns or t o i nf or m t he i n vesti gat or as t o w he n t hese 
d oc u me nts n o l o n ger nee d t o be retai ne d.  If t he i n vesti gat or rel ocates, or f or a n y reas o n 
desires t o dis p ose of t he rec or d s, t he st u d y rec or ds ma y be tra nsferre d t o a n ot her i nstit uti o n, 
a n ot her i n vesti gat or, or t o t h e s p o ns or u p o n writte n a gree me nt bet wee n t he i n vesti gat or a n d 
t he s p o ns or. 
1 6. 2 
R e c or di n g a n d C oll e cti n g of D at a 
I n acc or da nce wit h I C H a n d G C P g ui deli nes, t he i n vesti gat or will mai ntai n c o m plete, 
acc urate, le gi ble, a n d easil y retrie va ble data , a n d will all o w pers o n nel a ut h orize d b y All os 
access t o all st u d y data at a n y ti me.  S uc h data s hall als o be sec ure d i n or der t o pre ve nt l oss 
of data. 
1 6. 2. 1 
C a s e R e p ort F or m s 
All os ma y ma ke use of electr o nic da ta ca pt ure ( E D C) or pa per C R Fs. 
W he n usi n g pa per, All os’ C R Fs are pri nte d o n n o car b o n-re q uire d pa pe r t o per mit m ulti ple 
c o pies.  T he i n vesti gat or will retai n t he b ott o m c o p y f or his/ her st u d y files.  Data c ollecte d 
f or eac h patie nt will be rec or de d o n t he C R Fs.  T he i n vesti gat or is res p o nsi ble f or e ns uri n g 
t hat all data s u b mitte d are tr ue, acc urate, a n d ulti matel y c o m plete. 
C o m plete d C R Fs will be re vie we d a n d si g ne d b y a n i n vesti gat or liste d o n t he U S F or m F D A 
1 5 7 2 or e q ui vale nt.  T he C R A will verif y t he C R F data wit h t he patie nt’s s o urce data, 
e val uate t he data f or acc urac y, c o nsiste nc y, a n d c o m plete ness, a n d will e ns ure t hat all f or ms 
wit h missi n g data a n d/ or err ors are ulti matel y a d dresse d. 
W he n usi n g E D C, data c ollecte d f or eac h patie n t will be e ntere d b y site staff i nt o a n E D C 
data base.  T he i n vesti gat or is res p o nsi ble f o r e ns uri n g t hat all data s u b mitte d are tr ue, 
acc urate, a n d ulti matel y c o m plete. 
C o m plete d, E D C data will be re vie we d b y a n i n vesti gat or liste d o n t he U S F or m F D A 1 5 7 2 
or e q ui vale nt.  T his re vie w will be d oc u me nte d  b y t he i n vesti gat or or e q ui vale nt l o g gi n g i nt o 
t he E D C data base a n d pr o vi di n g si g n off usin g his/ her 2 1 C F R Part 1 1c o m plia nt electr o nic 
si g nat ure.  T he C R A will verif y t he C R F data wit h t he patie nt’s s o urce data, e val uate t he data 
f or acc urac y, c o nsiste nc y, a n d c o m plete ness, a n d will e ns ure t hat all scree ns wit h missi n g 
data a n d/ or err ors are ulti matel y a d dresse d. 
Acc urate a n d c o m plete C R Fs f or a patie nt, eit her  via pa per or E D C, m ust be s u b mitte d t o 
All os i n a ti mel y ma n ner. 
1 6. 2. 2 
D at a Cl arifi c ati o n F or m s 
Data Clarificati o n F or ms ( D C Fs), s uc h as Q u eries, Site N otificati o ns, a n d C R A A d de n da, 
will be use d b y All os staff or desi g nee t o atte m p t t o c orrect or clarif y missi n g, i nc o m plete, or 
ill o gical data.  Q ueries a n d Site N otificati o n ma y be c o m plete d i n di vi d uall y b y a n 
a p pr o priate pers o n o n t he Dele gati o n of A ut h orit y f or m, b ut m ust be re vie we d, a n d t he 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 7 9 of 9 5 
trac ki n g c o vers heet si g ne d b y, a n i n vesti gat or liste d o n t he U S F or m F D A 1 5 7 2 or 
e q ui vale nt.  C R A A d de n da ma y be c o m plete d b y  t he C R A b ut m ust be re vie we d a n d si g ne d 
b y a n i n vesti gat or liste d o n t he U S  F or m F D A 1 5 7 2 or e q ui vale nt. 
F or E D C st u dies, t his pr ocess is perf or me d electr o nicall y. 
1 6. 2. 3 
S elf- e vi d e nt C orr e cti o n s 
C R F data are e x pecte d t o be acc urate, c o nsis te nt, a n d c o m plete.  All os Cli nical Data 
Ma na ge me nt de part me nt or desi g nee (e g, a cli n ical researc h orga niza ti o n [ C R O]) ma y a p pl y 
t he f oll o wi n g c o n ve nti o ns t o c orrect t he All os data base wit h o ut iss ui n g a D C F t o site staff.  
H o we ver, a D C F ma y still be ge nerate d as nee de d f or clarificati o n/c o nfir mati o n. 
 
• 
Hea der data will be c orrecte d if t he err or is  o b vi o us a n d a c orrecti o n is s u p p orte d b y t he 
re mai n der of t he C R Fs. 
• 
D u plicate data will be delete d u nless t he C R F s pecificall y all o ws f or re peat val ues.  F or 
e xa m ple, if i de ntical la b val ues (i ncl u di n g date a n d ti me, if a p plica ble) are rec or de d f or a 
pr ot oc ol-s pecifie d visit a n d f or a miscella ne o us/ u nsc he d ule d visit,  o nl y t he pr ot oc ol 
s pecifie d visit data will be e ntere d i n t he data base. 
• 
Data rec or de d wit hi n t he case b o o k ca n be m o ve d t o t he a p pr o priate C R F fiel d if n o data 
are c ha n ge d.  
• 
Rele va nt c o m me nts or mar gi nalia will be a d de d t o t he C o m me nts secti o n. 
• 
Miss pelli n gs ma y be c orrecte d o nl y if t he c orrecti o n clarif ies (e g, e na bles c o di n g), b ut 
d oes n ot c ha n ge, t he mea ni n g or c o nte xt ual use of t he w or d.  
• 
L o n g te xt fiel ds will be s h or te ne d, if nee de d, usi n g ge nerall y acce pte d a b bre viati o ns t hat 
d o n ot c ha n ge t he cli nical mea ni n g of t he te xt. 
• 
Dates (e g, year b o u n dar y, da y/ m o nt h i n versi o n)  will be c orrecte d if t he c ha n ge is 
s u p p orte d b y t he re mai n der of t he C R Fs. 
• 
O nl y t he St o p Date will be rec or de d if a St o p Date a n d “ C o nti n ui n g" ( or si milar) are 
pr o vi de d. 
• 
A n i n dicat or fiel d left bla n k or mar ke d “ n o”  (e g, A Es prese nt?) will be u p date d t o “ yes” 
if data are prese nt. 
• 
If a fiel d w here “If Ot her, s pecif y” ( or si milar sit uati o n) i ncl u des data b ut t he b o x is bla n k 
( or si milar), t he b o x will be c hec ke d f or t he data base.  
• 
If t he res ol uti o n area of a Site N otificatio n ( S N) is bla n k b ut t h e S N is si g ne d, t he 
res p o nse fr o m t he site will be i nter prete d as “ A gree”. 
1 6. 2. 4 
Dr u g A c c o u nt a bilit y 
I n acc or da nce wit h all a p plica ble re g ulat or y re q uire me nts, t he i n vesti gat or or desi g nate d site 
staff m ust mai ntai n pralatre xate acc o u nta bilit y rec or ds t hr o u gh o ut t he c o urse of t he st u d y.  
T his pers o n(s) will d oc u me nt t he a m o u nt of pralatre xate a d mi nistere d t o patie nts.  T he C R A 
will re vie w i n ve nt or y a n d acc o u nta bilit y d oc u me ntati o n d uri n g m o nit ori n g visits. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 8 0 of 9 5 
T he i n vesti gat or will n ot s u p pl y i n vesti gati o nal st u d y dr u g t o other i n vesti gat ors n ot liste d o n 
t he U S F or m F D A 1 5 7 2 or e q ui valent.  I n vesti gati o nal st u d y dr u g use, ot her t ha n as directe d 
b y t his pr ot oc ol, is n ot all o we d wit h o ut pri or a ut h orizati o n fr o m All os. 
All u n use d vials of pralatre xate m ust be acc o u nte d  f or at t he site a n d mai ntai ne d i n a sec ure d, 
l oc ke d st ora ge area wit h access li mite d t o a ut h orize d st u d y pers o n nel o nl y.  Si nce 
pralatre xate is c yt ot o xic, use d vials will be de str o ye d per i nstit uti o n, l ocal, a n d all a p plica ble 
p olicies a n d pr oce d ures.  After st u d y c o ncl usi o n, all u n use d vials of pralatre xate ma y be 
destr o ye d at t he site, f oll o wi n g verificati o n of acc o u nta bilit y b y a n All os re prese ntati ve. 
1 6. 3 
Pr ot o c ol C o m pli a n c e 
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t he st u d y is c o n d ucte d i n acc or da nce wit h t he 
pr oce d ures a n d e val uati o ns de scri be d i n t his pr ot oc ol. 
1 6. 4 
S p o n s or R e s p o n si biliti e s 
1 6. 4. 1 
A m e n d m e nt s t o t h e Pr ot o c ol 
A n y a me n d me nt t o t he pr ot oc ol, as dee me d a p pr o priate b y All os, will be i m ple me nte d as t he 
st u d y pr o gresses.  All os ma y als o ma ke s uc h c h a n ges t o t he pr ot oc ol, as it dee ms necessar y 
f or safet y reas o ns, or as ma y be re q uire d b y t he re g ulat or y a ut h orities.  A me n d me nts will be 
s u b mitte d t o t he I R B/ E C/ R E B f or writte n a p pr o val, bef ore i m ple me ntati o n.  T he e x pe dite d 
re vie w pr oce d ure f or a n a me n d me nt is a p pr o priate o nl y if mi n or c ha n ges are ma de i n t he 
pr ot oc ol. 
1 6. 4. 2 
S af et y M o nit ori n g 
T he cli nical dr u g safet y of pr alatre xate will be c o nti n u o usl y  e val uate d b y t he St u d y Me dical 
M o nit or o n a n o n g oi n g basis d uri n g t he c o urse of t his cli nical st u d y.  All S A Es f or 
pralatre xate i n t his st u d y a n d all ot her o n g oi n g cli nical st u dies  wit h pralatre xate will be 
pr ocesse d i n c o m plia nce wit h c u rre nt re g ulat or y g ui deli nes b y t he All os Cli nical Dr u g Safet y 
a n d P har ma c o vi gila nce gr o u p.  T his pr ocessi n g will i ncl u de a f or mal assess me nt of eac h 
S A E b y t he p h ysicia n me dical m o nit or f or cli nical dr u g safet y.  I n a d diti o n, a c u m ulati ve 
re vie w of all S A Es fr o m all s o urces will be assesse d o n a bi m o nt hl y basis f or c ha n ge i n 
fre q ue nc y a n d se verit y of t he S A Es b y t he p h ysicia n me dical m o nit or f or cli nical dr u g safet y 
as a si g nal detecti o n/tre n d e val uati o n. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 8 1 of 9 5 
1 6. 5 
J oi nt I n v e sti g at or/ S p o n s or R e s p o n si biliti e s 
1 6. 5. 1 
A c c e s s t o I nf or m ati o n f or M o nit ori n g a n d A u diti n g 
I n acc or da nce wit h I C H G C P g ui deli nes a n d 2 1 C F R 3 1 2, t he C R A/a u dit or m ust ha ve direct 
access t o t he patie nt’s s o urce d oc u me ntati o n i n or der t o verif y t he data rec or de d i n t he C R Fs.  
T he C R A is res p o nsi ble f or r o uti ne re vie w of t he C R Fs at re g ular i nter vals t hr o u g h o ut t he 
st u d y a n d t o verif y a d here nce t o t he pr ot oc ol, as well as t he c o m plete ness, c o nsiste nc y, a n d 
acc urac y of t he data bei n g rec or de d.  T he C R A/a u dit or m ust ha ve access t o a n y patie nt 
rec or ds nee de d t o verif y t he e ntries o n t he C R Fs.  T he i n vesti gat or a grees t o c o o perate wit h 
t he m o nit or t o e ns ure t hat a n y pr o ble ms detecte d i n t he c o urse of t hese m o nit ori n g/a u diti n g 
visits are res ol ve d. 
1 6. 5. 2 
T er mi n ati o n of t h e St u d y 
F or reas o na ble ca use, eit her t he i n vesti gat or  or t he s p o ns or, All os, ma y ter mi nate t he 
i n vesti gat or’s partici pati o n i n t his st u d y, pro vi de d a writte n n otice is s u b mitte d wit hi n t he 
ti me peri o d pr o vi de d f or i n t he Cli nical Trial A gree me nt ( C T A).  I n a d diti o n, All os ma y 
ter mi nate t he st u d y at a n y ti me u p o n i m me diate n otice f or a n y reas o n, i ncl u di n g b ut n ot 
li mite d t o, All os’ belief t hat ter mi nati o n is necessar y f or t he safet y of patie nts. 
1 6. 5. 3 
P u bli c ati o n P oli c y 
All os rec o g nizes t he i m p orta nce of c o m m u nicati o n of me dical st u d y data, a n d e nc o ura ges t he 
p u blicati o n of s uc h data i n re p uta ble scie ntific j o ur nals a n d t he prese ntati o n of s uc h data at 
scie ntific se mi nars a n d c o nfere nces.  A n y pr o p ose d p u blicati o n or prese ntati o n of t he data 
ge nerate d fr o m t he st u d y m ust be  pr o vi de d t o All os f or ti mel y revie w i n acc or da nce wit h t he 
ter ms of t he C T A bet wee n t he i n vesti gat or, t he i nstit uti o n, a n d All os.  All os s hall n ot, i n its 
scie ntific p u blicati o ns or pr o m oti o nal material, q u ote fr o m p u blica ti o ns b y i n vesti gat ors 
wit h o ut f ull ac k n o wle d g me nt of t he s o urce.  Cr iteria f or i ncl usi o n i n a ut h ors hi p i n a n y 
p u blicati o ns res ulti n g fr o m t he st u d y will be deter mi ne d a n d c o m m u nicate d i n writi n g t o all 
partici pati n g pri nci pal i n vesti gat ors. 
1 6. 6 
C o nfi d e nti alit y 
All i nf or mati o n pr o vi de d t o t he i n vesti gat or b y All os, i ncl u di n g n o ncli nical data, pr ot oc ols, 
C R Fs, a n d ver bal a n d writte n i nf or mati o n, will be ke pt strictl y c o nfi de ntial a n d c o nfi ne d t o 
t he cli nical pers o n nel i n v ol ve d i n c o n d ucti n g t his st u d y, a n d n o discl os ure s hall be ma de 
e xce pt i n acc or da nce wit h a n y ri g ht of p u blicati o n gra nte d t o t h e i n vesti gat or.  All pers o n nel 
will ha n dle patie nt data i n a c o nfi de ntial ma n ner i n acc or da nce wit h a p plica ble re g ulati o ns 
g o ver ni n g cli nical researc h.  U p o n re q uest b y a re g ulat or y a ut h orit y s uc h as t he U S F D A a n d 
ot her re g ulat or y a ut h orities w orl d wi de, t he i n vesti gat or/i nstit uti o n m ust ma ke a vaila ble f or 
direct access all re q ueste d st u d y-re late d rec or ds or re p orts ge nerate d as a res ult of a patie nt’s 
partici pati o n i n t his st u d y.  T his i nf or ma ti o n ma y be relate d i n c o nfi de nce t o t he 
I R B/ E C/ R E B or ot her c o m mittee f u ncti o ni n g i n a si milar ca pacity.  I n a d diti o n, n o re p orts or 
i nf or mati o n a b o ut t he st u d y or its pr o gress will be pr o vi de d t o a n y o ne n ot i n v ol ve d i n t he 
st u d y ot her t ha n t o All os, or i n c o nfi de nce t o t he I R B/ E C/ R E B or si milar c o m mittee, e xce pt 
if re q uire d b y la w. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 8 2 of 9 5 
1 7 R E F E R E N C E S 
1 . 
T he N o n- H o d g ki n's L y m p h o ma Classificati o n Pr oject. A c li nical e val uati o n of t he 
I nter nati o nal L y m p h o ma St u d y Gr o u p classificati o n of  n o n- H o d g ki n's l y m p h o ma. . 
Bl o o d 1 9 9 7; 8 9( 1 1): 3 9 0 9- 1 8.  
 
2 . 
He n ness y B T, Ha nra ha n E O, Dal y P A. N o n- H o d g ki n l y m p h o ma: a n u p date. La ncet 
O nc ol 2 0 0 4; 5( 6): 3 4 1- 5 3.  
 
3 . 
Dear de n C E, F oss F M. Peri p heral T-cell l y m p h o mas: dia g n osis a n d ma na ge me nt. 
He mat ol O nc ol Cli n N ort h A m 2 0 0 3; 1 7( 6): 1 3 5 1- 6 6.  
 
4 . 
Z he n g T, Ma y ne S T, B o yle P, et al. E pi de mi ol o g y of n o n- H o d g ki n l y m p h o ma i n 
C o n nectic ut. 1 9 3 5- 1 9 8 8. Ca ncer 1 9 9 2; 7 0( 4): 8 4 0- 9.  
 
5 . 
Cart wri g ht R A, Gil ma n E A, G ur ne y K A. Ti me  tre n ds i n i nci de nce of hae mat ol o gical 
mali g na ncies a n d relate d c o n diti o ns . Br J Hae mat ol 1 9 9 9; 1 0 6( 2): 2 8 1- 9 5. 
 
6 . 
S ur veilla nce, e pi de mil o g y, a n d e n d res ults ( S E E R) Pr o gra m 
( w w w.seer.ca ncer. g o v/ p u blic data) S E E R Stat Data base:  I nci de nce- S E E R 9 Re gs 
P u blic Use. N o v. 2 0 0 3 S u b ( 1 9 7 3- 2 0 0 1), Nati o nal Ca ncer I nstit ute, D C C P S, 
S ur veilla nce Researc h Pr o gra m, Ca ncer St atistics Bra nc h, releas e d A pril 2 0 0 4, base d 
o n t he N o ve m ber 2 0 0 3 s u b missi o n.  
 
7 . 
De vesa S S, Fears T. N o n- H o d g ki n's l y m p h o ma ti me tre n ds: U nite d States a n d 
i nter nati o nal data. Ca ncer Res 1 9 9 2; 5 2( 1 9 S u p pl): 5 4 3 2s- 5 4 4 0s.  
 
8 . 
S wer dl o w S H, I nter nati o nal A ge nc y f o r Researc h o n Ca ncer., W orl d Healt h 
Or ga nizati o n. W H O classificati o n of t u m o urs of hae mat o p oietic a n d l y m p h oi d 
tiss ues. 4t h e d. L y o n, Fra nce: I nter natio nal A ge nc y f or Researc h o n Ca ncer; 2 0 0 8.  
 
9 . 
S hi p p M A. Pr o g n ostic fact ors i n a g gre ssi ve n o n- H o d g ki n's l y m p h o ma: w h o has 
" hi g h-ris k" disease? Bl o o d 1 9 9 4; 8 3( 5): 1 1 6 5- 7 3. 
 
1 0 . 
Gissel brec ht C, Ga ular d P, Le pa ge E, et al. Pr o g n ostic si g nifica nce of T-cell 
p he n ot y pe i n a g gressi ve n o n- H o d g ki n' s l y m p h o mas. Gr o u pe d' Et u des des 
L y m p h o mes de l' A d ulte ( G E L A). Bl o o d 1 9 9 8; 9 2( 1): 7 6- 8 2.  
 
1 1 . 
Harris N L, Jaffe E S, Stei n H, et al. A re vise d E ur o pea n- A merica n classificati o n of 
l y m p h oi d ne o plas ms: a pr o p osal fr o m t he I nter nati o nal L y m p h o ma St u d y Gr o u p. 
Bl o o d 1 9 9 4; 8 4( 5): 1 3 6 1- 1 3 9 2.  
 
1 2 . 
R u di ger T, Weise n b ur ger D D, A n ders o n J R , et al. Peri p heral T-cell l y m p h o ma 
(e xcl u di n g a na plastic lar ge-cell l y m p h oma): res ults fr o m t he N o n- H o d g ki n's 
L y m p h o ma Classificati o n Pr ojec t. A n n O nc ol 2 0 0 2; 1 3( 1): 1 4 0- 9. 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 8 3 of 9 5 
1 3 . 
F ur y M G, Kr u g L M, Azz oli C G, et al. A p ha se I cli nical p harmac ol o gic st u d y of 
pralatre xate i n c o m bi nati o n wit h pr o be neci d i n a d ults wit h a d va nce d s oli d t u m ors. 
Ca ncer C he m ot her P har mac ol 2 0 0 5: 1- 7.  
 
1 4 . 
O' C o n n or O A. De vel o pi n g ne w dr u gs f or t he treat me nt of l y m p h o ma. E ur J Hae mat ol 
S u p pl 2 0 0 5( 6 6): 1 5 0- 8.  
 
1 5 . 
Sa va ge KJ. Peri p heral T-cell l y m p h o mas. Bl o o d Re v 2 0 0 7; 2 1( 4): 2 0 1- 1 6.  
 
1 6 . 
Galla mi ni A, Zaja F, Patti C, et al. Ale mt uz u ma b ( Ca m pat h- 1 H) a n d C H O P 
c he m ot hera p y as first-li ne treat me nt of peri p heral T-cell l y m p h o ma: res ults of a 
GI TI L ( Gr u p p o Italia n o Tera pie I n n o vati ve nei Li nf o mi) pr os pecti ve m ultice nter trial. 
Bl o o d 2 0 0 7; 1 1 0( 7): 2 3 1 6- 2 3 2 3.  
 
1 7 . 
Ar mita ge J O, V ose J M, Weise n b ur ger D D. T o war ds u n dersta n di n g t he peri p heral T-
cell l y m p h o mas. A n n O nc ol 2 0 0 4; 1 5( 1 0): 1 4 4 7- 9.  
 
1 8 . 
V ose J, Ar mita ge J, Weise n b ur ger D. I n ter nati o nal peri p heral T-cell a n d nat ural 
killer/ T-cell l y m p h o ma st u d y: pat h ol o g y fi n di n gs a n d cli nical o utc o mes. J Cli n O nc ol 
2 0 0 8; 2 6( 2 5): 4 1 2 4- 3 0.  
 
1 9 . 
Wils o n W H, Gr oss bar d M L, Pittal u ga S, et al. D ose-a dj uste d E P O C H c he m ot hera p y 
f or u ntreate d lar ge B-cell l y m p h o mas: a p har mac o d y na mic a p pr oac h wit h hi g h 
efficac y. Bl o o d 2 0 0 2; 9 9( 8): 2 6 8 5- 9 3.  
 
2 0 . 
Riz vi M A, E ve ns A M, Tall ma n M S, et al. T-cell n o n- H o d g ki n l y m p h o ma. Bl o o d 
2 0 0 6; 1 0 7( 4): 1 2 5 5- 6 4.  
 
2 1 . 
M o u nier N, Gissel brec ht C, Briere J, et  al. Pr o g n ostic fact ors i n patie nts wit h 
a g gressi ve n o n- H o d g ki n's l y m p h o ma treate d b y fr o nt-li ne a ut otr a ns pla ntati o n after 
c o m plete re missi o n: a c o h ort st u d y b y t h e Gr o u pe d' Et u de des L y m p h o mes de 
l' A d ulte. J Cli n O nc ol 2 0 0 4; 2 2( 1 4): 2 8 2 6- 3 4. 
 
2 2 . 
Sc h mi d F A, Sir ot na k F M, Otter G M, et al. Ne w f olate a nal o gs of t he 1 0- deaza-
a mi n o pteri n series: mar ke dl y i ncrease d a ntit u m or acti vit y of t he 1 0-et h yl a nal o g 
c o m pare d t o t he pare nt c o m p o u n d a n d me t h otre xate a gai nst s o me h u ma n t u m or 
xe n o grafts i n n u de mice. Ca ncer Treat Re p 1 9 8 5; 6 9( 5): 5 5 1- 3.  
 
2 3 . 
Sir ot na k F M, De Gra w JI, M occi o D M, et al. Ne w f olate a nal o gs of t he 1 0- deaza-
a mi n o pteri n series. Basis f or str uct ural  desi g n a n d bi oc he mical a n d p har mac ol o gic 
pr o perties. Ca ncer C he m ot her P har mac ol 1 9 8 4; 1 2( 1): 1 8- 2 5.  
 
2 4 . 
Sir ot na k F M, De Gra w JI, Sc h mi d F A, et al. Ne w f olate a nal o gs of t he 1 0- deaza-
a mi n o pteri n series. F urt her e vi de nce f or mar ke dl y i ncrease d a ntit u m or efficac y 
c o m pare d wit h met h otre xate i n ascitic a n d s oli d m uri ne t u m or m o dels. Ca ncer 
C he m ot her P har mac ol 1 9 8 4; 1 2( 1): 2 6- 3 0.  
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 8 4 of 9 5 
2 5 . 
Sir ot na k F M, Sc h mi d F A, Sa m uels L L, et al. 1 0- Et h yl- 1 0- deaza-a mi n o pteri n: 
str uct ural desi g n a n d bi oc he mical, p har mac ol o gic, a n d a ntit u m or pr o perties. N CI 
M o n o gr 1 9 8 7; 5: 1 2 7- 3 1.  
 
2 6 . 
O' C o n n or O A, H or witz S, Ha mli n P, et al . P hase II-I-II st u d y of t w o differe nt d oses 
a n d sc he d ules of pralatre xate, a hi g h-affi nit y  s u bstrate f or t he re d uce d f olate carrier, 
i n patie nts wit h rela pse d or refract or y l y m p h o ma re veals mar ke d acti vit y i n T-cell 
mali g na ncies. J Cli n O nc ol 2 0 0 9; 2 7( 2 6): 4 3 5 7- 6 4.  
 
2 7 . 
S h ust o v A R, Pr o B, H or witz S M, et al . Pralatre xate i n patie nts wit h 
rela pse d/refract or y peri p heral T-cell l y m p h o ma ( P T C L): Relati o ns hi p bet wee n 
res p o nse a n d s ur vi val (a bstract 8 0 5 4). . A mer S oc of Cli nical O nc ol; 2 0 1 0. Accesse d: 
( 2 8J u n 2 0 1 0). 
htt p:// w w w.asc o. or g/ A S C O v 2/ Meeti n gs/ A bs tracts? & v m vie w =a bst _ detail _ vie w &c o n
fI D = 7 4 &a bstractI D = 5 4 2 1 8.  
 
2 8 . 
H or witz M, D u vic M, Ki m Y, et al. Pralatre xate efficac y a n d t olera bilit y i n patie nts 
wit h rela pse d or refract or y c uta ne o us  T-cell l y m p h o ma ( C T C L) (a bstract 0 3 0 0). 
Hae mat ol o gica 2 0 1 0; 9 5( S u p pl 2): 1 2 0.  
 
2 9 . 
H or witz S M, V ose J M, A d va ni R, et al. Pral atre xate a n d ge mcita bi ne i n patie nts wit h 
rela pse d or refract or y l y mp h o pr oliferati ve mali g na ncies:  p hase 1 res ults. ( p oster 
prese ntati o n). Prese nte d at A merica n S ociet y of He mat ol o g y ( A S H) 5 1st A n n ual 
Meeti n g, Dec 5- 8; Ne w Orlea ns, L A. 2 0 0 9.  
 
3 0 . 
Kr u g L M, N g K K, Kris M G, et al. P h ase I a n d p har mac o ki netic st u d y of 1 0-
pr o par g yl- 1 0- deazaa mi n o pteri n, a ne w a ntif olate. Cli n Ca ncer Res 2 0 0 0; 6( 9): 3 4 9 3- 8.  
 
3 1 . 
Kr u g L M, Azz oli C G, Kris M G, et al. 1 0- pr o par g yl- 1 0- deazaa mi n o pteri n: a n 
a ntif olate wit h acti vit y i n patie nts wit h pr e vi o usl y treate d n o n-s mall cell l u n g ca ncer. 
Cli n Ca ncer Res 2 0 0 3; 9( 6): 2 0 7 2- 8.  
 
3 2 . 
Azz oli C G, Kr u g L M, G o mez J, et al. A p hase  1 st u d y of pralatre xate i n c o m bi nati o n 
wit h paclita xel or d oceta xel i n patie nts w it h a d va nce d s oli d t u m ors. Cli n Ca ncer Res 
2 0 0 7; 1 3( 9): 2 6 9 2- 8.  
 
3 3 . 
Kr u g L M, Heela n R T, Kris M G, et al. P has e II Trial of Pralatre xate ( 1 0- Pr o par g yl-
1 0- deazaa mi n o pteri n, P D X) i n Patie nts wit h U nresecta ble Mali g na nt Ple ural 
Mes ot heli o ma. J T h orac O nc ol 2 0 0 7; 2( 4): 3 1 7- 3 2 0.  
 
3 4 . 
S mit h TJ, K hatc heressia n J, L y ma n G H, et al. 2 0 0 6 u p date of rec o m me n dati o ns f or 
t he use of w hite bl o o d cell gr o wt h fact ors: a n e vi de nce- base d cli nical practice 
g ui deli ne. J Cli n O nc ol 2 0 0 6; 2 4( 1 9): 3 1 8 7- 2 0 5.  
 
3 5 . 
Be nsi n ger W, Sc h u bert M, A n g K K, et al. N C C N Tas k F orce Re p ort. pre ve nti o n a n d 
ma na ge me nt of m uc ositis i n ca ncer care . J Natl C o m pr Ca nc Net w 2 0 0 8; 6 S u p pl 
1: S 1- 2 1; q uiz S 2 2- 4.  

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 8 5 of 9 5 
 
3 6 . 
Galla mi ni A, Stelita n o C, Cal vi R, et al. Peri p heral T-cell l y m p h o ma u ns pecifie d 
( P T C L- U): a ne w pr o g n ostic m o del fr o m a retr os pecti ve m ultice ntric cli nical st u d y. 
Bl o o d 2 0 0 4; 1 0 3( 7): 2 4 7 4- 9.  
 
3 7 . 
Merca dal S, Bri o nes J, Xic o y B, et  al. I nte nsi ve c he m ot hera p y ( hi g h- d ose 
C H O P/ E S H A P re gi me n) f oll o we d b y a ut o l o g o us ste m-cell tra ns pla ntati o n i n 
pre vi o usl y u ntreate d patie nts wit h peri p heral T-cell l y m p h o ma. A n n O nc ol 2 0 0 8.  
 
3 8 . 
Ki m J G, S o h n S K, C hae Y S, et al. C H O P  pl us et o p osi de a n d ge mcita bi ne ( C H O P-
E G) as fr o nt-li ne c he m ot hera p y f or patie nts wit h peri p heral T cell l y m p h o mas. 
Ca ncer C he m ot her P har mac ol 2 0 0 6; 5 8( 1): 3 5- 9.  
 
3 9 . 
A b o u ya bis A N, S he n o y PJ, Lec h o wicz MJ, et al. I nci de nce a n d o utc o mes of t he 
peri p heral T-cell l y m p h o ma s u bt y pes i n t he U nite d States. Le u k L y m p h o ma 
2 0 0 8; 4 9( 1 1): 2 0 9 9- 1 0 7.  
 
4 0 . 
O' Brie n P C, Fle mi n g T R. A m ulti ple testi n g pr oce d ure f or cli nical trials. Bi o metrics 
1 9 7 9; 3 5: 5 4 9- 5 6.  
 
4 1 . 
La n K K G, De Mets D L. Discrete se q ue ntial b o u n daries f or cli nical trials. Bi o metri ka 
1 9 8 3; 7 0( 3): 6 5 9- 6 3.  
 
4 2 . 
Kittels o n J M, E mers o n S S. A u nif yi n g fa m il y of gr o u p se q ue ntial test desi g ns. 
Bi o metrics 1 9 9 9; 5 5( 3): 8 7 4- 8 2.  
 
4 3 . 
C hes o n B D, Pfist ner B, J u wei d M E, et al . Re vise d res p o nse criteria f or mali g na nt 
l y m p h o ma. J Cli n O nc ol 2 0 0 7; 2 5( 5): 5 7 9- 8 6. 
 
 
 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1 
 
 
 
 
C o nfi de ntial 
Pa ge 8 8 of 9 5 
A p p e n di x 3  
E C O G P erf or m a n c e S c al e 
E C O G Gr a de  
Perf or m a nce  
0 
F ull y acti ve, a ble t o carr y o n a ll pre- disease perf or ma nce wit h o ut 
restricti o n. 
1 
Restricte d i n p h ysicall y stre n u o us acti vit y, b ut a m b ulat or y a n d a ble 
t o carr y o ut w or k of a li g ht or se de ntar y nat ure, e. g., li g ht h o use 
w or k, office w or k. 
2 
A m b ulat or y a n d ca pa ble of all self- care, b ut u na ble t o carr y o ut a n y 
w or k acti vities.  U p a n d a b o ut m ore t ha n 5 0 % of wa ki n g h o urs. 
3 
Ca pa ble of o nl y li mite d self-care, c o nfi ne d t o be d or c hair m ore 
t ha n 5 0 % of wa ki n g h o urs 
4 
C o m pletel y disa ble d.  Ca n n ot ca rr y o n a n y self-care.  T otall y 
c o nfi ne d t o be d or c hair. 
5 
Dea d 
 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
Re pri nte d wit h per missi o n.  © 2 0 0 8 A merica n S ociet y of Cli nical O nc ol o g y.  All ri g hts reser ve d. 
C hes o n, B D et al: J Cli n O nc ol 2 5( 5), 2 0 0 7: 5 7 9- 8 6. 
 
C o nfi de ntial 
Pa ge 8 9 of 9 5 
A p p e n di x 4  
T h e I nt er n ati o n al W or k s h o p Crit eri a 4 3      
T he desi g nati o n of c o m plete res p o nse ( C R) re q uires t he f oll o wi n g ( Ta ble 1 ): 
1.  
C o m plete disa p peara nce of all detect a ble cli nical e vi de nce of disease a n d 
disease-relate d s y m pt o ms if  prese nt bef ore t hera p y. 
2a.  T y picall y ( 1 8F)fl u or o de o x y gl uc ose ( F D G)-a vi d l y m p h o ma: i n patie nts wit h n o 
pretreat me nt p ositr o n e missi o n t o m o gra p h y ( P E T) sca n or w he n t he P E T sca n was 
p ositi ve bef ore t hera p y, a p ost-treat me nt resi d ual mass of a n y size is per mitte d as l o n g 
as it is P E T ne gati ve. 
2 b.  Varia bl y F D G-a vi d l y m p h o mas/ F D G a v i dit y u n k n o w n: i n patie nts wit h o ut a 
pretreat me nt P E T sca n, or if a pretreat me nt  P E T sca n was ne gati ve, all l y m p h n o des a n d 
n o dal masses m ust ha ve re gresse d o n c o m p ute d t o m o gra p h y ( C T) t o n or mal size 
( ≤ 1. 5 c m i n t heir greatest tra ns verse dia meter f or n o des > 1. 5 c m bef ore t hera p y).  
Pre vi o usl y i n v ol ve d n o des t hat  were 1. 1 t o 1. 5 c m i n t heir l o n g a xis a n d m ore t ha n 
1. 0 c m i n t heir s h ort a xis bef ore treat me nt m ust ha ve decrease d t o ≤ 1. 0 c m i n t heir s h ort 
a xis after treat me nt. 
3.  
T he s plee n a n d/ or li ver, if c o nsi dere d e nla r ge d bef ore t hera p y o n t he basis of a p h ysical 
e xa mi nati o n or C T sca n, s h o ul d n ot be pal p a ble o n p h ysical e xa mi nati o n a n d s h o ul d be 
c o nsi dere d n or mal size b y i ma gi n g st u dies , a n d n o d ules relate d t o l y m p h o ma s h o ul d 
disa p pear.  H o we ver, deter mi nati o n of s ple nic i n v ol ve me nt is n ot al wa ys relia ble 
beca use a s plee n c o nsi dere d n or mal i n si ze ma y still c o ntai n l y m p h o ma, w hereas a n 
e nlar ge d s plee n ma y reflect variati o ns  i n a nat o m y, bl o o d v ol u me, t he use of 
he mat o p oietic gr o wt h fact ors, or ca uses ot her t ha n l y m p h o ma. 
4.  If t he b o ne marr o w was i n v ol ve d b y l y m p h o ma  bef ore treat me nt, t he i nfiltrate m ust 
ha ve cleare d o n re peat b o ne marr o w bi o ps y.  T he bi o ps y sa m ple o n w hic h t his 
deter mi nati o n is ma de m ust be a de q uate ( wit h a g oal of > 2 0 m m u nilateral c ore).  If t he 
sa m ple is i n deter mi nate b y m or p h ol o g y, it s h o ul d be ne gati ve b y 
i m m u n o hist oc he mistr y.  A sa m ple t hat is negati ve b y i m m u n o hist oc he mistr y b ut t hat 
de m o nstrates a s mall p o p ulati o n of cl o nal l y m p h oc ytes b y fl o w c yt o metr y will be 
c o nsi dere d a C R u ntil data bec o me a vaila ble de m o nstrati n g a clear differe nce i n patie nt 
o utc o me. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
 Versi o n 2. 1 
 
 
 
 
Re pri nte d wit h per missi o n.  © 2 0 0 8 A merica n S ociet y of Cli nical O nc ol o g y.  All ri g hts reser ve d. 
C hes o n, B D et al: J Cli n O nc ol 2 5( 5), 2 0 0 7: 5 7 9- 8 6. 
 
C o nfi de ntial 
Pa ge 9 0 of 9 5 
T a bl e 1:  
R e s p o n s e D efi niti o n s f or Cli ni c al Tri al s 
Res p o nse 
Defi niti o n 
N o d al M asses 
S plee n, Li ver 
B o ne M arr o w 
C R 
Disa p peara nce of all 
e vi de nce of disease 
(a) F D G-a vi d or P E T p ositi ve pri or t o t hera p y; 
mass of a n y size per mitte d if P E T ne gati ve 
( b) Varia bl y F D G-a vi d or P E T ne gati ve; 
re gressi o n t o n or mal size o n C T 
N ot pal pa ble, n o d ules 
disa p peare d 
I nfiltrate cleare d o n re peat bi o ps y; 
if i n deter mi nate b y m or p h ol o g y, 
i m m u n o hist oc he mistr y s h o ul d be 
ne gati ve 
P R 
Re gressi o n of 
meas ura ble disease a n d 
n o ne w sites 
≥ 5 0 % decrease i n S P D of u p t o 6 lar gest 
d o mi na nt masses; n o i ncrease i n size of ot her 
n o des 
(a) F D G-a vi d or P E T p ositi ve pri or t o t hera p y; 
1 or m ore P E T p ositi ve at pre vi o usl y i n v ol ve d 
site 
( b) Varia bl y F D G-a vi d or P E T ne gati ve; 
re gressi o n o n C T 
≥ 5 0 % decrease i n S P D 
of n o d ules (f or si n gle 
n o d ule i n greatest 
tra ns verse dia meter); n o 
i ncrease i n size of li ver 
or s plee n 
Irrele va nt if p ositi ve pri or t o 
t hera p y; cell t y pe s h o ul d be 
s pecifie d 
S D 
Fail ure t o attai n C R/ P R 
or P D 
(a) F D G-a vi d or P E T p ositi ve pri or t o t hera p y; 
P E T p ositi ve at pri or sites of disease a n d n o 
ne w sites o n C T or P E T 
( b) Varia bl y F D G-a vi d or P E T ne gati ve; n o 
c ha n ge i n size of pre vi o us lesi o ns o n C T   
 
 
Rel a pse d dise ase 
or P D 
A n y ne w lesi o n or 
i ncrease b y ≥ 5 0 % of 
pre vi o usl y i n v ol ve d 
sites fr o m na dir 
A p peara nce of a ne w lesi o n(s) > 1. 5 c m i n a n y 
a xis, ≥ 5 0 % i ncrease i n S P D of m ore t ha n 
1 n o de, or ≥ 5 0 % i ncrease i n l o n gest dia meter 
of a pre vi o usl y i de ntifie d n o de > 1 c m i n s h ort 
a xis 
Lesi o ns P E T p ositi ve if F D G-a vi d l y m p h o ma 
or P E T p ositi ve pri or t o t hera p y 
> 5 0 % i ncrease fr o m 
na dir i n t he S P D of a n y 
pre vi o us lesi o ns 
Ne w or rec urre nt i n v ol ve me nt 
C R = c o m plete re missi o n 
P R = partial re missi o n 
F D G = ( 1 8F)fl u or o de o x y gl uc ose  
S P D = s u m of t he pr o d uct of t he dia meters 
P E T = p ositr o n e missi o n t o m o gra p h y  
S D = sta ble disease 
C T = c o m p ute d t o m o gra p h y   
P D = pr o gressi ve disease 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1 
 
 
 
 
Re pri nte d wit h per missi o n.  © 2 0 0 8 A merica n S ociet y of Cli nical O nc ol o g y.  All ri g hts reser ve d. 
C hes o n, B D et al: J Cli n O nc ol 2 5( 5), 2 0 0 7: 5 7 9- 8 6. 
 
C o nfi de ntial 
Pa ge 9 1 of 9 5 
T he use of t he a b o ve defi niti o n f or C R a n d t hat bel o w f or partial res p o nse ( P R) eli mi nates 
t he cate g or y of c o m plete res p o nse u nc o nfir me d ( C R u). 
T he desi g nati o n of P R re q uires al l of t he f oll o wi n g (Ta ble 1 ):  
1.  
At least a 5 0 % decrease i n t h e s u m of t he pr o d uct of t he di a meters ( S P D) of u p t o 6 of 
t he lar gest d o mi na nt n o des or n o dal masses. T hese n o des or masses s h o ul d be selecte d 
acc or di n g  t o all of t he f oll o wi n g: t he y s h o ul d be clearl y meas ura ble i n at least 
2 per pe n dic ular di me nsi o ns; if p ossi ble t he y s h o ul d be  fr o m dis parate re gi o ns of t he 
b o d y; a n d t he y  s h o ul d i ncl u de me diasti nal a n d retr o perit o neal areas of disease  w he ne ver 
t hese sites are i n v ol ve d. 
2.   N o i ncrease s h o ul d be o bser ve d i n t he size  of t he ot her n o des, li ver, or s plee n. 
3.   S ple nic a n d he patic  n o d ules m ust re gress b y ≥ 5 0 % i n t heir S P D or, f or si n gle n o d ules, 
i n t he greatest tra ns verse dia meter.  
4.   
Wit h t he  e xce pti o n of s ple nic a n d he patic n o d ules, i n v ol ve me nt  of ot her  or ga ns is 
us uall y assessa ble a n d n o meas ura ble  disease s h o ul d be prese nt.   
5.   B o ne marr o w assess me nt is irrele va nt f or deter mi nati o n  of  a P R if t he sa m ple was 
p ositi ve bef ore treat me nt.  H o we ver, if p ositi ve, t he cell t y pe s h o ul d be s pecifie d (e g, 
lar ge-cell l y m p h o ma or s mall ne o plastic B cells).  Patie nts w h o ac hie ve a C R b y t he 
a b o ve criteria, b ut w h o ha ve persiste nt m or p h ol o gic b o ne marr o w i n v ol ve me nt will be 
c o nsi dere d partial res p o n ders. 
W he n t he b o ne marr o w was i n v ol ve d bef ore t hera p y a n d a cli nical C R was ac hie ve d, 
b ut wit h n o b o ne marr o w assess me nt after tr eat me nt, patie nts s h o ul d be c o nsi dere d 
partial res p o n ders. 
6.   N o ne w sites of disease s h o ul d be o bser ve d.   
7.  
T y picall y F D G-a vi d l y m p h o ma: f or patie nts wit h n o pretreat me nt P E T sca n or if t he 
P E T sca n was p ositi ve bef ore t hera p y, t he p ost-treat me nt P E T s h o ul d be p ositi ve i n at 
least 1 pre vi o usl y i n v ol ve d site. 
8.  
Varia bl y F D G-a vi d l y m p h o mas/ F D G-a v i dit y u n k n o w n: f or patie nts wit h o ut a 
pretreat me nt P E T sca n, or if a pretreat me nt  P E T sca n was ne gati ve, C T criteria s h o ul d 
be use d. 
I n patie nts wit h f ollic ular l y m p h o ma or ma ntle-cell l y m p h o ma, a P E T sca n is o nl y 
i n dicate d wit h 1 or at m ost 2 resi d ual masses t hat ha ve re gresse d b y m ore t ha n 5 0 % o n 
C T; t h ose wit h m ore t ha n 2 resi d ual lesi o ns are u nli kel y t o be P E T ne gati ve a n d s h o ul d 
be c o nsi dere d partial res p o n ders. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1 
 
 
 
 
Re pri nte d wit h per missi o n.  © 2 0 0 8 A merica n S ociet y of Cli nical O nc ol o g y.  All ri g hts reser ve d. 
C hes o n, B D et al: J Cli n O nc ol 2 5( 5), 2 0 0 7: 5 7 9- 8 6. 
 
C o nfi de ntial 
Pa ge 9 2 of 9 5 
Sta ble disease ( S D) is defi ne d as t he f oll o wi n g ( Ta ble 1 ):  
1.   A patie nt is c o nsi dere d t o ha ve S D w he n he or s he fails t o attai n t he criteria nee de d f or a 
C R or P R, b ut d oes n ot f ulfill t h ose f or pr o gre ssi ve disease (see Rela pse d Disease [after 
C R]/ Pr o gressi ve Disease [after P R, S D]). 
2.  
T y picall y F D G-a vi d l y m p h o mas: t he P E T s h o ul d be p ositi ve at pri or sites of disease 
wit h n o ne w areas of i n v ol ve me nt o n t he p ost-treat me nt C T or P E T. 
3.  
Varia bl y F D G-a vi d l y m p h o mas/ F D G-a v i dit y u n k n o w n: f or patie nts wit h o ut a 
pretreat me nt P E T sca n or if t he pretreat me nt P E T was ne gati ve, t here m ust be n o 
c ha n ge i n t he size of t he pre vi o us le si o ns o n t he p ost-treat me nt C T sca n. 
Rela pse d Disease (after C R)/ Pr o gressi ve  Disease (after P R, S D) ( Ta ble 1) 
L y m p h n o des s h o ul d be c o nsi dere d a b n or mal if t h e l o n g a xis is m ore t ha n 1. 5 c m re gar dless 
of t he s h ort a xis.  If a l y m p h n o de has a l o n g a xis of 1. 1 t o 1. 5 c m, it s h o ul d o nl y be 
c o nsi dere d a b n or mal if its s h ort a xis is m ore t ha n 1. 0.  L y m p h n o des ≤ 1. 0 x ≤ 1. 0 c m will 
n ot be c o nsi dere d as a b n or mal f o r rela pse or pr o gressi ve disease. 
1.  
A p peara nce of a n y ne w lesi o n m ore t ha n 1. 5 c m i n a n y a xis d uri n g or at t he e n d of 
t hera p y, e ve n if ot her lesi o ns are decreasi n g i n size.  I ncrease d F D G u pta ke i n a 
pre vi o usl y u naffecte d site s h o ul d o nl y be c o nsi dere d rela pse d or pr o gressi ve disease 
after c o nfir mati o n wit h ot her mo dalities.  I n patie nts wit h n o  pri or hist or y of p ul m o nar y 
l y m p h o ma, ne w l u n g n o d ules i de ntifie d b y C T are m ostl y be ni g n.  T h us, a t hera pe utic 
decisi o n s h o ul d n ot be ma de s olel y o n t he basis of t he P E T wit h o ut hist ol o gic 
c o nfir mati o n. 
2.  
At least a 5 0 % i ncrease fr o m na dir i n t he S P D  of a n y pre vi o usl y i n v ol ve d n o des, or i n a 
si n gle i n v ol ve d n o de, or t he size of ot her lesi o ns (e g, s ple nic or he patic n o d ules).  T o be 
c o nsi dere d pr o gressi ve disease, a l y m p h n o de w it h a dia meter of t he s h ort a xis of less 
t ha n 1. 0 c m m ust i ncrease b y ≥ 5 0 % a n d t o a size of 1. 5 x 1. 5 c m or m ore t ha n 1. 5 c m i n 
t he l o n g a xis. 
3.  
At least a 5 0 % i ncrease i n t h e l o n gest dia meter of a n y si n gle pre vi o usl y i de ntifie d n o de 
m ore t ha n 1 c m i n its s h ort a xis. 
4.  
Lesi o ns s h o ul d be P E T p ositi ve if o bser ve d  i n a t y pical F D G-a vi d l y m p h o ma or t he 
lesi o n was P E T p ositi ve bef ore t hera p y u nless t he lesi o n is t o o s mall t o be detecte d wit h 
c urre nt P E T s yste ms ( < 1. 5 c m i n its l o n g a xis b y C T). 
Meas ura ble e xtra n o dal disease s h o ul d be asse sse d i n a ma n ner si milar t o t hat f or n o dal 
disease.  F or t hese rec o m me n dati o ns, t he s pl ee n is c o nsi dere d n o da l disease.  Disease 
t hat is o nl y assessa ble (e g, ple ural eff usi o ns, b o ne lesi o ns) will be rec or de d as prese nt or 
a bse nt o nl y, u nless, w hile a n a b n or malit y is  still n ote d b y i ma gin g st u dies or p h ysical 
e xa mi nati o n, it is f o u n d t o be hist ol o gicall y ne gati ve. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1 
 
 
 
 
Re pri nte d wit h per missi o n.  © 2 0 0 8 A merica n S ociet y of Cli nical O nc ol o g y.  All ri g hts reser ve d. 
C hes o n, B D et al: J Cli n O nc ol 2 5( 5), 2 0 0 7: 5 7 9- 8 6. 
 
C o nfi de ntial 
Pa ge 9 3 of 9 5 
I n cli nical trials w here P E T is u na vaila ble t o t he vast maj orit y of partici pa nts, or w here 
P E T is n ot dee me d necessar y or a p pr o priate  f or use (e g, a trial i n patie nts wit h M A L T 
l y m p h o ma), res p o nse s h o ul d be assesse d as ab o ve, b ut o nl y usi n g C T sca ns. H o we ver, 
resi d ual masses s h o ul d n ot be assi g ne d C R u stat us, b ut s h o ul d be c o nsi dere d partial 
res p o nses. 

Pralatre xate I njecti o n 
 
All os T hera pe utics, I nc. 
Cli nical St u d y Pr ot oc ol: P D X- 0 1 7 
 
Versi o n 2. 1  
 
 
 
 
C o nfi de ntial 
Pa ge 9 5 of 9 5 
A p p e n di x 6  
I n v e st i g at or Si g n at ur e 
St u d y Title: 
A M ulti-ce nter, Ra n d o mize d, P hase 3 St u d y of Se q ue ntial 
Pralatre xate Vers us O bser vati o n i n Patie nts wit h Pre vi o usl y 
U n dia g n ose d Peri p heral T-cell L y m p h o ma W h o Ha ve Ac hie ve d a n 
O bjecti ve Res p o nse F oll o wi n g I nitial Treat me nt wit h C H O P- base d 
C he m ot hera p y 
St u d y N u m ber: 
P D X- 0 1 7 
Versi o n N u m ber/ 
Fi n al D ate: 
2. 1/ 3 1 Oct 2 0 1 1 
I ha ve rea d t he pr ot oc ol, i ncl u di n g all a p pe n dices, a n d I a gree t hat it c o ntai ns all necessar y 
details f or me a n d m y staff t o c o n d uct t his st u d y as descri be d.  I will c o n d uct t his st u d y i n 
c o m plia nce wit h all a p plica ble re g ulati o ns a n d g u i deli nes as state d i n t he pr ot oc ol a n d ot her 
i nf or mati o n s u p plie d t o me.  I will ma ke a reaso na ble eff ort t o c o m plete t he st u d y wit hi n t he 
ti me desi g nate d. 
I will pr o vi de all st u d y pers o n nel u n der m y s u per visi o n wit h c o pies of t he pr ot oc ol a n d 
access t o all i nf or mati o n pr o vi de d b y All os T hera p e utics, I nc. or desi g nees.  I will disc uss 
t his material wit h t he m t o e ns ure t hat t he y are f ull y i nf or me d a b o ut t he dr u g(s) a n d t he st u d y. 
 
 
 
 
 
 
Pri nci pal I n vesti gat or Na me ( Pri nte d)  
 
Si g nat ure 
 
 
 
Date 
 
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