An Open-Label Phase 2 Trial of Acalabrutinib Plus Obinutuzumab in Patients With Untreated, Low Tumor Burden Follicular Lymphoma and Other Indolent Non-Hodgkin Lymphomas
Phase: PHASE2
Conditions: Grade 1 Follicular Lymphoma, Grade 2 Follicular Lymphoma, Grade 3a Follicular Lymphoma, Indolent Non-Hodgkin Lymphoma, Lymphoplasmacytic Lymphoma, Lymphoproliferative Disorder, Mantle Cell Lymphoma, Marginal Zone Lymphoma
Sponsor: Emory University

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
P R O T O C OL TI TL E:  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h 
U ntr e at e d, L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as
WI N S HI P P R O T O C OL #:
WI N S HI P 5 1 8 6- 2 0
C O O R DI N A TI N G C E N T E R:
Wi ns hi p C a nc er I nstit ut e of E m or y U ni v ersit y
P RI N CI P AL I N V E S TI G A T O R:
N a m e: J o n at h o n B. C o h e n, M D, M S
D e p art m e nt: H e m at ol o g y a n d M e dic al O nc ol o g y
T el e p h o n e N u m b er: 4 0 4- 7 7 8- 2 2 1 4
E m ail A d dr ess: j o n at h o n.c o h e n @ e m or y. e d u
C O-I N V E S TI G A T O R S:
N a m e: J as o n R o m a nci k, M D
Wi ns hi p C a nc er I nstit ut e of E m or y U ni v ersit y 
E m ail A d dr ess: jr o m a nc @ e m or y. e d u
S T A TI S TI CI A N:
N a m e: J eff S witc h e n k o 
R es e arc h Assist a nt Pr of ess or
D e p art m e nt of Bi ost atistics & Bi oi nf or m atics, R olli ns Sc h o ol of P u blic H e alt h
E m ail A d dr ess: js witc h @ e m or y. e d u
V E R SI O N: V ersi o n 3. 0; 1 1/ 1 5/ 2 0 2 3
F U N DI N G S O U R C E: I n d ustr y-s u p p ort e d b y Astr a Z e n ec a
I N V E S TI G A TI O N AL P R O D U C T (I P): Ac al a br uti ni b ( Astr a Z e n ec a)
O T H E R A G E N T( S): O bi n ut uz u m a b (c o m m erci al s u p pl y)
☒  St u d y E x e m pt fr o m I N D R e q uir e m e nts p er 2 1 C F R 3 1 2. 2( b).  

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
R E VI SI O N HI S T O R Y
R e visi o n #
V ersi o n D at e
S u m m ar y of C h a n g es
N/ A
N/ A
N/ A
1
9/ 8/ 2 2
U p d at e d A p p e n dix B - Dr u g Di ar y
2
1 1/ 1 5/ 2 3
U p d at e d Ac al a br uti ni b c a ps ul es t o t a bl ets

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
T a bl e of C o nt e nts
1. 
St u d y S u m m ar y....................................................................................................................................... 5
1. 1 S y n o ps ys.......................................................................................................................................... 5
1. 2  Sc h e m a........................................................................................................................................... 7
1. 3 Sc h e d ul e of Ass ess m e nts Sc h e d ul e of Ass ess m e nts D uri n g Scr e e ni n g a n d I n d ucti o n P h as es ....... 8
2. 
O bj ecti v es ( a n d E n d p oi nts).................................................................................................................... 1 2
3. 
B ac k gr o u n d........................................................................................................................................... 1 3
3. 1 St u d y R ati o n al e............................................................................................................................. 1 3
3. 2 Cli nic al Ex p eri e nc e........................................................................................................................ 1 6
4. 
St u d y I nt er v e nti o n/I n v esti g ati o n al A g e nt.............................................................................................. 1 8
4. 1 D escri pti o n.................................................................................................................................... 1 8
4. 2 Dr u g/ D e vic e H a n dli n g................................................................................................................... 1 9
4. 3 Acc o u nt a bilit y............................................................................................................................... 2 1
5. 
Pr oc e d ur es I n v ol v e d.............................................................................................................................. 2 1
5. 1 St u d y D esi g n ................................................................................................................................. 2 1
5. 2 St u d y P ar a m et ers.......................................................................................................................... 2 2
5. 3 D osi n g a n d A d mi nistr ati o n ........................................................................................................... 2 2
5. 4 D os e M o dific ati o n......................................................................................................................... 2 3
5. 5 C o nc o mit a nt M e dic ati o ns............................................................................................................. 2 5
5. 6 Dr u g- Dr u g I nt er acti o ns ................................................................................................................. 2 7
5. 7 St u d y Pr oc e d ur es.......................................................................................................................... 2 7
5. 8 D escri pti o n of St u d y Pr oc e d ur es................................................................................................... 2 8
5. 9 Ass ess m e nt of R es p o ns e t o Tr e at m e nt ........................................................................................ 3 2
5. 1 0 Tr e at m e nt T er mi n ati o n a n d S af et y F oll o w- U p ........................................................................... 3 3
5. 1 1 Miss e d E v al u ati o ns ..................................................................................................................... 3 4
6. 
D at a a n d S p eci m e n B a n ki n g.................................................................................................................. 3 4
7. 
S h ari n g of R es ults wit h P artici p a nts ...................................................................................................... 3 5
8. 
St u d y Ti m eli n es..................................................................................................................................... 3 5
8. 1 D ur ati o n of t h er a p y ...................................................................................................................... 3 5
8. 2 D ur ati o n of f oll o w- u p.................................................................................................................... 3 5
9. 
I ncl usi o n a n d E xcl usi o n Crit eri a............................................................................................................. 3 6
1 0.
L oc al N u m b er of P artici p a nts ................................................................................................................ 3 9
1 1.
R ecr uit m e nt M et h o ds ........................................................................................................................... 3 9
1 2.
Wit h dr a w al of P artici p a nts.................................................................................................................... 4 0
1 3.
Ris ks t o P artici p a nts.............................................................................................................................. 4 1
1 3. 1 Ris ks Ass oci at e d wit h Ac al a br uti ni b............................................................................................ 4 1
1 3. 2 Ris ks Ass oci at e d wit h O bi n ut uz u m a b......................................................................................... 4 3
1 3. 3 H e p atitis B R e acti v ati o n.............................................................................................................. 4 6
1 3. 4 Pr o gr essi v e M ultif oc al L e u k o e nc e p h al o p at h y ( P ML).................................................................. 4 6
1 3. 5 R e pr o d ucti v e T oxicit y.................................................................................................................. 4 6
1 3. 6 Ot h er Ris ks.................................................................................................................................. 4 9
1 4.
P ot e nti al B e n efits t o P artici p a nts.......................................................................................................... 4 9
1 5.
D at a M a n a g e m e nt a n d C o nfi d e nti alit y.................................................................................................. 4 9
1 5. 1 St atistic al c o nsi d er ati o ns............................................................................................................ 4 9
1 6. 2 D at a/s p eci m e ns:......................................................................................................................... 5 2

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
1 6.
Pr o visi o ns t o M o nit or t h e D at a t o E ns ur e t h e S af et y of P artici p a nts...................................................... 5 3
1 7.
Pr o visi o ns t o Pr ot ect t h e Pri v ac y I nt er ests of P artici p a nts..................................................................... 6 2
1 8.
Ec o n o mic B ur d e n t o P artici p a nts........................................................................................................... 6 3
1 9.
C o ns e nt Pr oc ess.................................................................................................................................... 6 3
2 0.
S etti n g 
...............................................................................................................................................
2 1.
R es o urc es A v ail a bl e .............................................................................................................................. 6 5
2 2.
R ef er e nc es ........................................................................................................................................... 6 7
A P P E N DI X A 
P erf or m a nc e St at us Crit eri a ................................................................................................ 7 0
A P P E N DI X B 
Dr u g Di ar y........................................................................................................................... 7 1
A P P E N DI X C 
A b br e vi ati o ns a n d d efi niti o n of t er ms................................................................................. 7 3
A P P E N DI X D  
K n o w n Str o n g i n Vi v o I n hi bit ors or I n d uc ers of C Y P 3 A......................................................... 7 6
A P P E N DI X E  
G EL F Crit eri a ....................................................................................................................... 7 6
A P P E N DI X F  
F A C T- G ( V ersi o n 4) Q u esti o n n air e....................................................................................... 7 8
A P P E N DI X G  
H os pit al A n xi et y a n d D e pr essi o n Sc al e ( H A D S).................................................................... 8 1
A P P E N DI X H  
P R O- C T C A E F O R M............................................................................................................... 8 2

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
1. St u d y S u m m ar y
1. 1 S y n o ps ys
Titl e:
A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h 
U ntr e at e d, L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n 
L y m p h o m as
St u d y 
D escri pti o n:
T his r es e arc h st u d y is a n o p e n l a b el, si n gl e ar m, P h as e II st u d y, d esi g n e d t o e v al u at e t h e 
t ol er a bilit y a n d effic ac y of t h e c o m bi n ati o n ac al a br uti ni b a n d o bi n ut uz u m a b i n s u bj ects 
wit h pr evi o usl y- u ntr e at e d, l o w-t u m or b ur d e n f ollic ul ar l y m p h o m a a n d ot h er i n d ol e nt n o n-
H o d g ki n L y m p h o m as. 
W e h y p ot h esiz e t h at t his c o m bi n ati o n will r es ult i n a hi g h er 
c o m pl et e r es p o ns e r at e c o m p ar e d t o w h at is hist oric all y s e e n wit h si n gl e- a g e nt rit uxi m a b.
O bj ecti v es:
Pri m ar y O bj ecti v e :  

T h e pri m ar y o bj ecti v e is t o d et er mi n e if tr e at m e nt ac al a br uti ni b a n d 
o bi n ut uz u m a b is eff ecti v e i n p ati e nts wit h u ntr e at e d, l o w t u m or b ur d e n f ollic ul ar 
l y m p h o m a a n d ot h er i n d ol e nt N HLs.
S ec o n d ar y O bj ecti v es:

D et er mi n e t h e C R r at e f or si n gl e a g e nt ac al a br uti ni b at t h e e n d of a si n gl e- a g e nt 
r u n-i n f or p ati e nts wit h u ntr e at e d l o w t u m or b ur d e n FL.

D et er mi n e t ol er a bilit y of ac al a br uti ni n b a n d o bi n ut uz u m a b vi a ass ess m e nt of 
p ati e nt-r e p ort e d o utc o m es a n d c o n v e nti o n al ass ess m e nts 

Ass ess d ur ati o n of r es p o ns e a n d l o n g-t er m o utc o m es i ncl u di n g pr o gr essi o n-fr e e 
s urvi v al a n d r at es of hist ol o gic tr a nsf or m ati o n. 

Ass ess t h e i m p act of e arl y tr e at m e nt wit h t his r e gi m e n o n h e alt h-r el at e d q u alit y 
of lif e.
E x pl or at or y O bj ecti v e:

E v al u at e t h e i m p act of tr e at m e nt disc o nti n u ati o n i n p ati e nts w h o h a v e ac hi e v e d a 
c o m pl et e r es p o ns e at t h e e n d of t h e i n d ucti o n p h as e.
E n d p oi nts:
Pri m ar y E n d p oi nt:  

C o m pl et e r es p o ns e r at e as of 6 m o nt hs b y t h e L u g a n o 2 0 1 4 crit eri a
S ec o n d ar y E n d p oi nts: 

O v er all r es p o ns e r at e

C R r at e f or ac al a br uti ni b m o n ot h er a p y at e n d of si n gl e- a g e nt r u n-i n

2- y e ar pr o gr essi o n fr e e s urvi v al 

2- y e ar r at e of hist ol o gic tr a nsf or m ati o n

O v er all s urvi v al

D ur ati o n of R es p o ns e

Ti m e t o n ext a nti-l y m p h o m a tr e at m e nt

Q u alit y of lif e ass ess m e nts
St u d y 
P o p ul ati o n:
T h e pri m ar y p o p ul ati o n of i nt er est f or t his st u d y is p ati e nts ≥ 1 8 y e ars of a g e wit h f ollic ul ar 
l y m p h o m a ( gr a d e 1- 3 a) a n d a l o w t u m or b ur d e n as d efi n e d b y t h e G EL F crit eri a (s e e 
A p p e n dix 4). W e will r e q uir e at l e ast 2 9 p ati e nts f or o ur pri m ar y a n al ysis usi n g a Si m o n 2-
st a g e d esi g n. I n t h e 1 st st a g e, 1 8 p ati e nts will b e accr u e d.  If t h er e ar e 2 or f e w er r es p o ns es 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
i n t h os e first 1 8 p ati e nts, t h e tri al will st o p.  Ot h er wis e, a n a d diti o n al 1 1 p ati e nts will b e 
accr u e d f or a t ot al s a m pl e siz e of 2 9.
W e als o pl a n t o e nr oll u p t o 2 0 p ati e nts wit h ot h er s u bt y p es of i n d ol e nt N HL a n d/ or t h e 
f oll o wi n g cli nic al sc e n ari os: 
1.
Pr evi o usl y u ntr e at e d f ollic ul ar l y m p h o m a ( gr a d e 1- 3 a) wit h a hi g h t u m or b ur d e n 
b y G EL F crit eri a w h o ar e u n a bl e or u n willi n g t o r ec ei v e st a n d ar d fr o nt-li n e 
tr e at m e nt a p pr o ac h es
2.
Pr evi o usl y u ntr e at e d m ar gi n al z o n e l y m p h o m a, l y m p h o pl as m ac ytic l y m p h o m a, 
or a n y ot h er i n d ol e nt B-c ell l y m p h o pr olif er ati v e dis or d er wit h a l o w t u m or 
b ur d e n b y G EL F crit eri a or w h o ar e u n a bl e/ u n willi n g t o r ec ei v e m or e i nt e nsi v e 
fr o nt-li n e tr e at m e nt
3.
Pr evi o usl y u ntr e at e d m a ntl e c ell l y m p h o m a w h o w o ul d ot h er wis e b e a p pr o pri at e 
c a n di d at es f or w atc hf ul w aiti n g O R w h o h a v e s y m pt o m atic dis e as e b ut ar e n ot 
c a n di d at es f or or d ecli n e st a n d ar d i n d ucti o n a p pr o ac h es. 
W e will ass ess f or pr eli mi n ar y evi d e nc e of effic ac y of t his tr e at m e nt r e gi m e n i n t h os e 
l y m p h o m a s u bt y p es a n d/ or cli nic al sc e n ari os, a n d w o ul d c o nsi d er a f ut ur e a m e n d m e nt 
ex p a n di n g o n e or m or e of t h os e p o p ul ati o ns if a n effic ac y si g n al is i d e ntifi e d.
As a r es ult, w e will pl a n t o e nr oll a t ot al of 4 9 p ati e nts t o t h e tri al, at l e ast 2 9 of w h o m 
will b e p ati e nts wit h l o w t u m or b ur d e n FL w h o ar e e v al u a bl e f or t h e pri m ar y e n d p oi nt.
P h as e:
P h as e II
D escri pti o n of 
Sit es/ F aciliti es 
E nr olli n g 
P artici p a nts:
Wi ns hi p C a nc er I nstit ut e of E m or y U ni v ersit y ( Atl a nt a, G A).  
D escri pti o n 
of 
St u d y 
I nt er v e nti o n:
F oll o wi n g st u d y c o ns e nt a n d scr e e ni n g ass ess m e nts, p ati e nts will e nt er t h e i n d ucti o n 
p h as e w h er e tr e at m e nt will b e d eli v er e d i n 2 8- d a y c ycl es. F or c ycl es 1 a n d 2 p ati e nts will 
r ec ei v e ac al a br uti ni b m o n ot h er a p y at t h e st a n d ar d d os e of 1 0 0 m g or all y t wic e d ail y. F or 
c ycl es 3- 8, p ati e nts will r ec ei v e c o m bi n ati o n t h er a p y wit h ac al a br uti ni b a n d 
o bi n ut uz u m a b. O bi n ut uz u m a b will b e gi v e n o n d a ys 1, 8, a n d 1 5 of c ycl e 3, t h e n o n d a y 1 
of c ycl es 4- 8 ( 6 t ot al c ycl es of o bi n ut uz u m a b). Aft er c o m pl eti n g tr e at m e nt wit h 
o bi n ut uz u m a b, all p ati e nts will c o nti n u e o n ac al a br uti ni b m o n ot h er a p y f or c ycl es 9 
t hr o u g h 1 2. P ati e nts w h o ac hi ev e a C R f oll o wi n g c ycl e 1 2 will b e r a n d o miz e d t o eit h er 
disc o nti n u e ac al a br uti ni b or c o nti n u e t h e m e dic ati o n u ntil dis e as e pr o gr essi o n or 
i nt ol er a nc e. P ati e nts wit h S D or P R aft er c ycl e 1 2 will c o nti n u e ac al a br uti ni b u ntil 
i nt ol er a nc e or P D.
St u d y D ur ati o n:
T h e esti m at e d ti m e fr o m w h e n t h e st u d y o p e ns t o e nr oll m e nt u ntil a n al ysis of t h e pri m ar y 
o utc o m e is 4 2 m o nt hs. P ati e nts i n t h e f oll o w- u p p h as e w h o disc o nti n u e st u d y t h er a p y will 
b e f oll o w e d f or 6 0 m o nt hs or u ntil t h e st art of n ext a nti-l y m p h o m a tr e at m e nt. P ati e nts 
w h o c o nti n u e ac al a br uti ni b d uri n g t h e f oll o w u p p h as e will b e tr e at e d o n st u d y u ntil 
u n acc e pt a bl e t oxicit y, d e at h, or st art of t h e n ext a nti-l y m p h o m a t h er a p y. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w T u m or B ur d e n F ollic ul ar 
L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
1. 2  Sc h e m a

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w T u m or B ur d e n F ollic ul ar 
L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
1. 3 Sc h e d ul e of Ass ess m e nts
Sc h e d ul e of Ass ess m e nts D uri n g Scr e e ni n g a n d I n d ucti o n P h as es
Scr e e ni n g P h as e
I n d ucti o n P h as e ( 2 8- d a y c ycl es)
Tr e at m e nt C ycl e/ Titl e:
Scr e e ni n g Visit a
C ycl es 1 a n d 2
C ycl e 3
C ycl es 4 t o 8
C ycl es 9 t o 1 2
E n d of I n d ucti o n Visit
D a y:
- 2 8 t o - 1
1 b
1 5 c
1 b
8
1 5
1 b
1 b
2 8( ± 1 4) d a ys aft er C 1 2 D 1
St u d y Visit:
1
2, 4
3
5
6
7 t o 1 1
1 2 t o 1 5
1 6
A d mi nistr ati v e Pr oc e d ur es
I nf or m e d C o ns e nt
X
I ncl usi o n/ Excl usi o n Crit eri a
X
D e m o gr a p hics a n d M e dic al Hist or y
X
Pri or a n d C o nc o mit a nt M e dic ati o n R e vi e w
X
T hr o u g h o ut
X
Ac al a br uti ni b A d mi nistr ati o n
T hr o u g h o ut (t wic e d ail y)
X
O bi n ut uz u m a b A d mi nistr ati o n
X l
X l
X l
X
R a n d o miz ati o n
X m
S urvi v al St at us
T hr o u g h o ut
X
Cli nic al a n d L a b or at or y Pr oc e d ur es/ Ass ess m e nts
R e vi e w A d v ers e E v e nts
T hr o u g h o ut
X
P ati e nt R e p ort e d O utc o m es 
Q u esti o n n air e d
X n
X
X
X
X
X
X
P h ysic al Ex a mi n ati o n
X
X
X
X
X
X
X
X
Vit al Si g ns e
X
X
X
X
X
X
X
X
E C O G P erf or m a nc e St at us
X
X
X
X
X
X
X
X
Q u alit y of Lif e Ass ess m e nts f
X
X
X o
X
Pr e g n a nc y T est – Uri n e or S er u m - H C Gg
X
X
X
X
X
Cli nic al C h e mistr y a n d H e m at ol o g y h
X
X
X
X
X
X
X
X
Uric Aci d
X
X
HI V, H Bs A g, H Bc A b, H C V t esti n g i
X
T u m or Bi o ps y, I m a gi n g, a n d Effic ac y M e as ur e m e nts
T u m or I m a gi n g j 
X p
X q
X r
X s
B o n e m arr o w bi o ps y a n d as pir at e
X t
X u
X u
X u
T u m or Bi o ps y k
X

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w T u m or B ur d e n F ollic ul ar 
L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Scr e e ni n g P h as e
I n d ucti o n P h as e ( 2 8- d a y c ycl es)
Tr e at m e nt C ycl e/ Titl e:
Scr e e ni n g Visit a
C ycl es 1 a n d 2
C ycl e 3
C ycl es 4 t o 8
C ycl es 9 t o 1 2
E n d of I n d ucti o n Visit
D a y:
- 2 8 t o - 1
1 b
1 5 c
1 b
8
1 5
1 b
1 b
2 8( ± 1 4) d a ys aft er C 1 2 D 1
St u d y Visit:
1
2, 4
3
5
6
7 t o 1 1
1 2 t o 1 5
1 6
a) 
T he scree ni n g peri o d e xte n ds fr o m Da y - 2 8 t o Da y 1. S u bjects m ust be scree ne d wit hi n 2 8 da ys pri or t o C ycle 1/ Da y 1. Scree ni n g visit ca n ser ve as baseli ne visit as l o n g as la bs a n d p h ysical 
e xa m perf or me d wit hi n 3 da ys of C ycle 1/ Da y 1. 
b)  
D uri n g i n d ucti o n p hase, da y 1 st u d y visits f or c ycles 2- 1 2 m ust occ ur wit hi n ± 7 da ys, b ut o bi n ut uz u ma b d ose s h o ul d be gi ve n ± 3 da ys. Patie nts s h o ul d c o nti n ue acala br uti ni b d uri n g t his ti me.  
c) 
C ycle 1 Da y 1 5 visit m ust occ ur ± 3 da ys. C ycle 2 Da y 1 5 visit is n ot re q uire d f or st u d y p ur p oses
d) 
Patie nt re p orte d o utc o mes assesse d via P R O- C T C A E a d mi nistere d at least m o nt hl y d uri n g i n d ucti o n p hase
e)  
Assess me nt will i ncl u de resti n g H R, B P, R R, a n d te m perat ure. 
f)
 Q ualit y of life assesse d usi n g F A C T- G a n d H A D S q uesti o n naires t o be a d mi nistere d i n pers o n at st u d y visit.
g)  
O nl y i n w o me n of c hil d beari n g p ote ntial
h) 
I ncl u des c o m plete bl o o d c o u nt wit h differe ntial, c o m pre he nsi ve meta b olic pa nel, a n d L D H
i) 
If n ot alrea d y d o ne wit hi n 6 m o nt hs of si g ni n g i nf or me d c o nse nt
j) 
F or f ollic ular l y m p h o ma a n d ma ntle cell l y m p h o ma i ma gi n g assess me nt will be P E T/ C T; after c ycle 1 2 ca n perf or m eit her C T nec k/c hest/a b d o me n/ pel vis or P E T/ C T base d o n patie nt a n d 
i n vesti gat or prefere nce. F or mar gi nal z o ne l y m p h o ma a n d ot her s u bt y pes of i n d ole nt N H L, all i ma gi n g assess me nt ca n be eit her wit h P E T/ C T or C T nec k/c hest/a b d o me n/ pel vis base d o n 
i n vesti gat or prefere nce. 
k) 
Patie nts will eit her nee d a fres h bi o ps y or arc hi ve d pat h ol o g y re vie we d at t he treati n g ce nter t hat c o nfir ms t he dia g n osis
l) 
If c ycle 3 da y 1 o bi n ut uz u ma b is gi ve n as s plit d ose, t he f ull d ose m ust be c o m plete d wit hi n 2 da ys. Wee kl y d oses of o bi n ut uz u ma b d uri n g c ycle 3 m ust be gi ve n wit hi n ± 3 da ys
m) 
Patie nts wit h S D or P R f oll o wi n g i n d ucti o n t hera p y will c o nti n ue acala br uti ni b u ntil i nt olera nce or pr o gressi ve disease. Patie nts wit h C R f oll o wi n g i n d ucti o n w h o are ra n d o mize d t o c o nti n ue 
acala br uti ni b will als o c o nti n ue u ntil i nt olera nce or pr o gressi ve disease.
n)  
Assess P R O wee kl y d uri n g c ycle 1
o) 
Perf or m Q O L assess me nts at C ycle 6 da y 1 visit
p)  
U p t o 4 2 da ys bet wee n baseli ne i ma gi n g a n d i nitiati o n of st u d y treat me nt is per mitte d
q)  
Wit hi n 7 da ys of c ycle 3 da y 1 – m ust be d o ne bef ore first o bi n ut uz u ma b d ose
r)  
Wit hi n 7 da ys bef ore or after c ycle 6 da y 1
s)  
Wit hi n 7 da ys bef ore e n d of i n d ucti o n visit
t) 
If b o ne marr o w bi o ps y d o ne wit hi n 1 2 m o nt hs of I C F a n d n o cli nical s us pici o n f or c ha n ge i n stat us, t he n t his is o pti o nal
u) 
If marr o w was pre vi o usl y i n v ol ve d, t he n re peat b o ne marr o w bi o ps y at first s us pici o n of c o m plete res p o nse 
Wi n d o ws f or Dise ase Rest a gi n g:
Disease resta gi n g will occ ur at t he f oll o wi n g ti me p oi nts: 

Wit hi n 7 da ys of C ycle 3, Da y 1 ( M U S T occ ur bef ore first d ose of o bi n ut uz u ma b)

Wit hi n 7 da ys bef ore or after C ycle 6, Da y 1

Wit hi n 7 da ys bef ore t he e n d of i n d ucti o n visit 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w T u m or B ur d e n F ollic ul ar 
L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Sc h e d ul e of Ass ess m e nts d uri n g F oll o w- U p P h as e
Tri al P eri o d:
P ati e nt s c o nti n ui n g 
a c al a br uti ni b
P ati e nt s R a n d o mi z e d t o 
O b s er v ati o n
P ati e nt s w h o di s c o nti n u e st u d y t h er a p y
Tr e at m e nt C y cl e/ Titl e:
F oll o w- u p vi sit s a
≤ 1 y e ar fr o m 
e n d of i n d u cti o n 
vi sit
> 1 y e ar fr o m e n d 
of i n d u cti o n vi sit
Tr e at m e nt 
T er mi n ati o n Vi sit
S af et y f oll o w- u p 
Vi sit
Di s c o nti n u ati o n 
F oll o w- u p Vi sit s b
Fr e q u e n c y:
E v er y 1 2 w e e k s ± 2 
w e e k s c
E v er y 1 2 w e e k s 
± 2 w e e k s
E v er y 2 4 w e e k s 
± 4 w e e k s
Wit hi n 7 d a y s l a st 
d o s e st u d y dr u g
4 w e e k s ± 7 
d a y s l a st d o s e 
st u d y dr u g
E v er y 1 2 w e e k s ± 
2 w e e k s d
Pri or a n d C o n c o mit a nt 
M e di c ati o n R e vi e w
X
X
X
A c al a br uti ni b A d mi ni str ati o n
C o nti n u o u s (t wi c e d ail y)
S ur vi v al St at u s
X
X
X
X
X
X
R e vi e w A d v er s e E v e nt s
X
X
X
P ati e nt- R e p ort e d O ut c o m e s 
Q u e sti o n n air e e
X
X
X
P h y si c al E x a mi n ati o n
X
X
X
Vit al Si g n s f
X
X
X
E C O G P erf or m a n c e St at u s
X
X
X
X
X
X
Q u alit y of Lif e A s s e s s m e nt g
X g
X
X
X
X
X
Pr e g n a n c y T e st – Uri n e or 
S er u m - H C Gh
X
Cli ni c al C h e mi str y a n d 
H e m at ol o g y i
X
X
X
X
X
X
T u m or A s s e s s m e nt j
X k
X k
X k
X k

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w T u m or B ur d e n F ollic ul ar 
L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Tri al P eri o d:
P ati e nt s c o nti n ui n g 
a c al a br uti ni b
P ati e nt s R a n d o mi z e d t o 
O b s er v ati o n
P ati e nt s w h o di s c o nti n u e st u d y t h er a p y
Tr e at m e nt C y cl e/ Titl e:
F oll o w- u p vi sit s a
≤ 1 y e ar fr o m 
e n d of i n d u cti o n 
vi sit
> 1 y e ar fr o m e n d 
of i n d u cti o n vi sit
Tr e at m e nt 
T er mi n ati o n Vi sit
S af et y f oll o w- u p 
Vi sit
Di s c o nti n u ati o n 
F oll o w- u p Vi sit s b
Fr e q u e n c y:
E v er y 1 2 w e e k s ± 2 
w e e k s c
E v er y 1 2 w e e k s 
± 2 w e e k s
E v er y 2 4 w e e k s 
± 4 w e e k s
Wit hi n 7 d a y s l a st 
d o s e st u d y dr u g
4 w e e k s ± 7 
d a y s l a st d o s e 
st u d y dr u g
E v er y 1 2 w e e k s ± 
2 w e e k s d
a. 
Patie nts w h o disc o nti n ue acala br uti ni b f or a n y reas o n (i ncl u di n g disease pr o gressi o n) d uri n g t he f oll o w- u p p hase will start f oll o w- u p sc he d ule f or patie nts w h o disc o nti n ue st u d y 
t hera p y.
b. 
Patie nts w h o disc o nti n ue st u d y t hera p y will c o nti n ue t o be f oll o we d o n st u d y f or f oll o w- u p of safet y a n d s ur vi val u nless t he y wit h dra w c o nse nt f or f urt her f oll o w- u p or start a n 
alter nati ve a nti-l y m p h o ma t hera p y.
c. 
T here will be at m ost 1 2 wee ks ± 2 wee ks bet wee n st u d y visits f or patie nts w h o c o nti n ue o n acala br uti ni b. If a patie nt is see n earlier t ha n t his i nter val, t he n t he ne xt f oll o w- u p visit ca n 
be sc he d ule d 1 2 wee ks fr o m t he ti me of t hat visit at t he discreti o n of t he treati n g p h ysicia n.
d. 
Patie nts f oll o w- u p e ver y 1 2 wee ks ± 2 wee ks fr o m t he last d ose of st u d y dr u g f or 1 year t he n ca n decrease fre q ue nc y of visits t o e ver y 2 4 wee ks ± 4 wee ks
e. 
Patie nt-re p orte d o utc o mes assesse d via P R O- C T C A E f or m a d mi nistere d i n pers o n at eac h st u d y visit.
f.  
Assess me nt will i ncl u de resti n g H R, B P, R R, a n d te m perat ure.  
g.  
Q ualit y of life is assesse d wit h t he F A C T- G a n d H A D S q uesti o n naires a n d will be c o n d ucte d i n pers o n at st u d y f oll o w- u p visits t hat c orres p o n d wit h sca n re vie w (i.e. e ver y 6 m o nt hs 
x 2 years t he n e ver y 1 2 m o nt hs x 3 years). Patie nts w h o miss a f oll o w- u p visit will be c o ntacte d b y tele p h o ne t o c o m plete Q o L assess me nts. Patie nts w h o start a ne w treat me nt a n d 
t h ose w h o st o p f oll o wi n g at t he st u d y site f or ot her reas o ns will n o l o n ger be re q uire d t o c o m plete t he Q o L q uesti o n naires. 
h. 
F or w o me n of c hil d beari n g p ote ntial
i. 
I ncl u des c o m plete bl o o d c o u nt wit h differe ntial, c o m pre he nsi ve meta b olic pa nel, a n d L D H
j.  
D uri n g f oll o w- u p p hase t u m or i ma gi n g ca n be wit h P E T/ C T or C T nec k/c hest/a b d o me n/ pel vis base d o n patie nt a n d i n vesti gat or prefere nce f or all disease t y pes. B o ne marr o w bi o ps y t o 
be perf or me d at first s us pici o n of C R (if marr o w pre vi o usl y i n v ol ve d) or if t here is cli nical c o ncer n f or ne w marr o w i n v ol ve me nt.
k.  
D uri n g t he f oll o w- u p p hase t u m or i ma gi n g will be o btai ne d e ver y 6 m o nt hs ( ± 1 m o nt h) x 2 years fr o m t he e n d of i n d ucti o n visit t he n e ver y 1 2 m o nt hs ( ± 1 m o nt h) x 3 years. Patie nts 
w h o disc o nti n ue st u d y t hera p y ca n c o nti n ue wit h t his i ma gi n g sc he d ule if dee me d a p pr o priate b y t he treati n g p h ysicia n.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
2.
O bj ecti v es ( a n d E n d p oi nts)
O BJ E C TI V E S
E N D P OI N T S
Pri m ar y
T h e pri m ar y o bj ecti v e is t o d et er mi n e if tr e at m e nt 
ac al a br uti ni b a n d o bi n ut uz u m a b is eff ecti v e i n 
p ati e nts wit h u ntr e at e d, l o w t u m or b ur d e n 
f ollic ul ar l y m p h o m a a n d ot h er i n d ol e nt N HLs.

T h e pri m ar y effic ac y e n d p oi nt is t h e 
c o m pl et e r es p o ns e r at e pri or t o c ycl e 6 of 
t h er a p y b y t h e L u g a n o 2 0 1 4 crit eri a  
S ec o n d ar y

D et er mi n e t h e C R r at e f or si n gl e a g e nt 
ac al a br uti ni b at t h e e n d of a si n gl e- a g e nt 
r u n-i n f or p ati e nts wit h u ntr e at e d l o w 
t u m or b ur d e n FL.

D et er mi n e t ol er a bilit y of ac al a br uti ni n b a n d 
o bi n ut uz u m a b vi a ass ess m e nt of p ati e nt-
r e p ort e d o utc o m es a n d c o n v e nti o n al 
ass ess m e nts 

Ass ess d ur ati o n of r es p o ns e a n d l o n g-t er m 
o utc o m es i ncl u di n g pr o gr essi o n-fr e e 
s urvi v al a n d r at es of hist ol o gic al 
tr a nsf or m ati o n. 

Ass ess t h e i m p act of e arl y tr e at m e nt wit h 
t his r e gi m e n o n h e alt h-r el at e d q u alit y of 
lif e. 

O v er all r es p o ns e r at e

C R r at e f or ac al a br uti ni b m o n ot h er a p y 
at e n d of si n gl e- a g e nt r u n-i n

2- y e ar pr o gr essi o n fr e e s urvi v al 

2- y e ar r at e of hist ol o gic 
tr a nsf or m ati o n

O v er all s urvi v al

D ur ati o n of R es p o ns e

Ti m e t o n ext a nti-l y m p h o m a tr e at m e nt

Q u alit y of lif e ass ess m e nts
T erti ar y/ Ex pl or at or y 

E v al u at e t h e i m p act of tr e at m e nt 
disc o nti n u ati o n i n p ati e nts w h o h a v e 
ac hi ev e d a c o m pl et e r es p o ns e at t h e e n d of 
t h e i n d ucti o n p h as e. 

T o ass ess t h e s af et y a n d effic ac y of 
ac al a br uti ni b a n d o bi n ut uz u m a b i n ot h er 
s u bt y p es of i n d ol e nt N HL.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
3. B ac k gr o u n d
3. 1 St u d y R ati o n al e
F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N HL wit h a L o w T u m or B ur d e n
F ollic ul ar l y m p h o m a ( FL) is t h e m ost c o m m o n i n d ol e nt n o n- H o d g ki n l y m p h o m a ( N HL) di a g n os e d i n t h e 
U nit e d St at es a n d W est er n E ur o p e wit h a n a n n u al i nci d e nc e of 3. 4- 5 c as es p er 1 0 0, 0 0 0 a n d a m e di a n 
a g e of di a g n osis of 6 5 y e ars. 1- 3 T h e m aj orit y of p ati e nts pr es e nt wit h a d v a nc e d (st a g e III or I V) dis e as e 
t h at is c urr e ntl y i nc ur a bl e wit h existi n g t h er a pi es, t h o u g h t h e pr o g n osis f or t h es e p ati e nts h as i m pr o v e d 
c o nsi d er a bl y i n r ec e nt y e ars wit h t h e i ntr o d ucti o n of n e w t h er a p e utic a g e nts. I n f act, t h e m e di a n o v er all 
s ur vi v al ( O S) h as n ot b e e n r e ac h e d f or p ati e nts wit h FL w h o st art e d tr e at m e nt i n t h e rit uxi m a b er a. 4- 7 
H o w e v er, FL is a bi ol o gic all y a n d cli nic all y h et er o g e n e o us dis e as e c h ar act eriz e d b y m ulti pl e r e missi o ns 
a n d r el a ps es, a n d s o m e p ati e nts will ex p eri e nc e a n a g gr essi v e cli nic al c o urs e. U p t o 2 0 % of p ati e nts will 
r el a ps e wit hi n 2 4 m o nt hs f oll o wi n g first-li n e t h er a p y, a n d t his is ass oci at e d wit h a p artic ul arl y p o or 
o utc o m e wit h a 5- y e ar O S r at e of l ess t h a n 5 0 % a n d a hi g h i nci d e nc e of tr a nsf or m ati o n t o a g gr essi v e 
N HL. 8, 9 
T h e tr e at m e nt a p pr o ac h f or p ati e nts wit h a d v a nc e d-st a g e FL is oft e n d et er mi n e d b y t u m or b ul k. T h e 
Gr o u p e d’ Et u d e d es L y m p h o m es F ollic ul air es ( G EL F) crit eri a w er e d ev el o p e d t o g ui d e cli nici a ns w h e n 
m a ki n g i niti al tr e at m e nt d ecisi o ns a n d i ncl u d es a n ass ess m e nt of t h e siz e of l y m p h n o d e a n d extr a n o d al 
m ass es, pr es e nc e of s yst e mic s y m pt o ms, c yt o p e ni as, a n d ris k of c o m pr essi o n of s urr o u n di n g 
str uct ur es. 1 0 F or p ati e nts w h o ar e as y m pt o m atic a n d h a v e a l o w t u m or b ur d e n at t h e ti m e of di a g n osis, 
a str at e g y of w atc hf ul w aiti n g is fr e q u e ntl y e m pl o y e d b as e d o n t h e r es ults of e arl y pr os p ecti v e tri als t h at 
s h o w e d n o s ur vi v al a d v a nt a g e t o e arl y tr e at m e nt wit h c h e m ot h er a p y. 1 0- 1 2 Wit h t his a p pr o ac h, t h e 
m e di a n ti m e t o first s yst e mic t h er a p y w as 3 y e ars. M or e r ec e ntl y, rit uxi m a b m o n ot h er a p y h as b e e n 
c o m p ar e d t o w atc hf ul w aiti n g i n l o w t u m or b ur d e n FL i n a p h as e 3 tri al w hic h s h o w e d t h at e arl y 
tr e at m e nt wit h rit uxi m a b si g nific a ntl y d el a ys dis e as e pr o gr essi o n a n d t h e ti m e u ntil first tr e at m e nt wit h 
c h e m ot h er a p y a n d r a di ot h er a p y. 1 3 T h er e w as n o O S b e n efit ass oci at e d wit h e arl y tr e at m e nt wit h 
rit uxi m a b at a m e di a n f oll o w- u p of 4 6 m o nt hs, b ut t h e esti m at e d p erc e nt a g e of p ati e nts w h o di d n ot 
n e e d n e w t o st art n e w t h er a p y at 3 y e ars w as 8 8 % i n t h e rit uxi m a b gr o u p c o m p ar e d t o 4 6 % i n t h e 
w atc hf ul w aiti n g gr o u p. I n a d diti o n, p ati e nts tr e at e d wit h e arl y rit uxi m a b s h o w e d si g nific a nt 
i m pr o v e m e nts i n q u alit y of lif e ( Q oL) b as e d o n t h e M e nt al A dj ust m e nt t o C a nc er sc al e a n d t h e Ill n ess 
C o pi n g St yl es ass ess m e nts. 
Si mil arl y, t h e R E S O R T tri al e v al u at e d t h e effic ac y of rit uxi m a b m o n ot h er a p y i n l o w t u m or b ur d e n FL 
w h e n gi v e n as a n i n d ucti o n p h as e f oll o w e d b y r a n d o miz ati o n of r es p o n di n g p ati e nts t o r ec ei v e eit h er 
m ai nt e n a nc e rit uxi m a b vs. rit uxi m a b r etr e at m e nt at ti m e of pr o gr essi o n.
1 4 P ati e nts u n d er w e nt r est a gi n g 
aft er t h e i n d ucti o n p h as e a n d t h e o v er all r es p o ns e r at e ( O R R) at t his ti m e p oi nt w as 7 0. 8 % wit h a 
c o m pl et e r es p o ns e ( C R) r at e of 1 1. 8 %. P ati e nts tr e at e d o n t his tri al als o h a d a pr ol o n g e d ti m e t o first 
c yt ot oxic t h er a p y; at 3 y e ars 9 5 % of p ati e nts tr e at e d wit h m ai nt e n a nc e rit uxi m a b a n d 8 4 % of p ati e nts 
m a n a g e d wit h rit uxi m a b r etr e at m e nt w er e c yt ot oxic t h er a p y fr e e. B as e d o n t h es e d at a t h e us e of 
rit uxi m a b m o n ot h er a p y i n l o w t u m or b ur d e n FL is n o w c o nsi d er e d a n a p pr o pri at e str at e g y, es p eci all y 
f or p ati e nts w h o ar e u nc o mf ort a bl e d ef erri n g t h er a p y or f or w h o m d el a yi n g m or e i nt e nsi v e tr e at m e nt is 
a pri orit y. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
T h e p h as e 2 B RI E F st u d y att e m pt e d t o i m pr o v e t h e o utc o m es f or p ati e nts wit h l o w t u m or b ur d e n FL a n d 
a FLI PI sc or e ≥ 2 b y tr e ati n g wit h 2 c ycl es of b e n d a m usti n e a n d rit uxi m a b f oll o w e d b y rit uxi m a b 
m ai nt e n a nc e f or 2 y e ars.
1 5 P ati e nts o n t his tri al h a d a 9 3 % O R R a n d 2 y e ar P F S of 8 5. 4 %, b ut t h er e w er e 
t hr e e u n ex p ect e d p ati e nt d e at hs d uri n g t h e m ai nt e n a nc e p h as e s o t his tr e at m e nt str at e g y is n ot 
r ec o m m e n d e d. 
N o n-f ollic ul ar i n d ol e nt N HLs s uc h as m ar gi n al z o n e l y m p h o m a ( M ZL), s m all l y m p h oc ytic l y m p h o m a ( SLL), 
a n d l y m p h o pl as m ac ytic l y m p h o m a/ W al d e nstr o m’s M acr o gl o b uli n e mi a (L PL/ W M) ar e als o ass oci at e d 
wit h pr ol o n g e d s urvi v al ti m es b ut ar e als o g e n er all y c o nsi d er e d i nc ur a bl e i n a d v a nc e d st a g es. Si mil ar t o 
FL, t h e o pti m al tr e at m e nt str at e g y i n as y m pt o m atic p ati e nts is n ot d efi n e d a n d m a n y of t h es e p ati e nts 
ar e als o m a n a g e d i niti all y wit h w atc hf ul w aiti n g. T h e R E S O R T tri al i ncl u d e d a s u bs et of p ati e nts wit h 
i n d ol e nt N HL w h o w er e als o tr e at e d wit h rit uxi m a b m o n ot h er a p y.1 6 W hil e t h e O R Rs w er e l o w er f or 
t h es e p ati e nts c o m p ar e d t o FL ( 2 2. 8 % f or SLL a n d 5 2. 1 % f or M ZL), t h e p ati e nts e nj o y e d a pr ol o n g e d ti m e 
t o first c yt ot oxic t h er a p y of at l e ast 6. 3 y e ars.
I n r ec e nt y e ars, a n u m b er of n o v el a g e nts s uc h as l e n ali d o mi d e a n d t h e B T K i n hi bit ors h a v e b e e n 
d e v el o p e d a n d ar e n o w us e d i n t h e tr e at m e nt of i n d ol e nt B-c ell N HLs. T h es e a g e nts ar e oft e n w ell-
t ol er at e d b ut t h e y h a v e y et t o b e ev al u at e d i n t h e s etti n g of l o w t u m or b ur d e n i n d ol e nt N HL t o s e e if 
t h eir us e c a n i m pr o v e u p o n t h e o utc o m es o bs er v e d wit h t h e us e of si n gl e- a g e nt rit uxi m a b. 
H e alt h- R el at e d Q u alit y of Lif e a n d P ati e nt- R e p ort e d O utc o m es
Pri or r etr os p ecti v e st u di es s u g g est t h at a di a g n osis of i n d ol e nt l y m p h o m a a n d dis e as e r ec urr e nc es ar e 
ass oci at e d wit h a n e g ati v e ps yc h ol o gic al i m p act a n d a d ecr e as e i n q u alit y of lif e. 1 7, 1 8 El ev at e d a nxi et y h as 
als o b e e n d oc u m e nt e d i n p ati e nts u n d er g oi n g tr e at m e nt f or h e m at ol o gic m ali g n a nci es as w ell as i n 
s ur vi v ors of N HL. 1 9, 2 0 A n e g ati v e p h ysic al i m p act of c yt ot oxic c h e m ot h er a p y h as als o b e e n r e p ort e d1 7, 
w h er e as t h e us e of n e w er a g e nts s uc h as rit uxi m a b all o w f or l ess t oxic tr e at m e nt f or i n d ol e nt l y m p h o m a 
a n d m a y n ot h a v e t h e s a m e d etri m e nt al i m p act o n q u alit y of lif e t h at tr a diti o n al c h e m ot h er a p y d o es. 2 1 
I n t h e c o nt ext of l o w t u m or b ur d e n i n d ol e nt N HL, t h e i m p act of tr e at m e nt wit h rit uxi m a b m o n ot h er a p y 
h as b e e n e v al u at e d i n t w o pr os p ecti v e cli nic al tri als w hic h als o s u g g est t h at t his tr e at m e nt a p pr o ac h is 
n ot ass oci at e d wit h a n y r e d ucti o n i n q u alit y of lif e a n d m a y act u all y l e a d t o i m pr o v e m e nts i n s o m e 
as p ects of Q oL. 1 3, 2 2 T h e i m p act of t h e n e w er a g e nts s uc h as ac al a br uti ni b a n d o bi n ut uz u m a b o n Q oL a n d 
ps yc h ol o gic al distr ess i n t his p ati e nt p o p ul ati o n is n ot k n o w n. 
T h e F u ncti o n al Ass ess m e nt of C a nc er T h er a p y – G e n er al ( F A C T- G) is a q u esti o n n air e t h at e v al u at es 
p h ysic al, s oci al, e m oti o n al, a n d f u ncti o n al w ell- b ei n g a n d h as b e e n v ali d at e d t o ass es q u alit y of lif e i n 
n o n- H o d g ki n L y m p h o m a p ati e nts. 2 3 T h e F A C T-l y m q u esti o n n air e w as d ev el o p e d m or e r ec e ntl y a n d 
c o nsists of t h e F A C T- G pl us 1 5 q u esti o ns m e as uri n g s y m pt o ms or c o nc er ns s p ecific t o p ati e nts b ei n g 
tr e at e d f or l y m p h o m a. S e v er al it e ms i n t h e l y m p h o m a-s p ecific s u bsc al e as k a b o ut s yst e mic s y m pt o ms 
s uc h as pr urit us a n d ni g ht s w e ats t h at ar e li k el y n ot a p plic a bl e t o p ati e nts di a g n os e d wit h l o w t u m or 
b ur d e n i n d ol e nt l y m p h o m a or t h os e w h o ar e b ei n g f oll o w e d o n o bs er v ati o n. F or t his r e as o n, w e will b e 
usi n g t h e F A C T- G t o m a k e Q oL ass ess m e nts. 
T h e H os pit al A nxi et y a n d D e pr essi o n Sc al e ( H A D S) h as b e e n pr e vi o usl y us e d i n l y m p h o m a p ati e nts a n d is 
c o m pris e d of a nxi et y a n d d e pr essi o n s u bsc al es t h at c o nsist of s e v e n it e ms e ac h. T ot al sc or es f or e ac h 
s u bsc al e r a n g e fr o m 0 t o 2 1 wit h hi g h er sc or es r e pr es e nti n g gr e at er a nxi et y or d e pr essi o n.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
P ati e nt-r e p ort e d o utc o m es ( P R Os) all o w f or p ati e nts t o s elf-r e p ort iss u es r el at e d t o t h eir p h ysic al a n d 
ps yc h ol o gic w ell- b ei n g a n d t h es e ass ess m e nts c a n h el p pr o vi d e i nf or m ati o n a b o ut a p ati e nt’s p h ysic al 
fit n ess a n d t ol er a nc e t o tr e at m e nt. R es e arc h h as d e m o nstr at e d t h at t h at i nt e gr ati n g P R Os i nt o t h e c ar e 
of p ati e nts wit h c a nc er h as t h e p ot e nti al t o i m pr o v e t h eir c ar e d eli v er y a n d o utc o m es, i ncl u di n g 
tr e at m e nt t ol er a bilit y, h os pit aliz ati o ns, a n d ev e n s ur vi v al.2 4 T h e P ati e nt- R e p ort e d O utc o m es v ersi o n of 
t h e C o m m o n T er mi n ol o g y Crit eri a f or A d v ers e E v e nts ( P R O- C T C A E) is a t o ol t o ass ess t h e p ati e nt’s 
s y m pt o m b ur d e n t h at h as b e e n s h o w n t o b e a v ali d a n d r eli a bl e ass ess m e nt of s y m pt o m atic a d v ers e 
eff ects f or p ati e nts u n d er g oi n g c a nc er tr e at m e nt. 2 5, 2 6 T his t o ol will b e i nc or p or at e d i n t h e sc h e d ul e d 
ass ess m e nts f or p ati e nts w h o c o nti n u e o n tr e at m e nt t o d et er mi n e h o w tr e at m e nt wit h ac al a br uti ni b 
a n d o bi n ut uz u m a b i m p acts t h e o v er all s y m pt o m b ur d e n f or p ati e nts o n st u d y t h er a p y.
R ati o n al e
T h e c o m bi n ati o n of o bi n ut uz u m a b a n d ac al a br uti ni b h as n ot b e e n ev al u at e d t o d at e i n t h e tr e at m e nt of 
FL a n d ot h er i n d ol e nt N HLs. A d diti o n all y, t h e us e of n o v el a g e nts li k e t h e B T K i n hi bit ors h as n ot b e e n 
e v al u at e d i n p ati e nts wit h l o w t u m or b ur d e n FL, w hic h is a gr o u p of p ati e nts t h at h as hist oric all y b e e n 
m a n a g e d eit h er wit h w atc hf ul w aiti n g or si n gl e- a g e nt rit uxi m a b. 
T h e c o m bi n ati o n of a nti- C D 2 0 m o n ocl o n al a nti b o di es a n d B T K i n hi bit ors h a v e cli nic al acti vit y i n t h e 
tr e at m e nt of FL. T h e c o m bi n ati o n of o bi n ut uz u m a b a n d ac al a br uti ni b h as b e e n ev al u at e d i n p ati e nts 
wit h CLL/ SLL i n t h e p h as e 3 EL E V A T E- T N tri al w hic h d e m o nstr at e d cli nic al effic ac y of t h e c o m bi n ati o n i n 
t his s etti n g wit h o ut a n y n e w s af et y si g n als.2 7 
O bs er v ati o n is c o nsi d er e d t h e c urr e nt st a n d ar d of c ar e f or m a n y p ati e nts w h o will b e eli gi bl e f or t his 
st u d y – wit h si n gl e- a g e nt rit uxi m a b b ei n g a r e as o n a bl e alt er n ati v e f or p ati e nts w h o ar e n ot c o mf ort a bl e 
wit h t his a p pr o ac h. T his is b ec a us e n o ot h er t h er a p e utic a p pr o ac h st u di e d i n t his p ati e nt p o p ul ati o n 
t h us f ar h as r es ult e d i n a n o v er all s ur vi v al b e n efit, n ot b ec a us e t h e c urr e nt r es ults f or p ati e nts ar e 
s atisf act or y. Cli nic al tri als usi n g n o v el, c h e m ot h er a p y-fr e e a p pr o ac h es i n t his p o p ul ati o n t o tr y a n d 
i m pr o v e o utc o m es a n d Q oL ar e w arr a nt e d.
I n t his st u d y, w e ai m t o ev al u at e t h e s af et y a n d effic ac y of o bi n ut uz u m a b a n d ac al a br uti ni b i n t h e 
tr e at m e nt of l o w t u m or b ur d e n FL t o s e e if w e c a n i m pr o v e u p o n t h e hist oric al C R r at e of 1 1. 8 % 
f oll o wi n g i n d ucti o n t h er a p y wit h si n gl e a g e nt rit uxi m a b t h at w as r e p ort e d i n t h e R E S O R T tri al.1 4 T h e 
i ncl usi o n a n d excl usi o n crit eri a ( S ecti o n 9) w er e d e v el o p e d t o i d e ntif y p ati e nts w h o ar e at hi g h ris k f or 
c o m plic ati o ns fr o m st u d y t h er a p y; t h es e p ati e nts will n ot b e off er e d cli nic al tri al e nr oll m e nt a n d will 
i nst e a d b e c o nsi d er e d f or st a n d ar d of c ar e a p pr o ac h es.
W e will us e t h e F A C T- G, H A D S, a n d P R O- C T C A E t o ass ess t h e i m p act of e arl y tr e at m e nt wit h 
o bi n ut uz u m a b a n d ac al a br uti ni b o n p ati e nt s af et y a n d h e alt h-r el at e d Q oL t o b ett er ass ess t h e o v er all 
ris k- b e n efit pr ofil e of t his n e w tr e at m e nt r e gi m e n. Fi n all y, w e ar e ex pl ori n g t h e i m p act of tr e at m e nt 
disc o nti n u ati o n i n r es p o n di n g p ati e nts. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
3. 2 Cli nic al E x p eri e nc e
Br ut o n T yr osi n e Ki n as e I n hi biti o n I n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N HLs
Br ut o n t yr osi n e ki n as e ( B T K) is a n o n-r ec e pt or e nz y m e i n t h e T ec ki n as e f a mil y t h at is ex pr ess e d 
a m o n g c ells of h e m at o p oi etic ori gi n, i ncl u di n g B-c ells, m y el oi d c ells, m ast c ells, a n d pl at el ets, 
w h er e it r e g ul at es m ulti pl e c ell ul ar pr oc ess es i ncl u di n g pr olif er ati o n, diff er e nti ati o n, a p o pt osis, 
a n d c ell mi gr ati o n. 2 8- 3 0 I n a d diti o n, B T K- d e p e n d e nt acti v ati o n of m ast c ells, m y el oi d c ells, a n d 
ot h er i m m u n oc yt es i n p erit u m or al i nfl a m m at or y str o m a h as b e e n s h o w n t o s ust ai n t h e c o m pl ex 
micr o e n vir o n m e nt n e e d e d f or l y m p h oi d a n d s oli d t u m or m ai nt e n a nc e.
3 1- 3 3 T a k e n t o g et h er, 
t h es e fi n di n gs s u g g est i n hi biti o n of B T K m a y off er a n attr acti v e str at e g y f or tr e ati n g B-c ell 
n e o pl as ms, ot h er h e m at ol o gic m ali g n a nci es, a n d s oli d t u m ors.
B T K i n hi biti o n h as b e e n s h o w n t o h a v e cli nic al acti vit y i n r el a ps e d/r efr act or y ( R/ R) FL b as e d o n 
t h e r es ults of a p h as e 2 cli nic al tri al w hic h s h o w e d t h at i br uti ni b m o n ot h er a p y i n t his s etti n gs 
yi el ds a n O R R of 3 7. 5 %, a c o m pl et e r es p o ns e C R r at e of 1 2. 5 %, a n d a m e di a n P F S of 1 4 
m o nt hs. 3 4 R es p o ns e r at es w er e si g nific a ntl y hi g h er a m o n g p ati e nts wit h rit uxi m a b-s e nsiti v e 
dis e as e ( O R R 5 2. 6 %) c o m p ar e d t o t h os e w h o w er e r efr act or y t o rit uxi m a b ( O R R 1 6. 7 %). I n 
p ati e nts wit h u ntr e at e d FL, tr e at m e nt wit h rit uxi m a b pl us i br uti ni b h as a n O R R of 8 2 % a n d a C R 
r at e of 2 7 % i n a p h as e 2 tri al.3 5 I n a p h as e 1 b tri al of ac al a br uti ni b ± rit uxi m a b, t h er e w er e 1 3 
p ati e nts wit h u ntr e at e d FL w h o r ec ei v e d c o m bi n ati o n t h er a p y a n d h a d a n O R R of 9 2 % a n d a C R 
r at e of 3 1 %.3 6   
B T K i n hi biti o n is als o eff ecti v e i n tr e ati n g ot h er s u bt y p es of i n d ol e nt N HL. I n a p h as e 2 tri al 
e v al u ati n g i br uti ni b m o n ot h er a p y i n R/ R M ZL, t h e O R R w as f o u n d t o b e 4 8 % wit h a C R r at e of 
3 %. 3 7 At m e di a n f oll o w- u p of 1 9. 4 m o nt hs, t h e m e di a n d ur ati o n of r es p o ns e w as n ot r e ac h e d, 
wit h 6 2 % of r es p o n d ers ali v e a n d pr o gr essi o n-fr e e at 1 8 m o nt hs. I n pr e vi o usl y u ntr e at e d a n d 
r el a ps e d L PL/ W M, i br uti ni b pl us rit uxi m a b w as c o m p ar e d t o pl ac e b o pl us rit uxi m a b i n a p h as e 3 
tri al w hic h s h o w e d a si g nific a ntl y hi g h er m aj or r es p o ns e r at e wit h i br uti ni b-rit uxi m a b c o m p ar e d 
t o pl ac e b o-rit uxi m a b ( 7 2 % vs. 3 2 %, p < 0. 0 1) as w ell as a si g nific a ntl y hi g h er r at e of P F S at 3 0 
m o nt hs ( 8 2 % vs 2 8 %).
3 8 
T h e o pti m al d ur ati o n of t h er a p y f or p ati e nts r ec ei vi n g B T K i n hi bit ors is n ot w ell- est a blis h e d. 
C urr e ntl y F D A l a b el e d i n dic ati o ns s u p p ort i n d efi nit e tr e at m e nt b ut it is n ot k n o w n w h et h er 
c o nti n u e d t h er a p y f or r es p o n di n g p ati e nts is tr ul y n e e d e d.  I n t his st u d y, w e will r a n d o miz e 
r es p o n di n g p ati e nts t o disc o nti n u e or c o nti n u e ac al a br uti ni b tr e at m e nt t o i d e ntif y t h e i m p act of 
c o nti n u e d tr e at m e nt o n r es p o ns e d ur ati o n, p ati e nt r e p ort e d q u alit y of lif e, a n d t oxicit y.
Ac al a br uti ni b ( A C P- 1 9 6)
Ac al a br uti ni b is F D A a p pr o v e d f or t h e tr e at m e nt of R/ R M CL b as e d o n t h e r es ults of t h e p h as e 2, 
o p e n-l a b el m o n ot h er a p y A C E-L Y- 0 0 4 st u d y. 3 9 S u bj ects i n t his st u d y r ec ei v e d ac al a br uti ni b 
1 0 0 m g BI D c o nti n u o usl y, i n r e p e at e d 2 8- d a y c ycl es u ntil dis e as e pr o gr essi o n or u n acc e pt a bl e 
dr u g-r el at e d t oxicit y, w hic h e v er occ urr e d first. T h e O R R w as 8 0. 6 %. A b est r es p o ns e of C R w as 
ac hi e v e d i n 4 2. 7 % of s u bj ects a n d a b est r es p o ns e of P R w as ac hi ev e d i n 3 7. 9 % of s u bj ects. T h e 
m e di a n d ur ati o n of r es p o ns e w as 2 5. 7 m o nt hs. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Ac al a br uti ni b is n o w a p pr o v e d f or us e i n tr e at m e nt- n aï v e or r el a ps e d CLL b as e d o n t h e r es ults of 
t h e EL E V A T E T N a n d A S C E N D tri als.2 7 I n EL E V A T E T N, p ati e nts wit h u ntr e at e d CLL w er e 
r a n d o miz e d t o r ec ei v e o bi n ut uz u m a b pl us ac al a br uti ni n b, ac al a br uti ni b al o n e, or o bi n ut uz u m a b 
pl us c hl or a m b ucil. At m e di a n f oll o w- u p of 2 8 m o nt hs, ac al a br uti ni b pl us o bi n ut uz u m a b 
si g nific a ntl y pr ol o n g e d P F S c o m p ar e d t o o bi n ut uz u m a b pl us c hl or a m b ucil ( m e di a n n ot r e ac h e d 
vs. 2 2. 6 m o nt hs; H R 0. 1 0, 9 5 % CI 0. 0 6- 0. 1 8, p < 0. 0 0 0 1). T h e m e di a n P F S wit h ac al a br uti ni b 
m o n ot h er a p y w as als o n ot r e ac h e d. T h e I R C- ass ess e d O R R wit h ac al a br uti ni b pl us 
o bi n ut uz u m a b w as 9 4 % wit h a 1 3 % C R r at e. T h e O R R f or ac al a br uti ni b m o n ot h er a p y w as 8 5 % 
wit h 1 p ati e nt ac hi e vi n g a C R. 
I n t h e p h as e 3 A S C E N D tri al, p ati e nts wit h R/ R CLL w er e r a n d o miz e d t o r ec ei v e eit h er 
ac al a br uti ni b m o n ot h er a p y or i n v esti g at or’s c h oic e of rit uxi m a b/i d el alisi b or 
rit uxi m a b/ b e n d a m usti n e.4 0 At m e di a n f oll o w- u p of 1 6. 1 m o nt hs, ac al a br uti ni b si g nific a ntl y 
pr ol o n g e d I R C- ass ess P F S vs rit uxi m a b/i d el alisi b or rit uxi m a b/ b e n d a m usti n e ( m e di a n n ot r e ac h 
vs. 1 6. 5 m o nt hs; H R 0. 3 1, 9 5 % CI 0. 2 0- 0. 4 9, p < 0. 0 0 0 1). O R R w as n ot si g nific a ntl y diff er e nt 
b et w e e n t h e t w o ar ms ( 8 1 % vs. 7 5 %).
F or m or e d et ails r e g ar di n g t h e cli nic al effic ac y of ac al a br uti ni b, pl e as e r ef er t o t h e I n v esti g at or’s 
Br oc h ur e.
O bi n ut uz u m a b ( G A- 1 0 1)
O bi n ut uz u m a b is a C D 2 0- dir ect e d c yt ol ytic a nti b o d y m o n ocl o n al a nti b o d y t h at is d eli v er e d as a n I V 
i nf usi o n. O bi n ut uz u m a b is a p pr o v e d i n t h e U S i n c o m bi n ati o n wit h b e n d a m usti n e f oll o w e d b y 
o bi n ut uz u m a b m o n ot h er a p y f or t h e tr e at m e nt of p ati e nts wit h FL w h o r el a ps e d aft er, or ar e r efr act or y 
t o, a rit uxi m a b-c o nt ai ni n g r e gi m e n. It is als o a p pr o v e d f or us e i n c o m bi n ati o n wit h c h e m ot h er a p y 
f oll o w e d b y o bi n ut uz u m a b m o n ot h er a p y f or u p t o t w o y e ars i n p ati e nts ac hi e vi n g at l e ast a p arti al 
r e missi o n, f or t h e tr e at m e nt of a d ult p ati e nts wit h pr evi o usl y u ntr e at e d st a g e II b ul k y, III, or I V f ollic ul ar 
l y m p h o m a.
P ati e nts wit h i n d ol e nt N HL w h o r ec ei v e d o bi n ut uz u m a b m o n ot h er a p y h a d a r es p o ns e r at e at t h e e n d of 
tr e at m e nt t h at r a n g e d fr o m 2 8 % ( 1 1/ 4 0 p ati e nts) t o 5 8 % ( 7/ 1 2 p ati e nts). S o m e p ati e nts i n st u di es 
B O 2 0 9 9 9, B O 2 1 0 0 3, a n d J O 2 1 9 0 0 h a d rit uxi m a b-r efr act or y dis e as e b ut still ac hi e v e d a C R b y t h e e n d- of-
tr e at m e nt ass ess m e nt.
T h e G A D OLI N tri al is a n o p e n-l a b el, m ultic e nt er, r a n d o miz e d st u d y i ncl u di n g 3 2 1 p ati e nts wit h FL w h o 
h a d n o r es p o ns e t o or h a v e pr o gr ess e d d uri n g or wit hi n 6 m o nt hs of rit uxi m a b pr o d uct or a rit uxi m a b 
pr o d uct-c o nt ai ni n g r e gi m e n. 4 1 T h es e p ati e nts w er e r a n d o miz e d t o r ec ei v e eit h er b e n d a m usti n e al o n e or 
b e n d a m usti n e i n c o m bi n ati o n wit h o bi n ut uz u m a b. P ati e nts w h o di d n ot h a v e dis e as e pr o gr essi o n at t h e 
e n d of 6 c ycl es of c o m bi n ati o n t h er a p y t h e n w e nt o n t o h a v e o bi n ut uz u m a b m o n ot h er a p y f or 2 y e ars. 
T h e pri m ar y o bj ecti v e of t his st u d y w as t o e v al u at e P F S as d et er mi n e d b y a n i n d e p e n d e nt r e vi e w 
c o m mitt e e (I R C). T h e m e di a n o bs er v ati o n ti m e w as 2 1. 1 m o nt hs. T h e m e di a n P F S i n t h e b e n d a m usti n e 
ar m w as 1 3. 8 m o nt hs. M e di a n P F S w as n ot r e ac h e d i n t h e o bi n ut uz u m a b pl us b e n d a m usti n e ar m ( H R = 
0. 4 8, 9 5 % CI: 0. 3 5- 0. 6 7; str atifi e d l o g-r a n k t est p- v al u e < 0. 0 0 0 1). 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
T h e G ALLI U M tri al is a n o p e n-l a b el, r a n d o miz e d st u d y i ncl u di n g 1 2 0 2 p ati e nts wit h pr e vi o usl y u ntr e at e d, 
st a g e II b ul k y, II, or I V FL. 4 2 P ati e nts w er e r a n d o miz e d 1: 1 t o r ec ei v e eit h er o bi n ut uz u m a b or rit uxi m a b 
pr o d uct i n c o m bi n ati o n wit h c h e m ot h er a p y ( C H O P, C V P, or b e n d a m usti n e) f or 6- 8 c ycl es. P ati e nts wit h 
at l e ast a P R t o c o m bi n ati o n t h er a p y r ec ei v e d m o n ot h er a p y wit h o bi nt uz u m a b or rit uxi m a b pr o d uct 
e v er y t w o m o nt hs u ntil dis e as e pr o gr essi o n or f or a m axi m u m of 2 y e ars. Effic ac y w as b as e d o n P F S p er 
I R C. Aft er a m e di a n f oll o w- u p of 3 4. 5 m o nt hs, a pl a n n e d i nt eri m a n al ysis s h o w e d t h at o bi n ut uz u m a b-
b as e d c h e m ot h er a p y r es ult e d i n a si g nific a ntl y l o w er ris k of pr o gr essi o n, r el a ps e, or d e at h t h a n t h e 
rit uxi m a b b as e d c h e m ot h er a p y wit h a n esti m at e d 3- y e ar P F S r at e of 8 0 % v ers us 7 3. 3 % ( h az ar d r ati o f or 
pr o gr essi o n, r el a ps e, or d e at h, 0. 6 6; 9 5 % CI, 0. 5 1 t o 0. 8 5; p = 0. 0 0 1). O R R w as si mil ar b et w e e n t h e t w o 
gr o u ps ( 8 8. 5 % i n t h e o bi n ut uz u m a b gr o u p a n d 8 6. 9 % i n t h e rit uxi m a b gr o u p).
4. St u d y I nt er v e nti o n/I n v esti g ati o n al A g e nt
4. 1 D escri pti o n
Ac al a br uti ni b ( A C P- 1 9 6)
Ac al a br uti ni b is a n i mi d az o p yr azi n e a n al o g u e wit h a m ol ec ul ar w ei g ht of 4 6 5. 5 g/ m ol.  T h e 
c o m p o u n d h as 1 st er e o g e nic c e nt er a n d ac al a br uti ni b is t h e S- e n a nti o m er.  Ac al a br uti ni b is 
or all y bi o a v ail a bl e i n h u m a ns a n d is s uit a bl e f or f or m ul ati n g i n t a bl ets. C al q u e nc e ® h as b e e n 
a p pr o v e d i n t h e U nit e d St at es a n d ot h er m ar k ets f or t h e tr e at m e nt of a d ult p ati e nts wit h 
m a ntl e c ell l y m p h o m a ( M CL) w h o h a v e r ec ei v e d at l e ast o n e pri or t h er a p y, c hr o nic l y m p h oc ytic 
l e u k e mi a ( CLL), a n d s m all l y m p h oc ytic l y m p h o m a ( SLL). It is als o u n d er e v al u ati o n f or t h e 
tr e at m e nt of p ati e nts wit h ot h er B-c ell m ali g n a nci es.
M ec h a nis m of Acti o n: 
Ac al a br uti ni b is a p ot e nt i n hi bit or of B T K i n vitr o a n d i n vi v o.  P h ar m ac ol o g y m o d els h a v e b e e n 
us e d t o d efi n e ki n as e s el ecti vit y of ac al a br uti ni b i n c o m p aris o n t o ot h er B T K i n hi bit ors, a n d t o 
i n v esti g at e f u ncti o n al eff ects of o n-t ar g et a n d off-t ar g et acti viti es.  Ac al a br uti ni b s h o ws 
i m pr o v e d s el ecti vit y f or B T K c o m p ar e d wit h i br uti ni b. F u ncti o n al i n hi biti o n of n o n-t ar g et c ells 
( e g, T c ells, N K c ells, pl at el ets) w as n ot o bs er v e d f or ac al a br uti ni b at cli nic all y r el e v a nt 
c o nc e ntr ati o ns.
S af et y P h ar m ac ol o g y:
I n vitr o a n d i n vi v o s af et y p h ar m ac ol o g y a n d t oxic ol o g y st u di es wit h ac al a br uti ni b h a v e 
d e m o nstr at e d a f a v or a bl e n o ncli nic al s af et y pr ofil e; f or d et ail e d i nf or m ati o n o n t h e s af et y 
p h ar m ac ol o g y of ac al a br uti ni b, r ef er t o t h e I n v esti g at or Br oc h ur e.
Dr u g- Dr u g I nt er acti o n P ot e nti al:
F or m or e d et ail e d i nf or m ati o n o n dr u g- dr u g i nt er acti o ns f or ac al a br uti ni b, r ef er t o t h e 
I n v esti g at or Br oc h ur e. Pl e as e r ef er t o S ecti o n 5. 6 f or g ui d a nc e o n dr u gs t h at m a y c a us e dr u g-
dr u g i nt er acti o ns.
O bi n ut uz u m a b ( G A- 1 0 1)
M ec h a nis m of Acti o n:
O bi n ut uz u m a b is a m o n ocl o n al a nti b o d y t h at t ar g ets t h e C D 2 0 a nti g e n ex pr ess e d o n t h e s urf ac e of pr e-
B a n d m at ur e B l y m p h oc yt es. Aft er bi n di n g t o C D 2 0, o bi n ut uz u m a b m e di at es B-c ell l ysis t hr o u g h t h e 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 1 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
e n g a g e m e nt of i m m u n e eff ect or c ells, dir ectl y acti v ati n g i ntr ac ell ul ar d e at h si g n ali n g p at h w a ys ( dir ect 
c ell d e at h), a n d/ or acti v ati o n of t h e c o m pl e m e nt c asc a d e. T h e i m m u n e eff ect or c ell m ec h a nis ms i ncl u d e 
a nti b o d y- d e p e n d e nt c ell ul ar c yt ot oxicit y ( A D C C) a n d a nti b o d y- d e p e n d e nt c ell ul ar p h a g oc yt osis. 
O bi n ut uz u m a b is a n a nti b o d y wit h a r e d uc e d f uc os e c o nt e nt s o it i n d uc es gr e at er A D C C acti vit y t h a n 
rit uxi m a b i n vitr o usi n g h u m a n c a nc er c ell li n es. O bi n ut uz u m a b als o d e m o nstr at e d a n i ncr e as e d a bilit y 
t o i n d uc e dir ect c ell d e at h w h e n c o m p ar e d t o rit uxi m a b. O bi n ut uz u m a b bi n ds t o F Cγ RIII  usi n g p urifi e d 
pr ot ei ns wit h a hi g h er affi nit y t h a n rit uxi m a b. O bi n ut uz u m a b a n d rit uxi m a b bi n d wit h si mil ar affi nit y t o 
o v erl a p pi n g e pit o p es o n C D 2 0.
S af et y P h ar m ac ol o g y:
I n vitr o a n d i n vi v o s af et y p h ar m ac ol o g y st u di es wit h o bi n ut uz u m a b h a v e d e m o nstr at e d a f a v or a bl e 
n o ncli nic al s af et y pr ofil e; f or d et ail e d i nf or m ati o n o n t h e s af et y p h ar m ac ol o g y of o bi n ut uz u m a b, pl e as e 
r ef er t o t h e c urr e nt U nit e d St at es P ac k a g e I ns ert ( U S PI).
Dr u g- Dr u g I nt er acti o n P ot e nti al:
F or m or e d et ail e d i nf or m ati o n o n dr u g- dr u g i nt er acti o n p ot e nti al f or o bi n ut uz u m a b, r ef er t o t h e U S PI. 
Pl e as e r ef er t o S ecti o n 5. 6 f or g ui d a nc e o n dr u gs t h at m a y c a us e dr u g- dr u g i nt er acti o ns
4. 2 Dr u g/ D e vic e H a n dli n g
Pr e m e dic ati o ns:
Ac al a br uti ni b
N o s p ecific pr e m e dic ati o ns or s u p p orti n g m e dic ati o ns ar e r e q uir e d i n c o nj u ncti o n wit h ac al a br uti ni b 
a d mi nistr ati o n. 
O bi n ut uz u m a b
P ati e nts m a y b e pr e m e dic at e d wit h gl uc oc ortic oi d, ac et a mi n o p h e n, a n d a nti- hist a mi n e at t h e 
pr ef er e nc e of t h e i n v esti g at or i n acc or d a nc e wit h t h e p ac k a g e i ns ert a n d/ or i nstit uti o n al 
g ui d eli n es/ pr actic e. Pl e as e r ef er t o t h e U S PI f or a d diti o n al i nf or m ati o n.
F or m ul ati o n, P ac k a gi n g, a n d St or a g e
Ac al a br uti ni b
T h e i n v esti g ati o n al pr o d uct, ac al a br uti ni b  f or or al a d mi nistr ati o n, is s u p pli e d as or a n g e, o v al, fil m-
c o at e d, bic o n v ex, d e b oss e d wit h ‘ A C A 1 0 0’ o n o n e si d e a n d pl ai n o n t h e ot h er t a bl et. I n acti v e 
i n gr e di e nts i n t h e t a bl et c or e ar e l o w-s u bstit ut e d h y dr ox y pr o p yl c ell ul os e, m a n nit ol, micr ocr yst alli n e 
c ell ul os e, a n d s o di u m st e ar yl f u m ar at e. T h e t a bl et c o ati n g c o nsists of c o p o vi d o n e, f erric oxi d e y ell o w, 
f erric oxi d e r e d, h y pr o m ell os e, m e di u m-c h ai n tri gl yc eri d es, p ol y et h yl e n e gl yc ol 3 3 5 0, p urifi e d w at er a n d 
tit a ni u m di oxi d e.
Ac al a br uti ni b m al e at e t a bl ets ar e p ac k e d i n w hit e, H D P E b ottl es c o nt ai ni n g a silic a g el d esicc a nt a n d 
s h o ul d b e st or e d acc or di n g t o t h e st or a g e c o n diti o ns as i n dic at e d o n t h e l a b el. St or e at 2 0° C- 2 5° C ( 6 8° F-
7 7° F); exc ursi o ns p er mitt e d t o 1 5° C- 3 0° C ( 5 9° F- 8 6° F)

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
R ef er t o t h e ac al a br uti ni b I n v esti g at or Br oc h ur e f or a d diti o n al i nf or m ati o n r e g ar di n g t h e dr u g pr o d uct 
t o b e us e d i n t his tri al.
O bi n ut uz u m a b
O bi nt uz u m a b 1 0 0 0 m g/ 4 0 mL ( 2 5 m g/ mL) si n gl e- d os e vi als c o nt ai ni n g pr es erv ati v e-fr e e s ol uti o n. ( N D C 
5 0 2 4 2- 0 7 0- 0 1) ar e st a bl e at 2⁰ C  t o 8⁰ C  ( 3 6⁰ F t o 4 6⁰ F).  Pr ot ect o bi n ut uz u m a b vi als fr o m li g ht. D o n ot 
fr e ez e. D o n ot s h a k e.
F or t h e dil ut e d pr o d uct, c h e mic al a n d p h ysic al st a bilit y h a v e b e e n d e m o nstr at e d i n 0. 9 % N a Cl at 
c o nc e ntr ati o ns of 0. 4 m g/ mL t o 2 0 m g/ mL f or 2 4 h o urs at 2° C t o 8° C ( 3 6⁰ F t o 4 6⁰ F)  f oll o w e d b y 4 8 h o urs 
(i ncl u di n g i nf usi o n ti m e) at r o o m t e m p er at ur e ( ≤ 3 0° C/ 8 6° F). O bi n ut uz u m a b d o es n ot c o nt ai n 
a nti micr o bi al pr es erv ati v es. T h er ef or e, c ar e m ust b e t a k e n t o e ns ur e t h at t h e s ol uti o n f or i nf usi o n is n ot 
micr o bi ol o gic all y c o m pr o mis e d d uri n g pr e p ar ati o n. T h e s ol uti o n f or i nf usi o n s h o ul d b e us e d 
i m m e di at el y. If n ot us e d i m m e di at el y, t h e pr e p ar e d s ol uti o n m a y b e st or e d u p t o 2 4 h o urs at 2 t o 8° C. 
N o i nc o m p ati biliti es b et w e e n o bi n ut uz u m a b a n d p ol y vi n yl c hl ori d e or p ol y ol efi n i nf usi o n m at eri als h a v e 
b e e n o bs er v e d i n c o nc e ntr ati o n r a n g es fr o m 0. 4 m g/ mL t o 2 0. 0 m g/ mL aft er dil uti o n of o bi n ut uz u m a b 
wit h 0. 9 % s o di u m c hl ori d e.
R ef er t o t h e P ac k a g e I ns ert f or a d diti o n al i nf or m ati o n r e g ar di n g t h e dr u g pr o d uct t o b e us e d i n t his tri al.
A d mi nistr ati o n of St u d y Dr u g
Ac al a br uti ni b
Ac al a br uti ni b t a bl et is a d mi nist er e d or all y t wic e d ail y. W h e n e v er p ossi bl e, it s h o ul d b e a d mi nist er e d at 
t h e s a m e ti m e e ac h d a y.  T h e t a bl ets s h o ul d b e s w all o w e d i nt act wit h w at er.  Ac al a br uti ni b t a bl ets 
s h o ul d b e s w all o w e d w h ol e wit h w at er.  S u bj ects s h o ul d n ot c h e w, cr us h, diss ol v e, or c ut t h e t a bl ets.  
Ac al a br uti ni b c a n b e t a k e n wit h or wit h o ut f o o d.
If a d os e is miss e d, it c a n b e t a k e n u p t o 3 h o urs aft er t h e sc h e d ul e d ti m e wit h a r et ur n t o t h e n or m al 
sc h e d ul e wit h t h e n ext d os e.  If it h as b e e n > 3 h o urs, t h e d os e s h o ul d n ot b e t a k e n a n d t h e s u bj ect 
s h o ul d t a k e t h e n ext d os e at t h e sc h e d ul e d ti m e.  T h e miss e d d os e will n ot b e m a d e u p a n d m ust b e 
r et ur n e d t o t h e sit e at t h e n ext sc h e d ul e d visit.
P ati e nts m ust r ec or d a d mi nistr ati o n of ac al a br uti ni b (ti m e a n d d at e of e ac h d os e, a n d miss e d d os es) o n 
t h e s u p pli e d p ati e nt j o ur n al.
G ui d a nc e o n c o- a d mi nistr ati o n of ac al a br uti ni b wit h a g e nts t h at aff ect g astric p H is pr o vi d e d i n S ecti o n 
5. 6.
O bi n ut uz u m a b
Pr e p ar e t h e s ol uti o n f or i nf usi o n, usi n g as e ptic t ec h ni q u e, as f oll o ws:

I ns p ect vis u all y f or a n y p artic ul at e m att er a n d disc ol or ati o n pri or t o a d mi nistr ati o n.

Dil ut e i nt o a 0. 9 % s o di u m c hl ori d e P V C or n o n- P V C p ol y ol efi n i nf usi o n b a g. D o n ot us e ot h er 
dil u e nts s uc h as d extr os e ( 5 %).

Wit h dr a w 4 0 mL of o bi n ut uz u m a b s ol uti o n fr o m t h e vi al. 

Dil ut e 4 0 mL ( 1 0 0 0 m g) i nt o a 2 5 0 mL 0. 9 % s o di u m c hl ori d e i nf usi o n b a g

Mix dil ut e d s ol uti o n b y g e ntl e i n v ersi o n. D o n ot s h a k e or fr e ez e. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

F or micr o bi ol o gic al st a bilit y, t h e dil ut e d o bi n ut uz u m a b i nf usi o n s ol uti o n s h o ul d b e us e d 
i m m e di at el y. Dil ut e u n d er a p pr o pri at e as e ptic c o n diti o ns. If n ot us e d i m m e di at el y, t h e s ol uti o n 
m a y b e st or e d i n a r efri g er at or at 2⁰ C  t o 8⁰ C  ( 3 6⁰ F t o 4 6⁰ F)  f or u p t o 2 4 h o urs pri or t o us e.

T h e pr o d uct c a n b e a d mi nist er e d at a fi n al c o nc e ntr ati o n of 0. 4 m g/ mL t o 4 m g/ mL
A d mi nist er as a n i ntr a v e n o us i nf usi o n o nl y. D o n ot a d mi nist er as a n i ntr a v e n o us p us h or b ol us. D o n ot 
mix o bi n ut uz u m a b wit h ot h er dr u gs. N o i nc o m p ati biliti es b et w e e n o bi n ut uz u m a b a n d P V C or n o n- P V C 
p ol y ol efi n b a gs a n d a d mi nistr ati o n s ets h a v e b e e n o bs er v e d.
4. 3 Acc o u nt a bilit y
T h e st u d y dr u g pr o vi d e d f or t his st u d y will b e us e d o nl y as dir ect e d i n t h e st u d y pr ot oc ol. T h e Wi ns hi p I D S  
(I n v esti g ati o n al Dr u g S er vic e) p ers o n n el will acc o u nt f or all st u d y dr u gs. Dr u g acc o u nt a bilit y s h o ul d b e 
p erf or m e d u ntil t h e p ati e nt st o ps st u d y tr e at m e nt c o m pl et el y. St u d y sit e p ers o n n el will acc o u nt f or all 
st u d y dr u gs r ec ei v e d at t h e sit e.
St u d y dr u g s u p pli es m ust b e k e pt i n a n a p pr o pri at e, s ec ur e l oc k e d ar e a a n d st or e d i n acc or d a nc e wit h t h e 
c o n diti o ns s p ecifi e d o n t h e l a b els. T h e I n v esti g at or, p h ar m acist, or d esi g n e e m ust m ai nt ai n a n acc ur at e 
r ec or d of dis p e nsi n g t h e st u d y dr u g/s i n a Dr u g Acc o u nt a bilit y L o g.
T h e Dr u g Acc o u nt a bilit y L o g m a y r ec or d s p ecifics t o st u d y dr u g dis p e ns ati o n s uc h as: 
• R ec or ds of pr o d uct d eli v er y, i n v e nt or y, t e m p er at ur e m o nit ori n g, d estr ucti o n, a n d r et ur n.
• D os a g es pr e p ar e d, ti m e pr e p ar e d, d os es dis p e ns e d. 
• D os es a n d/ or vi als d estr o y e d. 
• T h e Dr u g Acc o u nt a bilit y L o g m a y b e r e vi e w e d b y t h e m o nit or d uri n g sit e visits a n d at t h e c o m pl eti o n of 
t h e st u d y.
P ati e nts will b e as k e d t o r et ur n all u n us e d st u d y tr e at m e nt a n d p ac k a gi n g o n a r e g ul ar b asis, at 
t h e e n d of t h e st u d y or at t h e ti m e of st u d y tr e at m e nt disc o nti n u ati o n.
T h e st u d y dr u g s u p pl y will b e dis p os e d of p er Wi ns hi p’s I n v esti g ati o n al Dr u g S ervic e (I D S) S O P.
C o m pli a nc e will b e ass ess e d b y t h e i n v esti g at or a n d/ or st u d y p ers o n n el at e ac h p ati e nt visit a n d 
i nf or m ati o n pr o vi d e d b y t h e p ati e nt a n d/ or c ar e gi v er (c oll ecti o n of dr u g di ar y) will b e c a pt ur e d i n t h e 
Dr u g Acc o u nt a bilit y F or m. T his i nf or m ati o n m ust b e c a pt ur e d i n t h e s o urc e d oc u m e nt at e ac h p ati e nt 
visit. 
T h e p ati e nt mi g ht b e r e q u est e d t o m ai nt ai n a m e dic ati o n di ar y of e ac h d os e of m e dic ati o n.  T h e 
m e dic ati o n di ar y ( A p p e n dix B ) will b e r et ur n e d t o cli nic st aff at t h e e n d of e ac h c ycl e.
D os e c h a n g es a n d i nt err u pti o ns of st u d y dr u g m ust b e s p ecific all y d oc u m e nt e d i n t h e p ati e nt s o urc e 
d oc u m e nts a n d e C R F.
5. Pr oc e d ur es I n v ol v e d
5. 1 St u d y D esi g n
T his is a n o p e n-l a b el p h as e II st u d y of ac al a br uti ni b i n c o m bi n ati o n wit h o bi n ut uz m a b i n p ati e nts wit h 
u ntr e at e d, l o w t u m or b ur d e n f ollic ul ar l y m p h o m a a n d ot h er i n d ol e nt N HLs. T u m or b ur d e n will b e 
ass ess e d b as e d o n t h e G EL F crit eri a ( A p p e n dix E ). F oll o wi n g st u d y c o ns e nt a n d scr e e ni n g ass ess m e nts, 
p ati e nts will e nt er t h e i n d ucti o n p h as e w h er e tr e at m e nt will b e d eli v er e d i n 2 8- d a y c ycl es. F or c ycl es 1 
a n d 2, p ati e nts will r ec ei v e ac al a br uti ni b m o n ot h er a p y at t h e st a n d ar d d os e of 1 0 0 m g or all y t wic e d ail y. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
F or c ycl es 3- 8, p ati e nts will r ec ei v e c o m bi n ati o n t h er a p y wit h ac al a br uti ni b a n d o bi n ut uz u m a b. 
O bi n ut uz u m a b will b e gi v e n o n d a ys 1, 8, a n d 1 5 of c ycl e 3 t h e n o n d a y 1 of c ycl es 4- 8 ( 6 t ot al c ycl es of 
o bi n ut uz u m a b). Aft er c o m pl eti n g tr e at m e nt wit h o bi n ut uz u m a b, all p ati e nts will c o nti n u e o n 
ac al a br uti ni b m o n ot h er a p y f or c ycl es 9 t hr o u g h 1 2. 
R es p o ns e will b e ass ess e d aft er c ycl e 2 ( ac al a br uti ni b m o n ot h er a p y), aft er 3 c ycl es of t h e c o m bi n ati o n 
of o bi n ut uz u m a b/ ac al a br uti ni b, a n d aft er c ycl e 1 2. Aft er c o m pl eti n g c ycl e 1 2, p ati e nts will e nt er t h e 
f oll o w- u p p h as e. P ati e nts w h o ar e i n C R aft er c ycl e 1 2 will b e r a n d o miz e d t o eit h er disc o nti n u e 
ac al a br uti ni b or t o c o nti n u e ac al a br uti ni b m o n ot h er a p y u ntil i nt ol er a nc e or P D. All p ati e nts wit h P R or 
S D f oll o wi n g c ycl e 1 2 will c o nti n u e wit h ac al a br uti ni b m o n ot h er a p y u ntil i nt ol er a nc e or P D. P ati e nts 
wit h P D f oll o wi n g c ycl e 1 2 will disc o nti n u e st u d y tr e at m e nt. P ati e nts wit h P D at a n y ti m e pri or t o t h e 
c o ncl usi o n of c ycl e 1 2 m ay c o nti n u e st u d y t h er a p y if t h e y ar e f elt t o b e b e n efitti n g b y t h e tr e ati n g 
p h ysici a n, b ut n o o n e wit h P D will c o nti n u e t h er a p y p ast c ycl e 1 2. T h e st u d y will e nr oll 2 9 p ati e nts wit h 
f ollic ul ar l y m p h o m a f or o ur pri m ar y a n al ysis. T h e st u d y will als o e nr oll u p t o 2 0 p ati e nts wit h ot h er 
hist ol o gic s u bt y p es of i n d ol e nt N HL i n or d er t o i d e ntif y pr eli mi n ar y evi d e nc e of effic ac y of t his 
c o m bi n ati o n i n t h os e s u bt y p es a n d/ or cli nic al sc e n ari os.
5. 2 St u d y P ar a m et ers
Effic ac y P ar a m et ers
R es p o ns e t o tr e at m e nt will b e ass ess e d acc or di n g t o t h e L u g a n o Cl assific ati o n f or r es p o ns e 
ass ess m e nt i n l y m p h o m a 4 3 f or p ati e nts wit h FL a n d b as e d o n t h e a p pr o pri at e dis e as e r es p o ns e 
crit eri a f or n o n-f ollic ul ar l y m p h o m a. S e e S ecti o n 5. 8 f or a d escri pti o n of dis e as e r es p o ns e a n d 
pr o gr essi o n crit eri a.
S af et y P ar a m et ers
T h e s af et y of ac al a br uti ni b a n d o bi n ut uz u m a b will b e c h ar act eriz e d b y t h e t y p e, fr e q u e nc y, 
s e v erit y, ti mi n g of o ns et, d ur ati o n, a n d r el ati o ns hi p t o st u d y dr u g of a n y tr e at m e nt- e m er g e nt 
A Es or a b n or m aliti es of l a b or at or y t ests; S A Es, A Es of s p eci al i nt er est ( A E SI), or A Es l e a di n g t o 
disc o nti n u ati o n of st u d y tr e at m e nt or d e at h. 
F or c o nsist e nc y of i nt er pr et ati o n, A Es a n d l a b or at or y r es ults will b e c o d e d usi n g t h e M e dic al Dicti o n ar y 
f or R e g ul at or y Acti viti es ( M e d D R A), a n d t h e s e v erit y of A Es will b e gr a d e d usi n g t h e C o m m o n 
T er mi n ol o g y Crit eri a f or A d v ers e E v e nts ( C T C A E), V ersi o n 5. 0.  St a n d ar d d efi niti o ns f or s eri o us n ess will 
b e a p pli e d (s e e S ecti o n 1 7).
P ati e nt- R e p ort e d O utc o m e a n d H e alt h- R el at e d Q u alit y of Lif e Ass ess m e nts
T h e i m p act of tr e at m e nt wit h ac al a br uti ni b a n d o bi n ut uz u m a b o n h e alt h-r el at e d q u alit y of lif e 
a n d p ati e nt distr ess will b e ass ess e d usi n g t h e F A C T- G q u esti o n n air e, t h e H os pit al A nxi et y a n d 
D e pr essi o n Sc al e ( H A D S), a n d t h e P R O- C T C A E. S e e s ecti o n 5. 8 f or a d escri pti o n of Q oL, 
d e pr essi o n/ a nxi et y, a n d P R O ass ess m e nts.
5. 3 D osi n g a n d A d mi nistr ati o n
St u d y tr e at m e nt will b e a d mi nist er e d i n 2 8- d a y c ycl es.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Ac al a br uti ni b:
Ac al a br uti ni b 1 0 0 m g will b e a d mi nist er e d or all y t wic e d ail y, ev er y d a y st arti n g o n c ycl e 1 D a y 1 a n d will 
c o nti n u e t hr o u g h c ycl e 1 2 u nl ess t h e p ati e nt d e v el o ps i nt ol er a nc e t o ac al a br uti ni b or 
s y m pt o m atic/cli nic all y si g nific a nt dis e as e pr o gr essi o n. 
Aft er 1 2 c ycl e, p ati e nts w h o ac hi e v e C R will b e r a n d o miz e d t o eit h er c o nti n u e ac al a br uti ni b at t h e s a m e 
d os e u ntil i nt ol er a nc e or P D or disc o nti n u e t h e m e dic ati o n. P ati e nts wit h a P R or S D aft er 1 2 c ycl es of 
tr e at m e nt will c o nti n u e ac al a br uti ni b at t h e s a m e d os e u ntil i nt ol er a nc e or P D. 
O bi n ut uz u m a b:
E ac h d os e of o bi n ut uz u m a b is 1 0 0 0 m g a d mi nist er e d i ntr a v e n o usl y acc or di n g t o i nstit uti o n al pr ot oc ols 
a n d t h e U S PI. P ati e nts w h o ar e d e e m e d t o b e at hi g h ris k f or i nf usi o n-r el at e d r e acti o ns m ay  r ec ei v e t h e 
first d os e of o bi n ut uz u m a b as a s plit d os e ( 1 0 0 m g o n d a y 1, 9 0 0 m g o n d a y 2). T his o pti o n is o nl y 
a v ail a bl e f or t h e first d os e of o bi n ut uz u m a b. I n t his c as e, w e w o ul d r ec o m m e n d t h at p ati e nts r ec ei v e 
t h e d a y 1 d os e at 2 5 m g/ hr x 4 h o urs wit h o ut titr ati o n of t h e i nf usi o n r at e. 
O bi n ut uz u m a b will b e a d mi nist er e d d uri n g c ycl es 3 t hr o u g h 8. T h er e will b e n o o bi n ut uz u m a b 
m ai nt e n a nc e p h as e. R ef er t o t h e sc h e d ul e of ass ess m e nts ( S ecti o n 1. 3) f or t h e d osi n g sc h e d ul e. 
5. 4 D os e M o dific ati o n
T h e i n v esti g at or will d eci d e w h et h er a n y A E t h at occ urs is r el at e d t o eit h er or b ot h dr u gs a n d d et er mi n e 
w h et h er d os e m o dific ati o n or disc o nti n u ati o n of o n e or b ot h dr u gs is r e q uir e d p er t h e g ui d a nc e b el o w.
Ac al a br uti ni b
S u bj ects s h o ul d b e f oll o w e d cl os el y f or A Es or l a b or at or y a b n or m aliti es t h at mi g ht i n dic at e 
ac al a br uti ni b-r el at e d t oxicit y.  If a s u bj ect ex p eri e nc es a tr e at m e nt-r el at e d t oxicit y or ot h er i nt ol er a bl e 
A E d uri n g t h e c o urs e of t h er a p y, t h e n ac al a br uti ni b s h o ul d b e wit h h el d, as n ec ess ar y, u ntil t h e A E 
r et ur ns t o gr a d e 1 or b as eli n e. 
D os e m o dific ati o ns f or t h e f oll o wi n g tr e at m e nt- e m er g e nt t oxiciti es ar e pr o vi d e d b el o w:

Gr a d e 4 n e utr o p e ni a ( < 5 0 0/ μL)  f or > 7 d a ys ( n e utr o p hil gr o wt h f act ors ar e p er mitt e d p er 
A m eric a n S oci et y of Cli nic al O nc ol o g y ( A S C O) g ui d eli n es [ S mit h 2 0 0 6] a n d us e m ust b e r ec or d e d 
o n t h e c as e r e p ort f or m [ C R F]).

Gr a d e 3 t hr o m b oc yt o p e ni a i n pr es e nc e of si g nific a nt bl e e di n g.

Gr a d e 4 t hr o m b oc yt o p e ni a. 

Gr a d e 3 or 4 n a us e a, v o miti n g, or di arr h e a, if p ersist e nt d es pit e o pti m al a nti e m etic a n d/ or a nti-
di arr h e al t h er a p y.

A n y ot h er Gr a d e 4 t oxicit y or u n m a n a g e a bl e Gr a d e 3 t oxicit y.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Dr u g M o dific ati o n Acti o ns f or Ac al a br uti ni b
Occ urr e nc e
Acti o n
1 st – 2n d
H ol d ac al a br uti ni b u ntil r ec o v er y t o Gr a d e 1 or b as eli n e; m a y r est art at ori gi n al d os e 
l e v el
3 r d
H ol d ac al a br uti ni b u ntil r ec o v er y t o Gr a d e 1 or b as eli n e; r est art at o n e d os e l ev el 
l o w er ( 1 0 0 m g Q D)
4 t h
Disc o nti n u e ac al a br uti ni b
As a p pr o pri at e, c ert ai n l a b or at or y a b n or m aliti es m a y w arr a nt m or e fr e q u e nt m o nit ori n g ( e g, o nc e p er 
w e e k) u ntil a b n or m aliti es h a v e r ec o v er e d t o Gr a d e 1.  If ac al a br uti ni b is r e d uc e d f or a p p ar e nt 
tr e at m e nt-r el at e d t oxicit y, t h e d os e n e e d n ot b e r e- esc al at e d, e v e n if t h er e is mi ni m al or n o t oxicit y wit h 
t h e r e d uc e d d os e.  H o w e v er, if t h e s u bj ect t ol er at es a r e d uc e d d os e of ac al a br uti ni b f or ≥ 4 w e e ks t h e n 
t h e d os e m a y b e i ncr e as e d t o t h e n ext hi g h er d os e l ev el, at t h e discr eti o n of t h e i n v esti g at or.  S uc h 
r e- esc al ati o n m a y b e p artic ul arl y w arr a nt e d if f urt h er e v al u ati o n r e v e als t h at t h e A E t h at l e d t o t h e d os e 
r e d ucti o n w as n ot tr e at m e nt-r el at e d.  P ati e nts w h o r e- esc al at e ac al a br uti ni b tr e at m e nt w h o a g ai n 
ex p eri e nc e a n A E r e q uiri n g d os e r e d ucti o n m a y n ot r e- esc al at e a 2 n d ti m e a n d s h o ul d r e m ai n o n t h e 
l o w er d os e. T h e m axi m u m d os e of ac al a br uti ni b is 1 0 0 m g BI D.
Tr e at m e nt wit h ac al a br uti ni b s h o ul d b e wit h h el d f or a n y u n m a n a g e a bl e, p ot e nti all y st u d y dr u g-r el at e d 
t oxicit y t h at is Gr a d e ≥ 3 i n s ev erit y.  
E v er y att e m pt s h o ul d b e m a d e t o m a n a g e p ati e nts ex p eri e nci n g a gr a d e ≤2  t oxicit y wit h a g gr essi v e 
s u p p orti v e c ar e as n e e d e d a n d t o c o nti n u e ac al a br uti ni b t h er a p y at f ull d os e.  H o w e v er, p ati e nts 
ex p eri e nci n g a gr a d e ≤2  h e m at ol o gic or n o n- h e m at ol o gic t oxicit y t h at d o es n’t r es ol v e wit h s u p p orti v e 
c ar e m a y h ol d tr e at m e nt u ntil r es ol uti o n t o gr a d e 1 or b as eli n e or m a y r e d uc e t h e d os e t o t h e n ext 
l o w est d os e l e v el wit h o ut a n i nt er mitt e nt h ol d.  U p o n r ec o v er y t o gr a d e 1 or b as eli n e, p ati e nts m a y b e 
r est art e d at t h e f ull d os e l ev el or  m a y r ec ei v e o n e l o w er d os e l e v el b as e d o n i n v esti g at or/ p ati e nt 
pr ef er e nc e. 
O bi n ut uz u m a b:
N o d os e m o dific ati o ns of o bi n ut uz u m a b ar e all o w e d. If a p ati e nt is u n a bl e t o t ol er at e o bi n ut uz u m a b i n 
t h e ass ess m e nt of t h e i n v esti g at or, f urt h er d os es m a y b e h el d a n d t h e p ati e nt m a y c o nti n u e t o r ec ei v e 
ac al a br uti ni b o n st u d y at t h e discr eti o n of t h e i n v esti g at or.
P ati e nts ex p eri e nci n g a n y of t h e f oll o wi n g t oxiciti es s h o ul d h a v e o bi n ut uz u m a b h el d u ntil r es ol uti o n t o 
gr a d e 1 or b as eli n e:

Gr a d e ≥3  f e bril e n e utr o p e ni a

Gr a d e 4 n e utr o p e ni a or t hr o m b oc yt o p e ni a

Gr a d e ≥ 3 i nf ecti o n
M a n a g e m e nt of O bi n ut uz u m a b I nf usi o n R e acti o ns:
If a p ati e nt ex p eri e nc es a n i nf usi o n r e acti o n of a n y gr a d e d uri n g i nf usi o n, a dj ust t h e i nf usi o n as f oll o ws:

Gr a d e 4 (lif e-t hr e at e ni n g): St o p i nf usi o n i m m e di at el y a n d p er m a n e ntl y disc o nti n u e 
o bi n ut uz u m a b t h er a p y. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

Gr a d e 3 (s e v er e): I nt err u pt i nf usi o n a n d m a n a g e s y m pt o ms. U p o n r es ol uti o n of s y m pt o ms, 
c o nsi d er r est arti n g o bi n ut uz u m a b i nf usi o n at n o m or e t h a n h alf t h e pr evi o us r at e (t h e r at e 
b ei n g us e d at t h e ti m e t h at t h e i nf usi o n r e acti o n occ urr e d) a n d, if p ati e nt d o es n ot 
ex p eri e nc e a n y f urt h er i nf usi o n r e acti o n s y m pt o ms, i nf usi o n r at e esc al ati o n m a y r es u m e at 
t h e i ncr e m e nts a n d i nt er v als as a p pr o pri at e f or t h e tr e at m e nt c ycl e d os e. P er m a n e ntl y 
disc o nti n u e tr e at m e nt if p ati e nts ex p eri e nc e a Gr a d e 3 i nf usi o n-r el at e d s y m pt o m at 
r ec h all e n g e. 

Gr a d e 1 – 2 ( mil d t o m o d er at e): R e d uc e i nf usi o n r at e or i nt err u pt i nf usi o n a n d tr e at 
s y m pt o ms. U p o n r es ol uti o n of s y m pt o ms, c o nti n u e or r es u m e i nf usi o n a n d, if p ati e nt d o es 
n ot ex p eri e nc e a n y f urt h er i nf usi o n r e acti o n s y m pt o ms, i nf usi o n r at e esc al ati o n m a y r es u m e 
at t h e i ncr e m e nts a n d i nt er v als as a p pr o pri at e f or t h e tr e at m e nt c ycl e d os e. 
H ol di n g St u d y T h er a p y f or Pr oc e d ur es
If t h e p ati e nt r e q uir es a n i n v asi v e pr oc e d ur e d uri n g t h e c o urs e of t h e st u d y, it is p er missi bl e t o h ol d 
ac al a br uti ni b f or u p t o 7 d a ys pr e- a n d p ost- pr oc e d ur e. H ol di n g o bi n ut uz u m a b is n ot r e q uir e d i n t his 
s etti n g a n d eff orts s h o ul d b e m a d e t o d eli v er t h e o bi n ut uz u m a b d os e as sc h e d ul e d if d e e m e d 
a p pr o pri at e b y t h e i n v esti g at or. If it is n ot p ossi bl e t o a d mi nist er o bi n ut uz u m a b wit hi n ± 3 d a ys of t h e 
sc h e d ul e d visit, t h e n t h e d os e of o bi n ut uz u m a b c a n b e o mitt e d a n d t h e p ati e nt will b e all o w e d t o 
c o nti n u e o n st u d y.  
5. 5 C o nc o mit a nt M e dic ati o ns
M e dic ati o ns or v acci n ati o ns s p ecific all y pr o hi bit e d i n t h e excl usi o n crit eri a ar e n ot all o w e d d uri n g t h e 
o n g oi n g tri al.  If t h er e is a cli nic al i n dic ati o n f or o n e of t h es e or ot h er m e dic ati o ns or v acci n ati o ns 
s p ecific all y pr o hi bit e d d uri n g t h e tri al, disc o nti n u ati o n fr o m tri al t h er a p y will b e r e q uir e d if a s uit a bl e 
alt er n ati v e is n ot a v ail a bl e.
P er mitt e d C o nc o mit a nt T h er a p y
All tr e at m e nts t h at t h e i n v esti g at or c o nsi d ers n ec ess ar y f or a s u bj ect’s w elf ar e m a y b e a d mi nist er e d at 
t h e discr eti o n of t h e i n v esti g at or i n k e e pi n g wit h t h e c o m m u nit y st a n d ar ds of m e dic al c ar e. H o w ev er, if a 
pr o hi bit e d c o nc o mit a nt m e dic ati o n m ust b e a d mi nist er e d, t h e p ati e nt c a n n ot c o nti n u e st u d y t h er a p y. If 
it is a s h ort-t er m tr e at m e nt c o urs e ( < 2 w e e ks) t h e p ati e nt m a y h ol d ac al a br uti ni b d uri n g t h at ti m e a n d 
r est art w h e n t h e c o urs e is c o m pl et e d. If t h e p ati e nt r e q uir es a l o n g er c o urs e of tr e at m e nt wit h a n 
ot h er wis e pr o hi bit e d m e dic ati o n, t h e n t h e p ati e nt m ust disc o nti n u e st u d y t h er a p y.  All c o nc o mit a nt 
m e dic ati o n will b e r ec or d e d o n t h e c as e r e p ort f or m ( C R F) i ncl u di n g all pr escri pti o n, o v er-t h e-c o u nt er 
( O T C), h er b al s u p pl e m e nts, a n d I V m e dic ati o ns a n d fl ui ds.  If c h a n g es occ ur d uri n g t h e tri al p eri o d, 
d oc u m e nt ati o n of dr u g d os a g e, fr e q u e nc y, r o ut e, a n d d at e m a y als o b e i ncl u d e d o n t h e C R F. All 
c o nc o mit a nt m e dic ati o ns r ec ei v e d wit hi n 2 8 d a ys b ef or e t h e first d os e of tri al tr e at m e nt a n d 3 0 d a ys aft er 
t h e l ast d os e of tri al tr e at m e nt s h o ul d b e r ec or d e d.  C o nc o mit a nt m e dic ati o ns a d mi nist er e d u p t o 3 0 d a ys 
aft er t h e l ast d os e of tri al tr e at m e nt s h o ul d b e r ec or d e d. I n g e n er al, c o nc o mit a nt m e dic ati o ns a n d 
t h er a pi es d e e m e d n ec ess ar y f or t h e s u p p orti v e c ar e ( e. g. s uc h as a nti- e m etics, a nti- di arr h e a) a n d s af et y 
of t h e p ati e nt ar e all o w e d: 
    
M e dic ati o ns t o pr e v e nt or tr e at n a us e a or v o miti n g. 
A nti- di arr h e al m e dic ati o ns ( e. g., l o p er a mi d e) f or p ati e nts w h o d e v el o p di arr h e a. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
P ai n m e dic ati o n t o all o w t h e p ati e nt t o b e as c o mf ort a bl e as p ossi bl e. 
H e m at o p oi etic c ol o n y-sti m ul ati n g gr o wt h f act ors ( e. g. G- C S F, G M- C S F, M- C S F), t hr o m b o p oi eti n mi m etics 
or er yt hr oi d sti m ul ati n g a g e nts as p er l oc al or p u blis h e d g ui d eli n es; i n c as e of a n e mi a, t hr o m b oc yt o p e ni a 
or n e utr o p e ni a, p ot e nti al i m m u n e m e di at e d eti ol o g y s h o ul d b e r ul e d o ut 
N utriti o n al s u p p ort or a p p etit e sti m ul a nts ( e. g. m e g estr ol). 
Ox y g e n t h er a p y a n d bl o o d pr o d ucts or tr a nsf usi o ns. 
I n acti v at e d v acci n es.  
T h e p ati e nt m ust b e t ol d t o n otif y t h e i n v esti g ati o n al sit e a b o ut a n y n e w m e dic ati o ns h e/s h e t a k es aft er 
t h e st art of t h e st u d y dr u g. All m e dic ati o ns ( ot h er t h a n st u d y dr u g) a n d si g nific a nt n o n- dr u g t h er a pi es 
(i ncl u di n g p h ysic al t h er a p y, h er b al/ n at ur al m e dic ati o ns a n d bl o o d tr a nsf usi o ns) a d mi nist er e d d uri n g t h e 
st u d y m ust b e list e d o n t h e C o nc o mit a nt M e dic ati o ns.
M o nit ori n g a n d Tr e at m e nt f or H e p atitis B R e acti v ati o n
P ati e nts w h o ar e b ot h H Bs A g n e g ati v e a n d h e p atitis B c or e a nti b o d y ( a nti- H Bc) p ositi v e m a y b e 
i ncl u d e d. T h es e p ati e nts s h o ul d h a v e H B V D N A l ev els o bt ai n e d m o nt hl y f or at l e ast 1 2 m o nt hs aft er t h e 
l ast c ycl e of t h er a p y b y m e a ns of r e al-ti m e P C R wit h t h e us e of a n ass a y t h at h as a s e nsiti vit y of at l e ast 
1 0 I U/ mL. P ati e nts w h o ar e a nti- H Bc p ositi v e b ut wit h n o evi d e nc e of acti v e dis e as e, i ncl u di n g a n e g ati v e 
H Bs A g a n d u n d et ect a bl e H B V D N A s h o ul d r ec ei v e pr o p h yl axis a g ai nst h e p atitis B r e acti v ati o n as cl os e t o 
t h e b e gi n ni n g of t h er a p y as p ossi bl e a n d t his s h o ul d c o nti n u e f or at l e ast 6 m o nt hs aft er c o m pl eti o n of 
st u d y t h er a p y.
If t h e H B V D N A ass a y b ec o m es p ositi v e a n d is a b o v e t h e W orl d H e alt h Or g a niz ati o n’s c ut off of 1 0 0 
I U/ mL, st u d y tr e at m e nt s h o ul d b e disc o nti n u e d a n d t h e p ati e nt s h o ul d b e tr e at e d (f or at l e ast 1 y e ar 
aft er t h e l ast d os e of o bi n ut uz u m a b) wit h a n a p pr o pri at e n ucl e osi d e a n al o g u e a n d i m m e di at el y r ef err e d 
t o a g astr o e nt er ol o gist or h e p at ol o gist f or m a n a g e m e nt. P ati e nts m a y r es u m e st u d y tr e at m e nt o nc e 
H B V D N A l e v els d ecr e as e t o u n d et ect a bl e l e v els. 
If t h e H B V D N A ass a y b ec o m es p ositi v e a n d is ≤ 1 0 0 I U/ mL, t h e p ati e nt s h o ul d b e r et est e d wit hi n 2 
w e e ks. If t h e ass a y is still p ositi v e, tr e at m e nt wit h st u d y t h er a p y m ust b e disc o nti n u e d a n d t h e p ati e nt 
s h o ul d b e tr e at e d wit h a n a p pr o pri at e n ucl e osi d e a n al o g u e (f or at l e ast 1 y e ar aft er t h e l ast d os e of 
o bi n ut uz u m a b) a n d i m m e di at el y r ef err e d t o a g astr o e nt er ol o gist or h e p at ol o gist f or m a n a g e m e nt. 
P ati e nts m a y r es u m e st u d y tr e at m e nt o nc e t h e H B V D N A l e v els d ecr e as e t o u n d et ect a bl e l ev els. 
If a p ati e nt’s H B V D N A l e v el exc e e ds 1 0 0 I U/ mL w hil e t h e p ati e nt is r ec ei vi n g a nti vir al m e dic ati o n, st u d y 
tr e at m e nt m ust b e p er m a n e ntl y disc o nti n u e d. 
Pr o hi bit e d or R estrict e d C o nc o mit a nt T h er a p y

D uri n g t h e c o urs e of t h e st u d y, p ati e nts m ust n ot r ec ei v e ot h er a nti n e o pl astic t h er a pi es ( e. g. 
i n v esti g ati o n al dr u gs, d e vic es, c h e m ot h er a p y, i m m u n ot h er a pi es) or a n y ot h er t h er a pi es t h at 
m a y b e acti v e a g ai nst c a nc er or m o d ul at e t h e i m m u n e r es p o ns es. R a di ati o n t h er a p y s h o ul d 
als o n ot b e a d mi nist er e d w hil e o n st u d y.  If a p ati e nt r e q uir es tr e at m e nt wit h r a di ati o n 
t h er a p y, t h e y will n e e d t o b e r e m o v e d fr o m st u d y t h er a p y.
o
A s h ort c o urs e of st er oi ds is p er mitt e d f or p ati e nts asi d e fr o m t h os e i n t h e l o w t u m or 
b ur d e n FL c o h ort. T his c o urs e m a y b e n o m or e t h a n 1 4 d a ys a n d st er oi ds m ust b e 
disc o nti n u e d ( or t a p er e d t o ≤ 1 0 m g pr e d nis o n e or e q ui v al e nt) n o l at er t h a n 3 d a ys aft er 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
i niti ati o n of st u d y tr e at m e nt. T h e us e of s yst e mic st er oi d t h er a p y is all o w e d f or t h e 
tr e at m e nt of i nf usi o n r e acti o ns a n d f or pr o p h yl axis a g ai nst i m a gi n g c o ntr ast d y e all er g y, 
st a n d ar d pr e- m e dic ati o n f or c h e m ot h er a p y or r e pl ac e m e nt- d os e st er oi ds i n t h e s etti n g 
of a dr e n al i ns uffici e nc y ( pr o vi d e d t his is ≤ 1 0 m g/ d a y pr e d nis o n e or e q ui v al e nt). If 
s yst e mic c ortic ost er oi ds ar e r e q uir e d f or t h e c o ntr ol of i nf usi o n r e acti o ns, it m ust b e 
t a p er e d t o n o n-i m m u n os u p pr essi v e ( d os es ≤1 0  m g/ d a y pr e d nis o n e or e q ui v al e nt) 
wit hi n 2 w e e ks, t h e n st u d y t h er a p y m ust b e disc o nti n u e d. C o nc o mit a nt t h er a p y wit h 
i n h al e d st er oi ds f or ast h m a or C O P D as w ell as t o pic al st er oi ds is p er mitt e d. 

T h e us e of li v e v acci n es is n ot all o w e d t hr o u g h t h e w h ol e d ur ati o n of t h e st u d y. I n acti v at e d 
v acci n es ar e all o w e d. T h er e ar e n o pr o hi bit e d t h er a pi es d uri n g t h e p ost-tr e at m e nt f oll o w- u p 
p eri o d.

W arf ari n or e q ui v al e nt vit a mi n K a nt a g o nists ( e g, p h e n pr oc o u m o n) ar e pr o hi bit e d.
A v oi d c o- a d mi nistr ati o n of str o n g C Y P 3 A i n hi bit ors (s e e A p p d e n dix D) wit h ac al a br uti ni b. Alt er n ati v el y, if 
t h e i n hi bit or will b e us e d s h ort-t er m, i nt err u pt ac al a br uti ni b. Aft er disc o nti n u ati o n of str o n g C Y P 3 A 
i n hi bit or f or at l e ast 2 4 h o urs, r es u m e pr evi o us d os a g e of ac al a br uti ni b.  If t h e p ati e nt r e q uir es t h er a p y 
wit h a str o n g C Y P 3 A i n hi bit or f or l o n g er t h a n 2 w e e ks, t h e n st u d y t h er a p y m ust b e disc o nti n u e d. W h e n 
ac al a br uti ni b is a d mi nist er e d wit h m o d er at e C Y P 3 A i n hi bit ors, r e d uc e ac al a br uti ni b d os e t o 1 0 0 m g 
o nc e d ail y. A v oi d c o- a d mi nistr ati o n of str o n g C Y P 3 A i n d uc ers wit h ac al a br uti ni b. If a str o n g C Y P 3 A 
i n d uc er c a n n ot b e a v oi d e d, i ncr e as e t h e ac al a br uti ni b d os e t o 2 0 0 m g t wic e d ail y. It is n ot p ossi bl e t o 
pr o d uc e a n ex h a usti v e list of m e dic ati o ns t h at f all i nt o t h es e c at e g ori es, s o if i n q u esti o n, r ef er t o t h e 
a p pr o pri at e pr o d uct l a b el. F or a d diti o n al i nf or m ati o n o n dr u gs wit h p ot e nti al dr u g- dr u g i nt er acti o ns, 
r ef er t o S ecti o n 5. 6.
5. 6 Dr u g- Dr u g I nt er acti o ns
At t h e s yst e mic ex p os ur e l e v els ex p ect e d i n t his st u d y, ac al a br uti ni b i n hi biti o n of C Y P m et a b olis m is n ot 
a ntici p at e d. H o w e v er, ac al a br uti ni b is m et a b oliz e d b y C Y P 3 A.  C o nc o mit a nt a d mi nistr ati o n of 
ac al a br uti ni b wit h a str o n g C Y P 3 A a n d P- gl yc o pr ot ei n ( P- g p) i n hi bit or, itr ac o n az ol e i ncr e as e d ex p os ur e 
b y a p pr oxi m at el y 5-f ol d.  C o n v ers el y, c o nc o mit a nt a d mi nistr ati o n of ac al a br uti ni b wit h a str o n g C Y P 3 A 
i n d uc er, rif a m pi n, d ecr e as e d ac al a br uti ni b ex p os ur e a n d c o ul d r e d uc e effic ac y.  C o ns e q u e ntl y, t h e 
c o nc o mit a nt us e of str o n g i n hi bit ors/i n d uc ers of C Y P 3 A (s e e A p p e n dix 3) s h o ul d b e a v oi d e d w h e n 
p ossi bl e.  
5. 7 St u d y Pr oc e d ur es
T h e sc h e d ul e of ev e nts is pr o vi d e d i n S ecti o n 1. 3.  D escri pti o ns of t h e sc h e d ul e d e v al u ati o ns ar e 
o utli n e d b el o w a n d c o m pl et e i nf or m ati o n o n st u d y dr u g a n d d osi n g is pr o vi d e d i n S ecti o n 4. 2.
B ef or e st u d y e ntr y, t hr o u g h o ut t h e st u d y, a n d at t h e f oll o w- u p e v al u ati o n, v ari o us cli nic al a n d di a g n ostic 
l a b or at or y e v al u ati o ns ar e o utli n e d.  T h e p ur p os e of o bt ai ni n g t h es e d et ail e d m e as ur e m e nts is t o e ns ur e 
a d e q u at e s af et y a n d t ol er a bilit y ass ess m e nts.  Cli nic al e v al u ati o ns a n d l a b or at or y st u di es m a y b e 
r e p e at e d m or e fr e q u e ntl y if cli nic all y i n dic at e d.
B ef or e st u d y e ntr y, t hr o u g h o ut t h e st u d y, a n d f oll o wi n g st u d y dr u g disc o nti n u ati o n, v ari o us cli nic al a n d 
di a g n ostic l a b or at or y e v al u ati o ns ar e o utli n e d.  T h e p ur p os e of o bt ai ni n g t h es e d et ail e d m e as ur e m e nts is 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
t o e ns ur e a d e q u at e s af et y a n d t ol er a bilit y ass ess m e nts.  Cli nic al e v al u ati o ns a n d l a b or at or y st u di es m a y 
b e r e p e at e d m or e fr e q u e ntl y if cli nic all y i n dic at e d.  T h e Sc h e d ul es of Ass ess m e nts d uri n g t h e scr e e ni n g 
a n d tr e at m e nt p eri o d is pr o vi d e d f oll o wi n g t h e Pr ot oc ol S y n o psis . 
5. 8 D escri pti o n of St u d y Pr oc e d ur es
I nf or m e d C o ns e nt
T h e s u bj ect m ust r e a d, u n d erst a n d a n d si g n t h e I C F a p pr o v e d b y t h e i nstit uti o n al r e vi e w b o ar d or 
i n d e p e n d e nt et hics c o m mitt e e (I R B/I E C), c o nfir mi n g his or h er willi n g n ess t o p artici p at e i n t his st u d y 
b ef or e i niti ati n g a n y scr e e ni n g acti vit y t h at is n ot st a n d ar d of c ar e.  S u bj ects m ust als o gr a nt p er missi o n 
t o us e pr ot ect e d h e alt h i nf or m ati o n, if r e q uir e d b y l oc al r e g ul ati o ns.
T h e c urr e nt st a n d ar d of c ar e f or m a n y p ati e nts w h o will b e eli gi bl e t o e nr oll i n t h e tri al is o bs er v ati o n, 
t h o u g h si n gl e- a g e nt rit uxi m a b is a r e as o n a bl e alt er n ati v e i n p ati e nts n ot c o mf ort a bl e wit h t his 
tr e at m e nt a p pr o ac h. Pri or t o si g ni n g i nf or m e d c o ns e nt, t h e i n v esti g at or m ust disc uss a n d off er t h e m as 
r e as o n a bl e alt er n ati v es t o cli nic al tri al e nr oll m e nt. T h e i n v esti g at or m ust als o disc uss t h at t h e p ur p os e 
of t his cli nic al tri al is t o i n v esti g at e a n e w t h er a p y t h at will h o p ef ull y i m pr o v e o n t h e o utc o m es s e e n wit h 
o bs er v ati o n or si n gl e- a g e nt rit uxi m a b, b ut t h er e is n o g u ar a nt e e t h at t his will b e t h e c as e.
M e dic al Hist or y
C oll ect a n d r ec or d t h e s u bj ect’s c o m pl et e hist or y t hr o u g h r e vi e w of m e dic al r ec or ds a n d b y i nt ervi e w.  
C o nc urr e nt m e dic al si g ns a n d s y m pt o ms m ust b e d oc u m e nt e d t o est a blis h b as eli n e s ev eriti es.  A dis e as e 
hist or y, i ncl u di n g t h e d at e of i niti al di a g n osis a n d list of all pri or a ntic a nc er tr e at m e nts, a n d r es p o ns es 
a n d d ur ati o n of r es p o ns e t o t h es e tr e at m e nts, als o will b e r ec or d e d.
A d v ers e E v e nts
T h e acc e pt e d r e g ul at or y d efi niti o n f or a n A E a n d i m p ort a nt a d diti o n al r e q uir e m e nts f or r e p orti n g S A Es 
ar e ex pl ai n e d i n S ecti o n 1 7. 
C o nfir m ati o n of Eli gi bilit y
S u bj ect eli gi bilit y f or e nr oll m e nt will b e ass ess e d p er S ecti o n 9.  All scr e e ni n g pr oc e d ur es, u nl ess 
ot h er wis e i n dic at e d, s h o ul d b e c o m pl et e d wit hi n 2 8 d a ys of t h e first d os e of st u d y dr u g.
E C O G P erf or m a nc e St at us
T h e E C O G p erf or m a nc e i n d ex is pr o vi d e d i n A p p e n dix A.
P h ysic al E x a mi n ati o n, Vit al Si g ns, H ei g ht & W ei g ht
P h ysic al Ex a m
T h e scr e e ni n g p h ysic al ex a mi n ati o n will i ncl u d e, at a mi ni m u m, t h e g e n er al a p p e ar a nc e of t h e s u bj ect, 
h ei g ht (scr e e ni n g o nl y) a n d w ei g ht, a n d ex a m of ot h er s yst e ms as cli nic all y a p pr o pri at e a n d c o nsist e nt 
wit h r o uti n e c ar e.
S y m pt o m- dir ect e d p h ysic al ex a ms will b e d o n e d uri n g t h e tr e at m e nt p eri o d a n d at t h e s af et y f oll o w- u p 
( S F U) visits.
Vit al Si g ns
Vit al si g ns ( bl o o d pr ess ur e [ B P], p uls e, t e m p er at ur e, a n d r es pir ati o n r at e) will b e e v al u at e d acc or di n g t o 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 2 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
t h e ass ess m e nt sc h e d ul es.  Vit al si g ns o n d a ys of o bi n ut uz u m a b i nf usi o ns s h o ul d b e o bt ai n e d a n d 
d oc u m e nt e d i n t h e m e dic al r ec or d c o nsist e nt wit h st a n d ar d of c ar e i nf usi o n pr ot oc ols at t h e tr e ati n g 
i nstit uti o n. 
El ectr oc ar di o gr a m
R esti n g 1 2-l e a d E C Gs will b e r ec or d e d as cli nic all y i n dic at e d t hr o u g h o ut t h e st u d y.  If cli nic all y i n dic at e d, 
E C Gs s h o ul d b e o bt ai n e d aft er t h e p ati e nt h as b e e n i n a s u pi n e p ositi o n f or 5 mi n ut es a n d r ec or d e d w hil e 
t h e p ati e nt r e m ai ns i n t h at p ositi o n.
T h e I n v esti g at or or q u alifi e d S u b-I n v esti g at or will r e vi e w all E C G i nt er pr et ati o ns a n d i nt er v al d ur ati o n 
m e as ur e m e nts f or cli nic al si g nific a nc e.  A n y E C G i nt er pr et ati o n d e e m e d t o b e cli nic all y si g nific a nt will b e 
r e p ort e d as a n A E.
Uri n e or S er u m Pr e g n a nc y T est
Pr e g n a nc y t ests will b e r e q uir e d o nl y f or w o m e n of c hil d b e ari n g p ot e nti al. Uri n e or s er u m β- H C G  t esti n g 
will b e p erf or m e d at t h e scr e e ni n g visit a n d a g ai n o n D a y 1 of e ac h tr e at m e nt c ycl e f or w hic h a cli nic 
visit is r e q uir e d. A uri n e or s er u m pr e g n a nc y t est m ust als o b e o bt ai n e d at e ac h r e q uir e d st u d y visit 
d uri n g t h e f oll o w- u p p h as e f or p ati e nts w h o c o nti n u e o n ac al a br uti ni b.
H e m at ol o g y
F or t h e p ur p os es of t his st u d y, “ h e m at ol o g y” l a b or at or y t ests s h o ul d i ncl u d e t ot al w hit e bl o o d 
c ell c o u nt, h e m o gl o bi n, h e m at ocrit, pl at el et c o u nt a n d a W B C diff er e nti al.
S er u m C h e mistr y
Cli nic al c h e mistr y (s er u m or pl as m a) L a b or at or y T ests
Al b u mi n
Gl uc os e
Al k ali n e p h os p h at as e
L act at e d e h y dr o g e n as e
Al a ni n e a mi n otr a nsf er as e
P ot assi u m
As p art at e a mi n otr a nsf er as e
S o di u m
Bic ar b o n at e
T ot al bilir u bi n a
C alci u m 
T ot al pr ot ei n
C hl ori d e
Ur e a or bl o o d ur e a nitr o g e n, d e p e n di n g o n l oc al pr actic e
Cr e ati ni n e
a   If T ot al bilir u bi n is ≥2x UL N  ( a n d n o evi d e nc e of Gil b ert’s s y n dr o m e) t h e n fr acti o n at e i nt o dir ect a n d 
i n dir ect bilir u bi n
H e p atitis B a n d C T esti n g
H e p atitis s er ol o g y t esti n g m ust i ncl u d e h e p atitis B s urf ac e a nti g e n ( H Bs A g), h e p atitis B s urf ac e a nti b o d y 
( a nti- H Bs), a nti- H Bc, a n d H C V a nti b o d y.  I n a d diti o n, a n y s u bj ects t esti n g p ositi v e f or a n y h e p atitis 
s er ol o g y m ust h a v e P C R t esti n g d uri n g scr e e ni n g a n d o n st u d y (s e e excl usi o n crit eri o n # 1 7).    
S u bj ects w h o ar e a nti- H Bc p ositi v e s h o ul d h a v e q u a ntit ati v e P C R t esti n g f or H B V D N A p erf or m e d d uri n g 
scr e e ni n g a n d m o nt hl y t h er e aft er as p er i nstit uti o n al pr actic es.  A n y s u bj ect wit h a risi n g vir al l o a d 
( a b o v e l o w er li mit of d et ecti o n) s h o ul d disc o nti n u e st u d y dr u g a n d h a v e a nti vir al t h er a p y i nstit ut e d a n d 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
a c o ns ult ati o n wit h a p h ysici a n wit h ex p ertis e i n m a n a gi n g h e p atitis B.  As I VI G m a y c a us e f als e p ositi v e 
h e p atitis s er ol o g y, m o nt hl y P C R t esti n g is n ot r e q uir e d i n s u bj ects w h o ar e c urr e ntl y r ec ei vi n g or 
r ec ei v e d pr o p h yl actic I VI G wit hi n 3 m o nt hs b ef or e st u d y e nr oll m e nt a n d h a v e a d oc u m e nt e d n e g ati v e 
a nti- H Bc t est b ef or e t h e i niti ati o n of I VI G t h er a p y. P C R t esti n g s h o ul d b e p erf or m e d w h e n cli nic all y 
i n dic at e d ( e g, i n t h e s etti n g of risi n g tr a ns a mi n as e l ev els). 
S u bj ects wit h a k n o w n hist or y of h e p atitis C or w h o ar e h e p atitis C a nti b o d y p ositi v e s h o ul d b e t est e d 
f or H C V R N A p erf or m e d d uri n g t h e scr e e ni n g p h as e. P ati e nts w h o h a v e c o m pl et e d tr e at m e nt f or H C V 
a n d h a v e a n u n d et ect a bl e H C V R N A m a y e nr oll o n st u d y.
R ef er t o S ecti o n 5. 5 f or m or e i nf or m ati o n r e g ar di n g m o nit ori n g of s u bj ects w h o ar e a nti- H Bc p ositi v e or 
w h o h a v e a k n o w n hist or y of H B V.
H e alt h- R el at e d Q u alit y of Lif e Ass ess m e nt
H e alt h-r el at e d q u alit y of lif e will b e ass ess e d usi n g t h e F u ncti o n al Ass ess m e nt of C a nc er T h er a p y – 
G e n er al ( F A C T- G) a n d H os pit al A nxi et y a n d D e pr essi o n Sc al e ( H A D S)
T h e Q OL ass ess m e nt will b e a d mi nist er e d at t h e f oll o wi n g ti m e- p oi nts d uri n g t h e scr e e ni n g a n d 
i n d ucti o n p h as es:

At t h e scr e e ni n g visit

At t h e c ycl e 3 d a y 1 st u d y visit

At t h e c ycl e 6 d a y 1 st u d y visit

At t h e e n d of i n d ucti o n visit
D uri n g t h e f oll o w- u p p h as e, Q OL ass ess m e nts will b e o bt ai n e d e v er y 6 m o nt hs x 2 y e ars t h e n ev er y 1 2 
m o nt hs x 3 y e ars. 
P ati e nts w h o miss a f oll o w- u p visit will b e c o nt act e d b y t el e p h o n e t o c o m pl et e Q oL ass ess m e nts. 
P ati e nts w h o st art a n e w tr e at m e nt a n d t h os e w h o st o p f oll o wi n g at t h e st u d y sit e f or ot h er r e as o ns will 
n o l o n g er b e r e q uir e d t o c o m pl et e t h e Q oL q u esti o n n air es.
S e e A p p e n dic es F a n d G f or c o pi es of t h e F A C T- G a n d H A D S q u esti o n n air es. 
P ati e nt- R e p ort e d O utc o m es t o E v al u at e S y m pt o m atic T o xicit y
P ati e nt-r e p ort e d o utc o m e d at a will b e ass ess e d usi n g t h e P R O- C T C A E M e as ur e m e nt S yst e m t h at h as 
b e e n d e v el o p e d t o ev al u at e s y m pt o m atic t oxicit y i n p ati e nts o n c a nc er cli nic al tri als. T h e P R O- C T C A E will 
b e a d mi nist er e d el ectr o nic all y wit h a p a p er c o p y as a b ac k u p at t h e f oll o wi n g ti m e p oi nts:
D uri n g Scr e e ni n g a n d i n d ucti o n p h as es

At t h e c ycl e 1 d a y 1 a n d c ycl e 1 d a y 1 5 visits. If f e asi bl e, att e m pt t o a d mi nist er w e e kl y d uri n g 
c ycl e 1

At t h e c ycl e 3 d a y 1, 8, a n d 1 5 visits

At a mi ni m u m, a d mi nist er at t h e d a y 1 visits f or c ycl es 4 t hr o u g h 1 2

At t h e e n d of i n d ucti o n visit
F oll o w- u p p h as e

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

F or p ati e nts w h o c o nti n u e o n ac al a br uti ni b d uri n g t h e f oll o w- u p p h as e, a d mi nist er P R O- C T C A E 
at e ac h sc h e d ul e d st u d y visit

A d mi nist er t h e P R O- C T C A E at t h e Tr e at m e nt T er mi n ati o n Visit a n d S af et y f oll o w- u p visits f or 
p ati e nts w h o disc o nti n u e st u d y t h er a p y f or r e as o ns ot h er t h a n b ei n g r a n d o miz e d t o 
o bs er v ati o n.
T h e P R O- C T C A E is f or r es e arc h d at a c oll ecti o n o nl y. P R O- C T C A E d at a s h o ul d n ot b e us e d f or d et er mi ni n g 
attri b uti o n, d os e m o dific ati o ns, or r e p orti n g of s eri o us a d v ers e e v e nts.  St u d y st aff m ust cl e arl y c o n v e y 
t o t h e p ati e nt t h at t h e i nf or m ati o n r e g ar di n g s y m pt o ms c oll ect e d b y t h e P R O- C T C A E s elf-r e p ort ar e f or 
r es e arc h p ur p os es o nl y a n d ar e n ot m o nit or e d b y a p h ysici a n. St u d y st aff m ust a d vis e p ati e nts t o 
dir ectl y c o nt act t h eir cli nic al t e a m p er i nstit uti o n al st a n d ar ds f or a n y n e w or c o nc er ni n g s y m pt o ms t h at 
d e v el o p b et w e e n st u d y visits. P ati e nts will b e a d vis e d t o c o m pl et e t h e q u esti o n n air es pri or t o t h e 
a p p oi nt m e nt a n d will t a k e t h e m t o t h eir cli nic visit t o b e r e vi e w e d b y t h e cli nic al t e a m, a n d i n c as es 
w h er e a s elf-i d e ntifi e d A E o n t h e P R O- C T C A E is ev al u at e d b y t h e cli nic al t e a m, t h e gr a d e a n d attri b uti o n 
c a n b e ass ess b y c o n v e nti o n al m et h o ds as d escri b e d i n S ecti o n 1 7.
S e e A p p e n dix H f or a c o p y of t h e P R O- C T C A E f or m.
T u m or Ass ess m e nts:
F or all p ati e nts, pr etr e at m e nt i m a gi n g is r e q uir e d wit hi n 4 2 d a ys b ef or e t h e first d os e of st u d y dr u g. 
F or FL a n d M CL, a pr etr e at m e nt P E T/ C T sc a n is r e q uir e d wit hi n 4 2 d a ys b ef or e t h e first d os e of st u d y 
dr u g. O n-tr e at m e nt P E T/ C T sc a ns will b e d o n e f or t u m or ass ess m e nts as f oll o ws:

Wit hi n 7 d a ys of c ycl e 3 d a y 1 (sc a n m ust b e o bt ai n e d b ef or e t h e first d os e of o bi n ut uz u m a b)

Wit hi n 7 d a ys b ef or e or aft er c ycl e 6 d a y 1 

Wit hi n 1 4 d a ys b ef or e or aft er t h e e n d of i n d ucti o n visit f oll o wi n g c ycl e 1 2
D uri n g t h e f oll o w u p p h as e t u m or i m a gi n g will b e o bt ai n e d e v er y 6 m o nt hs ( +/- 1 m o nt h) x 2 y e ars t h e n 
e v er y 1 2 m o nt hs ( +/- 1 m o nt h) x 3 y e ars. D uri n g t his p h as e i m a gi n g c a n b e eit h er P E T/ C T or C T 
n ec k/c h est/ a b d o m e n/ p el vis wit h c o ntr ast ( u nl ess c o ntr ai n dic at e d).
F or M ZL a n d ot h er i N HL all i m a gi n g ass ess m e nts, i ncl u di n g pr etr e at m e nt i m a gi n g, c a n b e c o n d uct e d 
wit h eit h er P E T C T or C T n ec k/c h est/ a b d o m e n/ p el vis wit h c o ntr ast ( u nl ess c o ntr ai n dic at e d) b as e d o n 
i n v esti g at or pr ef er e nc e acc or di n g t o t h e s a m e sc h e d ul e o utli n e d a b o v e. 
A b o n e m arr o w bi o ps y d uri n g t h e scr e e ni n g p h as e is n ot r e q uir e d if o n e w as p erf or m e d wit hi n 1 2 
m o nt hs of si g ni n g i nf or m e d c o ns e nt a n d t h er e is n o c o nc er n f or a c h a n g e i n cli nic al st at us. A r e p e at 
b o n e m arr o w bi o ps y will b e p erf or m e d at first s us pici o n of C R if t h e m arr o w w as pr e vi o usl y i n v ol v e d b ut 
ot h er wis e r e p e at b o n e m arr o w bi o psi es n e e d o nl y b e c o m pl et e d as cli nic all y i n dic at e d.
Effic ac y e v al u ati o ns pri or t o c ycl es 3 a n d 6 will n ot b e us e d t o r e m o v e a n y p ati e nt fr o m t h er a p y if 
p ati e nts ar e ot h er wis e t ol er ati n g t h er a p y a n d f elt t o b e b e n efitti n g. E vi d e nc e of pr o gr essi v e dis e as e 
f oll o wi n g c ycl e 1 2 will r es ult i n disc o nti n u ati o n of t h er a p y.  
5. 9 Ass ess m e nt of R es p o ns e t o Tr e at m e nt

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
R es p o ns e ass ess m e nt f or p ati e nts wit h FL a n d M CL will b e ev al u at e d b y P E T/ C T b as e d o n t h e L u g a n o 
Cl assific ati o n  f or r es p o ns e ass ess m e nt i n l y m p h o m a, d ev el o p e d at t h e 2 0 1 4 I nt er n ati o n al C o nf er e nc e o n 
M ali g n a nt L y m p h o m a (I M CL ’ 1 4).
4 3 Aft er t h e p ati e nt h as c o m pl et e d 1 2 c ycl es of i n d ucti o n t h er a p y, t h e 
r es p o ns e ass ess m e nt c a n b e c o n d uct e d wit h eit h er C T of t h e n ec k, c h est, a b d o m e n, a n d p el vis wit h I V 
c o ntr ast ( u nl ess c o ntr ast is c o ntr ai n dic at e d) or P E T/ C T b as e d o n p ati e nt a n d i n v esti g at or pr ef er e nc e. 
T h e r es p o ns e ass ess m e nt f or p ati e nts wit h M ZL or ot h er i n d ol e nt f or ms of N HL c a n b e ev al u at e d b y 
eit h er P E T/ C T or C T of t h e n ec k, c h est, a b d o m e n, a n d p el vis wit h I V c o ntr ast ( u nl ess c o ntr ast is 
c o ntr ai n dic at e d) b as e d o n t h e L u g a n o Cl assific ati o n crit eri a o utli n e d f or t h e i m a gi n g m o d alit y us e d.
F or t h e s m all n u m b er of p ati e nts ex p ect e d t o e nr oll wit h a f or m of i n d ol e nt N HL t h at d o es n ot h a v e 
est a blis h e d r es p o ns e crit eri a, t h e c h oic e of i m a gi n g m o d alit y us e d t o r e ass ess k n o w n sit es of dis e as e as 
w ell as d et er mi n ati o n of C R, P R, S D, or P D will b e l eft t o t h e discr eti o n of t h e i n v esti g at or. 
If t h e b o n e m arr o w w as pr e vi o usl y i n v ol v e d, t h e n a r e p e at b o n e m arr o w bi o ps y is r e q uir e d at first 
s us pici o n of C R a n d m ust h a v e n o m or p h ol o gic e vi d e nc e of dis e as e t o c o nfir m C R.
T h e f oll o wi n g ar e exc er pts fr o m t h e L u g a n o Cl assific ati o n f or P E T/ C T- b as e d r es p o ns e:
C o m pl et e R es p o ns e

P E T/ C T i m a gi n g wit h a sc or e of 1- 3 o ut of 5 usi n g t h e D e a u vill e Crit eri a.  It is r ec o g niz e d t h at i n 
W al d e y er’s ri n g or extr a n o d al sit es wit h hi g h p h ysi ol o gic u pt a k e or wit h acti v ati o n wit hi n t h e 
s pl e e n or m arr o w ( e g, wit h c h e m ot h er a p y or m y el oi d c ol o n y-sti m ul ati n g f act ors), u pt a k e m a y 
b e gr e at er t h a n n or m al m e di asti n u m a n d/ or li v er.  I n t his circ u mst a nc e, c o m pl et e m et a b olic 
r es p o ns e m a y b e i nf err e d if u pt a k e at sit es of i niti al i n v ol v e m e nt is n o gr e at er t h a n s urr o u n di n g 
n or m al tiss u e ev e n if t h e tiss u e h as hi g h p h ysi ol o gic u pt a k e.

N o F D G- a vi d dis e as e i n b o n e m arr o w a n d b o n e m arr o w n or m al b y m or p h ol o g y if i n v ol v e d at 
di a g n osis.
P arti al R es p o ns e

Sc or e of 4 or 5 usi n g t h e D e a u vill e Crit eri a, b ut r e d uc e d u pt a k e c o m p ar e d wit h b as eli n e a n d 
r esi d u al m ass( es) of a n y siz e.

R esi d u al u pt a k e hi g h er t h a n u pt a k e i n n or m al m arr o w b ut r e d uc e d c o m p ar e d t o b as eli n e 
( diff us e u pt a k e c o m p ati bl e wit h r e acti v e c h a n g es fr o m c h e m ot h er a p y all o w e d).  If t h er e ar e 
p ersist e nt f oc al c h a n g es i n t h e m arr o w i n t h e c o nt ext of n o d al r es p o ns e, c o nsi d er ati o n s h o ul d 
b e gi v e n t o f urt h er e v al u ati o n wit h M RI or bi o ps y or a n i nt erv al sc a n.
St a bl e Dis e as e

Sc or e of 4 or 5 usi n g t h e D e a u vill e Crit eri a, wit h n o si g nific a nt c h a n g e i n F D G u pt a k e fr o m 
b as eli n e at i nt eri m or e n d of tr e at m e nt

N o c h a n g e i n b as eli n e m arr o w a vi dit y
Pr o gr essiv e Dis e as e
Sc or e of 4 or 5 usi n g t h e D e a u vill e Crit eri a wit h a n i ncr e as e i n i nt e nsit y of u pt a k e fr o m b as eli n e a n d/ or 
n e w F D G- a vi d f oci c o nsist e nt wit h l y m p h o m a.
T h e f oll o wi n g ar e exc er pts fr o m t h e L u g a n o Cl assific ati o n f or C T- b as e d r es p o ns e:
C o m pl et e R es p o ns e

T ar g et n o d es/ n o d al m ass es m ust r e gr ess t o ≤ 1. 5c m i n l o n g est tr a ns v ers e di a m et er (L Di)

N o extr al y m p h atic sit es of dis e as e 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

All n o n- m e as ur e d l esi o ns m ust b e a bs e nt a n d a n y or g a n e nl ar g e m e nt m ust r e gr ess t o n or m al
P arti al R es p o ns e

≥ 5 0 % d ecr e as e i n t h e s u m of t h e pr o d uct of t h e p er p e n dic ul ar di a m et ers f or m ulti pl e l esi o ns 
( S P D) of u p t o 6 t ar g et m e as ur a bl e n o d es a n d extr a n o d al sit es. W h e n a l esi o n is t o o s m all t o 
m e as ur e o n C T, assi g n 5 m m x 5 m m as t h e d ef a ult v al u e. W h e n n o l o n g er visi bl e, 0 x 0 m m. F or a 
n o d e > 5 m m x 5 m m, b ut s m all er t h a n n or m al, us e act u al m e as ur e m e nt f or c alc ul ati o n

N o n m e as ur e d l esi o ns m ust b e a bs e nt/ n or m al or r e gr ess e d, b ut n o i ncr e as e

S pl e e n m ust h a v e r e gr ess e d b y > 5 0 % i n l e n gt h b e y o n d n or m al 

N o n e w l esi o ns 
St a bl e Dis e as e

< 5 0 % d ecr e as e fr o m b as eli n e i n S P D of u p t o 6 d o mi n a nt, m e as ur a bl e n o d es a n d extr a n o d al 
sit es; n o crit eri a f or pr o gr essi v e dis e as e ar e m et.

N o i ncr e as e i n n o n m e as ur e d l esi o ns c o nsist e nt wit h pr o gr essi o n

N o i ncr e as e i n or g a n e nl ar g e m e nt c o nsist e nt wit h pr o gr essi o n

N o n e w l esi o ns
Pr o gr essiv e Dis e as e – r e q uir es at l e ast 1 of t h e f oll o wi n g

A n i n di vi d u al n o d e/l esi o n m ust b e a b n or m al wit h: L Di > 1. 5 c m a n d i ncr e as e b y ≥ 5 0 % fr o m P P D 
n a dir a n d a n i ncr e as e i n L Di or S Di fr o m n a dir of 0. 5c m f or l esi o ns ≤ 2 c m or 1. 0 c m f or l esi o ns > 
2 c m. 

I n t h e s etti n g of s pl e n o m e g al y, t h e s pl e nic l e n gt h m ust i ncr e as e b y > 5 0 % of t h e ext e nt of its 
pri or i ncr e as e b e y o n d b as eli n e ( e g, a 1 5-c m s pl e e n m ust i ncr e as e t o > 1 6c m. If n o pri or 
s pl e n o m e g al y, m ust i ncr e as e b y at l e ast 2 c m fr o m b as eli n e. 

N e w or cl e ar pr o gr essi o n of pr e existi n g n o n m e as ur e d l esi o ns. 

R e gr o wt h of pr e vi o usl y r es ol v e d l esi o ns

A n e w n o d e > 1. 5 c m i n a n y axis

A n e w extr a n o d al sit e > 1. 0c m i n a n y axis; if < 1. 0 c m i n a n y axis, its pr es e nc e m ust b e 
u n e q ui v oc al a n d m ust b e attri b ut a bl e t o l y m p h o m a
5. 1 0 Tr e at m e nt T er mi n ati o n a n d S af et y F oll o w- U p
Tr e at m e nt T er mi n ati o n a n d S af et y F oll o w- U p Visits
A tr e at m e nt t er mi n ati o n ( T T) visit is r e q uir e d f or s af et y ass ess m e nts f or a n y s u bj ects w h o p er m a n e ntl y 
disc o nti n u e st u d y dr u g f or a n y r e as o n (i ncl u di n g dis e as e pr o gr essi o n) exc e pt f or p ati e nts i n C R w h o 
w er e r a n d o miz e d t o disc o nti n u e ac al a br uti ni b aft er t h e i n d ucti o n p h as e. T h e T T visit s h o ul d b e 
sc h e d ul e d wit hi n 7 d a ys of t h e l ast d os e of st u d y dr u g, if p ossi bl e, a n d is n ot r e q uir e d f or s u bj ects w h o 
disc o nti n u e fr o m t h e st u d y wit hi n 1 0 d a ys of a sc h e d ul e d st u d y visit.  
E ac h s u bj ect s h o ul d b e f oll o w e d u ntil t h e s af et y f oll o w- u p ( S F U) visit at 4 w e e ks ( +/- 7) d a ys aft er his or 
h er l ast d os e of st u d y dr u g t o m o nit or f or r es ol uti o n or pr o gr essi o n of A Es a n d t o d oc u m e nt t h e 
occ urr e nc e of a n y n e w ev e nts, r e g ar dl ess of w h et h er t h e s u bj ect r ec ei v es a n e w a nti-l y m p h o m a t h er a p y 
or d e m o nstr at es dis e as e pr o gr essi o n wit hi n t his ti m efr a m e. F or p ati e nts r a n d o miz e d t o o bs er v ati o n, t h e 
e n d of i n d ucti o n visit s h all b e us e d as t h e s af et y f oll o w- u p visit.  S u bj ects w h o wit h dr a w c o ns e nt f or 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
st u d y tr e at m e nt s h o ul d still b e e nc o ur a g e d t o c o m pl et e t h e S F U ass ess m e nts, b ut t h es e ass ess m e nts 
c a n n ot b e m a n d at e d if s u bj ect c o ns e nt f or f urt h er st u d y p artici p ati o n is wit h dr a w n.  If t h e T T visit a n d 
t h e S F U visit c oi nci d e, t h e n t h es e c a n b e c o m bi n e d i nt o 1 visit.  T h e Sc h e d ul e of Ass ess m e nts ( S ecti o n 
1. 2) d escri b es t h e pr oc e d ur es r e q uir e d f or t h e T T a n d S F U visits.
F oll o w U p f or Pr o gr essi o n a n d S ur vi v al
E ac h s u bj ect s h o ul d b e f oll o w e d u ntil t h e st art of alt er n ati v e a nti-l y m p h o m a t h er a p y.  If n eit h er of t h es e 
h as occ urr e d at t h e ti m e of t h e 3 0- d a y S F U visit, disc o nti n u ati o n f oll o w- u p ( D F U) visits s h o ul d occ ur 
a p pr oxi m at el y ev er y 1 2 w e e ks ( +/- 2 w e e ks) f or 1 y e ar a n d t h er e aft er ev er y 6 m o nt hs ( +/- 1 m o nt h) u ntil 
dis e as e pr o gr essi o n or n ext a nti-l y m p h o m a tr e at m e nt.  D uri n g t his p eri o d, s u bj ects will b e f oll o w e d p er 
t h e sc h e d ul e of acti viti es (s e e S ecti o n 1. 3).
L o n g- T er m F oll o w- U p
P ati e nts w h o i niti at e a s u bs e q u e nt a nti-l y m p h o m a t h er a p y f or a n y r e as o n will n o l o n g er b e r e q uir e d t o 
c o m pl et e st u d y f oll o w- u p.  H o w e v er, w h e n f e asi bl e w e will i d e ntif y t h e s u bs e q u e nt tr e at m e nts r ec ei v e d 
a n d will als o f oll o w t h e p ati e nt u ntil d e at h or u ntil t h e y ar e l ost t o f oll o w- u p. P ati e nts will n ot b e c o nt act e d 
dir ectl y b ut st u d y st aff m a y f oll o w p ati e nts t hr o u g h t h e el ectr o nic m e dic al r ec or d t o ass ess s u bs e q u e nt 
tr e at m e nts a n d s urvi v al, exc e pt i n c as es w h er e a p ati e nt h as r ev o k e d s uc h c o ns e nt.
5. 1 1 Miss e d E v al u ati o ns
Miss e d e v al u ati o ns s h o ul d b e r esc h e d ul e d a n d p erf or m e d as cl os e t o t h e ori gi n al sc h e d ul e d d at e as 
p ossi bl e.  A n exc e pti o n is m a d e w h e n r esc h e d uli n g b ec o m es, i n t h e i n v esti g at or’s o pi ni o n, m e dic all y 
u n n ec ess ar y or u ns af e b ec a us e it is t o o cl os e i n ti m e t o t h e n ext sc h e d ul e d ev al u ati o n.  I n t h at c as e, t h e 
miss e d e v al u ati o n s h o ul d b e a b a n d o n e d.
6.
D at a a n d S p eci m e n B a n ki n g 
Bl o o d (t u m or, b o n e m arr o w etc.) s a m pl es  will b e o bt ai n e d a n d us e d f or m e dic al r es e arc h b y t h e 
i n v esti g at ors of t his st u d y. D at a a n d s p eci m e ns fr o m t his st u dy m ay b e us ef ul f or ot h er r es e arc h b ei n g 
d o n e by i nv esti g at ors at E m ory or els e w h er e. T o h el p f urt h er sci e nc e, I nv esti g at ors m ay pr ovi d e d e-
i d e ntifi e d d at a a n d/ or s p eci m e ns t o ot h er r es e arc h ers. A ny i nf or m ati o n t h at c o ul d i d e ntify p artici p a nts 
will n ot b e i ncl u d e d. If d at a or s p eci m e ns ar e l a b el e d wit h st u dy I D, w e will n ot all o w ot h er i nv esti g at ors 
t o li n k t h at I D t o i d e ntifi a bl e i nf or m ati o n.
S a m pl es a n d d at a c oll ect e d u n d er t his pr ot oc ol m a y b e us e d t o st u d y l y m p h o m a. Acc ess t o st or e d s a m pl es 
will b e li mit e d t o I R B- a p pr ov e d i nv esti g at ors. S a m pl es a n d d at a will b e st or e d usi n g c o d es assi g n e d b y t h e 
i n v esti g at ors or t h eir d esi g n e es. D at a will b e k e pt i n p ass w or d- pr ot ect e d c o m p ut ers. O nly i n v esti g at ors 
will h a v e acc ess t o t h e s a m pl es a n d d at a.
All st or e d s a m pl es will b e m ai nt ai n e d i n t h e l a b or at or y t o w hic h it w as s e nt i niti all y f or a n al ysis. St u d y 
p artici p a nts w h o r e q u est d estr ucti o n of s a m pl es will b e n otifi e d of c o m pli a nc e wit h s uc h r e q u est a n d all 
s u p p orti n g d et ails will b e m ai nt ai n e d f or tr ac ki n g.
T h e r es ults of s o m e st u d y t ests a n d pr oc e d ur es will b e us e d o nl y f or r es e arc h p ur p os es a n d will n ot b e 
pl ac e d i n s u bj ect’s m e dic al r ec or d.  F or t his st u d y, t h os e it e ms i ncl u d e: r es e arc h bl o o d c oll ecti o n. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
7. S h ari n g of R es ults wit h P artici p a nts
I n g e n er al, st u dy st aff will n ot pr ovi d e a ny i n divi d u al r es ults t o s u bj ects ( ex. o utc o m e tri al r es ults or r es ults 
fr o m s u bj ect’s s a m pl es st u di es). If s o m et hi n g of ur g e nt m e dic al i m p ort a nc e t o t h e p artici p ati n g s u bj ects 
will b e f o u n d, t h e PI ( or c o-Is) will i nf or m t h e s u bj ect, alt h o u g h w e ex p ect t h at t his will b e a v ery r ar e 
occ urr e nc e. S a m pl es a n d d at a will o nl y b e us e d f or r es e arc h.
8. St u d y Ti m eli n es
8. 1 D ur ati o n of t h er a p y
Ac al a br uti ni b
Ac al a br uti ni b 1 0 0 m g will b e a d mi nist er e d or all y t wic e d ail y, e v er y d a y st arti n g o n C ycl e 1 D a y 1 a n d will 
c o nti n u e t hr o u g h C ycl e 1 2 ( of a 2 8- d a y c ycl e) u nl ess t h e p ati e nt d ev el o ps i nt ol er a nc e t o ac al a br uti ni b or 
s y m pt o m atic/cli nic all y si g nific a nt pr o gr essi v e dis e as e. 
Aft er 1 2 c ycl es, p ati e nts w h o ac hi e v e C R will b e r a n d o miz e d t o eit h er c o nti n u e ac al a br uti ni b at t h e s a m e 
d os e u ntil i nt ol er a nc e or P D or disc o nti n u e t h e m e dic ati o n a n d o bs er v e. P ati e nts wit h a P R or S D aft er 
1 2 c ycl es of tr e at m e nt will c o nti n u e ac al a br uti ni b at t h e s a m e d os e u ntil i nt ol er a nc e or pr o gr essi v e 
dis e as e.
O bi n ut uz u m a b
O bi n ut uz u m a b will b e a d mi nist er e d C ycl e 3 t hr o u g h C ycl e 8. T h er e will b e n o o bi n ut uz u m a b 
m ai nt e n a nc e p h as e. R ef er t o t h e sc h e d ul e of acti viti es ( S ecti o n 1. 3) f or d osi n g sc h e d ul e. 
8. 2 D ur ati o n of f oll o w- u p 
T h e esti m at e d ti m e fr o m w h e n t h e st u d y o p e ns t o e nr oll m e nt u ntil a n al ysis of t h e pri m ar y o utc o m e is 
4 0 m o nt hs. P ati e nts i n t h e f oll o w- u p p h as e w h o h a v e disc o nti n u e d st u d y t h er a p y will b e f oll o w e d f or 6 0 
m o nt hs or u ntil t h e st art of n ext a nti-l y m p h o m a tr e at m e nt. P ati e nts w h o c o nti n u e ac al a br uti ni b d uri n g 
t h e f oll o w u p p h as e will b e tr e at e d o n st u d y u ntil u n acc e pt a bl e t oxicit y, d e at h, or st art of t h e n ext a nti-
l y m p h o m a t h er a p y.
P ati e nt r ec or ds m a y b e r e vi e w e d u ntil d e at h t o ass ess pr o gr essi o n a n d s ur vi v al.  S urvi v al i nf or m ati o n m a y 
b e c oll ect e d b y cli nic visit, e m ail, or t el e p h o n e aft er e n di n g pr ot oc ol tr e at m e nt a n d u ntil t h e st u d y is 
t er mi n at e d, t h e p ati e nt di es, or t h e p ati e nt is l ost t o f oll o w- u p.
A p artici p a nt will b e c o nsi d er e d l ost t o f oll o w- u p if h e f ails t o r et ur n f or t hr e e sc h e d ul e d visits a n d is u n a bl e 
t o b e c o nt act e d b y t h e st u d y sit e st aff aft er t hr e e att e m pts at c o nt act b y p h o n e.
T h e f oll o wi n g acti o ns m ust b e t a k e n if a p artici p a nt f ails t o r et ur n t o t h e cli nic f or a r e q uir e d st u d y visit:
T h e sit e will att e m pt t o c o nt act t h e p artici p a nt a n d r esc h e d ul e t h e miss e d visit a n d c o u ns el t h e p artici p a nt 
o n t h e i m p ort a nc e of m ai nt ai ni n g t h e assi g n e d visit sc h e d ul e a n d asc ert ai n if t h e p artici p a nt wis h es t o 
a n d/ or s h o ul d c o nti n u e i n t h e st u d y.
R e as o ns f or r e m o v al of a s u bj ect fr o m t h e st u d y ar e:

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

S u bj ect’s wit h dr a w al of c o ns e nt fr o m st u d y

D ecisi o n b y i n v esti g at or

S u bj ect l ost t o f oll o w- u p

U n acc e pt a bl e t oxicit y

D e at h
P ati e nts r e m o v e d fr o m st u d y f or u n acc e pt a bl e a d v ers e ev e nt(s) will b e f oll o w e d u ntil r es ol uti o n or 
st a biliz ati o n of t h e a d v ers e ev e nt.
P ati e nts w h o h a v e n ot i niti at e d a n e w a nti n e o pl astic r e gi m e n will h a v e t h e f oll o wi n g ass ess m e nts:
 • R a di ol o gic t u m or ass ess m e nts p er t h e Sc h e d ul e of E v e nts (s e e S ecti o n 1. 3)
 • I n c as e of a cli nic all y si g nific a nt A E, p ati e nt will b e f oll o w e d f or s af et y u ntil r es ol uti o n or p er m a n e nt 
s e q u el a e of all t oxiciti es attri b ut a bl e t o st u d y dr u g(s). If t h e p ati e nt disc o nti n u es st u d y dr u g f or a cli nic all y 
si g nific a nt A E, t h e p ati e nt will b e f oll o w e d u ntil r es ol uti o n of t h e A E or t h e ev e nt is c o nsi d er e d t o b e st a bl e 
a n d/ or c hr o nic. 
9. I ncl usi o n a n d E xcl usi o n Crit eri a
I ncl usi o n Crit eri a
Eli gi bl e s u bj ects will b e c o nsi d er e d f or i ncl usi o n i n t his st u d y if t h e y m e et all  of t h e f oll o wi n g crit eri a: 
1)
M e n a n d w o m e n ≥ 1 8 y e ars of a g e.
2)
P ati e nts will n e e d t o h a v e o n e of t h e f oll o wi n g cli nic al sc e n ari os:
a)
Pr e vi o usl y u ntr e at e d f ollic ul ar l y m p h o m a gr a d e 1- 3 a wit h l o w t u m or b ur d e n b y G EL F crit eri a 
(s e e A p p e n dix E)
b)
Pr e vi o usl y u ntr e at e d f ollic ul ar l y m p h o m a gr a d e 1- 3 a wit h hi g h t u m or b ur d e n b y G EL F crit eri a 
b ut w h o ar e u n a bl e or u n willi n g t o r ec ei v e st a n d ar d fr o nt-li n e tr e at m e nt a p pr o ac h es
c)
Pr e vi o usl y u ntr e at e d m ar gi n al z o n e l y m p h o m a, l y m p h o pl as m ac ytic l y m p h o m a, or a n y ot h er 
i n d ol e nt B-c ell l y m p h o pr olif er ati v e dis or d er wit h l o w t u m or b ur d e n b y G EL F crit eri a or w h o ar e 
u n a bl e/ u n willi n g t o r ec ei v e m or e i nt e nsi v e fr o nt-li n e tr e at m e nt.
d)
Pr e vi o usl y u ntr e at e d m a ntl e c ell l y m p h o m a w h o w o ul d ot h er wis e b e a p pr o pri at e c a n di d at es f or 
w atc hf ul w aiti n g O R w h o h a v e s y m pt o m atic dis e as e b ut ar e n ot c a n di d at es f or or d ecli n e 
st a n d ar d i n d ucti o n a p pr o ac h es.
3)
P ati e nts wit h pr e vi o usl y u ntr e at e d l o w t u m or b ur d e n FL (crit eri o n 2 a) m ust h a v e m e as ur a bl e a n d/ or 
ass ess a bl e dis e as e d efi n e d as at l e ast o n e i n v ol v e d l y m p h n o d e or extr a n o d al dis e as e sit e t h at 
m e as ur es ≥ 1. 5c m i n gr e at est di a m et er.
4)
P ati e nts w h o m e et i ncl usi o n crit eri a 2 b, 2c, or 2 d a b o v e ar e eli gi bl e as l o n g as t h e y m e et o n e of t h e 
f oll o wi n g crit eri a f or m e as ur a bl e/ ass ess a bl e dis e as e:
a)
At l e ast o n e i n v ol v e d l y m p h n o d e or extr a n o d al dis e as e sit e m e as uri n g > 1. 5c m i n gr e at est 
di a m et er
b)
P at h ol o gic all y-c o nfir m e d b o n e m arr o w or p eri p h er al bl o o d i n v ol v e m e nt t h at c a n b e r e ass ess e d 
f or r es p o ns e
c)
P at h ol o gic all y c o nfir m e d s pl e nic or extr a n o d al i n v ol v e m e nt wit h at l e ast o n e k n o w n sit e of 
dis e as e r e m ai ni n g aft er di a g n ostic bi o ps y t h at c a n b e r e ass ess e d (i e, p ati e nts wit h s pl e nic 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
m ar gi n al z o n e l y m p h o m a w h o c o m pl et e s pl e n ect o m y a n d h a v e n o ot h er d et ect a bl e dis e as e 
w o ul d n ot b e eli gi bl e).
5)
E ast er n C o o p er ati v e O nc ol o g y Gr o u p ( E C O G) p erf or m a nc e st at us of 0- 2 ( A p p e n dix 2). 
6)
W o m a n of c hil d b e ari n g p ot e nti al ( W O C B P) a n d m e n e nr oll e d o n t his pr ot oc ol m ust a gr e e t o us e 
a d e q u at e c o ntr ac e pti o n ( h or m o n al or b arri er m et h o d of birt h c o ntr ol; a bsti n e nc e) pri or t o st u d y 
e ntr y f or t h e d ur ati o n of st u d y p artici p ati o n, a n d f or at l e ast 2 d a ys aft er t h e l ast d os e of 
ac al a br uti ni b or 1 8 m o nt hs aft er t h e l ast d os e of o bi n ut uz u m a b, w hic h e v er is l o n g er. S h o ul d a 
w o m a n b ec o m e pr e g n a nt or s us p ect s h e is pr e g n a nt w hil e s h e or h er p art n er is p artici p ati n g i n t his 
st u d y, s h e s h o ul d i nf or m h er tr e ati n g p h ysici a n i m m e di at el y. R ef er t o S ecti o n 1 3. 5 f or m or e d et ails 
r e g ar di n g r e pr o d ucti v e st at us ass ess m e nt.
7)
W o m e n of c hil d b e ari n g p ot e nti al m ust h a v e a n e g ati v e s er u m or uri n e pr e g n a nc y t est pri or t o 
st arti n g t h er a p y.
8)
Willi n g a n d a bl e t o p artici p at e i n all r e q uir e d e v al u ati o ns a n d pr oc e d ur es i n t his st u d y pr ot oc ol.
9)
A bilit y t o u n d erst a n d t h e p ur p os e a n d ris ks of t h e st u d y a n d pr o vi d e si g n e d a n d d at e d i nf or m e d 
c o ns e nt a n d a ut h oriz ati o n t o us e pr ot ect e d h e alt h i nf or m ati o n A bilit y t o u n d erst a n d t h e p ur p os e 
a n d ris ks of t h e st u d y a n d pr o vi d e si g n e d a n d d at e d i nf or m e d c o ns e nt a n d a ut h oriz ati o n t o us e 
pr ot ect e d h e alt h i nf or m ati o n.  
E xcl usi o n crit eri a
S u bj ects will b e i n eli gi bl e f or t his st u d y if t h e y m e et a n y  of t h e f oll o wi n g crit eri a:
1)
T h e pr es e nc e or hist or y of hist ol o gic all y tr a nsf or m e d or c o- existi n g hi g h- gr a d e or a g gr essi v e n o n-
H o d g ki n l y m p h o m a
2)
C o nfir m e d acti v e or pri or c e ntr al n erv o us s yst e m dis e as e
3)
Pri or r ec ei pt of l y m p h o m a- dir ect e d t h er a p y or pri or a nti b o d y- b as e d t h er a p y ( exc e pt f or a nti-
micr o bi al t h er a p y f or i nf ecti o n- ass oci at e d m ar gi n al z o n e l y m p h o m a s uc h as h e p atitis C or H p yl ori).
( a)
A s h ort c o urs e of st er oi ds is p er mitt e d f or p ati e nts asi d e fr o m t h os e i n t h e l o w t u m or b ur d e n FL 
c o h ort.  T his c o urs e m a y b e n o m or e t h a n 1 4 d a ys a n d st er oi ds m ust b e disc o nti n u e d ( or 
t a p er e d t o ≤ 1 0 m g pr e d nis o n e or e q ui v al e nt) n o l at er t h a n 3 d a ys aft er i niti ati o n of st u d y 
tr e at m e nt. 
P ati e nts i n t h e l o w t u m or b ur d e n FL c o h ort m a y n ot  r ec ei v e c ortic ost er oi ds as a n a nti-l y m p h o m a 
t h er a p y at a n y ti m e b ef or e st arti n g tr e at m e nt.  
4)
Pri or m ali g n a nc y ( or a n y ot h er m ali g n a nc y r e q uiri n g acti v e tr e at m e nt), exc e pt f or a d e q u at el y 
tr e at e d b as al c ell or s q u a m o us c ell s ki n c a nc er, i n sit u c er vic al c a nc er, or ot h er c a nc er fr o m w hic h 
t h e s u bj ect h as b e e n dis e as e fr e e f or ≥ 2 y e ars or  w hic h will n ot li mit s ur vi v al t o < 5 y e ars.  
5)
Cli nic all y si g nific a nt c ar di o v asc ul ar dis e as e s uc h as s y m pt o m atic v e ntric ul ar arr h yt h mi as, c o n g esti v e 
h e art f ail ur e, or m y oc ar di al i nf arcti o n wit hi n 6 m o nt hs of scr e e ni n g, or a n y Cl ass 3 or 4 c ar di ac 
dis e as e as d efi n e d b y t h e N e w Y or k H e art Ass oci ati o n F u ncti o n al Cl assific ati o n. N ot e: S u bj ects wit h 
c o ntr oll e d, as y m pt o m atic atri al fi brill ati o n c a n e nr oll o n st u d y if d e e m e d a p pr o pri at e b y t h e 
i n v esti g at or. 
6)
H as diffic ult y wit h or is u n a bl e t o s w all o w or al m e dic ati o n, or h as si g nific a nt g astr oi nt esti n al dis e as e 
t h at w o ul d li mit a bs or pti o n of or al m e dic ati o n. 
7)
K n o w n hist or y of HI V or a n y acti v e si g nific a nt i nf ecti o n ( e g, b act eri al, vir al, or f u n g al) wit hi n 1 4 d a ys 
of c ycl e 1. P ati e nts wit h u nc o m plic at e d vir al or b act eri al i nf ecti o ns t h at ar e b ei n g m a n a g e d wit h or al 
a nti bi otics a n d/ or s u p p orti v e c ar e al o n e ar e eli gi bl e. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
8)
K n o w n hist or y of h y p ers e nsiti vit y or a n a p h yl axis t o st u d y dr u g(s) i ncl u di n g acti v e pr o d uct or 
exci pi e nt c o m p o n e nts. 
9)
Acti v e bl e e di n g or hist or y of bl e e di n g di at h esis ( e g, h e m o p hili a or v o n Will e br a n d dis e as e).
1 0) U nc o ntr oll e d AI H A ( a ut oi m m u n e h e m ol ytic a n e mi a) or I T P (i di o p at hic t hr o m b oc yt o p e nic p ur p ur a).
1 1) Pr es e nc e of a g astr oi nt esti n al ulc er di a g n os e d b y e n d osc o p y wit hi n 3 m o nt hs b ef or e scr e e ni n g. 
1 2) R e q uir es tr e at m e nt wit h a str o n g c yt oc hr o m e P 4 5 0 3 A 4 ( C Y P 3 A 4) i n hi bit or/i n d uc er.
1 3) R e q uir es or r ec ei vi n g a ntic o a g ul ati o n wit h w arf ari n or e q ui v al e nt vit a mi n K a nt a g o nists. N ot e: us e of 
dir ect or al a ntic o a g ul a nts is p er mitt e d. P ati e nts wit h a r ec e nt hist or y of v e n o us t hr o m b o e m b olis m 
ar e p er mitt e d t o e nr oll as l o n g as t h e y d o n ot r e q uir e tr e at m e nt wit h a vit a mi n K a nt a g o nist.
1 4) Hist or y of si g nific a nt c er e br o v asc ul ar dis e as e/ e v e nt, i ncl u di n g str o k e or i ntr acr a ni al h e m orr h a g e, 
wit hi n 6 m o nt hs b ef or e t h e first d os e of st u d y dr u g. P ati e nts wit h a tr a nsi e nt isc h e mic att ac k w hic h 
h as r es ol v e d a n d f or w hic h t h er e ar e n o o n g oi n g s y m pt o ms ar e eli gi bl e.
1 5)
M aj or s ur gic al pr oc e d ur e wit hi n 2 8 d a ys of first d os e of st u d y dr u g ( n ot i ncl u di n g a di a g n ostic 
pr oc e d ur e t o m a k e t h e l y m p h o m a di a g n osis).  N ot e:  If a s u bj ect h a d m aj or s ur g er y, t h e y m ust h a v e 
r ec o v er e d a d e q u at el y fr o m a n y t oxicit y a n d/ or c o m plic ati o ns fr o m t h e i nt er v e nti o n b ef or e t h e first 
d os e of st u d y dr u g.
1 6) H e p atitis B or C s er ol o gic st at us: s u bj ects w h o ar e h e p atitis B c or e a nti b o d y ( a nti- H Bc) p ositi v e a n d 
w h o ar e h e p atitis B s urf ac e a nti g e n ( H Bs A g) n e g ati v e will n e e d t o h a v e a n e g ati v e p ol y m er as e c h ai n 
r e acti o n ( P C R) a n d m ust b e willi n g t o u n d er g o D N A P C R t esti n g d uri n g t h e st u d y t o b e 
eli gi bl e.  T h os e w h o ar e H Bs A g p ositi v e or h e p atitis B P C R p ositi v e will b e excl u d e d.  
S u bj ects w h o ar e h e p atitis C a nti b o d y p ositi v e will n e e d t o h a v e a n e g ati v e P C R r es ult t o b e 
eli gi bl e a n d h a v e c o m pl et e d a p pr o pri at e a nti- vir al tr e at m e nt.  T h os e w h o ar e h e p atitis C P C R 
p ositi v e will b e excl u d e d.  A nti- vir al t h er a p y f or p ati e nts wit h h e p atitis- C ass oci at e d m ar gi n al 
z o n e l y m p h o m a will n ot b e c o nsi d er e d a pri or a nti-l y m p h o m a tr e at m e nt.
1 7)  H e m at ol o gic: A N C < 1, 0 0 0/ mcL, pl at el et c o u nt < 5 0, 0 0 0/ mcL ( U nl ess f elt t o b e r el at e d t o u n d erl yi n g 
dis e as e)
1 8)  H e p atic: T ot al bilir u bi n ≥ 1. 5x t h e u p p er li mit of n or m al ( UL N). Is ol at e d bilir u bi n > 1. 5x UL N is 
p er mitt e d if t h e dir ect pr o p orti o n is < 3 5 %. A S T/ AL T > 2. 5x UL N. 
1 9)  Cr e ati ni n e cl e ar a nc e ≤ 4 0 mL/ mi n/ 1. 7 3 m 2
2 0) Br e astf e e di n g or pr e g n a nt.
2 1) C o nc urr e nt p artici p ati o n i n a n ot h er t h er a p e utic cli nic al tri al.  
1 0.L oc al N u m b er of P artici p a nts
W e will b e r ecr uiti n g u p t o 4 9 t ot al p ati e nts.  P ati e nts will b e r e gist er e d aft er si g ni n g of t h e i nf or m e d 
c o ns e nt d oc u m e nt a n d m e eti n g all e ntr y r e q uir e m e nts.
1 1. R ecr uit m e nt M et h o ds
I n v esti g at ors, n urs es ( C R Ns), r es e arc h c o or di n at ors ( C R Cs) a n d/ or d at a m a n a g ers r evi e w lists of p ati e nts 
wit h l y m p h o m a a n d will d et er mi n e if t h er e ar e p ati e nts w h o mi g ht b e eli gi bl e f or a cli nic al tri al. T h e 
C R N/ C R C/ d at a m a n a g er r e vi e ws acc essi bl e m e dic al r ec or ds t o scr e e n f urt h er f or eli gi bilit y. T h e C R N/ C R C 
r e vi e ws t h e eli gi bilit y wit h t h e p h ysici a n.  

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 3 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
S u bj ects will b e i d e ntifi e d b y t h eir tr e ati n g p h ysici a ns. Cli nic al c ar e t e a m at Wi ns hi p will i nf or m p ot e nti al 
s u bj ects a b o ut t h e k n o w n b e n efits a n d p ot e nti al ris ks of a cli nic al tri al as w ell as ot h er a v ail a bl e tr e at m e nt 
o pti o ns.
S o m e of t h e s u bj ects r ecr uit e d f or t his pr ot oc ol will b e p ati e nts b ei n g tr e at e d at E m or y a n d u n d er 
t h e c ar e of o n e or m or e of t h e st u d y i n v esti g at ors. S o m e p ot e nti al s u bj ects will b e i d e ntifi e d b y 
t h eir tr e ati n g p h ysici a n a n d r ef err e d t o E m or y f or p ossi bl e p artici p ati o n i n t h e pr ot oc ol.
N o i nc e nti v es ar e pr o vi d e d t o p ati e nts f or tri al p artici p ati o n.
St u d y 
p ers o n n el 
will 
n otif y 
Wi ns hi p 
C e ntr al 
S u bj ect 
R e gistr ati o n ( W C S R) 
b y 
e m ail 
at 
wi ns hi pcsr @ e m or y. e d u , o nc e s u bj ect h as b e e n c o ns e nt e d f or a tri al. 
E m ail n otific ati o n m ust b e d o n e wit hi n 2 4 h o urs aft er c o ns e nt h as b e e n o bt ai n e d a n d it will i ncl u d e 
sc a n n e d c o pi es of:

Si g n e d p ati e nt c o ns e nt f or m

HI P A A a ut h oriz ati o n f or m

E m or y R es e arc h M a n a g e m e nt S yst e m ( E R M S;  htt ps:// er ms. e m ory. e d u) E nr oll m e nt F ax C o v er 
T h e W C S R will e nt er t h e s u bj ect i nt o t h e O n C or e R es e arc h M a n a g e m e nt S yst e m, w hic h is t h e s yst e m of 
r ec or d f or Wi ns hi p C a nc er I nstit ut e Cli nic al Tri als.
E nr olli n g a s u bj ect r e q uir es c ar ef ul scr e e ni n g a n d d et er mi n ati o n of eli gi bilit y. 
Eli gi bl e p ati e nts will b e e nr oll e d o n st u d y c e ntr all y at Wi ns hi p C a nc er I nstit ut e b y t h e St u d y C o or di n at or.  
W h e n all r e q uir e d t est r es ults ar e a v ail a bl e, c o m pl et e t h e eli gi bilit y c h ec klist a n d pr o vi d e t h e c h ec klist a n d 
t h e s u p p orti n g d oc u m e nt ati o n t o t h e I R B a p pr o v e d i n v esti g at or f or r evi e w a n d si g n- off. O nc e t h e 
i n v esti g at or (s u b-i n v esti g at or, C o-I n v esti g at or) h as si g n e d t h e eli gi bilit y c h ec klist, r a n d o miz ati o n a n d or 
e nr oll m e nt m a y pr oc e e d. O n C or e a n d E R M S m ust b e u p d at e d t o r efl ect eli gi bilit y a n d o n tr e at m e nt st at us. 
F oll o wi n g e nr oll m e nt, p ati e nts s h o ul d b e gi n pr ot oc ol tr e at m e nt wit hi n 2 8 d a ys. Iss u es t h at w o ul d c a us e 
tr e at m e nt d el a ys s h o ul d b e disc uss e d wit h t h e Pri nci p al I n v esti g at or.  
1 2. Wit h dr a w al of P artici p a nts
Disc o nti n u ati o n fr o m t h e st u d y tr e at m e nt wit h ac al a br uti ni b a n d o bi n ut uz u m a b d o es n ot 
m e a n 
disc o nti n u ati o n fr o m t h e st u d y, a n d r e m ai ni n g st u d y pr oc e d ur es s h o ul d b e c o m pl et e d as i n dic at e d b y t h e 
st u d y pr ot oc ol.  If a cli nic all y si g nific a nt fi n di n g is i d e ntifi e d (i ncl u di n g, b ut n ot li mit e d t o c h a n g es fr o m 
b as eli n e) aft er e nr oll m e nt, t h e i n v esti g at or or q u alifi e d d esi g n e e will d et er mi n e if a n y c h a n g e i n 
p artici p a nt m a n a g e m e nt is n e e d e d. A n y n e w cli nic all y r el e v a nt fi n di n g will b e r e p ort e d as a n a d v ers e 
e v e nt ( A E).
P ati e nts m a y c h o os e t o disc o nti n u e t h e tri al at a n y ti m e, f or a n y r e as o n, a n d wit h o ut pr ej u dic e t o f urt h er 
tr e at m e nt.  T h e tr e at m e nt t er mi n ati o n visit (i e, e n d of tr e at m e nt visit) will occ ur wit hi n 7 d a ys of t h e l ast 
d os e of t h e st u d y dr u g. T h e s af et y f oll o w- u p visit will occ ur wit hi n 2 8 ( +/- 7) d a ys of t h e l ast d os e of t h e 
st u d y dr u g or b ef or e a n e w a nti n e o pl astic r e gi m e n h as b e e n i niti at e d.  

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
R e as o ns f or disc o nti n ui n g st u d y i nt er v e nti o n ar e: 

C o m pl eti o n of st u d y t h er a p y

P D i n t h e a bs e nc e of cli nic al b e n efit as d et er mi n e d b y t h e I n v esti g at or.

Occ urr e nc e of a cli nic all y si g nific a nt A E f o u n d t o b e u n acc e pt a bl e or n o n-r es ol uti o n of cli nic all y 
si g nific a nt A Es f or > 6 w e e ks. 

S y m pt o m atic d et eri or ati o n. 

N o nc o m pli a nc e of t h e p ati e nt wit h pr ot oc ol- m a n d at e d pr oc e d ur es b as e d o n t h e j u d g m e nt a n d 
a gr e e m e nt of b ot h t h e I n v esti g at or a n d st u d y s u p p ort er. 

C o nti n u e d p artici p ati o n is n o l o n g er i n t h e p ati e nt’s b est i nt er est i n t h e o pi ni o n of t h e I n v esti g at or. 

B ec o m es pr e g n a nt or br e astf e e di n g

Wit h dr a w al of c o ns e nt. 

Disc o nti n u ati o n of t h e cli nic al tri al b y t h e st u d y i n v esti g at or
I n t h e e v e nt of a p ati e nt’s wit h dr a w al, t h e I n v esti g at or will pr o m ptl y n otif y t h e s u p p orti n g s p o ns or a n d 
m a k e e v er y eff ort t o c o m pl et e t h e tr e at m e nt t er mi n ati o n a n d s af et y f oll o w- u p pr oc e d ur es s p ecifi e d i n 
t h e Sc h e d ul e of E v e nts.
T h e r e as o n f or p artici p a nt disc o nti n u ati o n or wit h dr a w al fr o m t h e st u d y will b e r ec or d e d o n t h e C as e 
R e p ort F or m ( C R F). 
S u bj ects w h o si g n t h e i nf or m e d c o ns e nt f or m b ut d o n ot r ec ei v e t h e st u d y i nt er v e nti o n m a y b e r e pl ac e d 
f or t h e p ur p os es of t h e pri m ar y e n d p oi nt.  S u bj ects w h o si g n t h e i nf or m e d c o ns e nt f or m, a n d ar e assi g n e d 
a n d r ec ei v e t h e st u d y i nt er v e nti o n, a n d s u bs e q u e ntl y wit h dr a w, or ar e wit h dr a w n or disc o nti n u e d fr o m 
t h e st u d y, will n ot b e r e pl ac e d a n d will b e c o nsi d er e d n o n-r es p o n d ers i n t h e i nt e nti o n t o tr e at a n al ysis.
S u bj ects w h o disc o nti n u e st u d y t h er a p y will c o nti n u e t o b e f oll o w e d o n st u d y f or f oll o w- u p of s af et y a n d 
s ur vi v al u nl ess t h e y wit h dr a w c o ns e nt f or f urt h er f oll o w- u p.  T h us, all s u bj ects r ec ei vi n g ≥ 1 d os e of 
st u d y dr u g will b e f oll o w e d d uri n g t h e i m m e di at e p ost-t h er a p y a n d l o n g-t er m f oll o w- u p ass ess m e nts 
u nl ess t h e s u bj ect wit h dr a ws c o ns e nt f or s uc h f oll o w- u p t o b e c o n d uct e d.
1 3. Ris ks t o P artici p a nts
1 3. 1 Ris ks Ass oci at e d wit h Ac al a br uti ni b
Ac al a br uti ni b m o n ot h er a p y h as d e m o nstr at e d effic ac y i n s u bj ects wit h r el a ps e d/r efr act or y M CL a n d i n 
s u bj ects wit h tr e at m e nt n aï v e or r el a ps e d/r efr act or y CLL.
B as e d o n r e vi e w of t h e a v ail a bl e s af et y a n d effic ac y d at a f or ac al a br uti ni b as w ell as c o nsi d er ati o n of 
m e as ur es i m pl e m e nt e d i n t h e ac al a br uti ni b cli nic al d e v el o p m e nt pr o gr a m t o mi ni miz e p ot e nti al ris ks t o 
s u bj ects, t h e o v er all b e n efit-ris k ass ess m e nt pr ofil e of ac al a br uti ni b f or t h e i n dic ati o n u n d er 
i n v esti g ati o n r e m ai ns f a v o ur a bl e f or c o nti n ui n g cli nic al d ev el o p m e nt a n d is j ustifi e d b y t h e p erc ei v e d 
b e n efits t h at m a y b e aff or d e d t o t h e p ati e nts.
M or e d et ail e d i nf or m ati o n a b o ut t h e k n o w n a n d ex p ect e d b e n efits a n d p ot e nti al ris ks of ac al a br uti ni b 
m a y b e f o u n d i n t h e I n v esti g at or’s Br oc h ur e a n d D ev el o p m e nt S af et y U p d at e R e p ort ( D S U R).

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Ris k Ass ess m e nt
C o ntr ai n dic ati o ns
N o c o ntr ai n dic ati o ns ar e k n o w n f or ac al a br uti ni b.
I m p ort a nt I d e ntifi e d Ris ks
T h e f oll o wi n g s u m m ariz es t h e i m p ort a nt i d e ntifi e d ris ks o bs er v e d wit h ac al a br uti ni b i n h e m at ol o gic al 
c a nc er st u di es. F ull d et ails r e g ar di n g t h e cli nic al s af et y of ac al a br uti ni b ar e pr es e nt e d i n t h e 
ac al a br uti ni b I n v esti g at or’s Br oc h ur e.
H e m orr h a g e
S eri o us h e m orr h a gic e v e nts, i ncl u di n g f at al e v e nts, h a v e occ urr e d i n cli nic al tri als wit h ac al a br uti ni b.
T h e m ec h a nis m f or h e m orr h a g e is n ot w ell u n d erst o o d. P ati e nts r ec ei vi n g a ntit hr o m b otic a g e nts m a y 
b e at i ncr e as e d ris k of  h e m orr h a g e. Us e c a uti o n wit h a ntit hr o m b otic a g e nts a n d c o nsi d er a d diti o n al 
m o nit ori n g f or si g ns of bl e e di n g w h e n c o nc o mit a nt us e is m e dic all y n ec ess ar y. 
C o nsi d er t h e b e n efit-ris k of wit h h ol di n g ac al a br uti ni b f or at l e ast 3 d a ys pr e- a n d p ost-s ur g er y. 
S u bj ects wit h h e m orr h a g e s h o ul d b e m a n a g e d p er i nstit uti o n al g ui d eli n es wit h s u p p orti v e c ar e a n d 
di a g n ostic e v al u ati o ns as cli nic all y i n dic at e d.
I nf ecti o ns
S eri o us i nf ecti o ns ( b act eri al, vir al, a n d f u n g al), i ncl u di n g f at al e v e nts, h a v e occ urr e d i n cli nic al st u di es 
wit h ac al a br uti ni b. T h e m ost fr e q u e nt r e p ort e d Gr a d e ≥3  i nf ecti o n w as p n e u m o ni a ( pr ef err e d t er m). 
Acr oss t h e ac al a br uti ni b cli nic al d ev el o p m e nt pr o gr a m (i ncl u di n g s u bj ects tr e at e d wit h ac al a br uti ni b i n 
c o m bi n ati o n wit h ot h er dr u gs), c as es of h e p atitis B vir us ( H B V) r e acti v ati o n, as p er gill osis, a n d 
pr o gr essi v e m ultif oc al l e u k o e nc e p h al o p at h y ( P ML) h a v e occ urr e d.
C o nsi d er pr o p h yl axis i n s u bj ects w h o ar e at i ncr e as e d ris k f or o p p ort u nistic i nf ecti o ns. S u bj ects s h o ul d 
b e m o nit or e d f or si g ns a n d s y m pt o ms of i nf ecti o n a n d tr e at e d as m e dic all y a p pr o pri at e.
S u bj ects wit h i nf ecti o n ev e nts s h o ul d b e m a n a g e d acc or di n g t o i nstit uti o n al g ui d eli n es wit h m axi m al 
s u p p orti v e c ar e a n d di a g n ostic ev al u ati o ns as cli nic all y i n dic at e d.
C yt o p e ni as
Tr e at m e nt- e m er g e nt Gr a d e 3 or 4 c yt o p e ni as, i ncl u di n g n e utr o p e ni a, a n a e mi a, a n d t hr o m b oc yt o p e ni a 
h a v e occ urr e d i n cli nic al st u di es wit h ac al a br uti ni b. M o nit or bl o o d c o u nts as s p ecifi e d i n t h e sc h e d ul e of 
ass ess m e nts a n d as m e dic all y a p pr o pri at e.
S u bj ects wit h c yt o p e ni as s h o ul d b e m a n a g e d acc or di n g t o i nstit uti o n al g ui d eli n es wit h m axi m al 
s u p p orti v e c ar e a n d di a g n ostic ev al u ati o ns as cli nic all y i n dic at e d.  S u bj ects s h o ul d b e cl os el y m o nit or e d 
as a p pr o pri at e.
S ec o n d Pri m ar y M ali g n a nci es

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
E v e nts of s ec o n d pri m ar y m ali g n a nci es, i ncl u di n g n o n- m el a n o m a s ki n c arci n o m as, h a v e b e e n r e p ort e d 
i n cli nic al st u di es wit h ac al a br uti ni b. T h e m ost fr e q u e ntl y r e p ort e d  s ec o n d pri m ar y m ali g n a nc y w as s ki n 
c a nc er ( b as al c ell c arci n o m a).
S u bj ects s h o ul d b e m o nit or e d f or si g ns a n d s y m pt o ms of m ali g n a nc y. S u bj ects w h o d ev el o p a s ec o n d 
pri m ar y m ali g n a nc y s h o ul d b e m a n a g e d acc or di n g t o i nstit uti o n al g ui d eli n es wit h di a g n ostic ev al u ati o ns 
as cli nic all y i n dic at e d, a n d it m a y b e n ec ess ar y f or s u bj ects t o p er m a n e ntl y disc o nti n u e st u d y tr e at m e nt. 
C o nti n u ati o n of ac al a br uti ni b tr e at m e nt s h o ul d b e disc uss e d wit h t h e m e dic al m o nit or.  
Atri al Fi brill ati o n
E v e nts of atri al fi brill ati o n/fl utt er h a v e occ urr e d i n cli nic al st u di es wit h ac al a br uti ni b, p artic ul arl y i n 
s u bj ects wit h c ar di ac ris k f act ors, h y p ert e nsi o n, di a b et es m ellit us, ac ut e i nf ecti o ns, or a pr evi o us hist or y 
of atri al fi brill ati o n.
M o nit or f or s y m pt o ms of atri al fi brill ati o n a n d atri al fl utt er ( e. g., p al pit ati o ns, dizzi n ess, s y nc o p e, c h est 
p ai n, d ys p n e a) a n d o bt ai n a n E C G as cli nic all y i n dic at e d. S u bj ects wit h atri al fi brill ati o n s h o ul d b e 
m a n a g e d p er i nstit uti o n al g ui d eli n es wit h s u p p orti v e c ar e a n d di a g n ostic ev al u ati o ns as cli nic all y 
i n dic at e d.
I m p ort a nt P ot e nti al Ris ks 
T h er e is o n e i m p ort a nt p ot e nti al ris k f or ac al a br uti ni b m o n ot h er a p y. I nf or m ati o n r el at e d t o t his 
i m p ort a nt p ot e nti al ris k is pr es e nt e d b el o w. F ull d et ails r e g ar di n g t h e cli nic al s af et y of ac al a br uti ni b ar e 
pr es e nt e d i n t h e ac al a br uti ni b I n v esti g at or’s Br oc h ur e. 
H e p at ot o xicit y 
T h e m ec h a nis m u n d erl yi n g h e p at ot oxicit y ev e nts of n o n-i nf ecti o us eti ol o g y is c urr e ntl y u n k n o w n. 
F oll o wi n g a c o m pr e h e nsi v e r e vi e w of h e p at ot oxicit y ev e nts i n t h e ac al a br uti ni b cli nic al pr o gr a m, t h er e 
w as i ns uffici e nt evi d e nc e t o est a blis h a n ass oci ati o n b et w e e n h e p at ot oxicit y ev e nts a n d ac al a br uti ni b 
d u e t o t h e c o ntri b uti o n of c o nf o u n di n g f act ors, a bs e nc e of cli nic al s y m pt o ms, a n d q uic k r ec o v er y 
wit h o ut tr e at m e nt f or p ati e nts wit h tr a ns a mi n as e el e v ati o ns. T h er e is li mit e d evi d e nc e r e g ar di n g 
h e p at ot oxicit y of n o n-i nf ecti o us eti ol o g y fr o m lit er at ur e f or ot h er B T K i n hi bit ors.
A d v ers e E v e nts:
A n a g gr e g at e s af et y a n al ysis of ac al a br uti ni b m o n ot h er a p y w as c o n d uct e d i n or d er t o ass ess s af et y f or 
ac al a br uti ni b- ex p os e d s u bj ects wit h h e m at ol o gic m ali g n a nci es wit h o ut c o nf o u n di n g t oxicit y fr o m 
c o m bi n ati o n t h er a p y dr u gs. T h e a n al ysis w as p erf or m e d o n a 7-st u d y i nt e gr at e d m o n ot h er a p y 
p o p ul ati o n ‘I N T- 7’, w hic h c o nsist e d of tr e at e d s u bj ects i n 5 ac al a br uti ni b m o n ot h er a p y st u di es ( 1 5- H-
0 0 1 6, A C E- CL- 0 0 1, A C E-L Y- 0 0 2, A C E-L Y- 0 0 4, A C E- W M- 0 0 1) a n d tr e at e d s u bj ects i n t h e ac al a br uti ni b 
m o n ot h er a p y tr e at m e nt ar ms of 2 a d diti o n al c o m bi n ati o n st u di es ( A C E-L Y- 0 0 3 a n d A C E- M Y- 0 0 1). As of 
t h e 0 3 S e pt e m b er 2 0 1 7 d at a extr acti o n d at e, t h e p o ol e d I N T- 7 p o p ul ati o n r e pr es e nt e d 6 1 4 
ac al a br uti ni b- ex p os e d s u bj ects wit h a m e di a n ex p os ur e of 2 1. 9 m o nt hs (r a n g e, 0. 0 3 t o 4 2. 4 m o nt hs). 
O v er all, t h e s af et y of m o n ot h er a p y ac al a br uti ni b i n s u bj ects wit h h e m at ol o gic m ali g n a nci es h as b e e n 
acc e pt a bl e i n t h e i nt e gr at e d a n al ysis. A n o v er vi e w of A Es f or t his p o p ul ati o n is pr es e nt e d i n T a bl e 4- 1.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
T A B L E 1 3- 1. O V E R VI E W O F T R E A T M E N T- E M E R G E N T A D V E R S E E V E N T S 
O F T H E I N T- 7 A L L M O N O T H E R A P Y P O P U L A TI O N 
A d v er s e E v e nt C at e g or y 
N = 6 1 4 n ( %) 
A n y tr e at m e nt- e m er g e nt a d v er s e e v e nt s 
A n y gr a d e 
6 0 9 ( 9 9. 2) 
Gr a d e ≥3  
3 3 4 ( 5 4. 4) 
A n y a d v er s e e v e nt r el at e d t o a c al a br uti ni b 
A n y gr a d e 
4 5 9 ( 7 4. 8) 
Gr a d e ≥3  
1 2 8 ( 2 0. 8) 
A n y s eri o u s a d v er s e e v e nt s 
2 5 6 ( 4 1. 7) 
A d v er s e e v e nt s l e a di n g t o st u d y dr u g 
di s c o nti n u ati o n 
4 4 ( 7. 2) 
Gr a d e 5 (f at al) a d v er s e e v e nt 
2 7 ( 4. 4) 
I N T- 7 st u di e s i n cl u d e 1 5- H- 0 0 1 6, A C E- C L- 0 0 1, A C E- L Y- 0 0 2, A C E- L Y- 0 0 3, A C E- L Y- 0 0 4, A C E-
M Y- 0 0 1, a n d A C E- W M- 0 0 1. 
N ot e: A s u bj e ct wit h m ulti pl e s e v erit y gr a d e s f or a gi v e n a d v er s e e v e nt w a s c o u nt e d o n c e u n d er 
t h e m a xi m u m s e v erit y. 
D at a a s of 0 3 S e p 2 0 1 7. 
Al m ost all s u bj ects ( 6 0 9 [ 9 9. 2 %]) h a d at l e ast 1 A E, a n d a b o ut h alf ( 3 3 4 [ 5 4. 4 %]) h a d at l e ast 1 Gr a d e ≥3  
A E. T h e m ost c o m m o nl y r e p ort e d A Es of a n y gr a d e w er e h e a d ac h e ( 4 2. 3 %), di arr h e a ( 4 0. 4 %), f ati g u e 
( 2 4. 6 %), n a us e a ( 2 3. 6 %), c o nt usi o n ( 2 3. 5 %), c o u g h ( 2 2. 1 %), a n d u p p er r es pir at or y tr act i nf ecti o n ( 2 1. 7). 
T h e m ost fr e q u e ntl y r e p ort e d Gr a d e ≥3  A Es w er e n e utr o p e ni a ( 1 0. 4 %), a n e mi a ( 7. 5 %), p n e u m o ni a 
( 6. 5 %), t hr o m b oc yt o p e ni a ( 3. 7 %), a n d h y p ert e nsi o n ( 3. 1 %). 
Tr e at m e nt-r el at e d A Es w er e r e p ort e d f or 4 5 9 ( 7 4. 8 %) s u bj ects, a n d 1 2 8 ( 2 0. 8 %) s u bj ects h a d Gr a d e ≥3  
tr e at m e nt-r el at e d A Es. T h e m ost fr e q u e ntl y r e p ort e d tr e at m e nt-r el at e d A Es of a n y gr a d e w er e 
h e a d ac h e ( 2 9. 5 %), di arr h e a ( 1 7. 4 %), c o nt usi o n ( 1 4. 5 %), n a us e a ( 9. 3 %), f ati g u e ( 7. 5 %), p et ec hi a e ( 7. 5 %), 
n e utr o p e ni a ( 7. 0 %), art hr al gi a ( 5. 9 %), a n d dizzi n ess ( 5. 0 %). T h e m ost fr e q u e ntl y r e p ort e d tr e at m e nt-
r el at e d Gr a d e ≥3  A Es w as n e utr o p e ni a ( 6. 8 %).
F or m or e c o m pr e h e nsi v e i nf or m ati o n o n t h e s af et y pr ofil e of ac al a br uti ni b, r ef er t o t h e c urr e nt 
I n v esti g at ors Br oc h ur e.
1 3. 2 Ris ks Ass oci at e d wit h O bi n ut uz u m a b
T h e f oll o wi n g s u m m ariz es si g nific a nt ris ks wit h o bi n ut uz u m a b b as e d o n o bi n ut uz u m a b 
C o ntr ai n dic ati o ns a n d W ar ni n gs & Pr ec a uti o ns. F or a d diti o n al i nf or m ati o n, pl e as e r ef er t o 
o bi n ut uz u m a b l oc al pr escri bi n g i nf or m ati o n a n d p ac k a g e i ns ert.
C o ntr ai n dic ati o ns 
O bi n ut uz u m a b is c o ntr ai n dic at e d i n p ati e nts wit h k n o w n h y p ers e nsiti vit y r e acti o ns ( e. g., a n a p h yl axis) t o 
o bi n ut uz u m a b or a n y of t h e exci pi e nts, i ncl u di n g s er u m sic k n ess wit h pri or o bi n ut uz u m a b us e.
W ar ni n gs a n d Pr ec a uti o ns

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

I nf usi o n R e acti o ns
O bi n ut uz u m a b c a n c u as e s e v er e a n d lif e-t hr e at e ni n g i nf usi o n r e acti o ns. 6 5 % of p ati e nts wit h 
CLL ex p eri e nc e d a r e acti o n t o t h e first 1 0 0 0 m g of o bi n ut uz u m a b i nf us e d. 3 8 % of p ati e nts wit h 
R/ R N HL a n d 6 0 % of p ati e nts wit h pr e vi o usl y u ntr e at e d N HL ex p eri e nc e d a r e acti o n o n D a y 1 of 
o bi n ut uz u m a b i nf usi o n. Pr e m e dic at e p ati e nts wit h gl uc oc ortic oi d, ac et a mi n o p h e n, a n d a nti-
hist a mi n e. M o nit or p ati e nts cl os el y d uri n g i nf usi o ns. I nt err u pt or disc o nti n u e i nf usi o n f or 
r e acti o ns. S e e p ac k a g e i ns ert f or f urt h er d et ails. 

H y p ers e nsiti vit y R e acti o ns I ncl u di n g S er u m Sic k n ess
H y p ers e nsiti vit y r e acti o ns h a v e b e e n r e p ort e d i n p ati e nts tr e at e d wit h o bi n ut uz u m a b. Si g ns of 
i m m e di at e- o ns et h y p ers e nsiti vit y i ncl u d e d ys p n e a, br o nc h os p as m, h y p ot e nsi o n, urtic ari al, a n d 
t ac h yc ar di a. L at e- o ns et h y p ers e nsiti vit y di a g n os e d as s er u m sic k n ess h as als o b e e n r e p ort e d, 
wit h s y m pt o ms t h at i ncl u d e c h est p ai n, diff us e art hr al gi as, a n d f e v er. H y p ers e nsiti vit y r e acti o ns 
m a y b e diffic ult t o cli nic all y disti n g uis h fr o m i nf usi o n r el at e d r e acti o ns. H o w ev er, 
h y p ers e nsiti vit y v er y r ar el y occ urs wit h t h e first i nf usi o n a n d, w h e n o bs erv e d, oft e n occ urs aft er 
pr e vi o us ex p os ur e. If a h y p ers e nsiti vit y r e acti o n is s us p ect e d d uri n g or aft er a n i nf usi o n, t h e 
i nf usi o n m ust b e st o p p e d a n d tr e at m e nt p er m a n e ntl y disc o nti n u e d. 

T u m or L ysis S y n dr o m e
A ntici p at e t u m or l ysis s y n dr o m e; pr e m e dic at e wit h a nti- h y p er uric e mics a n d a d e q u at e h y dr ati o n 
es p eci all y f or p ati e nts wit h hi g h t u m or b ur d e n, hi g h circ ul ati n g l y m p h oc yt e c o u nt or r e n al 
i m p air m e nt. C orr ect el ectr ol yt e a b n or m aliti es, pr o vi d e s u p p orti v e c ar e, a n d m o nit or r e n al 
f u ncti o n a n d fl ui d b al a nc e. 

I nf ecti o ns
F at al a n d s eri o us b act eri al, f u n g al, a n d n e w or r e acti v at e d vir al i nf ecti o ns c a n occ ur d uri n g a n d 
f oll o wi n g o bi n ut uz u m a b t h er a p y. W h e n o bi n ut uz u m a b is a d mi nist er e d wit h c h e m ot h er a p y 
f oll o w e d b y o bi n ut uz u m a b m o n ot h er a p y, Gr a d e 3 t o 5 i nf ecti o ns h a v e b e e n r e p ort e d i n u p t o 
8 % of p ati e nts d uri n g t h e c o m bi n ati o n t h er a p y, u p t o 1 3 % of p ati e nts d uri n g m o n ot h er a p y, a n d 
u p t o 8 % of p ati e nts aft er tr e at m e nt. M o nit or f or i nf ecti o ns d uri n g a n d aft er tr e at m e nt.

N e utr o p e ni a
S e v er e a n d lif e t hr e at e ni n g n e utr o p e ni a, i ncl u di n g f e bril e n e utr o p e ni a, h as b e e n r e p ort e d 
d uri n g tr e at m e nt wit h o bi n ut uz u m a b. M o nit or p ati e nts wit h Gr a d e 3 t o 4 n e utr o p e ni a 
fr e q u e ntl y wit h r e g ul ar l a b or at or y t ests u ntil r es ol uti o n. A ntici p at e, e v al u at e, a n d tr e at a n y 
s y m pt o ms or si g ns of d e v el o pi n g i nf ecti o n. N e utr o p e ni a c a n als o b e of l at e o ns et ( occ urri n g 
m or e t h a n 2 8 d a ys aft er c o m pl eti o n of tr e at m e nt a n d/ or pr ol o n g e d (l asti n g l o n g er t h a n 2 8 
d a ys). 

T hr o m b oc yt o p e ni a
S e v er e a n d lif e t hr e at e ni n g t hr o m b oc yt o p e ni a h as b e e n r e p ort e d d uri n g tr e at m e nt wit h 
o bi n ut uz u m a b i n c o m bi n ati o n wit h c h e m ot h er a p y. F at al h e m orr h a gic e v e nts h a v e b e e n 
r e p ort e d i n p ati e nts wit h N HL a n d CLL tr e at e d wit h o bi n ut uz u m a b i n c o m bi n ati o n wit h 
c h e m ot h er a p y, i ncl u di n g d uri n g C ycl e 1. M o nit or pl at el et c o u nts a n d f or bl e e di n g. M a n a g e m e nt 
of h e m orr h a g e m a y r e q uir e bl o o d pr o d uct s u p p ort.

I m m u niz ati o n
T h e s af et y a n d effic ac y of i m m u niz ati o n wit h li v e or att e n u at e d vir al v acci n es d uri n g or f oll o wi n g 
o bi n ut uz u m a b t h er a p y h a v e n ot b e e n st u di e d. I m m u niz ati o n wit h li v e vir us v acci n es is n ot 
r ec o m m e n d e d d uri n g tr e at m e nt a n d u ntil B- C ell r ec o v er y. 
A d v ers e E v e nts

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
F or m or e i nf or m ati o n r e g ar di n g t h e a d v ers e ev e nts ass oci at e d wit h t h e us e of o bi n ut uz u m a b, pl e as e 
r ef er t o t h e U S PI. 
T h e G ALLI U M tri al ev al u at e d t h e s af et y of o bi n ut uz u m a b as c o m p ar e d t o rit uxi m a b pr o d uct i n 1 3 8 5 
p ati e nts wit h pr evi o usl y u ntr e at e d f ollic ul ar l y m p h o m a ( 8 6 %) or m ar gi n al z o n e l y m p h o m a ( 1 4 %). 
P ati e nts r ec ei v e d c h e m ot h er a p y ( b e n d a m usti n e, C H O P, or C V P) c o m p ar e d wit h eit h er o bi n ut uz u m a b 
( 6 9 1 p ati e nts) or rit uxi m a b pr o d uct ( 6 9 4), f oll o w e d i n r es p o n di n g p ati e nts b y o bi n ut uz u m a b or 
rit uxi m a b pr o d uct m o n ot h er a p y e v er y t w o m o nt hs u ntil dis e as e pr o gr essi o n or f or a m axi m u m of t w o 
y e ars. T h e c h e m ot h er a p y w as b e n d a m usti n e i n 5 9 %, C H O P i n 3 1 %, a n d C V P i n 1 0 % of p ati e nts. 
F oll o wi n g c o m bi n ati o n t h er a p y, 6 2 4 p ati e nts ( 9 0 %) i n t h e o bi n ut uz u m a b ar m a n d 6 1 2 p ati e nts ( 8 8 %) i n 
t h e rit uxi m a b pr o d uct ar m r ec ei v e d m o n ot h er a p y.
S eri o us a d v ers e r e acti o ns occ urr e d i n 5 0 % of p ati e nts o n t h e o bi nt uz u m a b ar m a n d 4 3 % of p ati e nts o n 
t h e rit uxi m a b pr o d uct ar m. F at al a d v ers e r e acti o ns w er e r e p ort e d d uri n g tr e at m e nt i n 3 % i n t h e 
o bi n ut uz u m a b ar m a n d 4 % of t h e rit uxi m a b pr o d uct ar m, wit h i nf ecti o ns a n d s ec o n d m ali g n a nci es b ei n g 
t h e l e a di n g c a us es. I n t h e o bi n ut uz u m a b ar m, f at al i nf ecti o ns occ urr e d i n 2 % of p ati e nts c o m p ar e d t o 
< 1 % i n t h e rit uxi m a b pr o d uct ar m. 
T hr o u g h o ut tr e at m e nt a n d f oll o w- u p, t h e m ost c o m m o n a d v ers e r e acti o ns (i nci d e nc e ≥2 0 %)  o bs er v e d 
at l e ast 2 % m or e i n t h e o bi n ut uz u m a b ar m i ncl u d e d i nf usi o n r el at e d r e acti o ns, n e utr o p e ni a, u p p er 
r es pir at or y tr act i nf ecti o n, c o u g h, c o nsti p ati o n, a n d di arr h e a. N e utr o p e ni a, i nf usi o n r el at e d r e acti o ns, 
f e bril e n e utr o p e ni a, a n d t hr o m b oc yt o p e ni a w er e t h e m ost c o m m o n Gr a d e 3 t o 5 a d v ers e r e acti o ns 
(i nci d e nc e ≥5 %)  o bs erv e d m or e fr e q u e ntl y i n t h e o bi n ut uz u m a b ar m. 
D uri n g t h e m o n ot h er a p y p eri o d, t h e c o m m o n a d v ers e r e acti o ns (i nci d e nc e ≥1 0 %)  o bs erv e d at l e ast 2 % 
m or e wit h o bi n ut uz u m a b w er e u p p er r es pir at or y tr act i nf ecti o n ( 4 0 %), c o u g h ( 2 3 %), m usc ul os k el et al 
p ai n ( 2 0 %), n e utr o p e ni a ( 1 9 %), a n d h er p es vir us i nf ecti o n ( 1 3 %). 
Gr a d e 3 t o 4 a b n or m aliti es r e p ort e d at l e ast 2 % m or e i n t h e o bi n ut uz u m a b ar m w er e l y m p h o p e ni a, 
l e u k o p e ni a, n e utr o p e ni a, t hr o m b oc yt o p e ni a, a n d h y p er uric e mi a. P ati e nts i n t h e o bi n ut uz u m a b ar m, as 
c o m p ar e d t o t h e rit uxi m a b pr o d uct ar m, h a d hi g h er i nci d e nc es of Gr a d e 4 n e utr o p e ni a ( 3 8 % vs. 3 0 %, 
r es p ecti v el y), Gr a d e 4 l y m p h o p e ni a ( 3 3 % vs. 2 2 %), a n d Gr a d e 4 l e u k o p e ni a ( 1 7 % vs. 1 2 %). 
I n t h e m o n ot h er a p y p h as e, n e w- o ns et Gr a d e 3 or 4 n e utr o p e ni a w as r e p ort e d i n 2 1 % of p ati e nts i n t h e 
o bi n ut uz u m a b ar m ( Gr a d e 4, 1 0 %) a n d 1 7 % of p ati e nts i n t h e rit uxi m a b pr o d uct ar m ( Gr a d e 4, 9 %). 
I nf usi o n R e acti o ns
I n G ALLI U M, 7 2 % of p ati e nts i n t h e o bi n ut uz u m a b tr e at e d ar m ex p eri e nc e d a n i nf usi o n r e acti o n ( all 
gr a d es). S y m pt o ms m a y i ncl u d e h y p ot e nsi o n, t ac h yc ar di a, d ys p n e a, a n d r es pir at or y s y m pt o ms ( e. g. 
br o nc h os p as m, l ar y nx a n d t hr o at irrit ati o n, w h e ezi n g a n d l ar y n g e al e d e m a). T h e m ost fr e q u e ntl y 
r e p ort e d s y m pt o ms i ncl u d e n a us e a, f ati g u e, c h est disc o mf ort, d ys p n e a, dizzi n ess, v o miti n g, di arr h e a, 
r as h, h y p ert e nsi o n, h y p ot e nsi o n, fl us hi n g, h e a d ac h e, p yr exi a, a n d c hills. T h e i nci d e nc e of Gr a d e 3 t o 4 
i nf usi o n r e acti o ns f or t h es e p ati e nts w as 1 2 %. I n c ycl e 1, t h e i nci d e nc e of i nf usi o n r e acti o ns ( all gr a d es) 
w as 6 2 %) i n t h e o bi ut uz u m a b tr e at e d ar m wit h Gr a d e 3 t o 4 i nf usi o n r e acti o ns r e p ort e d i n 1 0 %). T h e 
i nci d e nc e of i nf usi o n r e acti o ns ( all gr a d es) w as hi g h est o n D a y 1 ( 6 0 %) a n d d ecr e as e d o n D a ys 8 a n d 1 5 
( 9 % a n d 6 %, r es p ecti v el y). 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
D uri n g C ycl e 2, t h e i nci d e nc e of i nf usi o n r e acti o ns ( all gr a d es) i n t h e o bi n ut uz u m a b tr e at e d ar m w as 
1 3 % a n d d ecr e as e d wit h s u bs e q u e nt c ycl es.
D uri n g o bi n ut uz u m a b m o n ot h er a p y tr e at m e nt i n G ALLI U M, i nf usi o n r e acti o ns ( all gr a d es) w er e 
o bs er v e d i n 9 % of p ati e nts. 
O v er all, 1 % of p ati e nts i n G ALLI U M ex p eri e nc e d a n i nf usi o n r e acti o n l e a di n g t o disc o nti n u ati o n of 
o bi n ut uz u m a b. 
H y p ers e nsiti vit y R e acti o ns I ncl u di n g S er u m Sic k n ess
H y p ers e nsiti vit y r e acti o ns h a v e b e e n r e p ort e d i n p ati e nts tr e at e d wit h o bi n ut uz u m a b. Si g ns of 
i m m e di at e- o ns et h y p ers e nsiti vit y i ncl u d e d ys p n e a, br o nc h os p as m, h y p ot e nsi o n, urtic ari al, a n d 
t ac h yc ar di a. L at e- o ns et h y p ers e nsiti vit y di a g n os e d as s er u m sic k n ess h as als o b e e n r e p ort e d wit h 
s y m pt o ms t h at i ncl u d e c h est p ai n, diff us e art hr al gi a, a n d f ev er. H y p ers e nsiti vit y r e acti o ns m a y b e 
diffic ult t o cli nic all y disti n g uis h fr o m i nf usi o n r el at e d r e acti o ns. H o w e v er, h y p ers e nsiti vit y v er y r ar el y 
occ urs wit h t h e first i nf usi o n a n d, w h e n o bs erv e d, oft e n occ urs aft er pr evi o us ex p os ur e. If a 
h y p ers e nsiti vit y r e acti o n is s us p ect e d d uri n g or aft er a n i nf usi o n, t h e i nf usi o n m ust b e st o p p e d a n d 
tr e at m e nt p er m a n e ntl y disc o nti n u e d. P ati e nts wit h k n o w n h y p ers e nsiti vit y r e acti o ns t o o bi n ut uz u m a b, 
i ncl u di n g s er u m sic k n ess, m ust n ot b e r etr e at e d. 
H e p atitis B R e acti v ati o n
H e p atitis B vir us ( H B V) r e acti v ati o n, i n s o m e c as es r es ulti n g i n f ul mi n a nt h e p atitis, h e p atic f ail ur e, a n d 
d e at h, c a n occ ur i n p ati e nts tr e at e d wit h a nti- C D 2 0 a nti b o di es s uc h as o bi n ut uz u m a b. H B V r e acti v ati o n 
h as b e e n r e p ort e d i n p ati e nts w h o ar e h e p atitis B s urf ac e a nti g e n ( H Bs A g) p ositi v e a n d als o i n p ati e nts 
w h o ar e H Bs A g n e g ati v e b ut ar e h e p atitis B c or e a nti b o d y ( a nti- H Bc) p ositi v e. R e acti v ati o n h as als o 
occ urr e d i n p ati e nts w h o a p p e ar t o h a v e r es ol v e d h e p atitis B i nf ecti o n (i. e., H Bs A g n e g ati v e, a nti- H Bc 
p ositi v e, a n d h e p atitis B s urf ac e a nti b o d y p ositi v e).
H B V r e acti v ati o n is d efi n e d as a n a br u pt i ncr e as e i n H B V r e plic ati o n m a nif esti n g as a r a pi d i ncr e as e i n 
s er u m H B V D N A l e v el or d et ecti o n of H Gs A g i n a p ers o n w h o w as pr evi o usl y H Bs A g n e g ati v e a n d a nti-
H Bc p ositi v e. R e acti v ati o n of H B V r e plic ati o n is oft e n f oll o w e d b y h e p atitis, i. e., i ncr e as e i n tr a ns a mi n as e 
l e v els a n d, i n s e v er e c as es, i ncr e as e i n bilir u bi n l e v els, li v er f ail ur e, a n d d e at h. 
Pr o gr essi v e M ultif oc al L e u k o e nc e p h al o p at h y
J C vir us i nf ecti o n r es ulti n g i n pr o gr essi v e m ultif oc al l e u k o e nc e p h al o p at h y ( P ML), w hic h c a n b e f at al, w as 
o bs er v e d i n p ati e nts tr e at e d wit h o bi n ut uz u m a b. C o nsi d er t h e di a g n osis of P ML i n a n y p ati e nt 
pr es e nti n g wit h n e w o ns et or c h a n g es t o pr e existi n g n e ur ol o gic m a nif est ati o ns. 
1 3. 3 H e p atitis B R e acti v ati o n
S eri o us or lif e-t hr e at e ni n g r e acti v ati o n of vir al h e p atitis m a y occ ur i n s u bj ects tr e at e d wit h ac al a br uti ni b 
a n d o bi n ut uz u m a b. Pl e as e r ef er t o S ecti o n 5. 5 f or d et ails o n vir al h e p atitis scr e e ni n g a n d m o nit ori n g f or 
t his st u d y.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
1 3. 4 Pr o gr essi v e M ultif oc al L e u k o e nc e p h al o p at h y ( P ML)
S eri o us or lif e-t hr e at e ni n g occ urr e nc e of P ML m a y occ ur i n s u bj ects tr e at e d wit h ac al a br uti ni b a n d 
o bi n ut uz u m a b.
Si g ns a n d s y m pt o ms of P ML m a y i ncl u d e c o g niti v e a n d b e h a vi or al c h a n g es, l a n g u a g e dist ur b a nc es, 
vis u al dist ur b a nc es, s e ns or y d eficits, w e a k n ess, a n d c o or di n ati o n a n d g ait diffic ulti es.
If P ML is s us p ect e d, h ol d f urt h er st u d y tr e at m e nt ( as a p plic a bl e, b as e d o n ris ks i n t h e I n v esti g at or 
Br oc h ur e or l oc al pr escri bi n g i nf or m ati o n) u ntil P ML is excl u d e d. A di a g n ostic ev al u ati o n m a y i ncl u d e 
( b ut is n ot li mit e d t o):

N e ur ol o gic c o ns ult ati o n

Br ai n M RI

P C R a n al ysis f or J o h n C u n ni n g h a m or J C vir us D N A i n c er e br os pi n al fl ui d
If P ML is c o nfir m e d, p er m a n e ntl y disc o nti n u e st u d y tr e at m e nt ( as a p plic a bl e, b as e d o n ris ks i n t h e 
I n v esti g at or Br oc h ur e or l oc al pr escri bi n g i nf or m ati o n).
1 3. 5 R e pr o d ucti v e T o xicit y
Ac al a br uti ni b
T h e p ot e nti al f or ac al a br uti ni b t o b e excr et e d i n br e ast mil k of n ursi n g m ot h ers is u n k n o w n. F or 
r es ults of ac al a br uti ni b n o ncli nic al r e pr o d ucti v e t oxicit y st u di es, i ncl u di n g d efi niti v e e m br y of et al 
d e v el o p m e nt st u di es, pl e as e r ef er t o t h e I n v esti g at or Br oc h ur e. W o m e n of c hil d b e ari n g 
p ot e nti al ( W O C B P) w h o ar e s ex u all y acti v e m ust us e hi g hl y eff ecti v e m et h o ds of c o ntr ac e pti o n 
d uri n g tr e at m e nt a n d f or 2 d a ys aft er t h e l ast d os e of ac al a br uti ni b. F or m al e s u bj ects wit h a 
pr e g n a nt or n o n- pr e g n a nt W O C B P p art n er, n o c o ntr ac e pti o n m e as ur es ar e r e q uir e d. 
S u bj ects s h o ul d pr o m ptl y n otif y t h e i n v esti g at or if t h e y, or t h eir p art n er, b ec o m e pr e g n a nt d uri n g t his 
st u d y, wit hi n 2 d a ys aft er t h e l ast d os e of ac al a br uti ni b, or 1 8 m o nt hs wit hi n aft er t h e l ast d os e of 
o bi n ut uz u m a b, w hic h ev er is l o n g er.  If a f e m al e s u bj ect b ec o m es pr e g n a nt d uri n g t h e tr e at m e nt p eri o d, 
s h e m ust disc o nti n u e ac al a br uti ni b i m m e di at el y.  Pr e g n a nc y i n a f e m al e s u bj ect or a m al e s u bj ect’s 
p art n er m ust b e r e p ort e d as o utli n e d i n S ecti o n 1 7.
O bi n ut uz u m a b
O bi n ut uz u m a b is li k el y t o c a us e f et al B-c ell d e pl eti o n b as e d o n fi n di n gs fr o m a ni m al st u di es a n d t h e 
dr u g’s m ec h a nis m of acti o n. T h er e ar e n o d at a wit h o bi n ut uz u m a b us e i n pr e g n a nt w o m e n t o i nf or m a 
dr u g- ass oci at e d ris k. M o n ocl o n al a nti b o di es ar e tr a nsf err e d acr oss t h e pl ac e nt a. I n a ni m al r e pr o d ucti o n 
st u di es, w e e kl y i ntr a v e n o us a d mi nistr ati o n of o bi n ut uz u m a b t o pr e g n a nt c y n o m ol g us m o n k e ys fr o m 
d a y 2 0 of pr e g n a nc y u ntil p art uriti o n w hic h i ncl u d es t h e p eri o d of or g a n o g e n esis at d os es wit h 
ex p os ur es u p t o 2. 4 ti m es t h e ex p os ur e at t h e cli nic al d os e of 1 0 0 0 m g m o ntl y pr o d uc e d o p p ort u nistic 
i nf ecti o ns a n d i m m u n e c o m pl ex m e di at e d h y p ers e nsiti vit y r e acti o ns. N o e m br y o-t oxic or t er at o g e nic 
eff ects w er e o bs erv e d i n t h e m o n k e ys. 
A v oi d a d mi nist eri n g li v e v acci n es t o n e o n at es a n d i nf a nts ex p os e d t o o bi n ut uz u m a b i n ut er o u ntil B-c ell 
r ec o v er y occ urs.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
T h er e is n o i nf or m ati o n r e g ar di n g t h e pr es e nc e of o bi n ut uz u m a b i n h u m a n mil k, t h e eff ects o n t h e 
br e astf e d c hil d, or t h e eff ects o n mil k pr o d ucti o n. H o w ev er, l o w l e v els of o bi n ut uz u m a b w er e pr es e nt i n 
t h e mil k of l act ati n g c y n o m ol g us m o n k e ys. H u m a n I g G is k n o w n t o b e pr es e nt i n h u m a n br e ast mil k. 
P u blis h e d d at a s u g g ests t h at a nti b o di es i n br e ast mil k d o n ot e nt er t h e n e o n at al a n d c hil d circ ul ati o ns i n 
s u bst a nti al a m o u nts. 
R e pr o d ucti v e St at us Ass ess m e nt a n d Pr e g n a nc y T esti n g

R e pr o d ucti v e St at us Ass ess m e nt f or Cli nic al Tri als
o
I n v esti g at or, Cli nic al R es e arc h C o or di n at or ( C R C) or Cli nic al R es e arc h N urs e ( C R N) will 
e ns ur e t h at t h e s u bj ect h as c o m pl et e d t h e R e pr o d ucti v e St at us Ass ess m e nt a n d Birt h 
C o ntr ol F or m pri or t o d et er mi n ati o n of st u d y eli gi bilit y.
o
I n v esti g at or is r es p o nsi bl e f or ass essi n g a n d si g ni n g t h e R e pr o d ucti v e St at us Ass ess m e nt 
a n d Birt h C o ntr ol F or m d oc u m e nti n g if birt h c o ntr ol is r e q uir e d b y st u d y pr ot oc ol a n d 
w h et h er t h e s u bj ect is a m al e or w o m a n of c hil d- b e ari n g p ot e nti al ( W O C B P) or w o m a n 
n ot of c hil d- b e ari n g p ot e nti al. 
o
S u bj ects will b e c o nsi d er e d n ot of c hil d- b e ari n g p ot e nti al if:

F e m al e w h o h as h a d a h yst er ect o m y or bil at er al o o p h or ect o m y

F e m al e w h o is p ost- m e n o p a us al. F e m al es ar e c o nsi d er e d p ost- m e n o p a us al 
w h e n:

A g e ≥ 5 5 y e ars a n d o n y e ar or m or e of a m e n orr h e a

A g e < 5 5 y e ars a n d o n e y e ar or m or e of a m e n orr h e a, estr a di ol < 2 0 O R 
estr a di ol < 4 0 wit h F S H > 4 0 i n w o m e n n ot o n estr o g e n r e pl ac e m e nt 
t h er a p y

N ot e: A m e n orr h e a f oll o wi n g c a nc er t h er a p y d o es n ot r ul e o ut c hil d-
b e ari n g p ot e nti al.
o
S o urc e d oc u m e nts, e. g. O B G Y N n ot e, w hic h d oc u m e nt r e pr o d ucti v e st at us will b e fil e d 
i n t h e s u bj ect’s r es e arc h r ec or d.

Pr e g n a nc y T est V erific ati o n o n t h e St u d y Dr u g Or d ers
o
T h e r e pr o d ucti v e st at us ass ess m e nt a n d t h e pr e g n a nc y t est v erific ati o n m ust b e 
d oc u m e nt e d eit h er o n t h e pr e g n a nc y t est s ecti o n i m b e d d e d i nt o t h e st u d y dr u g or d er 
or o n t h e stic k er wit h pr e g n a nc y t est l a n g u a g e pl ac e d o n t h e st u d y dr u g or d er.
Lic e ns e d m e dic al pr of essi o ns s uc h as M e dic al D oct or ( M D), P h ar m ac y D oct or 
( P h ar m. D.), Cli nic al R es e arc h N urs e ( C R N), R e gist er e d N urs e ( R N), A d v a nc e d Pr actic e 
Pr o vi d ers ( A P P) will r e vi e w t his i nf or m ati o n t o e ns ur e acc ur ac y, si g n a n d d at e t h e 
a p pr o pri at e r e pr o d ucti v e st at us ass ess m e nt b ox. 
If t h e s u bj ect is a W O C B P, t h e lic e ns e d m e dic al pr of essi o n will als o r e vi e w, si g n a n d d at e 
t h e r es ults of t h e m ost r ec e nt pr e g n a nc y t est pri or t o st u d y dr u g a d mi nistr ati o n.
o
T h e pr e g n a nc y t est m ust b e d o n e w h e n r e q uir e d p er pr ot oc ol if s u bj ect is W O C B P. 
C o ntr ac e pti v e m et h o ds s uc h as t u b al li g ati o n or s p o us e’s s ucc essf ul v as ect o m y d o n ot 
w ai v e pr e g n a nc y t est r e q uir e m e nt.
o
T h e pr e g n a nc y t est is n ot r e q uir e d if:

S u bj ect is m al e

N ot r e q uir e d p er pr ot oc ol
S u bj ect is f e m al e t h at is n ot a W O C B P

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 4 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
D efi niti o n f or Hi g hl y Eff ecti v e M et h o ds of C o ntr ac e pti o n
Hi g hl y eff ecti v e m et h o ds of c o ntr ac e pti o n (t o b e us e d d uri n g h et er os ex u al acti vit y) ar e d efi n e d as 
m et h o ds t h at c a n ac hi e v e a f ail ur e r at e of < 1 % p er y e ar w h e n us e d c o nsist e ntl y a n d c orr ectl y.  S uc h 
m et h o ds i ncl u d e: 

C o m bi n e d ( estr o g e n a n d pr o g est o g e n c o nt ai ni n g) h or m o n al c o ntr ac e pti o n ass oci at e d wit h 
i n hi biti o n of o v ul ati o n, w hic h m a y b e or al, i ntr a v a gi n al, or tr a ns d er m al 

Pr o g est o g e n- o nl y h or m o n al c o ntr ac e pti o n ass oci at e d wit h i n hi biti o n of o v ul ati o n, w hic h m a y b e 
or al, i nj ect a bl e, or i m pl a nt a bl e

I ntr a ut eri n e d evic e (I U D) or i ntr a ut eri n e h or m o n e-r el e asi n g s yst e m (I U S)

Bil at er al t u b al occl usi o n

V as ect o m y of a f e m al e s u bj ect’s m al e p art n er ( wit h m e dic al ass ess m e nt a n d c o nfir m ati o n of 
v as ect o m y s ur gic al s ucc ess)

S ex u al a bsti n e nc e ( o nl y if r efr ai ni n g fr o m h et er os ex u al i nt erc o urs e d uri n g t h e e ntir e p eri o d of 
ris k ass oci at e d wit h t h e st u d y tr e at m e nts)
H or m o n al c o ntr ac e pti o n m a y b e s usc e pti bl e t o i nt er acti o n wit h st u d y or ot h er dr u gs, w hic h m a y r e d uc e 
t h e effic ac y of t h e c o ntr ac e pti o n m et h o d.
A bsti n e nc e (r el ati v e t o h et er os ex u al acti vit y) c a n o nl y b e us e d as t h e s ol e m et h o d of c o ntr ac e pti o n if it 
is c o nsist e ntl y e m pl o y e d d uri n g t h e e ntir e p eri o d of ris k ass oci at e d wit h t h e st u d y tr e at m e nts as t h e 
s u bj ect’s pr ef err e d a n d us u al lif est yl e.  P eri o dic a bsti n e nc e ( e. g., c al e n d ar, o v ul ati o n, s y m pt o-t h er m al, 
a n d p ost- o v ul ati o n m et h o ds) a n d wit h dr a w al ar e n ot acc e pt a bl e m et h o ds of c o ntr ac e pti o n.
If a c o ntr ac e pti v e m et h o d is r estrict e d b y l oc al r e g ul ati o ns/ g ui d eli n es, t h e n it d o es n ot q u alif y as a n 
acc e pt a bl e hi g hl y eff ecti v e m et h o d of c o ntr ac e pti o n f or s u bj ects p artici p ati n g at sit es i n t h e r el ev a nt 
c o u ntr y/r e gi o n.
1 3. 6 Ot h er Ris ks
A d diti o n al bl o o d dr a ws  - T h e p h ysic al ris k of dr a wi n g bl o o d is l oc al p ai n a n d br uisi n g at t h e sit e of 
v e ni p u nct ur e. Q u alifi e d p hl e b ot o mists or d esi g n e e will dr a w bl o o d s a m pl es. C ar e will b e t a k e n t o o bt ai n 
t h es e s p eci m e ns i n a s af e a n d h y gi e nic m a n n er. A s m all n u m b er of p e o pl e ex p eri e nc e li g ht h e a d e d n ess or 
f ai nti n g. T h er e is a sli g ht ris k of i nf ecti o n. T o mi ni miz e t h es e ris ks, att e m pts will b e m a d e t o dr a w st u d y 
bl o o d s a m pl es at t h e s a m e ti m e as bl o o d dr a ws n e e d e d f or r o uti n e cli nic al c ar e ar e o bt ai n e d. R e p e at e d 
bl o o d dr a wi n g m a y b e ass oci at e d wit h ir o n d efici e nc y a n e mi a.
D at a s ec urit y- S u bj ects will b e as k e d t o pr o vi d e p ers o n al h e alt h i nf or m ati o n ( P HI). All att e m pts will b e 
m a d e t o k e e p t his P HI c o nfi d e nti al wit hi n t h e li mits of t h e l a w. H o w e v er, t h er e is a c h a nc e t h at 
u n a ut h oriz e d p ers o ns will s e e t h e s u bj ects’ P HI. All r ec or ds will b e k e pt i n a l oc k e d fil e c a bi n et or 
m ai nt ai n e d i n a l oc k e d r o o m at t h e p artici p ati n g sit es. El ectr o nic fil es will b e p ass w or d pr ot ect e d b e hi n d 
a n ac a d e mic i nstit uti o n al fir e w all. O nl y p e o pl e w h o ar e i n v ol v e d i n t h e c o n d uct, o v ersi g ht, m o nit ori n g, or 
a u diti n g of t his st u d y will b e all o w e d acc ess t o t h e P HI t h at is c oll ect e d. A n y p u blic ati o ns fr o m t his st u d y 
will n ot us e i nf or m ati o n t h at will i d e ntif y s u bj ects. Or g a niz ati o ns t h at m a y i ns p ect a n d/ or c o p y r es e arc h 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
r ec or ds m ai nt ai n e d at t h e p artici p ati n g sit es f or q u alit y ass ur a nc e a n d d at a a n al ysis i ncl u d e gr o u ps s uc h 
as t h e N ati o n al C a nc er I nstit ut e ( N CI) a n d F o o d a n d Dr u g A d mi nistr ati o n ( F D A).
1 4. P ot e nti al B e n efits t o P artici p a nts
T h er e is n o g u ar a nt e e of b e n efit t o s u bj ects w h o e nr oll i n t his pr ot oc ol.
1 5. D at a M a n a g e m e nt a n d C o nfi d e nti alit y
1 5. 1 St atistic al c o nsi d er ati o ns
T his is a P h as e 2, si n gl e- ar m tri al d esi g n e d t o ass ess t h e s af et y a n d effic ac y of ac al a br uti ni b a n d 
o bi n ut uz u m a b i n s u bj ects wit h l o w t u m or b ur d e n FL a n d ot h er i n d ol e nt N HLs. A n al ysis of t h e pri m ar y 
e n d p oi nt will b e d o n e pri or t o c ycl e 6 of t h e i n d ucti o n p h as e. D escri pti v e st atistics will b e us e d t o 
s u m m ariz e b as eli n e d e m o gr a p hic a n d dis e as e c h ar act eristics.  
R ati o n al e f or S a m pl e Siz e
T h e pri m ar y p o p ul ati o n of i nt er est f or t his st u d y will b e p ati e nts wit h FL w h o h a v e a l o w t u m or 
b ur d e n as d efi n e d b y t h e G EL F crit eri a (s e e A p p e n dix 4). T h e pri m ar y e n d p oi nt f or t his st u d y is 
t h e C R r at e at 6 m o nt hs ( pri or t o c ycl e 6 of i n d ucti o n t h er a p y). W e will c o m p ar e o ur C R r at e t o a 
hist oric al c o ntr ol of 1 1. 8 % f or si n gl e a g e nt rit uxi m a b t h at w as r e p ort e d i n t h e R E S O R T tri al. I n 
or d er t o h a v e a p o w er of 8 0 % t o d et ect a n i m pr o v e m e nt i n t h e C R r at e fr o m 1 2 % t o 3 0 %, w e will 
r e q uir e at l e ast 2 9 p ati e nts f or o ur pri m ar y a n al ysis usi n g a Si m o n 2-st a g e d esi g n. T h e n ull 
h y p ot h esis t h at t h e tr u e r es p o ns e r at e is 1 2 % will b e t est e d a g ai nst a 1-si d e d alt er n ati v e.  I n t h e 
1 st st a g e, 1 8 p ati e nts will b e accr u e d.  If t h er e ar e 2 or f e w er r es p o ns es i n t h os e first 1 8 p ati e nts, 
t h e tri al will st o p.  Ot h er wis e, a n a d diti o n al 1 1 p ati e nts will b e accr u e d f or a t ot al s a m pl e siz e of 
2 9.  T h e PI or d esi g n e e m ust pr o vi d e t h e D S M C a r e p ort o utli ni n g t h e o v er all e nr oll m e nt a n d 
p at h t o d ecisi o n t o o p e n t h e n ext e nr oll m e nt c o h ort. D S M C a p pr o v al is n e e d e d i n or d er t o m o v e 
t o t h e s ec o n d st a g e of t h e st u d y. T h e n ull h y p ot h esis will b e r ej ect e d if 7 or m or e r es p o ns es ar e 
o bs er v e d i n 2 9 p ati e nts.  T his d esi g n yi el ds a T y p e I err or r at e of 0. 0 5 a n d p o w er of 8 0 % w h e n 
t h e tr u e r es p o ns e r at e is 3 0 %.  W e als o pl a n t o e nr oll u p t o 2 0 p ati e nts wit h ot h er s u bt y p es of 
i n d ol e nt N HL or cli nic al sc e n ari os d oc u m e nt e d a b o v e i n or d er t o i d e ntif y pr eli mi n ar y evi d e nc e of 
effic ac y of t his tr e at m e nt i n t h os e s u bt y p es a n d/ or cli nic al sc e n ari os, a n d w o ul d c o nsi d er a 
f ut ur e a m e n d m e nt ex p a n di n g o n e or m or e of t h os e p o p ul ati o ns if a n effic ac y si g n al is i d e ntifi e d. 
T his 2 0 p ati e nt c o h ort will b e p o ol e d wit h t h e pri m ar y c o h ort f or t h e s af et y a n al ysis b ut will b e 
a n al yz e d s e p ar at el y fr o m t h e pri m ar y p ati e nt p o p ul ati o n i n t er ms of effic ac y o utc o m es. As a 
r es ult, w e will pl a n t o e nr oll a t ot al of 4 9 p ati e nts t o t h e tri al, at l e ast 2 9 of w h o m will b e 
p ati e nts wit h l o w t u m or b ur d e n FL w h o ar e ev al u a bl e f or t h e pri m ar y e n d p oi nt.
A n al ysis P o p ul ati o ns:
All effic ac y a n al ysis will b e p erf or m e d usi n g t h e i nt e nti o n t o tr e at p o p ul ati o n, w hic h c o nsists of all 
p ati e nts w h o c o m pl et e t h e c o ns e nt f or m a n d m e et eli gi bilit y crit eri a. S u bj ects w h o r ec ei v e a n y a m o u nt 
of st u d y tr e at m e nt s h all b e i ncl u d e d i n t h e s af et y a n al ys es. T h e a n al ysis of D O R will o nl y i ncl u d e s u bj ects 
w h o h a v e ac hi e v e d o bj ecti v e r es p o ns e.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Missi n g D at a H a n dli n g
N o i m p ut ati o n of v al u es f or missi n g d at a will b e p erf or m e d exc e pt t h at missi n g or p arti al st art a n d e n d 
d at es f or A Es a n d c o nc o mit a nt m e dic ati o n will b e i m p ut e d acc or di n g t o pr e-s p ecifi e d, c o ns erv ati v e 
i m p ut ati o n r ul es.  S u bj ects l ost t o f oll o w- u p ( or dr o p o ut) will b e i ncl u d e d i n st atistic al a n al ys es t o t h e 
p oi nt of t h eir l ast e v al u ati o n ( a n d will b e c o nsi d er e d n o n-r es p o n d ers if t h e y ar e l ost t o f oll o w- u p pri or t o 
t h eir first sc h e d ul e d r es p o ns e ass ess m e nt).
Effic ac y E n d p oi nts
T h e pri m ar y effic ac y e n d p oi nt is t h e c o m pl et e r es p o ns e r at e pri or t o c ycl e 6 of t h er a p y. 
S ec o n d ar y e n d p oi nts i ncl u d e:

O v er all r es p o ns e r at e

C R r at e f or ac al a br uti ni b m o n ot h er a p y at e n d of si n gl e- a g e nt r u n-i n

2- y e ar pr o gr essi o n fr e e s urvi v al 

2- y e ar r at e of hist ol o gic tr a nsf or m ati o n

O v er all s urvi v al

D ur ati o n of R es p o ns e

Ti m e t o n ext a nti-l y m p h o m a tr e at m e nt

Q u alit y of lif e ass ess m e nts
S af et y E n d p oi nts
S af et y e n d p oi nts i ncl u d e:

Gr a d e 3 + a d v ers e ev e nts

All gr a d e a d v ers e e v e nts

P ati e nt-r e p ort e d a d v ers e e v e nts p er P R O- C T C A E ass ess m e nts

R at e of tr e at m e nt disc o nti n u ati o n a n d fr e q u e nc y of c o m pl eti o n of st u d y t h er a p y
St u d y Tr e at m e nt A d mi nistr ati o n a n d C o m pli a nc e
D escri pti v e i nf or m ati o n will b e pr o vi d e d r e g ar di n g t h e n u m b er of ac al a br uti ni b d os es pr escri b e d, t h e 
t ot al n u m b er of d os es t a k e n, t h e n u m b er of d a ys of tr e at m e nt, a n d t h e n u m b er a n d ti mi n g of pr escri b e d 
d os e d el a y, r e d ucti o ns a n d i nt err u pti o ns.  
F or e ac h s u bj ect, ac al a br uti ni b c o m pli a nc e will b e d escri b e d i n t er ms of t h e pr o p orti o n of st u d y dr u g 
act u all y t a k e n.
A n al ysis of Pri m ar y Effic ac y E n d p oi nt
C o m pl et e r es p o ns e r at e will b e c alc ul at e d, a n d a 9 5 % c o nfi d e nc e i nt er v al will b e esti m at e d usi n g t h e 
Cl o p p er- P e ars o n m et h o d.  T his a n al ysis a p pli es as w ell t o o v er all r es p o ns e r at e a n d C R r at e f or 
ac al a br uti ni b m o n ot h er a p y at e n d of si n gl e- a g e nt r u n-i n.
S u bj ects w h o ulti m at el y d o n ot r ec ei v e st u d y t h er a p y d u e t o r e as o ns ot h er t h a n b ei n g i n eli gi bl e or t h os e 
w h o d o n ot h a v e a r es p o ns e ass ess m e nt d u e t o n o n-c o m pl ai nc e or d u e t o e arl y tr e at m e nt 
disc o nti n u ati o n s h all b e c o nsi d er e d n o n-r es p o n d ers. P ati e nts wit h cli nic all y s us p ect e d P D s h o ul d, if 
f e asi bl e, c o m pl et e r a di o gr a p hic ass ess m e nt t o c o nfir m t his b ut if t his is n ot f e asi bl e, p ati e nts w h o h a v e 
cli nic al e vi d e nc e of pr o gr essi o n r es ulti n g i n disc o nti n u ati o n s h all b e c o nsi d er e d as h a vi n g P D.
A n al ysis of S ec o n d ar y Effic ac y E n d p oi nt

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
F or s u bj ects w h o ac hi ev e o bj ecti v e r es p o ns e, D O R is d efi n e d as t h e ti m e fr o m t h e first t u m or 
ass ess m e nt s u p p orts t h e r es p o ns e t o t h e ti m e of c o nfir m e d dis e as e pr o gr essi o n or d e at h d u e t o a n y 
c a us e, w hic h ev er occ urs first.  S u bj ects w h o ar e still ali v e a n d fr e e fr o m pr o gr essi o n at t h e ti m e of d at a 
c ut off d at e, l ost t o f oll o w- u p, h a v e disc o nti n u e d st u d y, or h a v e i niti at e d ot h er n o n- pr ot oc ol a nti-t u m or 
t h er a p y ( N P T) will b e c e ns or e d at t h e l ast t u m or ass ess m e nt w h e n s u bj ects ar e pr o gr essi o n-fr e e.  D O R 
will b e esti m at e d usi n g K a pl a n- M ei er m et h o d.  A p pr oxi m at e 9 5 % CIs f or m e di a n D O R will b e c o m p ut e d 
usi n g t h e Br o o k m e y er a n d Cr o wl e y m et h o d.
P F S is d efi n e d as t h e ti m e fr o m first d os e t o d oc u m e nt e d dis e as e pr o gr essi o n, or d e at h fr o m a n y c a us e, 
w hic h e v er occ urs first.  D at a f or s u bj ects w h o ar e still ali v e a n d fr e e fr o m pr o gr essi o n at t h e ti m e of d at a 
c ut off d at e, l ost t o f oll o w- u p, h a v e disc o nti n u e d t h e st u d y, or h a v e i niti at e d N P T will b e c e ns or e d o n l ast 
ass ess m e nt pri or t o af or e m e nti o n e d e v e nts ( or, if n o b as eli n e/ p ost- b as eli n e t u m or ass ess m e nt, at t h e 
ti m e of first d os e pl us 1 d a y).  P F S will b e esti m at e d usi n g K a pl a n- M ei er m et h o d ol o g y.  A p pr oxi m at e 9 5 % 
CIs f or m e di a n P F S will b e c o m p ut e d usi n g t h e Br o o k m e y er a n d Cr o wl e y m et h o d. P ati e nts w h o d o n ot 
r ec ei v e tr e at m e nt will b e excl u d e d fr o m t h e P F S a n al ysis. 
O S is d efi n e d as t h e ti m e fr o m first d os e t o d e at h fr o m a n y c a us e.  D at a f or s u bj ects w h o ar e still ali v e at 
t h e ti m e of d at a c ut off d at e, l ost t o f oll o w- u p, h a v e disc o nti n u e d t h e st u d y ( or, if n o p ost- b as eli n e 
ass ess m e nt, at t h e ti m e of first d os e pl us 1 d a y).  D ur ati o n of O S will b e esti m at e d usi n g K a pl a n- M ei er 
m et h o d ol o g y.  A p pr oxi m at e 9 5 % CIs f or m e di a n O S will c o m p ut e d usi n g t h e Br o o k m e y er a n d Cr o wl e y 
m et h o d.
Ti m e t o n ext a nti-l y m p h o m a tr e at m e nt is d efi n e d as t h e ti m e fr o m t h e e n d of i n d ucti o n visit u p t o a n d 
i ncl u di n g t h e d at e of i niti ati o n of n ext tr e at m e nt f or a n y r e as o n. T his i ncl u d es a n y c h e m ot h er a p y, 
a nti b o d y t h er a p y, or al t h er a p y, a n d r a di ati o n t h er a p y. Ti m e t o n ext a nti-l y m p h o m a tr e at m e nt will b e 
esti m at e d usi n g K a pl a n- M ei er m et h o d ol o g y. A p pr oxi m at e 9 5 % CIs f or m e di a n ti m e t o n ext a nti-
l y m p h o m a tr e at m e nt will b e c o m p ut e d usi n g t h e Br o o k m e y er a n d Cr o wl e y m et h o d.
Q OL m e as ur es fr o m t h e F A C T- G o bt ai n e d d uri n g tr e at m e nt will b e c o m p ar e d t o t h e b as eli n e v al u es 
o bt ai n e d at t h e scr e e ni n g visit usi n g p air e d t-t ests, Mc N e m ar’s t ests, or t h eir n o n p ar a m etric 
e q ui v al e nts, w h er e a p pr o pri at e.
C at e g oric al P R O- C T C A E v ari a bl es will b e s u m m ariz e d usi n g fr e q u e nci es a n d p erc e nt a g es, a n d n u m eric 
P R O- C T C A E v ari a bl es will b e s u m m ariz e d usi n g m e a n, m e di a n, st a n d ar d d e vi ati o n, i nt er q u artil e r a n g e 
(I Q R), a n d r a n g e.
1 6. 2 D at a/s p eci m e ns:
P artici p a nt c o nfi d e nti alit y is strictl y h el d i n tr ust b y t h e p artici p ati n g i n v esti g at ors, t h eir st aff, a n d t h e 
s p o ns or(s) a n d t h eir a g e nts. T h er ef or e, t h e st u d y pr ot oc ol, d oc u m e nt ati o n, d at a, a n d all ot h er i nf or m ati o n 
g e n er at e d will b e h el d i n strict c o nfi d e nc e. N o i nf or m ati o n c o nc er ni n g t h e st u d y or t h e d at a will b e 
r el e as e d t o a n y u n a ut h oriz e d t hir d p art y wit h o ut pri or writt e n a p pr o v al of t h e Pri nci p al I n v esti g at or. T h e 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
st u d y p artici p a nt’s c o nt act i nf or m ati o n will b e s ec ur el y st or e d at e ac h cli nic al sit e f or i nt er n al us e d uri n g 
t h e st u d y. At t h e e n d of t h e st u d y, all r ec or ds will c o nti n u e t o b e k e pt i n a s ec ur e l oc ati o n f or as l o n g a 
p eri o d as dict at e d b y l oc al I R B a n d I nstit uti o n al r e g ul ati o ns.
D at a a n d/ or d at a f or ms will b e s u b mitt e d i n t h e cli nic al m a n a g e m e nt s yst e m - O nli n e C oll a b or ati v e 
R es e arc h E n vir o n m e nt ( O N C O R E)- p er Wi ns hi p S O P 4. 2 D at a C o m pl eti o n M etrics.
All i nf or m ati o n i n ori gi n al r ec or ds a n d c ertifi e d c o pi es of ori gi n al r ec or ds or cli nic al fi n di n gs, o bs er v ati o ns, 
or ot h er acti viti es n ec ess ar y f or t h e r ec o nstr ucti o n a n d ev al u ati o n of t h e tri al is c o nsi d er e d s o urc e d at a. 
S o urc e d at a ar e c o nt ai n e d i n s o urc e d oc u m e nts, w hic h c a n b e ori gi n al r ec or ds or c ertifi e d c o pi es of 
h os pit al r ec or ds, cli nic al a n d offic e c h arts, l a b or at or y n ot es, m e m or a n d a, s u bj ects' di ari es of e v al u ati o n 
c h ec klists, p h ar m ac y dis p e nsi n g r ec or ds, r ec or d e d d at a fr o m a ut o m at e d i nstr u m e nts, c o pi es or 
tr a nscri pti o ns c ertifi e d aft er v erific ati o n as b ei n g acc ur at e a n d c o m pl et e, micr ofic h es, p h ot o gr a p hic 
n e g ati v es, micr ofil m or m a g n etic m e di a, x-r a ys, s u bj ect fil es, a n d r ec or ds k e pt at t h e p h ar m ac y, at t h e 
l a b or at ori es, a n d at m e dic o-t ec h nic al d e p art m e nts i n v ol v e d i n t h e cli nic al tri al. C as e R e p ort F or ms ( C R Fs) 
- S o urc e d at a m a y b e c oll ect e d i n t h e s o urc e d oc u m e nts or e nt er e d dir ectl y o nt o t h e c as e r e p ort f or ms.
All d oc u m e nt ati o n of a d v ers e e v e nts, r ec or ds of st u d y dr u g r ec ei pt a n d dis p e ns ati o n, a n d all I R B 
c orr es p o n d e nc e will b e m ai nt ai n e d f or at l e ast 2 y e ars aft er t h e i n v esti g ati o n is c o m pl et e d.
St u d y p artici p a nt r es e arc h d at a, w hic h is f or p ur p os es of st atistic al a n al ysis a n d sci e ntific r e p orti n g, will 
b e st or e d. T his will n ot i ncl u d e t h e p artici p a nt’s c o nt act or i d e ntif yi n g i nf or m ati o n. R at h er, i n di vi d u al 
p artici p a nts a n d t h eir r es e arc h d at a will b e i d e ntifi e d b y a u ni q u e st u d y i d e ntific ati o n n u m b er. T h e st u d y 
d at a e ntr y a n d st u d y m a n a g e m e nt s yst e ms us e d b y cli nic al sit es a n d r es e arc h st aff will b e s ec ur e d a n d 
p ass w or d pr ot ect e d. At t h e e n d of t h e st u d y, all st u d y d at a b as es will b e d e-i d e ntifi e d a n d arc hi v e d.
S a m pl es a n d d at a c oll ect e d u n d er t his pr ot oc ol m a y b e us e d t o st u d y n o n- H o d g ki n L y m p h o m a. Acc ess t o 
st or e d s a m pl es will b e li mit e d t o I R B- a p pr o v e d i n v esti g at ors. S a m pl es a n d d at a will b e st or e d usi n g 
c o d es assi g n e d b y t h e i n v esti g at ors or t h eir d esi g n e es. D at a will b e k e pt i n p ass w or d- pr ot ect e d 
c o m p ut ers. O nl y i n v esti g at ors will h a v e acc ess t o t h e s a m pl es a n d d at a.
All st or e d s a m pl es will b e m ai nt ai n e d i n t h e l a b or at or y t o w hic h it w as s e nt i niti all y f or a n al ysis. 
St u d y p artici p a nts w h o r e q u est d estr ucti o n of s a m pl es will b e n otifi e d of c o m pli a nc e wit h s uc h 
r e q u est a n d all s u p p orti n g d et ails will b e m ai nt ai n e d f or tr ac ki n g
1 6. Pr o visi o ns t o M o nit or t h e D at a t o E ns ur e t h e S af et y of P artici p a nts
D efi niti o n of A d v ers e E v e nts ( A E)
A d v ers e e v e nt m e a ns a n y u nt o w ar d m e dic al occ urr e nc e ass oci at e d wit h t h e us e of a n i nt er v e nti o n i n 
h u m a ns, w h et h er or n ot c o nsi d er e d i nt er v e nti o n-r el at e d ( 2 1 C F R 3 1 2. 3 2 ( a)).

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
T his i ncl u d es t h e f oll o wi n g:

A Es n ot pr e vi o usl y o bs er v e d i n t h e s u bj ect t h at e m er g e d uri n g t h e pr ot oc ol-s p ecifi e d A E 
r e p orti n g p eri o d, i ncl u di n g si g ns or s y m pt o ms ass oci at e d wit h n o n- H o d g ki n L y m p h o m a t h at 
w er e n ot pr es e nt b ef or e t h e A E r e p orti n g p eri o d.

Pr e- existi n g m e dic al c o n diti o ns ( ot h er t h a n t h e c o n diti o n b ei n g st u di e d) j u d g e d b y t h e 
i n v esti g at or t o h a v e w ors e n e d i n s e v erit y or fr e q u e nc y or c h a n g e d i n c h ar act er d uri n g t h e 
pr ot oc ol-s p ecifi e d A E r e p orti n g p eri o d.

A b n or m al l a b or at or y v al u es c o nsi d er e d cli nic all y si g nific a nt b y t h e i n v esti g at or s h o ul d b e 
r e p ort e d as a n A E.  
T h e f oll o wi n g ar e N O T c o nsi d er e d a n A E:

Pr e- e xisti n g c o n diti o n t h at h as n ot w ors e n e d : A pr e- existi n g c o n diti o n ( d oc u m e nt e d o n t h e 
m e dic al hist or y C R F) is n ot c o nsi d er e d a n A E u nl ess t h e s e v erit y, fr e q u e nc y, or c h ar act er of t h e 
e v e nt w ors e ns d uri n g t h e st u d y p eri o d.

Pr e pl a n n e d h os pit aliz ati o n : A h os pit aliz ati o n pl a n n e d b ef or e si g ni n g t h e I C F is n ot c o nsi d er e d 
a n S A E, b ut r at h er a t h er a p e utic i nt er v e nti o n.  H o w ev er, if d uri n g t h e pr e pl a n n e d h os pit aliz ati o n 
a n e v e nt occ urs, w hic h pr ol o n gs t h e h os pit aliz ati o n or m e ets a n y ot h er S A E crit eri a, t h e e v e nt 
will b e c o nsi d er e d a n S A E.  S ur g eri es or i nt erv e nti o ns t h at w er e u n d er c o nsi d er ati o n, b ut n ot 
p erf or m e d b ef or e si g ni n g t h e I C F, will n ot b e c o nsi d er e d s eri o us if t h e y ar e p erf or m e d aft er 
si g ni n g t h e I C F f or a c o n diti o n t h at h as n ot c h a n g e d fr o m its b as eli n e l ev el.  El ecti v e 
h os pit aliz ati o ns f or s oci al r e as o ns, s ol el y f or t h e a d mi nistr ati o n of c h e m ot h er a p y, or d u e t o l o n g 
tr a v el dist a nc es ar e als o n ot S A Es. I n a d diti o n, el ecti v e h os pit aliz ati o ns s ol el y f or TL S 
pr o p h yl axis, a n d wit h o ut occ urr e nc e of TL S or ot h er A E d uri n g t h e h os pit aliz ati o n, als o s h o ul d 
n ot b e r e p ort e d as A Es or S A Es.

Di a g n ostic t esti n g a n d pr oc e d ur es : T esti n g a n d pr oc e d ur es s h o ul d n ot b e r e p ort e d as A Es or 
S A Es, b ut r at h er t h e c a us e f or t h e t est or pr oc e d ur e s h o ul d b e r e p ort e d.   If a t est or pr oc e d ur e 
is d o n e t o r ul e o ut a di a g n osis, t h e si g n or s y m pt o m l e a di n g t o t h e t est/ pr oc e d ur e s h o ul d b e t h e 
e v e nt t er m, a n d t h e ev e nt t er m s h o ul d o nl y b e u p d at e d t o t h e di a g n osis if/ w h e n t h e di a g n osis is 
c o nfir m e d.   T esti n g a n d pr oc e d ur es p erf or m e d s ol el y as scr e e ni n g m e as ur es ( e g, r o uti n e 
scr e e ni n g m a m m o gr a p h y or c ol o n osc o p y) s h o ul d n ot b e r e p ort e d as A Es or S A Es.

A b n or m al l a b or at or y r es ults t h at t h e i n v esti g at or c o nsi d ers t o n ot b e cli nic all y 
si g nific a nt:  A b n or m al l a b or at or y r es ults ar e n ot A Es u nl ess t h e y ar e cli nic all y si g nific a nt.  F or 
ex a m pl e, a cli nic all y si g nific a nt l a b or at or y r es ult is o n e t h at r e q uir es tr e at m e nt (f or ex a m pl e a 
bl o o d tr a nsf usi o n f or l o w h e m o gl o bi n) or r e q uir es a c h a n g e i n st u d y dr u g ( e g, l o w eri n g t h e d os e 
or wit h h ol di n g st u d y dr u g w hil e t h e l a b or at or y fi n di n g r es ol v es or st a biliz es).

Pr o gr essi o n of u n d erl yi n g m ali g n a nc y :  Pr o gr essi o n of u n d erl yi n g m ali g n a nc y will n ot b e 
r e p ort e d as a n A E if it is cl e arl y c o nsist e nt wit h t h e s us p ect e d pr o gr essi o n of t h e u n d erl yi n g 
c a nc er.  H os pit aliz ati o n d u e s ol el y t o t h e pr o gr essi o n of u n d erl yi n g m ali g n a nc y s h o ul d N O T b e 
r e p ort e d as a n S A E.  Cli nic al s y m pt o ms of pr o gr essi o n m a y b e r e p ort e d as A Es if t h e s y m pt o ms 
c a n n ot b e d et er mi n e d as excl usi v el y d u e t o t h e pr o gr essi o n of t h e u n d erl yi n g m ali g n a nc y, or if 
t h e y d o n ot fit t h e ex p ect e d p att er n of pr o gr essi o n f or t h e dis e as e u n d er st u d y.
If t h er e is a n y u nc ert ai nt y a b o ut a n A E b ei n g d u e o nl y t o t h e dis e as e u n d er st u d y, it s h o ul d b e 
r e p ort e d as a n A E or S A E.
S y m pt o m atic d et eri or ati o n m a y occ ur i n s o m e s u bj ects.  S y m pt o m atic d et eri or ati o n is w h e n 
pr o gr essi o n is evi d e nt i n t h e s u bj ect’s cli nic al s y m pt o ms a n d t h e i n v esti g at or m a y el ect n ot t o 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
p erf or m f urt h er dis e as e ass ess m e nts.  If t h er e is a n y u nc ert ai nt y a b o ut a n A E b ei n g d u e o nl y t o 
t h e dis e as e u n d er st u d y, it s h o ul d b e r e p ort e d as a n A E or S A E.
A d v ers e E v e nts of S p eci al I nt er est ( A E SI)
T h e f oll o wi n g ev e nts ar e a d v ers e e v e nts of s p eci al i nt er est ( A E SIs) f or s u bj ects ex p os e d t o ac al a br uti ni b, 
a n d m ust b e r e p ort e d t o t h e s u p p ort er ex p e diti o usl y irr es p ecti v e of r e g ul at or y s eri o us n ess crit eri a or 
c a us alit y:

V e ntric ul ar arr h yt h mi as ( e. g., v e ntric ul ar extr as yst ol es, v e ntric ul ar t ac h yc ar di a, v e ntric ul ar 
arr h yt h mi a, v e ntric ul ar fi brill ati o n, etc.)
O bi n ut uz u m a b ev e nts of s p eci al i nt er est ar e: 

TL S (s eri o us a n d n o n-s eri o us ev e nts)

S ec o n d m ali g n a nci es
D efi niti o n of S eri o us A d v ers e E v e nts ( S A E) 
A n a d v ers e ev e nt ( A E) or s us p ect e d a d v ers e r e acti o n is c o nsi d er e d "s eri o us" if, i n t h e vi e w of eit h er t h e 
i n v esti g at or or s p o ns or, it r es ults i n a n y of t h e f oll o wi n g o utc o m es: 

D e at h

Lif e-t hr e at e ni n g a d v ers e e v e nt 

I n p ati e nt h os pit aliz ati o n or pr ol o n g ati o n of existi n g h os pit aliz ati o n

A p ersist e nt or si g nific a nt i nc a p acit y or s u bst a nti al disr u pti o n of t h e a bilit y t o c o n d uct n or m al lif e 
f u ncti o ns, or a c o n g e nit al a n o m al y/ birt h d ef ect. 

I m p ort a nt 
m e dic al e v e nts t h at 
m a y n ot r es ult i n d e at h, b e lif e-t hr e at e ni n g, or r e q uir e 
h os pit aliz ati o n m a y b e c o nsi d er e d s eri o us w h e n, b as e d u p o n a p pr o pri at e m e dic al j u d g m e nt, t h e y 
m a y j e o p ar diz e t h e p artici p a nt a n d m a y r e q uir e m e dic al or s ur gic al i nt er v e nti o n t o pr e v e nt o n e 
of t h e o utc o m es list e d i n t his d efi niti o n. ( Ex a m pl es of s uc h m e dic al ev e nts i ncl u d e all er gic 
br o nc h os p as m r e q uiri n g i nt e nsi v e tr e at m e nt i n a n e m er g e nc y r o o m or at h o m e, bl o o d d yscr asi as 
or c o n v ulsi o ns t h at d o n ot r es ult i n i n p ati e nt h os pit aliz ati o n, or t h e d ev el o p m e nt of dr u g 
d e p e n d e nc y or dr u g a b us e).
A d v ers e E v e nts ( A Es) f or m ali g n a nt t u m ors r e p ort e d d uri n g a st u d y s h o ul d g e n er all y b e ass ess e d as 
S eri o us A Es. If n o ot h er s eri o us n ess crit eri a a p pl y, t h e ‘I m p ort a nt M e dic al E v e nt’ crit eri o n s h o ul d b e 
us e d. I n c ert ai n sit u ati o ns, h o w ev er, m e dic al j u d g e m e nt o n a n i n di vi d u al e v e nt b asis s h o ul d b e 
a p pli e d t o cl arif y t h at t h e m ali g n a nt t u m or ev e nt s h o ul d b e ass ess e d a n d r e p ort e d as a N o n- S eri o us 
A E. F or ex a m pl e, if t h e t u m or is i ncl u d e d as m e dic al hist or y a n d pr o gr essi o n occ urs d uri n g t h e 
st u d y, b ut t h e pr o gr essi o n d o es n ot c h a n g e tr e at m e nt a n d/ or pr o g n osis of t h e m ali g n a nt t u m or, 
t h e A E m a y n ot f ulfill t h e attri b ut es f or b ei n g ass ess e d as S eri o us, alt h o u g h r e p orti n g of t h e 
pr o gr essi o n of t h e m ali g n a nt t u m or as a n A E is v ali d a n d s h o ul d occ ur. Als o, s o m e t y p es of 
m ali g n a nt t u m ors, w hic h d o n ot s pr e a d r e m ot el y aft er a r o uti n e tr e at m e nt t h at d o es n ot r e q uir e 
h os pit aliz ati o n, m a y b e ass ess e d as N o n- S eri o us; ex a m pl es i ncl u d e St a g e 1 b as al c ell c arci n o m a a n d 
St a g e 1 A 1 c ervic al c a nc er r e m o v e d vi a c o n e bi o ps y. F or st u di es i n E arl y St a g e a n d L at e St a g e 
I m m u n o- O nc ol o g y a n d O nc ol o g y St u di es: T h e a b o v e i nstr ucti o n a p pli es o nl y w h e n t h e m ali g n a nt 
t u m or e v e nt i n q u esti o n is a n e w m ali g n a nt t u m or (i. e., it is n ot t h e t u m or f or w hic h e ntr y i nt o t h e 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
st u d y is a crit eri o n a n d t h at is b ei n g tr e at e d b y t h e I P u n d er st u d y a n d is n ot t h e d e v el o p m e nt of 
n e w or pr o gr essi o n of existi n g m et ast asis t o t h e t u m or u n d er st u d y). M ali g n a nt t u m ors t h at – as 
p art of n or m al, if r ar e, pr o gr essi o n – u n d er g o tr a nsf or m ati o n ( e. g., Ric ht er's tr a nsf or m ati o n of B 
c ell c hr o nic l y m p h oc ytic l e u k e mi a i nt o diff us e l ar g e B c ell l y m p h o m a) s h o ul d n ot b e c o nsi d er e d a 
n e w m ali g n a nt t u m or.
I n a d diti o n t o t h e d efi niti o n a b o v e, a n y s us p ect e d tr a ns missi o n vi a a m e dici n al pr o d uct of a n 
i nf ecti o us a g e nt is als o c o nsi d er e d a n S A E a n d m a y b e s u bj ect t o ex p e dit e d r e p orti n g r e q uir e m e nts 
i n s o m e c o u ntri es. A n y or g a nis m, vir us or i nf ecti o us p articl e (f or ex a m pl e Pri o n Pr ot ei n 
Tr a ns mitti n g Tr a ns missi bl e S p o n gif or m E nc e p h al o p at h y), p at h o g e nic or n o n- p at h o g e nic, is 
c o nsi d er e d a n i nf ecti o us a g e nt.
El e v ati o ns i n li v er bi oc h e mistr y t h at m e et H y’s L a w crit eri a ar e r e p ort e d as S A Es, usi n g t h e i m p ort a nt 
m e dic al e v e nt s eri o us crit eri o n if n o ot h er crit eri a ar e a p plic a bl e.
S p eci al Sit u ati o ns
S p eci al sit u ati o ns ar e ot h er sit u ati o ns of r el ev a nc e f or m o nit ori n g t h e s af et y of Ac ert a/ A Z pr o d ucts a n d 
w hic h m a y or m a y n ot b e ass oci at e d wit h a n A E. T h es e s p eci al sit u ati o ns m ust b e c oll ect e d/r ec ei v e d, 
e v e n if n o A E occ urr e d:

Ex p os ur e t o pr o d uct d uri n g pr e g n a nc y 

Ex p os ur e t o pr o d uct w hilst br e astf e e di n g

O v er d os e

A b us e

Mis us e

Off-l a b el Us e

M e dic ati o n err or

Occ u p ati o n al ex p os ur e

L ac k of effic ac y

Dr u g i nt er acti o ns

U n ex p ect e d b e n efit
Cl assific ati o n of a n A d v ers e E v e nt
S e v erit y of E v e nt
D efi niti o ns f o u n d i n t h e C T C A E v ersi o n 5. 0 will b e us e d f or gr a di n g t h e s e v erit y (i nt e nsit y) of A Es.  T h e 
C T C A E dis pl a ys Gr a d es 1 t hr o u g h 5 wit h u ni q u e cli nic al d escri pti o ns of s e v erit y f or e ac h r ef er e nc e d A E.  
S h o ul d a s u bj ect ex p eri e nc e a n y A E n ot list e d i n t h e C T C A E, t h e f oll o wi n g gr a di n g s yst e m s h o ul d b e us e d 
t o ass ess s e v erit y:

Gr a d e 1 ( Mil d A E) – ex p eri e nc es w hic h ar e us u all y tr a nsi e nt, r e q uiri n g n o s p eci al 
tr e at m e nt, a n d n ot i nt erf eri n g wit h t h e s u bj ect’s d ail y acti viti es

Gr a d e 2 ( M o d er at e A E) – ex p eri e nc es w hic h i ntr o d uc e s o m e l ev el of i nc o n v e ni e nc e or 
c o nc er n t o t h e s u bj ect, a n d w hic h m a y i nt erf er e wit h d ail y acti viti es, b ut ar e us u all y 
a m eli or at e d b y si m pl e t h er a p e utic m e as ur es

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

Gr a d e 3 ( S ev er e A E) – ex p eri e nc es w hic h ar e u n acc e pt a bl e or i nt ol er a bl e, si g nific a ntl y 
i nt err u pt t h e s u bj ect’s us u al d ail y acti vit y, a n d r e q uir e s yst e mic dr u g t h er a p y or ot h er 
tr e at m e nt

Gr a d e 4 (Lif e-t hr e at e ni n g or dis a bli n g A E) – ex p eri e nc es w hic h c a us e t h e s u bj ect t o b e i n 
i m mi n e nt d a n g er of d e at h

Gr a d e 5 ( D e at h r el at e d t o A E) – ex p eri e nc es w hic h r es ult i n s u bj ect d e at h
R el ati o ns hi p t o St u d y I nt erv e nti o n
All a d v ers e e v e nts ( A Es) m ust h a v e t h eir r el ati o ns hi p t o st u d y i nt erv e nti o n ass ess e d b y t h e cli nici a n w h o 
ex a mi n es a n d e v al u at es t h e p artici p a nt b as e d o n t e m p or al r el ati o ns hi p a n d his/ h er cli nic al j u d g m e nt. 
T h e d e gr e e of c ert ai nt y a b o ut c a us alit y will b e gr a d e d usi n g t h e c at e g ori es b el o w. I n a cli nic al tri al, t h e 
st u d y pr o d uct m ust al w a ys b e s us p ect. 
•
D efi nit el y R el at e d – T h er e is cl e ar e vi d e nc e t o s u g g est a c a us al r el ati o ns hi p, a n d ot h er p ossi bl e 
c o ntri b uti n g f act ors c a n b e r ul e d o ut. T h e cli nic al e v e nt, i ncl u di n g a n a b n or m al l a b or at or y t est 
r es ult, occ urs i n a pl a usi bl e ti m e r el ati o ns hi p t o st u d y i nt er v e nti o n a d mi nistr ati o n a n d c a n n ot b e 
ex pl ai n e d b y c o nc urr e nt dis e as e or ot h er dr u gs or c h e mic als. T h e r es p o ns e t o wit h dr a w al of t h e 
st u d y i nt er v e nti o n ( d ec h all e n g e) s h o ul d 
b e cli nic all y 
pl a usi bl e. 
T h e 
ev e nt 
m ust 
b e 
p h ar m ac ol o gic all y or p h e n o m e n ol o gic all y d efi niti v e, wit h us e of a s atisf act or y r ec h all e n g e 
pr oc e d ur e if n ec ess ar y.
•
Pr o b a bl y R el at e d – T h er e is e vi d e nc e t o s u g g est a c a us al r el ati o ns hi p, a n d t h e i nfl u e nc e of ot h er 
f act ors is u nli k el y. T h e cli nic al ev e nt, i ncl u di n g a n a b n or m al l a b or at or y t est r es ult, occ urs wit hi n a 
r e as o n a bl e ti m e aft er a d mi nistr ati o n of t h e st u d y i nt er v e nti o n, is u nli k el y t o b e attri b ut e d t o 
c o nc urr e nt dis e as e or ot h er dr u gs or c h e mic als, a n d f oll o ws a cli nic all y r e as o n a bl e r es p o ns e o n 
wit h dr a w al ( d ec h all e n g e). R ec h all e n g e i nf or m ati o n is n ot r e q uir e d t o f ulfill t his d efi niti o n.
•
P ot e nti all y R el at e d – T h er e is s o m e e vi d e nc e t o s u g g est a c a us al r el ati o ns hi p ( e. g., t h e e v e nt 
occ urr e d wit hi n a r e as o n a bl e ti m e aft er a d mi nistr ati o n of t h e tri al m e dic ati o n). H o w ev er, ot h er 
f act ors m a y h a v e c o ntri b ut e d t o t h e ev e nt ( e. g., t h e p artici p a nt’s cli nic al c o n diti o n, ot h er 
c o nc o mit a nt ev e nts). Alt h o u g h a n A E m a y r at e o nl y as “ p ossi bl y r el at e d” s o o n aft er disc o v er y, it 
c a n b e fl a g g e d as r e q uiri n g m or e i nf or m ati o n a n d l at er b e u p gr a d e d t o “ pr o b a bl y r el at e d” or 
“ d efi nit el y r el at e d”, as a p pr o pri at e.
•
U nli k el y t o b e r el at e d – A cli nic al e v e nt, i ncl u di n g a n a b n or m al l a b or at or y t est r es ult, w h os e 
t e m p or al r el ati o ns hi p t o st u d y i nt er v e nti o n a d mi nistr ati o n 
m a k es a c a us al r el ati o ns hi p 
i m pr o b a bl e ( e. g., t h e e v e nt di d n ot occ ur wit hi n a r e as o n a bl e ti m e aft er a d mi nistr ati o n of t h e 
st u d y i nt er v e nti o n) a n d i n w hic h ot h er dr u gs or c h e mic als or u n d erl yi n g dis e as e pr o vi d es pl a usi bl e 
ex pl a n ati o ns ( e. g., t h e p artici p a nt’s cli nic al c o n diti o n, ot h er c o nc o mit a nt tr e at m e nts).
•
N ot R el at e d – T h e A E is c o m pl et el y i n d e p e n d e nt of st u d y i nt er v e nti o n a d mi nistr ati o n, a n d/ or 
e vi d e nc e exists t h at t h e e v e nt is d efi nit el y r el at e d t o a n ot h er eti ol o g y. T h er e m ust b e a n 
alt er n ati v e, d efi niti v e eti ol o g y d oc u m e nt e d b y t h e cli nici a n.
Pr e g n a nc y
I n v esti g at ors s h o ul d r e p ort all pr e g n a nci es a n d pr e g n a nci es i n t h e p art n ers of s u bj ects t o t h e s u p p orti n g 
S p o ns or wit hi n 2 4 h o urs of t h e a w ar e n ess d at e. T h e Pri nci p al I n v esti g at or s h o ul d r e p ort a n y occ urr e nc es 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
t o t h e I R B a n d t h e i n v esti g at or s h o ul d r e p ort a n y occ urr e nc es t o t h e F D A p er i nstit uti o n al a n d/ or 
r e g ul at or y g ui d eli n es, a n d t o Ac ert a/ A Z p er c o ntr act u al g ui d eli n es. 
A n y u nc o m plic at e d pr e g n a nc y t h at occ urs wit h t h e s u bj ect or wit h t h e p art n er of a tr e at e d s u bj ect 
d uri n g t his st u d y will b e r e p ort e d.  All pr e g n a nci es a n d p art n er pr e g n a nci es t h at ar e i d e ntifi e d d uri n g or 
aft er t his st u d y, w h er ei n t h e esti m at e d d at e of c o nc e pti o n is d et er mi n e d t o h a v e occ urr e d fr o m t h e 
ti m e of c o ns e nt t o 2 d a ys aft er t h e l ast d os e of ac al a br uti ni b or 1 8 m o nt hs aft er t h e l ast d os e of 
o bi n ut uz u m a b will b e r e p ort e d, f oll o w e d t o c o ncl usi o n, a n d t h e o utc o m e r e p ort e d.
S u bj ects s h o ul d b e i nstr uct e d t o i m m e di at el y n otif y t h e i n v esti g at or of a n y pr e g n a nci es.  A n y f e m al e 
s u bj ects r ec ei vi n g st u d y dr u g w h o b ec o m e pr e g n a nt m ust i m m e di at el y disc o nti n u e st u d y dr u gs.  T h e 
i n v esti g at or s h o ul d c o u ns el t h e s u bj ect, disc ussi n g a n y ris ks of c o nti n ui n g t h e pr e g n a nc y a n d a n y 
p ossi bl e eff ects o n t h e f et us.
Pr e g n a nci es i n F e m al e P art n ers of M al e P ati e nts
If t h e f e m al e p art n er of m al e p ati e nts b ec o m e pr e g n a nt w hil e r ec ei vi n g t h e st u d y dr u g or wit hi n 
6 m o nt hs aft er t h e l ast d os e of o bi n ut uz u m a b or 3 0 d a ys aft er t h e l ast d os e of ac al a br uti ni b, w hic h e v er 
is l o n g er, a r e p ort s h o ul d b e c o m pl et e d a n d ex p e diti o usl y s u b mitt e d t o t h e i n v esti g at or. T h e pr e g n a nt 
p art n er will n e e d t o si g n a n A ut h oriz ati o n f or Us e a n d Discl os ur e of Pr e g n a nc y H e alt h I nf or m ati o n t o 
all o w f or f oll o w- u p o n h er pr e g n a nc y.  Aft er t h e a ut h oriz ati o n h as b e e n si g n e d, t h e i n v esti g at or will 
s u b mit a Pr e g n a nc y R e p ort w h e n u p d at e d i nf or m ati o n o n t h e c o urs e a n d o utc o m e of t h e pr e g n a nc y 
b ec o m es a v ail a bl e. 
C o n g e nit al A n o m ali es/ Birt h D ef ects a n d A b orti o ns
A b orti o n, w h et h er acci d e nt al, t h er a p e utic, or s p o nt a n e o us, s h o ul d al w a ys b e cl assifi e d as s eri o us, a n d 
ex p e diti o usl y r e p ort e d as a s eri o us a d v ers e ev e nts. Si mil arl y, a n y c o n g e nit al a n o m al y/ birt h d ef ect i n a 
c hil d b or n t o a f e m al e p ati e nt ex p os e d t o st u d y dr u g or t h e f e m al e p art n er of a m al e p ati e nt ex p os e d t o 
st u d y dr u g s h o ul d b e cl assifi e d as a s eri o us a d v ers e ev e nt.
O v er d os e
Cli nic al i nf or m ati o n r el e v a nt t o o v er d os e is n ot a v ail a bl e. F or r es ults fr o m n o ncli nic al o v er d os e st u di es i n 
r ats a n d d o gs, pl e as e r ef er t o t h e I n v esti g at or Br oc h ur e.
St u d y dr u g o v er d os e is t h e acci d e nt al or i nt e nti o n al us e of t h e dr u g i n a n a m o u nt hi g h er t h a n t h e d os e 
b ei n g st u di e d. A n o v er d os e or i nc orr ect a d mi nistr ati o n of st u d y dr u g is n ot a n A E u nl ess it r es ults i n 
u nt o w ar d m e dic al eff ects.
A n y st u d y dr u g o v er d os e or i nc orr ect a d mi nistr ati o n of st u d y dr u g s h o ul d b e n ot e d o n t h e a p pr o pri at e 
C R F.
All A Es ass oci at e d wit h a n o v er d os e or i nc orr ect a d mi nistr ati o n of st u d y dr u g s h o ul d b e r ec or d e d o n t h e 
C R F.   
If t h e ass oci at e d A E f ulfills s eri o us crit eri a, I n v esti g at ors s h o ul d r e p ort t h e ev e nt t o t h e s u p p orti n g 
S p o ns or wit hi n 2 4 h o urs usi n g t h e S A E r e p orti n g f or m. T h e Pri nci p al I n v esti g at or s h o ul d r e p ort a n y S A Es 
t o t h e I R B a n d t o t h e F D A p er i nstit uti o n al a n d/ or r e g ul at or y g ui d eli n es, a n d t o Ac ert a/ A Z p er 
c o ntr act u al g ui d eli n es.
Ac al a br uti ni b

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 5 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
I n t h e e v e nt of s u bj ect i n g esti o n of m or e t h a n t h e r ec o m m e n d e d ac al a br uti ni b d os a g e, o bs erv ati o n f or 
a n y s y m pt o m atic si d e eff ects s h o ul d b e i nstit ut e d, a n d vit al si g ns, bi oc h e mic al a n d h e m at ol o gic 
p ar a m et ers s h o ul d b e f oll o w e d cl os el y (c o nsist e nt wit h t h e pr ot oc ol or m or e fr e q u e ntl y, as n e e d e d).  
A p pr o pri at e s u p p orti v e m a n a g e m e nt t o miti g at e a d v ers e eff ects s h o ul d b e i niti at e d.  If t h e o v er d os e 
i n g esti o n of ac al a br uti ni b is r ec e nt a n d s u bst a nti al, a n d if t h er e ar e n o m e dic al c o ntr ai n dic ati o ns, us e of 
g astric l a v a g e or i n d ucti o n of e m esis m a y b e c o nsi d er e d.
O bi n ut uz u m a b
T h er e h as b e e n n o ex p eri e nc e wit h o v er d os e i n h u m a n cli nic al tri als. F or p ati e nts w h o ex p eri e nc e 
o v er d os e, tr e at m e nt s h o ul d c o nsist of i m m e di at e i nt err u pti o n or r e d ucti o n of o bi n ut uz u m a b a n d 
s u p p orti v e t h er a p y.
A d v ers e E v e nt a n d S eri o us A d v ers e E v e nt R e p orti n g 
T h e i n v esti g at or is r es p o nsi bl e f or e ns uri n g t h at all A Es, S A Es, a n d S p eci al Sit u ati o ns t h at ar e o bs er v e d or 
r e p ort e d d uri n g t h e st u d y, as o utli n e d i n t h e pri or s ecti o ns, ar e r ec or d e d o n t h e C R F. 
As d escri b e d i n S ecti o n 5. 8, t h e P R O- C T C A E d at a is us e d f or r es e arc h p ur p os es o nl y a n d will n ot b e us e d 
f or t h e c oll ecti o n a n d r e p orti n g of A Es. St u d y st aff m ust cl e arl y c o n v e y t o t h e p ati e nt t h at t h e 
i nf or m ati o n r e g ar di n g s y m pt o ms c oll ect e d b y t h e P R O- C T C A E ar e n ot m o nit or e d b y a p h ysici a n a n d t h e 
p ati e nt m ust c o nt act t h e cli nic al t e a m dir ectl y f or a n y c o nc er ni n g s y m pt o ms. I n c as es w h er e a s elf-
i d e ntifi e d A E o n t h e P R O- C T C A E is e v al u at e d b y t h e cli nic al t e a m, t h e gr a d e a n d attri b uti o n c a n b e 
ass ess b y c o n v e nti o n al m et h o ds as d escri b e d i n t his s ecti o n.
Ex p ect e d n ess 
Pri nci p al I n v esti g at or will b e r es p o nsi bl e f or d et er mi ni n g w h et h er a n a d v ers e ev e nt ( A E) is ex p ect e d or 
u n ex p ect e d.  A n A E will b e c o nsi d er e d u n ex p ect e d if t h e n at ur e, s ev erit y, or fr e q u e nc y of t h e e v e nt is n ot 
c o nsist e nt wit h t h e ris k i nf or m ati o n pr e vi o usl y d escri b e d f or t h e st u d y i nt erv e nti o n.
A d v ers e E v e nt R e p orti n g 
Fr o m t h e ti m e of tr e at m e nt all oc ati o n/r a n d o miz ati o n t hr o u g h 3 0 d a ys f oll o wi n g c ess ati o n of tr e at m e nt 
or at d oc u m e nt e d dis e as e pr o gr essi o n ( w hic h e v er is l o n g er), all a d v ers e ev e nts, t h at b e gi n or w ors e n aft er 
i nf or m e d c o ns e nt, m ust b e r ec or d e d  b y t h e i n v esti g at or or d esi g n e e at e ac h ex a mi n ati o n o n t h e A d v ers e 
E v e nt c as e r e p ort f or ms/ w or ks h e ets.  
T h e i n v esti g at or will m a k e e v er y att e m pt t o f oll o w all s u bj ects wit h n o n-s eri o us a d v ers e e v e nts f or 
o utc o m e.
C o n diti o ns t h at w er e alr e a d y pr es e nt at t h e ti m e of i nf or m e d c o ns e nt s h o ul d b e r ec or d e d i n t h e M e dic al 
Hist or y p a g e of t h e p ati e nt’s C R F/ w or ks h e et.
A d v ers e e v e nts will b e ass ess e d a n d gr a d e d acc or di n g t o t h e C o m m o n T er mi n ol o g y Crit eri a f or A d v ers e 
E v e nts ( C T C A E) v ersi o n 5. 0. Gr a d e 1 t o 5 will b e us e d t o c h ar act eriz e t h e s e v erit y of t h e A d v ers e E v e nt. 
If C T C A E gr a di n g d o es n ot exist f or a n a d v ers e e v e nt, t h e s e v erit y of mil d, m o d er at e, s e v er e, a n d lif e-
t hr e at e ni n g, d e at h r el at e d t o t h e A E c orr es p o n di n g r es p ecti v el y t o Gr a d es 1 - 5, will b e us e d. I nf or m ati o n 
a b o ut a n y d e at hs (r el at e d t o a n A d v ers e E v e nt or n ot) will als o b e c oll ect e d t hr o u g h a D e at h f or m ( or 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
E O T/ S E C/ S ur vi v al I nf or m ati o n i n N O V D D). T h e occ urr e nc e of a d v ers e ev e nts s h o ul d b e s o u g ht b y n o n-
dir ecti v e q u esti o ni n g of t h e p ati e nt ( p ati e nt) d uri n g t h e scr e e ni n g pr oc ess aft er si g ni n g i nf or m e d c o ns e nt 
a n d at e ac h visit d uri n g t h e st u d y. A d v ers e e v e nts als o m a y b e d et ect e d w h e n t h e y ar e v ol u nt e er e d b y 
t h e p ati e nt ( p ati e nt) d uri n g t h e scr e e ni n g pr oc ess or b et w e e n visits, or t hr o u g h p h ysic al ex a mi n ati o n, 
l a b or at or y t est, or ot h er ass ess m e nts. As f ar as p ossi bl e, e ac h a d v ers e e v e nt s h o ul d b e e v al u at e d t o 
d et er mi n e: 
1. T h e s e v erit y gr a d e ( C T C A E Gr a d e 1- 5) 
2. Its d ur ati o n ( St art a n d e n d d at es)  
3. Its r el ati o ns hi p t o t h e st u d y tr e at m e nt ( R e as o n a bl e p ossi bilit y t h at A E is r el at e d: N o, Y es) or Its 
r el ati o ns hi p t o t h e st u d y tr e at m e nt ( R e as o n a bl e p ossi bilit y t h at A E is r el at e d: N o, Y es, i n v esti g ati o n al 
tr e at m e nt, Y es, t h e st u d y tr e at m e nt ( n o n-i n v esti g ati o n al), Y es, b ot h a n d/ or i n disti n g uis h a bl e) 
4. Acti o n t a k e n wit h r es p ect t o st u d y or i n v esti g ati o n al tr e at m e nt ( n o n e, d os e a dj ust e d, t e m p or aril y 
i nt err u pt e d, p er m a n e ntl y disc o nti n u e d, u n k n o w n, n ot a p plic a bl e) 
5. W h et h er m e dic ati o n or t h er a p y w as gi v e n ( n o c o nc o mit a nt m e dic ati o n/ n o n- dr u g t h er a p y, c o nc o mit a nt 
m e dic ati o n/ n o n- dr u g t h er a p y) 
6. W h et h er it is s eri o us, w h er e a s eri o us a d v ers e e v e nt ( S A E) is d efi n e d as i n S ecti o n 9. 2 a n d w hic h 
s eri o us n ess crit eri a h a v e b e e n m et (i ncl u d e f or N C D S tri als).
7. O utc o m e ( n ot r ec o v er e d/ n ot r es ol v e d, r ec o v er e d/r es ol v e d, r ec o v eri n g/r es ol vi n g, r ec o v er e d/r es ol v e d 
wit h s e q u el a e, f at al, u n k n o w n)  
 
If t h e e v e nt w ors e ns t h e ev e nt s h o ul d b e r e p ort e d a s ec o n d ti m e i n t h e C R F n oti n g t h e st art d at e w h e n 
t h e e v e nt w ors e ns i n t oxicit y. F or gr a d e 3 a n d 4 a d v ers e e v e nts o nl y, if i m pr o v e m e nt t o a l o w er gr a d e is 
d et er mi n e d a n e w e ntr y f or t his e v e nt s h o ul d b e r e p ort e d i n t h e C R F n oti n g t h e st art d at e w h e n t h e e v e nt 
i m pr o v e d fr o m h a vi n g b e e n Gr a d e 3 or Gr a d e 4.   F or p h as e I st u di es a n y A E t h at c o nstit ut es a DL T s h o ul d 
b e r e p ort e d li k e a gr a d e 3 a n d 4 a d v ers e e v e nt.  All a d v ers e ev e nts s h o ul d b e tr e at e d a p pr o pri at el y. If a 
c o nc o mit a nt m e dic ati o n or n o n- dr u g t h er a p y is gi v e n, t his acti o n s h o ul d b e r ec or d e d o n t h e A d v ers e E v e nt 
C R F.
O nc e a n a d v ers e e v e nt is d et ect e d, it s h o ul d b e f oll o w e d u ntil its r es ol uti o n or u ntil it is j u d g e d t o b e 
p er m a n e nt, a n d ass ess m e nt s h o ul d b e m a d e at e ac h visit ( or m or e fr e q u e ntl y, if n ec ess ar y) of a n y c h a n g es 
i n s e v erit y, t h e s us p ect e d r el ati o ns hi p t o t h e st u d y tr e at m e nt, t h e i nt er v e nti o ns r e q uir e d t o tr e at it, a n d 
t h e o utc o m e. Pr o gr essi o n of m ali g n a nc y (i ncl u di n g f at al o utc o m es), if d oc u m e nt e d b y us e of a p pr o pri at e 
m et h o d (f or ex a m pl e, as p er R E CI S T crit eri a f or s oli d t u m ors), s h o ul d n ot b e r e p ort e d as a s eri o us a d v ers e 
e v e nt. 
A d v ers e e v e nts s e p ar at e fr o m t h e pr o gr essi o n of m ali g n a nc y ( ex a m pl e, d e e p v ei n t hr o m b osis at t h e ti m e 
of pr o gr essi o n or h e m o pt ysis c o nc urr e nt wit h fi n di n g of dis e as e pr o gr essi o n) will b e r e p ort e d as p er us u al 
g ui d eli n es us e d f or s uc h e v e nts wit h pr o p er attri b uti o n r e g ar di n g r el at e d n ess t o t h e dr u g.
L a b or at or y a b n or m aliti es t h at c o nstit ut e a n A d v ers e e v e nt i n t h eir o w n ri g ht ( ar e c o nsi d er e d cli nic all y 
si g nific a nt, i n d uc e cli nic al si g ns or s y m pt o ms, r e q uir e c o nc o mit a nt t h er a p y or r e q uir e c h a n g es i n st u d y 
tr e at m e nt), s h o ul d b e r ec or d e d o n t h e A d v ers e E v e nts C R F.
L a b or at or y a b n or m aliti es, t h at d o n ot m e et t h e d efi niti o n of a n a d v ers e ev e nt, s h o ul d n ot b e r e p ort e d as 
a d v ers e e v e nts. A Gr a d e 3 or 4 ev e nt (s ev er e) as p er C T C A E d o es n ot a ut o m atic all y i n dic at e a S A E u nl ess 
it m e ets t h e d efi niti o n of s eri o us as d efi n e d b el o w a n d/ or as p er i n v esti g at or’s discr eti o n. A d os e h ol d or 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
m e dic ati o n f or t h e l a b a b n or m alit y m a y b e r e q uir e d b y t h e pr ot oc ol i n w hic h c as e t h e l a b a b n or m alit y 
w o ul d still, b y d efi niti o n, b e a n a d v ers e ev e nt a n d m ust b e r e p ort e d as s uc h.
S eri o us A d v ers e E v e nt R e p orti n g 
F or t h e ti m e p eri o d b e gi n ni n g wit h tr e at m e nt i niti ati o n t hr o u g h 3 0 d a ys f oll o wi n g c ess ati o n of tr e at m e nt, 
or u ntil s u bj ect i niti at es n e w a ntic a nc er t h er a p y, w hic h ev er is e arli er. A n y s eri o us a d v ers e ev e nt, or f oll o w 
u p t o a s eri o us a d v ers e e v e nt, i ncl u di n g d e at h d u e t o a n y c a us e w h et h er or n ot r el at e d t o t h e st u d y dr u g, 
m ust b e s u b mitt e d o n a n S A E f or m a n d ass ess e d b y PI i n or d er t o d et er mi n e r e p orti n g crit eri a t o 
r e g ul at or y a ut h oriti es, I R B, D S M C, or F D A .
All S A Es will b e f oll o w e d u ntil s atisf act or y r es ol uti o n or u ntil t h e sit e i n v esti g at or d e e ms t h e ev e nt t o b e 
c hr o nic or t h e a d h er e nc e t o b e st a bl e. Ot h er s u p p orti n g d oc u m e nt ati o n of t h e e v e nt m a y b e r e q u est e d 
b y t h e st u d y PI a n d s h o ul d b e pr o vi d e d as s o o n as p ossi bl e. All s u bj ects wit h s eri o us a d v ers e ev e nts m ust 
b e f oll o w e d u p f or o utc o m e.
A n y a d diti o n al i nf or m ati o n f or t h e S A E i ncl u di n g c o m plic ati o ns, pr o gr essi o n of t h e i niti al S A E, a n d 
r ec urr e nt e pis o d es m ust b e r e p ort e d as f oll o w- u p t o t h e ori gi n al e pis o d e. A n S A E occ urri n g at a diff er e nt 
ti m e i nt er v al or ot h er wis e c o nsi d er e d c o m pl et el y u nr el at e d t o a pr e vi o usl y r e p ort e d o n e s h o ul d b e 
r e p ort e d s e p ar at el y as a n e w ev e nt. A n y S A Es ex p eri e nc e d aft er t h e r e p orti n g p eri o d d escri b e d a b o v e 
s h o ul d o nl y b e r e p ort e d t o F D A/I R B if t h e i n v esti g at or s us p ects a c a us al r el ati o ns hi p t o t h e st u d y 
tr e at m e nt.
I nf or m ati o n a b o ut all S A Es is c oll ect e d a n d r ec or d e d o n t h e S eri o us A d v ers e E v e nt R e p ort F or m; all 
a p plic a bl e s ecti o ns of t h e f or m m ust b e c o m pl et e d i n or d er t o pr o vi d e a cli nic all y t h or o u g h r e p ort. T h e 
i n v esti g at or m ust ass ess a n d r ec or d t h e r el ati o ns hi p of e ac h S A E t o e ac h s p ecific st u d y tr e at m e nt (if t h er e 
is m or e t h a n o n e st u d y tr e at m e nt), c o m pl et e t h e S A E R e p ort F or m, a n d s u b mit t h e c o m pl et e d f or m. E ac h 
r e occ urr e nc e, c o m plic ati o n, or pr o gr essi o n of t h e ori gi n al ev e nt s h o ul d b e r e p ort e d as a f oll o w- u p t o t h at 
e v e nt r e g ar dl ess of w h e n it occ urs. T h e f oll o w- u p i nf or m ati o n s h o ul d d escri b e w h et h er t h e ev e nt h as 
r es ol v e d or c o nti n u es, if a n d h o w it w as tr e at e d, w h et h er t h e bli n d w as br o k e n or n ot, a n d w h et h er t h e 
p ati e nt c o nti n u e d or wit h dr e w fr o m st u d y p artici p ati o n.
All S A Es, s ec o n d ar y m ali g n a nci es, Pr e g n a nc y, O v er d os e a n d ot h er S p eci al Sit u ati o n r e p orts, A d v ers e 
E v e nts of S p eci al I nt er est a n d H y’s L a w r e p orts ar e t o b e s u b mitt e d t o t h e Astr a Z e n ec a Pr o d uct S af et y 
m ail b o x: A E M ail b ox Cli nic al Tri al T C S @ astr az e n ec a.c o m
S ec o n d a n d s ec o n d ar y m ali g n a nc y
A s ec o n d ary m ali g n a ncy is a c a nc er c a us e d b y tr e at m e nt f or a pr e vi o us m ali g n a nc y (e. g. , tr e at m e nt wit h 
i n v esti g ati o n al a g e nt/i nt erv e nti o n, r a di ati o n or c h e m ot h er a p y). A s ec o n d ar y m ali g n a nc y is n ot c o nsi d er e d 
a m et ast asis of t h e i niti al n e o pl as m. 
All s ec o n d ar y m ali g n a nci es t h at occ ur f oll o wi n g tr e at m e nt wit h a n a g e nt u n d er a n I N D/I D E m ust b e 
r e p ort e d t hr o u g h O N C O R E.  
T hr e e o pti o ns ar e a v ail a bl e t o d escri b e t h e ev e nt: 

L e u k e mi a s ec o n d ar y t o o nc ol o g y c h e m ot h er a p y ( e. g. , ac ut e m y el oc ytic l e u k e mi a [ A ML]) 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

M y el o d ys pl astic s y n dr o m e ( M D S) 

Tr e at m e nt-r el at e d s ec o n d ar y m ali g n a nc y 
A n y m ali g n a nc y p ossi bl y r el at e d t o c a nc er tr e at m e nt (i ncl u di n g A ML/ M D S) s h o ul d als o b e r e p ort e d vi a 
t h e r o uti n e r e p orti n g m ec h a nis ms o utli n e d i n e ac h pr ot oc ol.
A s ec o n d m ali g n a nc y is o n e u nr el at e d t o t h e tr e at m e nt of a pri or m ali g n a nc y ( a n d is N O T a m et ast asis 
fr o m t h e i niti al m ali g n a nc y).  
D efi niti o n of u n a ntici p at e d pr o bl e ms ( U P) a n d r e p orti n g r e q uir e m e nts
T h e Offic e f or H u m a n R es e arc h Pr ot ecti o ns ( O H R P) c o nsi d ers u n a ntici p at e d pr o bl e ms i n v ol vi n g ris ks t o 
p artici p a nts or ot h ers t o i ncl u d e, i n g e n er al, a n y i nci d e nt, ex p eri e nc e, or a n o utc o m e t h at m e ets all  t h e 
f oll o wi n g crit eri a:  U n ex p ect e d i n t er ms of n at ur e, s ev erit y, or fr e q u e nc y gi v e n ( a) t h e r es e arc h pr oc e d ur es 
t h at ar e d escri b e d i n t h e pr ot oc ol-r el at e d d oc u m e nts, s uc h as t h e I R B- a p pr o v e d r es e arc h pr ot oc ol a n d 
i nf or m e d c o ns e nt d oc u m e nt; a n d ( b) t h e c h ar act eristics of t h e p artici p a nt p o p ul ati o n b ei n g st u di e d; 
R el at e d or p ossi bl y r el at e d t o p artici p ati o n i n t h e r es e arc h (“ p ossi bl y r el at e d” m e a ns t h er e is a r e as o n a bl e 
p ossi bilit y t h at t h e i nci d e nt, ex p eri e nc e, or o utc o m e m a y h a v e b e e n c a us e d b y t h e pr oc e d ur es i n v ol v e d 
i n t h e r es e arc h); a n d S u g g ests t h at t h e r es e arc h pl ac es p artici p a nts or ot h ers at a gr e at er ris k of h ar m 
(i ncl u di n g p h ysic al, ps yc h ol o gic al, ec o n o mic, or s oci al h ar m) t h a n w as pr e vi o usl y k n o w n or r ec o g niz e d.  
T his st u d y will us e t h e O H R P d efi niti o n of u n a ntici p at e d pr o bl e ms. I nci d e nts or e v e nts t h at m e et t h e O H R P 
crit eri a f or U Ps r e q uir e t h e cr e ati o n a n d c o m pl eti o n of a U P r e p ort f or m. It is t h e sit e i n v esti g at or’s 
r es p o nsi bilit y t o r e p ort U Ps t o t h eir I R B a n d t o t h e D C C/st u d y s p o ns or. T h e U P r e p ort will i ncl u d e t h e 
f oll o wi n g i nf or m ati o n:  Pr ot oc ol i d e ntif yi n g i nf or m ati o n: pr ot oc ol titl e a n d n u m b er, PI’s n a m e, a n d t h e 
I R B pr oj ect n u m b er; A d et ail e d d escri pti o n of t h e e v e nt, i nci d e nt, ex p eri e nc e, or o utc o m e; A n ex pl a n ati o n 
of t h e b asis f or d et er mi ni n g t h at t h e e v e nt, i nci d e nt, ex p eri e nc e, or o utc o m e r e pr es e nts a n U P; A 
d escri pti o n of a n y c h a n g es t o t h e pr ot oc ol or ot h er c orr ecti v e acti o ns t h at h a v e b e e n t a k e n or ar e 
pr o p os e d i n r es p o ns e t o t h e U P.  T h e i n v esti g at or will m a k e a n ass ess m e nt of w h et h er t h e e v e nt 
c o nstit ut es a n u n a ntici p at e d pr o bl e m p osi n g ris ks t o s u bj ects or ot h ers ( U P). T his ass ess m e nt will b e 
pr o vi d e d t o t h e E m or y U ni v ersit y I R B.  If t h e E m or y I R B d et er mi n es a n ev e nt is a U P it will n otif y t h e 
a p pr o pri at e r e g ul at or y a g e nci es a n d i nstit uti o n al offici als. 
T h e D at a a n d S af et y M o nit ori n g C o m mitt e e ( D S M C)
T h e D at a a n d S af et y M o nit ori n g C o m mitt e e ( D S M C) of t h e Wi ns hi p C a nc er I nstit ut e will pr o vi d e o v ersi g ht 
f or t h e c o n d uct of t his st u d y. T h e D S M C f u ncti o ns i n d e p e n d e ntl y wit hi n Wi ns hi p C a nc er I nstit ut e t o 
c o n d uct i nt er n al m o nit ori n g f u ncti o ns t o e ns ur e t h at r es e arc h b ei n g c o n d uct e d b y 
Wi ns hi p C a nc er 
I nstit ut e I n v esti g at ors pr o d uc es hi g h- q u alit y sci e ntific d at a i n a m a n n er c o nsist e nt wit h g o o d cli nic al 
pr actic e ( G C P) a n d a p pr o pri at e r e g ul ati o ns t h at g o v er n cli nic al r es e arc h. D e p e n di n g o n t h e ris k l ev el of 
t h e pr ot oc ol as d et er mi n e d b y C T R C, t h e D S M C r e vi e w m a y occ ur e v er y 6 m o nt hs or a n n u all y. F or st u di es 
d e e m e d Hi g h Ris k, i niti al st u d y m o nit ori n g will occ ur wit hi n 6 m o nt hs fr o m t h e d at e of t h e first s u bj ect 
accr u e d, wit h 2 of t h e first 5 s u bj ects b ei n g r e vi e w e d. F or st u di es d e e m e d M o d er at e Ris k, i niti al st u d y 
m o nit ori n g will occ ur wit hi n 1 y e ar fr o m t h e d at e of t h e first s u bj ect accr u e d, wit h 2 of t h e first 5 s u bj ects 
b ei n g r e vi e w e d. S u bs e q u e nt m o nit ori n g will occ ur i n r o uti n e i nt erv als p er t h e Wi ns hi p D at a a n d S af et y 
M o nit ori n g Pl a n ( D S M P).  T h e D S M C will r e vi e w p erti n e nt as p ects of t h e st u d y t o ass ess s u bj ect s af et y, 
c o m pli a nc e wit h t h e pr ot oc ol, d at a c oll ecti o n, a n d ris k- b e n efit r ati o. S p ecific all y, t h e Wi ns hi p C a nc er 
I nstit ut e I nt er n al M o nit ors assi g n e d t o t h e D S M C m a y v erif y i nf or m e d c o ns e nt, eli gi bilit y, d at a e ntr y, 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
acc ur ac y a n d a v ail a bilit y of s o urc e d oc u m e nts, A Es/ S A Es, a n d ess e nti al r e g ul at or y d oc u m e nts. F oll o wi n g 
t h e m o nit ori n g r evi e w, m o nit ors will pr o vi d e a pr eli mi n ar y r e p ort of m o nit ori n g fi n di n gs t o t h e PI a n d 
ot h er p erti n e nt i n di vi d u als i n v ol v e d i n t h e c o n d uct of t h e st u d y. T h e PI is r e q uir e d t o a d dr ess a n d r es p o n d 
t o all t h e d efici e nci es n ot e d i n t h e pr eli mi n ar y r e p ort. Pri or t o t h e c o m pl eti o n of t h e fi n al s u m m ar y r e p ort, 
m o nit ors will disc uss t h e pr eli mi n ar y r e p ort r es p o ns es wit h t h e PI a n d ot h er t e a m m e m b ers ( w h e n 
a p pr o pri at e). A fi n al m o nit ori n g s u m m ar y r e p ort will t h e n b e pr e p ar e d b y t h e m o nit or. Fi n al D S M C r e vi e w 
will i ncl u d e t h e fi n al m o nit ori n g s u m m ar y r e p ort wit h c orr es p o n di n g PI r es p o ns e, s u b mitt e d C A P A ( w h e n 
a p plic a bl e), PI S u m m ar y st at e m e nt, a n d a v ail a bl e a g gr e g at e t oxicit y a n d s af et y d at a.  T h e D S M C will 
r e n d er a r ec o m m e n d ati o n a n d r ati n g b as e d o n t h e o v er all tri al c o n d uct. T h e PI is r es p o nsi bl e f or e ns uri n g 
t h at i nst a nc es of e gr e gi o us d at a i ns uffici e nci es ar e r e p ort e d t o t h e I R B. C o nti n ui n g R e vi e w s u b missi o ns 
will i ncl u d e t h e D S M C r ec o m m e n d ati o n l ett er. S h o ul d a n y r evisi o ns b e m a d e t o t h e pr ot oc ol-s p ecific 
m o nit ori n g pl a n aft er i niti al D S M C a p pr o v al, t h e PI will b e r es p o nsi bl e f or n otif yi n g t h e D S M C of s uc h 
c h a n g es. T h e C o m mitt e e r es erv es t h e ri g ht t o c o n d uct a d diti o n al a u dits if n ec ess ar y.  
1 7.  Pr o visi o ns t o Pr ot ect t h e Pri v ac y I nt er ests of P artici p a nts
P artici p a nts will b e ass ur e d of t h eir v ol u nt ar y p artici p ati o n i n t h e st u d y, t h eir c h oic e t o a ns w er or n ot 
a ns w er a n y q u esti o n, a n d t h e pr ot oc ol f or m ai nt ai ni n g c o nfi d e nti alit y.
P artici p a nt c o nfi d e nti alit y is strictl y h el d i n tr ust by t h e p artici p ati n g i n v esti g at ors, t h eir st aff, a n d t h e 
s p o ns or(s) a n d t h eir a g e nts. T his c o nfi d e nti alit y is ext e n d e d t o c o v er t esti n g of bi ol o gic al s a m pl es a n d 
g e n etic t ests i n a d diti o n t o t h e cli nic al i nf or m ati o n r el ati n g t o p artici p a nts. T h er ef or e, t h e st u d y pr ot oc ol, 
d oc u m e nt ati o n, d at a, a n d all ot h er i nf or m ati o n g e n er at e d will b e h el d i n strict c o nfi d e nc e. N o 
i nf or m ati o n c o nc er ni n g t h e st u d y or t h e d at a will b e r el e as e d t o a n y u n a ut h oriz e d t hir d p art y wit h o ut 
pri or writt e n a p pr o v al of t h e s p o ns or.
T h e st u d y m o nit or, ot h er a ut h oriz e d r e pr es e nt ati v es of t h e s p o ns or, r e pr es e nt ati v es of t h e I R B or 
p h ar m ac e utic al c o m p a n y s u p pl yi n g st u d y pr o d uct m a y i ns p ect all d oc u m e nts a n d r ec or ds r e q uir e d t o b e 
m ai nt ai n e d by t h e i n v esti g at or, i ncl u di n g b ut n ot li mit e d t o, m e dic al r ec or ds ( offic e, cli nic, or h os pit al) 
a n d p h ar m ac y r ec or ds f or t h e p artici p a nts i n t his st u d y. T h e cli nic al st u dy sit e will p er mit acc ess t o s uc h 
r ec or ds.
T h e st u d y p artici p a nt’s c o nt act i nf or m ati o n will b e s ec ur el y st or e d at e ac h cli nic al sit e f or i nt er n al us e 
d uri n g t h e st u d y. At t h e e n d of t h e st u d y, all r ec or ds will c o nti n u e t o b e k e pt i n a s ec ur e l oc ati o n f or as 
l o n g a p eri o d as dict at e d b y l oc al I R B a n d I nstit uti o n al r e g ul ati o ns.
St u d y p artici p a nt r es e arc h d at a, w hic h is f or p ur p os es of st atistic al a n al ysis a n d sci e ntific r e p orti n g, will 
b e tr a ns mitt e d t o a n d st or e d. T his will n ot i ncl u d e t h e p artici p a nt’s c o nt act or i d e ntif yi n g i nf or m ati o n. 
R at h er, i n di vi d u al p artici p a nts a n d t h eir r es e arc h d at a 
will b e i d e ntifi e d b y a u ni q u e st u d y i d e ntific ati o n 
n u m b er. T h e st u dy d at a e ntr y a n d st u d y m a n a g e m e nt s yst e ms us e d b y cli nic al sit es a n d r es e arc h st aff 
will b e s ec ur e d a n d p ass w or d pr ot ect e d. At t h e e n d of t h e st u d y, all st u dy d at a b as es will b e d e-i d e ntifi e d 
a n d arc hi v e d.
1 8.   Ec o n o mic B ur d e n t o P artici p a nts
T h e st u d y s p o ns or will p a y f or c ert ai n it e ms a n d s er vic es t h e s u bj ect m a y r ec ei v e i n t his st u d y.  S u bj ects 
will h a v e t o p a y f or t h e it e ms or s er vic es f or w hic h t h e st u d y s p o ns or d o es n ot p a y. T h e s p o ns or will n ot 
p a y f or r e g ul ar m e dic al c ar e. If s u bj ects h a v e i ns ur a nc e, E m or y will s u b mit cl ai ms t o t h e i ns ur a nc e f or 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
it e ms a n d s er vic es t h at t h e s p o ns or d o es n ot c o v er.  E m or y will s e n d i n o nl y t h os e cl ai ms f or it e ms a n d 
s er vic es t h at it r e as o n a bl y b eli ev es t h e i ns ur a nc e will p a y a n d t h at t h e s p o ns or h as n ot p ai d. T h e act u al 
a m o u nt t h at p artici p a nts h a v e t o p a y d e p e n ds o n w h et h er or n ot t h e y h a v e h e alt h i ns ur a nc e a n d 
w h et h er or n ot t h at i ns ur a nc e will p a y f or a n y r es e arc h st u d y c osts. G e n er all y, i ns ur a nc e c o m p a ni es will 
n ot p a y f or it e ms a n d s er vic es t h at ar e r e q uir e d j ust f or a r es e arc h st u d y. S o m e i ns ur a nc e c o m p a ni es will 
n ot p a y f or r e g ul ar m e dic al tr e at m e nt or tr e at m e nt f or c o m plic ati o ns if i n a st u d y.  If s u bj ect d o n ot h a v e 
i ns ur a nc e, E m or y will r e vi e w t h at p artic ul ar c as e as p art of its pr o gr a m f or l o w-i nc o m e p ati e nt c ar e.  T h e 
st a n d ar d p olici es of t h at pr o gr a m will a p pl y.  T h e pr o gr a m will fi g ur e o ut if s u bj ects h a v e t o p a y a n y c osts 
f or t a ki n g p art i n t h e st u d y a n d w h at t h os e c osts will b e
1 9.  C o ns e nt Pr oc ess
T h e i niti al i nf or m e d c o ns e nt disc ussi o n will occ ur i n Wi ns hi p C a nc er I nstit ut e or t h e E m or y Cli nic.
At Wi ns hi p C a nc er I nstit ut e, t h e i nf or m e d c o ns e nt is a n o n g oi n g, i nt er acti v e pr oc ess r at h er t h a n a o n e-
ti m e i nf or m ati o n s essi o n. T h e c o ns e nt f or m d oc u m e nt is d esi g n e d t o b e gi n t h e i nf or m e d c o ns e nt pr oc ess, 
w hic h pr o vi d es t h e p ati e nt wit h o n g oi n g ex pl a n ati o ns t h at will h el p t h e m m a k e e d uc ati o n al d ecisi o ns 
a b o ut w h et h er t o b e gi n or c o nti n u e p artici p ati n g i n t h e tri al. T h e r es e arc h t e a m k n o ws t h at a writt e n 
d oc u m e nt al o n e m a y n ot e ns ur e t h at t h e p ati e nt f ull y u n d erst a n ds w h at p artici p ati o n m e a ns. T h er ef or e, 
t h e r es e arc h t e a m will disc uss wit h t h e p ati e nt t h e tri al's p ur p os e, pr oc e d ur es, ris ks a n d p ot e nti al b e n efits, 
a n d t h eir ri g hts as a p artici p a nt. T h e t e a m will c o nti n u e t o u p d at e t h e p ati e nt o n a n y n e w i nf or m ati o n 
t h at m a y aff ect t h eir sit u ati o n.
C o ns e nt will b e o bt ai n e d pri or t o a n y r es e arc h- dri v e n pr oc e d ur es. T h e i n v esti g at or will ass ess t h e p ati e nt’s 
c a p acit y d uri n g his/ h er e nc o u nt ers wit h hi m or h er. T h e i n v esti g at or will gi v e t h e p ers o n pr o vi di n g c o ns e nt 
a d e q u at e o p p ort u nit y t o r e a d t h e c o ns e nt d oc u m e nt b ef or e it is si g n e d a n d d at e d.
It will b e ex pl ai n e d t o pr os p ecti v e p artici p a nts t h at t h e st u d y i n v ol v es r es e arc h, t h e p ur p os e of t h e 
r es e arc h, t h e ex p ect e d d ur ati o n of p artici p ati o n, as w ell as t h e a p pr oxi m at e n u m b er of p artici p a nts t o b e 
e nr oll e d. T h e st u d y pr oc e d ur es, a n d i d e ntific ati o n of r es e arc h pr oc e d ur es v. n o n-r es e arc h will als o b e 
t h or o u g hl y disc uss e d. It will b e ex pl ai n e d t o p artici p a nts t h at p artici p ati o n is v ol u nt ar y a n d t h at t h e 
s u bj ect m a y disc o nti n u e at a n y ti m e.
R ef us al t o p artici p at e or wit h dr a w will n ot i n v ol v e a p e n alt y or l oss of b e n efits t o w hic h t h e p artici p a nt is 
ot h er wis e e ntitl e d. R ef us al will i n n o w a y aff ect t h e p artici p a nt's f ut ur e ar e. T h e p artici p a nt will als o b e 
t ol d of t h e p ossi bl e c o ns e q u e nc es of t h e d ecisi o n t o wit h dr a w fr o m t h e r es e arc h, a n d pr oc e d ur es f or 
or d erl y t er mi n ati o n of p artici p ati o n.
A n y si g nific a nt n e w fi n di n gs d ev el o p e d d uri n g t h e c o urs e of t h e r es e arc h t h at m a y aff ect t h e p artici p a nt's 
willi n g n ess t o c o nti n u e t o p artici p at e will b e pr o vi d e d. Als o ex pl ai n e d will b e a ntici p at e d circ u mst a nc es 
u n d er w hic h t h e s u bj ect's p artici p ati o n m a y b e t er mi n at e d b y t h e i n v esti g at or wit h o ut t h e p artici p a nt's 
c o ns e nt.
Pr os p ecti v e p artici p a nts will b e pr o vi d e d wit h a d escri pti o n of a n y r e as o n a bl y f ors e e a bl e ris ks or 
disc o mf orts as w ell as a d escri pti o n of a n y b e n efits t o t h e p artici p a nt or t o ot h ers t h at mi g ht b e r e as o ns 
ex p ect e d fr o m t h e r es e arc h. Alt er n ati v e pr oc e d ur es or c o urs es of tr e at m e nt will als o b e t h or o u g hl y 
disc uss e d.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Pr os p ecti v e p artici p a nts will als o b e gi v e n d et ail e d i nf or m ati o n d escri bi n g t h e ext e nt t o w hic h 
c o nfi d e nti alit y of r ec or ds i d e ntif yi n g t h e p artici p a nt will b e m ai nt ai n e d a n d w h at r ec or ds m a y b e 
ex a mi n e d b y t h e r es e arc h st aff, I R Bs, s p o ns or, t h eir r e pr es e nt ati v es, a n d p ossi bl y t h e F D A or O H R P.
Als o c o m m u nic at e d t o t h e p artici p a nt will b e a n ex pl a n ati o n t h at e m er g e nc y m e dic al c ar e will b e arr a n g e d 
f or a st u d y-r el at e d ill n ess or i nj ur y, a n d a n ex pl a n ati o n of w h et h er f u n ds ar e s et asi d e t o p a y f or t his c ar e 
a n d/ or c o m p e ns ati o n, a n d if s o b y w h o m ( e. g., s p o ns or, s u bj ect, i ns ur er). T h e p artici p a nt is t ol d t h e s o urc e 
of t h e st u d y's f u n di n g.
All p artici p a nts will b e t ol d of a n y a d diti o n al c osts t h at m a y r es ult fr o m p artici p ati o n i n t h e r es e arc h.
C o ns e nt will b e d o n e i n p ers o n or r e m ot el y t hr o u g h s ec ur e d e m ail, p h o n e or b y el ectr o nic c o ns e nti n g 
usi n g o n e of t h e m et h o ds t h at is E m or y LI T S a p pr o v e d ( e. g. D oc u Si g n) w h e n a v ail a bl e.  W e will f oll o w 
E m or y’s g ui d a nc e o n us e of el ectr o nic i nf or m e d c o ns e nt.
N o n- E n glis h- S p e a ki n g P artici p a nts   
A c ertifi e d tr a nsl at or/i nt er pr et er will b e pr es e nt d uri n g t h e c o ns e nti n g pr oc ess a n d all q u esti o ns a n d 
c o nc er ns will b e a ns w er e d b y t h e tr e ati n g p h ysici a n. 
A S h ort F or m i n t h at s p ecific l a n g u a g e will b e us e d. A c ertifi e d tr a nsl at or/i nt er pr et er will b e pr es e nt d uri n g 
t h e c o ns e nti n g pr oc ess a n d t his will b e d oc u m e nt e d. W e will us e w h at's a v ail a bl e o n E m or y I R B w e bsit e. 
F or t h e l a n g u a g es t h at ar e n ot a v ail a bl e, w e will h a v e t h e s h ort f or m tr a nsl at e d t o t h at l a n g u a g e a n d 
s u b mit t h e I R B f or r evi e w a n d a p pr o v al pri or t o us e. Pr oc ess t o D oc u m e nt C o ns e nt i n Writi n g: Wi ns hi p 
S O P 2. 1:” O bt ai ni n g I nf or m e d c o ns e nt f or I nt erv e nti o n al cli nic al tri al” will b e f oll o w e d.
P artici p a nts w h o ar e n ot y et a d ults (i nf a nts, c hil dr e n, t e e n a g ers)   
N/ A
C o g niti v el y I m p air e d A d ults   
N/ A
A d ults U n a bl e t o C o ns e nt
Us e of L A R, if a p plic a bl e
2 0.   S etti n g
T h e r es e arc h will b e c o n d uct e d at E m or y U ni v ersit y.  If n o n- E m or y sit es ar e a d d e d t o t his st u d y i n t h e 
f ut ur e, t h e pr ot oc ol will b e a m e n d e d t o r efl ect t his. 
P ot e nti al p artici p a nts will b e i d e ntifi e d i n m e dic al o nc ol o g y cli nics, m ulti disci pli n ar y c a nc er cli nic, 
s ur gic al o nc ol o g y cli nics, m ulti disci pli n ar y t u m or b o ar d at E m or y U ni v ersit y.  
2 1.  R es o urc es A v ail a bl e
E m or y U ni v ersit y w as f o u n d e d i n 1 8 3 6 a n d is a n ati o n al c e nt er f or t e ac hi n g, r es e arc h, a n d s ervic e. E m or y 
U ni v ersit y h as b e e n n a m e d as o n e of t h e n ati o n’s t o p 2 5 u ni v ersiti es f or m or e t h a n a d ec a d e b y t h e U. S. 

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
N e ws a n d W orl d R e p ort. E m or y U ni v ersit y r es e arc h p art n ers i ncl u d e t h e G e or gi a I nstit ut e of T ec h n ol o g y, 
t h e U ni v ersit y of G e or gi a, M or e h o us e Sc h o ol of M e dici n e, t h e U S C e nt ers f or Dis e as e C o ntr ol a n d 
Pr e v e nti o n, C hil dr e n's H e alt hc ar e of Atl a nt a, a n d t h e G e or gi a Cli nic al a n d Tr a nsl ati o n al Sci e nc e Alli a nc e 
( G A C T S A). E m or y U ni v ersit y r es e arc h ers r ec ei v e d $ 7 3 4 milli o n fr o m ext er n al f u n di n g a g e nci es i n fisc al 
y e ar 2 0 1 8, i ncl u di n g a p pr oxi m at el y $ 4 4 1 milli o n i n f u n di n g fr o m f e d er al a g e nci es, $ 3 5 9 milli o n of t his 
fr o m t h e N ati o n al I nstit ut es of H e alt h ( NI H).
Wi ns hi p C a nc er I nstit ut e ( Wi ns hi p)  is G e or gi a's first a n d o nl y N ati o n al C a nc er I nstit ut e ( N CI)- d esi g n at e d 
C o m pr e h e nsi v e C a nc er C e nt er ( P 3 0 C A 1 3 8 2 9 2) a n d is d e dic at e d t o t h e i nt e gr ati o n of i n n o v ati v e cli nic al 
a n d b asic sci e nc e r es e arc h wit h o utst a n di n g p ati e nt c ar e f or t h e pr ev e nti o n, tr e at m e nt a n d c o ntr ol of 
c a nc er. First d esi g n at e d i n 2 0 0 9, Wi ns hi p’s N CI d esi g n ati o n w as r e n e w e d i n 2 0 1 2 a n d 2 0 1 6, ac hi e vi n g a n 
“ o utst a n di n g” r ati n g. Wi ns hi p e ar n e d t h e pr esti gi o us C o m pr e h e nsi v e C a nc er C e nt er d esi g n ati o n fr o m t h e 
N CI i n 2 0 1 6, aft er d e m o nstr ati n g t h at its o utst a n di n g pr o gr a ms ar e r e d uci n g t h e c a nc er b ur d e n o n t h e 
st at e of G e or gi a t hr o u g h r es e arc h c o n d uct e d i n its l a b or at ori es, its cli nic al tri al pr o gr a m, a n d its 
p o p ul ati o n- b as e d sci e nc e. T h e i nstit uti o n al s u p p ort f or Wi ns hi p w as r at e d as ‘ exc e pti o n al’ b y t h e r e vi e w 
p a n el.
T h e Wi ns hi p Cli nic B uil di n g C  h o us es t h e pri m ar y offic es a n d cli nic al s p ac e f or c a nc er s er vic es i ncl u di n g 
t h e m e dic al o nc ol o g y, h e m at ol o g y, a n d s ur gic al o nc ol o g y cli nics, t h e r a di ati o n o nc ol o g y pr o gr a m, a n d t h e 
Wi ns hi p A m b ul at or y I nf usi o n C e nt er.  I n s u m m er 2 0 1 7, E m or y H e alt hc ar e c o m pl et e d t h e ex p a nsi o n of 
E m or y U ni v ersit y H os pit al T o w er  o n Clift o n R o a d. T his ni n e-fl o or f acilit y a d ds 1 4 4 i n p ati e nt b e ds t o t h e 
h os pit al, of 
w hic h 
m or e t h a n 8 0 % ar e d e dic at e d t o c a nc er c ar e. T h e h os pit al ex p a nsi o n als o 
acc o m m o d at es c a nc er p ati e nt-s p ecific i nt e nsi v e c ar e u nits, a n ex p a n d e d B M T U nit wit h p eri-tr a ns pl a nt 
cli nics t o f acilit at e c o nti n uit y of c ar e, a n d a 2 4- h o ur c a nc er ur g e nt c ar e c e nt er, w hic h s erv es as b ot h a 
tri a g e f acilit y a n d s h ort st a y tr e at m e nt c e nt er f or p ati e nts wit h c a nc er-r el at e d m e dic al c o nc er ns. 
T h e Wi ns hi p P h as e I U nit , o n t h e f o urt h fl o or of t h e E m or y U ni v ersit y H os pit al T o w er, is t h e l ar g est u nit 
i n G e or gi a d e dic at e d t o t h e e arli est a n d m ost critic al p h as e of n e w c a nc er t h er a p y ev al u ati o n. T h er e is 
s p ac e f or 1 5 pri v at e tr e at m e nt b a ys, f o ur cli nic r o o ms, its o w n l a b f or d oi n g p ati e nt bl o o d w or k, a 
d e dic at e d s ec ur e m e dic ati o n r o o m, c o m p ut er w or ks p ac e f or r es e arc h a n d ot h er s u p p ort st aff, a n d a "f ast 
tr ac k" b a y wit h t hr e e c h airs f or r a pi d us e i n p ati e nts w h o, f or ex a m pl e, mi g ht n e e d o nl y a r es e arc h l a b 
t est d o n e.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
2 2.  R ef er e nc es
1.
T er as L R, D e S a ntis C E, C er h a n J R, M ort o n L M, J e m al A, Fl o w ers C R. 2 0 1 6 U S l y m p h oi d 
m ali g n a nc y st atistics b y W orl d H e alt h Or g a niz ati o n s u bt y p es. C A C a nc er J Cli n. 2 0 1 6; 6 6( 6): 4 4 3-
4 5 9.
2.
Dr e yli n g M, G hi el mi ni M, R ul e S, S all es G, Vit ol o U, L a d ett o M. N e wl y di a g n os e d a n d r el a ps e d 
f ollic ul ar l y m p h o m a: E S M O Cli nic al Pr actic e G ui d eli n es f or di a g n osis, tr e at m e nt a n d f oll o w- u p. 
A n n O nc ol. 2 0 1 6; 2 7(s u p pl 5): v 8 3- v 9 0.
3.
S mit h A, Cr o uc h S, L ax S, et al. L y m p h o m a i nci d e nc e, s ur vi v al a n d pr e v al e nc e 2 0 0 4- 2 0 1 4: s u b-
t y p e a n al ys es fr o m t h e U K's H a e m at ol o gic al M ali g n a nc y R es e arc h N et w or k. Br J C a nc er. 
2 0 1 5; 1 1 2( 9): 1 5 7 5- 1 5 8 4.
4.
Li u Q, F a y a d L, C a b a nill as F, et al. I m pr o v e m e nt of o v er all a n d f ail ur e-fr e e s urvi v al i n st a g e I V 
f ollic ul ar l y m p h o m a: 2 5 y e ars of tr e at m e nt ex p eri e nc e at T h e U ni v ersit y of T ex as M. D. A n d ers o n 
C a nc er C e nt er. J Cli n O nc ol. 2 0 0 6; 2 4( 1 0): 1 5 8 2- 1 5 8 9.
5.
Fis h er RI, L e Bl a nc M, Pr ess O W, M al o n e y D G, U n g er J M, Mill er T P. N e w tr e at m e nt o pti o ns h a v e 
c h a n g e d t h e s ur vi v al of p ati e nts wit h f ollic ul ar l y m p h o m a. J Cli n O nc ol. 2 0 0 5; 2 3( 3 3): 8 4 4 7- 8 4 5 2.
6.
S w e ns o n W T, W o ol dri d g e J E, L y nc h C F, F or m a n- H off m a n VL, C hrisc hill es E, Li n k B K. I m pr o v e d 
s ur vi v al of f ollic ul ar l y m p h o m a p ati e nts i n t h e U nit e d St at es. J Cli n O nc ol. 2 0 0 5; 2 3( 2 2): 5 0 1 9-
5 0 2 6.
7.
T a n D, H or ni n g SJ, H o p p e R T, et al. I m pr o v e m e nts i n o bs er v e d a n d r el ati v e s ur vi v al i n f ollic ul ar 
gr a d e 1- 2 l y m p h o m a d uri n g 4 d ec a d es: t h e St a nf or d U ni v ersit y ex p eri e nc e. Bl o o d. 
2 0 1 3; 1 2 2( 6): 9 8 1- 9 8 7.
8.
C as ul o C, B yrt e k M, D a ws o n KL, et al. E arl y R el a ps e of F ollic ul ar L y m p h o m a Aft er Rit uxi m a b Pl us 
C ycl o p h os p h a mi d e, D ox or u bici n, Vi ncristi n e, a n d Pr e d nis o n e D efi n es P ati e nts at Hi g h Ris k f or 
D e at h: A n A n al ysis Fr o m t h e N ati o n al L y m p h o C ar e St u d y. J Cli n O nc ol. 2 0 1 5; 3 3( 2 3): 2 5 1 6- 2 5 2 2.
9.
Fr e e m a n CL, Kri d el R, M occi a A A, et al. E arl y pr o gr essi o n aft er b e n d a m usti n e-rit uxi m a b is 
ass oci at e d wit h hi g h ris k of tr a nsf or m ati o n i n a d v a nc e d st a g e f ollic ul ar l y m p h o m a. Bl o o d. 
2 0 1 9; 1 3 4( 9): 7 6 1- 7 6 4.
1 0. Bric e P, B asti o n Y, L e p a g e E, et al. C o m p aris o n i n l o w-t u m or- b ur d e n f ollic ul ar l y m p h o m as 
b et w e e n a n i niti al n o-tr e at m e nt p olic y, pr e d ni m usti n e, or i nt erf er o n alf a: a r a n d o miz e d st u d y 
fr o m t h e Gr o u p e d' Et u d e d es L y m p h o m es F ollic ul air es. Gr o u p e d' Et u d e d es L y m p h o m es d e 
l' A d ult e. J Cli n O nc ol. 1 9 9 7; 1 5( 3): 1 1 1 0- 1 1 1 7.
1 1. Y o u n g R C, L o n g o DL, Gl atst ei n E, I h d e D C, J aff e E S, D e Vit a V T, Jr. T h e tr e at m e nt of i n d ol e nt 
l y m p h o m as: w atc hf ul w aiti n g v a g gr essi v e c o m bi n e d m o d alit y tr e at m e nt. S e mi n H e m at ol. 
1 9 8 8; 2 5( 2 S u p pl 2): 1 1- 1 6.
1 2. Ar d es h n a K M, S mit h P, N ort o n A, et al. L o n g-t er m eff ect of a w atc h a n d w ait p olic y v ers us 
i m m e di at e s yst e mic tr e at m e nt f or as y m pt o m atic a d v a nc e d-st a g e n o n- H o d g ki n l y m p h o m a: a 
r a n d o mis e d c o ntr oll e d tri al. L a nc et. 2 0 0 3; 3 6 2( 9 3 8 3): 5 1 6- 5 2 2.
1 3. Ar d es h n a K M, Qi a n W, S mit h P, et al. Rit uxi m a b v ers us a w atc h- a n d- w ait a p pr o ac h i n p ati e nts 
wit h a d v a nc e d-st a g e, as y m pt o m atic, n o n- b ul k y f ollic ul ar l y m p h o m a: a n o p e n-l a b el r a n d o mis e d 
p h as e 3 tri al. L a nc et O nc ol. 2 0 1 4; 1 5( 4): 4 2 4- 4 3 5.
1 4. K a hl B S, H o n g F, Willi a ms M E, et al. Rit uxi m a b ext e n d e d sc h e d ul e or r e-tr e at m e nt tri al f or l o w-
t u m or b ur d e n f ollic ul ar l y m p h o m a: e ast er n c o o p er ati v e o nc ol o g y gr o u p pr ot oc ol e 4 4 0 2. J Cli n 
O nc ol. 2 0 1 4; 3 2( 2 8): 3 0 9 6- 3 1 0 2.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
1 5. G y a n E, S o n et A, Bric e P, et al. B e n d a m usti n e a n d rit uxi m a b i n el d erl y p ati e nts wit h l o w-t u m o ur 
b ur d e n f ollic ul ar l y m p h o m a. R es ults of t h e L Y S A p h as e II B RI E F st u d y. Br J H a e m at ol. 
2 0 1 8; 1 8 3( 1): 7 6- 8 6.
1 6.
Willi a ms M E, H o n g F, G asc o y n e R D, et al. Rit uxi m a b ext e n d e d sc h e d ul e or r etr e at m e nt tri al f or 
l o w t u m o ur b ur d e n n o n-f ollic ul ar i n d ol e nt B-c ell n o n- H o d g ki n l y m p h o m as: E ast er n C o o p er ati v e 
O nc ol o g y Gr o u p Pr ot oc ol E 4 4 0 2. Br J H a e m at ol. 2 0 1 6; 1 7 3( 6): 8 6 7- 8 7 5.
1 7.
W e bst er K, C ell a D. Q u alit y of lif e i n p ati e nts wit h l o w- gr a d e n o n- H o d g ki n's l y m p h o m a. O nc ol o gy 
( Willist o n P ar k, N Y). 1 9 9 8; 1 2( 5): 6 9 7- 7 1 4; disc ussi o n 7 1 4, 7 1 7, 7 2 1.
1 8.
M o nt g o m er y C, P oc oc k M, Titl e y K, Ll o y d K. I n di vi d u al q u alit y of lif e i n p ati e nts wit h l e u k a e mi a 
a n d l y m p h o m a. Psyc h o o nc ol o gy. 2 0 0 2; 1 1( 3): 2 3 9- 2 4 3.
1 9. Zitt o u n R, Ac h ar d S, R usz ni e ws ki M. Ass ess m e nt of q u alit y of lif e d uri n g i nt e nsi v e c h e m ot h er a p y 
or b o n e m arr o w tr a ns pl a nt ati o n. Psyc h o o nc ol o gy. 1 9 9 9; 8( 1): 6 4- 7 3.
2 0.
M o nt g o m er y C, P oc oc k M, Titl e y K, Ll o y d K. Pr e dicti n g ps yc h ol o gic al distr ess i n p ati e nts wit h 
l e u k a e mi a a n d l y m p h o m a. J Psyc h os o m R es. 2 0 0 3; 5 4( 4): 2 8 9- 2 9 2.
2 1.
Witz e ns- H ari g M, R eiz M, H eiss C, et al. Q u alit y of lif e d uri n g m ai nt e n a nc e t h er a p y wit h t h e a nti-
C D 2 0 a nti b o d y rit uxi m a b i n p ati e nts wit h B c ell n o n- H o d g ki n's l y m p h o m a: r es ults of a 
pr os p ecti v e r a n d o miz e d c o ntr oll e d tri al. A n n H e m at ol. 2 0 0 9; 8 8( 1): 5 1- 5 7.
2 2.
W a g n er LI, Z h a o F, H o n g F, et al. A nxi et y a n d h e alt h-r el at e d q u alit y of lif e a m o n g p ati e nts wit h 
l o w-t u m or b ur d e n n o n- H o d g ki n l y m p h o m a r a n d o ml y assi g n e d t o t w o diff er e nt rit uxi m a b d osi n g 
r e gi m e ns: r es ults fr o m E C O G tri al E 4 4 0 2 ( R E S O R T). J Cli n O nc ol. 2 0 1 5; 3 3( 7): 7 4 0- 7 4 8.
2 3. Y ost KJ, T h o m ps o n C A, Et o n D T, et al. T h e F u ncti o n al Ass ess m e nt of C a nc er T h er a p y - G e n er al 
( F A C T- G) is v ali d f or m o nit ori n g q u alit y of lif e i n p ati e nts wit h n o n- H o d g ki n l y m p h o m a. L e u k 
Ly m p h o m a. 2 0 1 3; 5 4( 2): 2 9 0- 2 9 7.
2 4. B asc h E, D e al A M, Kris M G, et al. S y m pt o m M o nit ori n g Wit h P ati e nt- R e p ort e d O utc o m es D uri n g 
R o uti n e C a nc er Tr e at m e nt: A R a n d o miz e d C o ntr oll e d Tri al. J Cli n O nc ol. 2 0 1 6; 3 4( 6): 5 5 7- 5 6 5.
2 5. H a y JL, At ki ns o n T M, R e e v e B B, et al. C o g niti v e i nt ervi e wi n g of t h e U S N ati o n al C a nc er I nstit ut e's 
P ati e nt- R e p ort e d O utc o m es v ersi o n of t h e C o m m o n T er mi n ol o g y Crit eri a f or A d v ers e E v e nts 
( P R O- C T C A E). Q u al Lif e R es. 2 0 1 4; 2 3( 1): 2 5 7- 2 6 9.
2 6. D u ec k A C, M e n d oz a T R, Mitc h ell S A, et al. V ali dit y a n d R eli a bilit y of t h e U S N ati o n al C a nc er 
I nstit ut e's P ati e nt- R e p ort e d O utc o m es V ersi o n of t h e C o m m o n T er mi n ol o g y Crit eri a f or A d v ers e 
E v e nts ( P R O- C T C A E). J A M A O nc ol. 2 0 1 5; 1( 8): 1 0 5 1- 1 0 5 9.
2 7. S h ar m a n J P, B a n erji V, F o gli att o L M, et al. EL E V A T E T N: P h as e 3 St u d y of Ac al a br uti ni b C o m bi n e d 
wit h O bi n ut uz u m a b ( O) or Al o n e Vs O Pl us C hl or a m b ucil ( Cl b) i n P ati e nts ( Pts) wit h Tr e at m e nt-
N ai v e C hr o nic L y m p h oc ytic L e u k e mi a ( CLL). Bl o o d. 2 0 1 9; 1 3 4( S u p pl e m e nt _ 1): 3 1- 3 1.
2 8. K h a n W N. R e g ul ati o n of B l y m p h oc yt e d e v el o p m e nt a n d acti v ati o n b y Br ut o n's t yr osi n e ki n as e. 
I m m u n ol R es. 2 0 0 1; 2 3( 2- 3): 1 4 7- 1 5 6.
2 9.
M o h a m e d AJ, Y u L, B ac k esj o C M, et al. Br ut o n's t yr osi n e ki n as e ( Bt k): f u ncti o n, r e g ul ati o n, a n d 
tr a nsf or m ati o n wit h s p eci al e m p h asis o n t h e P H d o m ai n. I m m u n ol R ev. 2 0 0 9; 2 2 8( 1): 5 8- 7 3.
3 0. Br a ds h a w J M. T h e Src, S y k, a n d T ec f a mil y ki n as es: disti nct t y p es of m ol ec ul ar s witc h es. C ell 
Si g n al. 2 0 1 0; 2 2( 8): 1 1 7 5- 1 1 8 4.
3 1. S o uc e k L, B u g g y JJ, K ortl e v er R, et al. M o d eli n g p h ar m ac ol o gic al i n hi biti o n of m ast c ell 
d e gr a n ul ati o n as a t h er a p y f or i ns uli n o m a. N e o pl asi a. 2 0 1 1; 1 3( 1 1): 1 0 9 3- 1 1 0 0.
3 2. P o n a d er S, C h e n S S, B u g g y JJ, et al. T h e Br ut o n t yr osi n e ki n as e i n hi bit or P CI- 3 2 7 6 5 t h w arts 
c hr o nic l y m p h oc ytic l e u k e mi a c ell s ur vi v al a n d tiss u e h o mi n g i n vitr o a n d i n vi v o. Bl o o d. 
2 0 1 2; 1 1 9( 5): 1 1 8 2- 1 1 8 9.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 6 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
3 3. d e R o oij M F, K uil A, G e est C R, et al. T h e cli nic all y acti v e B T K i n hi bit or P CI- 3 2 7 6 5 t ar g ets B-c ell 
r ec e pt or- a n d c h e m o ki n e-c o ntr oll e d a d h esi o n a n d mi gr ati o n i n c hr o nic l y m p h oc ytic l e u k e mi a. 
Bl o o d. 2 0 1 2; 1 1 9( 1 1): 2 5 9 0- 2 5 9 4.
3 4. B artl ett NL, C ost ell o B A, L a Pl a nt B R, et al. Si n gl e- a g e nt i br uti ni b i n r el a ps e d or r efr act or y 
f ollic ul ar l y m p h o m a: a p h as e 2 c o ns orti u m tri al. Bl o o d. 2 0 1 8; 1 3 1( 2): 1 8 2- 1 9 0.
3 5. F o wl er N, N ast o u pil L, d e V os S, et al. I br uti ni b C o m bi n e d wit h Rit uxi m a b i n Tr e at m e nt- N ai v e 
P ati e nts wit h F ollic ul ar L y m p h o m a: Ar m 1 + Ar m 2 R es ults fr o m a M ultic e nt er, O p e n-L a b el P h as e 
2 St u d y. Bl o o d. 2 0 1 6; 1 2 8( 2 2): 1 8 0 4- 1 8 0 4.
3 6. F o wl er N H, C ol e m a n M, St ev e ns D A, et al. Ac al a br uti ni b al o n e or i n c o m bi n ati o n wit h rit uxi m a b 
( R) i n f ollic ul ar l y m p h o m a ( FL). J Cli n O nc ol. 2 0 1 8; 3 6( 1 5 _s u p pl): 7 5 4 9- 7 5 4 9.
3 7. N o y A, d e V os S, T hi e bl e m o nt C, et al. T ar g eti n g Br ut o n t yr osi n e ki n as e wit h i br uti ni b i n 
r el a ps e d/r efr act or y m ar gi n al z o n e l y m p h o m a. Bl o o d. 2 0 1 7; 1 2 9( 1 6): 2 2 2 4- 2 2 3 2.
3 8. Di m o p o ul os M A, T e d esc hi A, Tr ot m a n J, et al. P h as e 3 tri al of i br uti ni b pl us rit uxi m a b i n 
W al d e nstr o m’s M acr o gl o b uli n e mi a. N E n gl J M e d. 2 0 1 8; 3 7 8: 2 3 9 9- 2 4 1 0.
3 9.
W a n g M, R ul e S, Zi nz a ni PL, et al. Ac al a br uti ni b i n r el a ps e d or r efr act or y m a ntl e c ell l y m p h o m a 
( A C E-L Y- 0 0 4): a si n gl e- ar m, m ultic e ntr e, p h as e 2 tri al. L a nc et. 2 0 1 8; 3 9 1( 1 0 1 2 1): 6 5 9- 6 6 7.
4 0. G hi a P, Pl ut a A, W ac h M, et al. A S C E N D: P h as e III, R a n d o miz e d Tri al of Ac al a br uti ni b V ers us 
I d el alisi b Pl us Rit uxi m a b or B e n d a m usti n e Pl us Rit uxi m a b i n R el a ps e d or R efr act or y C hr o nic 
L y m p h oc ytic L e u k e mi a. J Cli n O nc ol. 2 0 2 0; 3 8( 2 5): 2 8 4 9- 2 8 6 1. 
4 1. S e h n L H, C h u a N, M a y er J, et al. O bi n ut uz u m a b pl us b e n d a m usti n e v ers us b e n d a m usti n e 
m o n ot h er a p y i n p ati e nts wit h rit uxi m a b-r efr act or y i n d ol e nt n o n- H o d g ki n l y m p h o m a ( G A D OLI N): 
a r a n d o mis e d, c o ntr oll e d, o p e n-l a b el, m ultic e ntr e, p h as e 3 tri al. L a nc et O nc ol. 2 0 1 6; 1 7( 8): 1 0 8 1-
1 0 9 3. 
4 2. M arc us R, D a vi es A, A n d o K, et al. O bi n ut uz u m a b f or t h e first-li n e tr e at m e nt of f ollic ul ar 
l y m p h o m a. N E n gl J M e d. 2 0 1 7; 3 7 7: 1 3 3 1- 1 3 4 4. 
4 3. C h es o n B D, Fis h er RI, B arri n gt o n S F, et al. R ec o m m e n d ati o ns f or i niti al e v al u ati o n, st a gi n g, a n d 
r es p o ns e ass ess m e nt of H o d g ki n a n d n o n- H o d g ki n l y m p h o m a: t h e L u g a n o cl assific ati o n. J Cli n 
O nc ol. 2 0 1 4; 3 2( 2 7): 3 0 5 9- 3 0 6 8.

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X A
P erf or m a nc e St at us Crit eri a
E C O G P erf or m a nc e St at us Sc al e
K ar n ofs k y P erf or m a nc e Sc al e
Gr a d e
D escri pti o ns
P erc e nt
D escri pti o n
1 0 0
N or m al, n o c o m pl ai nts, n o evi d e nc e of 
dis e as e.
0
N or m al acti vit y.  F ull y acti v e, a bl e t o 
c arr y o n all pr e- dis e as e p erf or m a nc e 
wit h o ut r estricti o n.
9 0
A bl e t o c arr y o n n or m al acti vit y; mi n or 
si g ns or s y m pt o ms of dis e as e.
8 0
N or m al acti vit y wit h eff ort; s o m e si g ns 
or s y m pt o ms of dis e as e.
1
S y m pt o ms,  
b ut  
a m b ul at or y.  
R estrict e d i n 
p h ysic all y str e n u o us 
acti vit y, b ut a m b ul at or y a n d a bl e t o 
c arr y o ut w or k of a li g ht or s e d e nt ar y 
n at ur e ( e. g. , li g ht h o us e w or k, offic e 
w or k).
7 0
C ar es f or s elf, u n a bl e t o c arr y o n n or m al 
acti vit y or t o d o acti v e w or k.
6 0
R e q uir es occ asi o n al assist a nc e, b ut is 
a bl e t o c ar e f or m ost of his/ h er n e e ds.
2
I n b e d < 5 0 % of t h e ti m e.  A m b ul at or y 
a n d c a p a bl e of all s elf-c ar e, b ut u n a bl e 
t o c arr y o ut a n y w or k acti viti es.  U p 
a n d a b o ut m or e t h a n 5 0 % of w a ki n g 
h o urs.
5 0
R e q uir es c o nsi d er a bl e assist a nc e a n d 
fr e q u e nt m e dic al c ar e.
4 0
Dis a bl e d, r e q uir es s p eci al c ar e a n d 
assist a nc e.
3
I n b e d > 5 0 % of t h e ti m e.  C a p a bl e of 
o nl y li mit e d s elf-c ar e, c o nfi n e d t o b e d 
or c h air m or e t h a n 5 0 % of w a ki n g 
h o urs.
3 0
S e v er el y  
dis a bl e d,  
h os pit aliz ati o n 
i n dic at e d.  D e at h n ot i m mi n e nt.
2 0
V er y sic k, 
h os pit aliz ati o n i n dic at e d. 
D e at h n ot i m mi n e nt.
4
1 0 0 %  
b e dri d d e n.  
  
C o m pl et el y 
dis a bl e d.  C a n n ot c arr y o n a n y s elf-
c ar e.  T ot all y c o nfi n e d t o b e d or c h air.
1 0
M ori b u n d, f at al pr oc ess es pr o gr essi n g 
r a pi dl y.
5
D e a d.
0
D e a d.
As p u blis h e d i n A m. J. Cli n. O nc ol.:  O k e n, M. M., Cr e ec h, R. H., T or m ey, D. C., H ort o n, J., D avis, T. E., Mc F a d d e n, E. T., 
C ar b o n e, P. P.: T oxicity A n d R es p o ns e Crit eri a Of T h e E ast er n C o o p er ativ e O nc ol o gy Gr o u p. A m J Cli n O nc ol 5: 6 4 9-
6 5 5, 1 9 8 2. T h e E ast er n C o o p er ati v e O nc ol o g y Gr o u p, R o b ert C o mis M. D., Gr o u p C h air

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X B 
Dr u g Di ar y
St u d y I D:
Ac al a br uti ni b Pill Di ar y
S u bj ect I niti als: _ _ _ _ _ _ _ _  S u bj ect I D: _ _ _ _ _ _ _ _ _ _ C ycl e: _ _ _ _ _ _ _ _ _ _ _ _
I nstr ucti o ns: 
Pl a n n e d D ail y D os e: _ _ _ _ _ m g
R E MI N D E R S:
1.
2. 
D a y:
D at e:
Ti m e:
A M            P M
# of T a bl ets 
T a k e n
C o m m e nts:
1
2
3
4
5
6
7
8
9
1 0
1 1
1 2
1 3
1 4
1 5
1 6
1 7
1 8
1 9
2 0
2 1
2 2
2 3
2 4
2 5
2 6
2 7
2 8
P ati e nt Si g n at ur e: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
D at e Si g n e d: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
N a m e of M e dic ati o n:
W h y di d y o u t a k e 
t his m e dic ati o n ?
D at e M e dic ati o n 
St art e d:
D at e M e dic ati o n 
St o p p e d: 
Pl e as e r ec or d all m e dic ati o ns t a k e n d uri n g t his c ycl e, i ncl u di n g pr escri pti o n m e dic ati o ns a n d 
o v er t h e c o u nt er m e dic ati o ns i ncl u di n g vit a mi ns a n d s u p pl e m e nts. 
If y o u h a v e a n y q u esti o ns, pl e as e c all: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X C 
A b br e vi ati o ns a n d d efi niti o n of t er ms
T h e f oll o wi n g a b br e vi ati o ns a n d s p eci al t er ms ar e us e d i n t his st u d y Cli nic al St u d y Pr ot oc ol.
A D C C
A nti b o d y- d e p e n d e nt c ell ul ar c yt ot oxicit y
A E
a d v ers e e v e nt
A E SI
a d v ers e e v e nts of s p eci al i nt er est
AL T
al a ni n e a mi n otr a nsf er as e
A N C
a bs ol ut e n e utr o p hil c o u nt
a P T T
Acti v at e d p arti al t hr o m b o pl asti n ti m e
A S T
as p art at e a mi n otr a nsf er as e
BI D
t wic e p er d a y ( d osi n g)
B T K
Br ut o n t yr osi n e ki n as e
B U N
bl o o d ur e a nitr o g e n
C B C
c o m pl et e bl o o d c o u nt
C D
cl ust er of diff er e nti ati o n (c ell s urf ac e m ar k er)
C F R
C o d e of F e d er al R e g ul ati o ns
c G M P
c urr e nt G o o d M a n uf act uri n g Pr actic e
CIs
c o nfi d e nc e i nt er v als
CLL
c hr o nic l y m p h oc ytic l e u k e mi a
C O P D
c hr o nic o bstr ucti v e p ul m o n ar y dis e as e
C R
c o m pl et e r es p o ns e (r e missi o n)
C R F
c as e r e p ort f or m
C S S F
Cli nic al S u p pli es S hi p pi n g R ec ei pt F or m
C T
c o m p ut e d t o m o gr a p h y
C T C A E
C o m m o n T er mi n ol o g y Crit eri a F or A d v ers e E v e nts
C Y P
c yt oc hr o m e p 4 5 0
D C R
dis e as e c o ntr ol r at e
D F U
Disc o nti n u ati o n f oll o w- u p
DL T
d os e-li miti n g t oxicit y
D O R
d ur ati o n of r es p o ns e
E C G
el ectr oc ar di o gr a m
E C O G
E ast er n C o o p er ati v e O nc ol o g y Gr o u p

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
F A C T- G
F u ncti o n al Ass ess m e nt of C a nc er T h er a p y - G e n er al
F D A
F o o d a n d Dr u g A d mi nistr ati o n
FL
F ollic ul ar L y m p h o m a
G
o bi n ut uz u m a b
G C P
G o o d Cli nic al Pr actic e
G EL F
Gr o u p e d’ Et u d e d es L y m p h o m es F ollic ul air es
H B V
h e p atitis B vir us
H C V
h e p atitis C vir us
HI V
h u m a n i m m u n o d efici e nc y vir us
I C F
i nf or m e d c o ns e nt f or m
I E C
i n d e p e n d e nt et hics c o m mitt e e
I N D
I n v esti g ati o n n e w dr u g
I R C
I n d e p e n d e nt r e vi e w c o m mitt e e
I R B
i nstit uti o n al r e vi e w b o ar d
I V
i ntr a v e n o us or i ntr a v e n o usl y 
J C vir us
J o h n C u n ni n g h a m vir us
L D H
l act at e d e h y dr o g e n as e
L PL/ W M
L y m p h o pl as m ac ytic l y m p h o m a/ W al d e nstr o m’s m acr o gl o b uli n e mi a
M CL
M a ntl e C ell L y m p h o m a
M e d D R A
M e dic al Dicti o n ar y f or R e g ul at or y Acti viti es
M ZL
M ar gi n al Z o n e L y m p h o m a
N K
n at ur al kill er (c ells)
N HL
N o n- H o d g ki n L y m p h o m a
O R R
o v er all r es p o ns e r at e
O S
o v er all s ur vi v al
P C R
P ol y m er as e c h ai n r e acti o n
P F S
pr o gr essi o n-fr e e s ur vi v al
P D
p h ar m ac o d y n a mic, p h ar m ac o d y n a mics, or pr o gr essi v e dis e as e
P E T
P ositr o n e missi o n t o m o gr a p h y
P- g p
p- gl yc o pr ot ei n 1 (tr a ns p ort er)
P ML
Pr o gr essi v e M ultif oc al L e u k o e nc e p h al o p at h y
P R
p arti al r es p o ns e (r e missi o n)
P R O
P ati e nt-r e p ort e d o utc o m e

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
P T
Pr ot hr o m bi n ti m e
R/ R
R el a ps e d/r efr act or y
Q D
o nc e p er d a y ( d osi n g)
Q T c
c orr ect e d Q T i nt er v al
Q oL
Q u alit y of lif e
R SI
R ef er e nc e S af et y I nf or m ati o n
S A E
s eri o us a d v ers e e v e nt
S F U
S af et y f oll o w- u p
S D
st a bl e dis e as e or st a n d ar d d e vi ati o n
SLL
S m all l y m p h oc ytic l y m p h o m a
S U S A R
s us p ect e d u n ex p ect e d s eri o us a d v ers e r e acti o n
T T
Tr e at m e nt t er mi n ati o n
UL N
u p p er li mit of n or m al
U S PI
U nit e d St at es p ac k a g e i ns ert
W O C B P
W o m e n of c hil d b e ari n g p ot e nti al

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 6 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X D  
K n o w n Str o n g i n Vi v o I n hi bit ors or I n d uc ers of C Y P 3 A
Str o n g I n hi bit ors of C Y P 3 A a
Str o n g I n d uc ers of C Y P 3 A d
b oc e pr e vir
c ar b a m az e pi n e e
cl arit hr o m yci n b
p h e n yt oi n e
c o ni v a pti n b
rif a m pi ne
i n di n a vir
St J o h n's w ort e 
itr ac o n az ol eb
k et oc o n az ol e b
l o pi n a vir/rit o n a virb (c o m bi n ati o n dr u g)
mi b efr a dil c
n ef az o d o n e
n elfi n a vir
p os ac o n az ol e
rit o n a virb
s a q ui n a vir
t el a pr e vir
t elit hr o m yci n
v oric o n az ol e
A str o n g i n hi bit or is d efi n e d as a n i n hi bit or t h at i ncr e as es t h e A U C of a s u bstr at e b y ≥ 5-f ol d.
b. 
I n vi v o i n hi bit or of P- gl yc o pr ot ei n.
c.  
Wit h dr a w n fr o m t h e U nit e d St at es m ar k et b ec a us e of s af et y r e as o ns.
d. 
A str o n g i n d uc er is d efi n e d as a n i n d uc er t h at r es ults i n ≥ 8 0 % d ecr e as e i n t h e A U C of a s u bstr at e.
e. 
I n vi v o i n d uc er of P- gl yc o pr ot ei n.  
N ot e: T h e list of dr u gs i n t h es e t a bl es is n ot ex h a usti v e.  A n y q u esti o ns a b o ut dr u gs n ot o n t his list s h o ul d b e a d dr ess e d t o 
t h e S p o ns or of t h e pr ot oc ol.
S o urc e:
F D A Dr u g D ev el o p m e nt a n d Dr u g I nt er acti o ns: T a bl e of S u bstr at es, I n hi bit ors a n d I n d uc ers . W e b li n k Acc ess e d 1 1 J u n e 
2 0 1 5: 
htt p:// w w w.f d a. g o v/ Dr u gs/ D e v el o p m e nt A p pr o v al Pr oc ess/ D e v el o p m e nt R es o urc es/ Dr u gI nt er acti o nsL a b eli n g/ uc m 0 9 3 6 6 4.
ht m #i n Vi v o

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, 
L o w T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 7 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X E  
G EL F Crit eri a
I n v ol v e m e nt of > 3 n o d al sit es, e ac h wit h a 
di a m et er of > 3c m
A n y n o d al or extr a n o d al t u m or m ass wit h a 
di a m et er of 7c m
Pr es e nc e of B s y m pt o ms
Ris k of l oc al c o m pr essi v e s y m pt o ms t h at m a y 
r es ult i n or g a n c o m pr o mis e
C yt o p e ni as (l e u k oc yt es < 1. 0 x 1 0 9/L a n d/ or 
pl at el ets < 1 0 0 x 1 0 9/L
L e u k e mic P h as e ( > 5. 0 x 1 0 9/L m ali g n a nt c ells)
S pl e n o m e g al y ( > 1 6c m o n C T sc a n)
Pl e ur al eff usi o n or p erit o n e al ascit es
D at a t a k e n fr o m r ef er e nc e [ 1 0]

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 8 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X F  
F A C T- G ( V ersi o n 4) Q u esti o n n air e
B el o w is a list of st at e m e nts t h at ot h er p e o pl e wit h y o ur ill n ess h a v e s ai d ar e i m p ort a nt . 
Pl e as e circl e or m ar k o n e n u m b er p er li n e t o i n dic at e y o ur r es p o ns e as it a p pli es t o t h e p ast 
7 d a ys.
P H Y SI C A L W E L L- B EI N G
N ot 
at 
all
A little 
bit
S o me
- w h at
Q uite 
a bit
Ver y 
m uc h
G P 1
I ha ve a lac k of e ner g y
........................................................................................................
0
1
2
3
4
G P 2
I ha ve na usea
........................................................................................................
0
1
2
3
4
G P 3
Beca use of m y p h ysical c o n diti o n, I ha ve tr o u ble 
meeti n g t he nee ds of m y fa mil y
........................................................................................................
0
1
2
3
4
G P 4
I ha ve pai n
........................................................................................................
0
1
2
3
4
G P 5
I a m b ot here d b y si de effects of treat me nt
........................................................................................................
0
1
2
3
4
G P 6
I feel ill
........................................................................................................
0
1
2
3
4
G P 7
I a m f orce d t o s pe n d ti me i n be d
........................................................................................................
0
1
2
3
4
S O CI A L/ F A MI L Y W E L L- B EI N G
N ot 
at 
all
A little 
bit
S o me
- w h at
Q uite
a bit
Ver y 
m uc h
G S 1
I feel cl ose t o m y frie n ds
........................................................................................................
0
1
2
3
4
G S 2
I get e m oti o nal s u p p ort fr o m m y fa mil y
........................................................................................................
0
1
2
3
4
G S 3
I get s u p p ort fr o m m y frie n ds
........................................................................................................
0
1
2
3
4
G S 4
M y fa mil y has acce pte d m y ill ness
0
1
2
3
4

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 7 9 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
Pl e as e circl e or m ar k o n e n u m b er p er li n e t o i n dic at e y o ur r es p o ns e as it a p pli es t o t h e p ast 
7 d a ys.
E M O TI O N AL W ELL- B EI N G
N ot 
at all
A littl e 
bit
S o m e-
w h at
Q uit
e a 
bit
V er y m uc h
G E 1
I f e el s a d
.......................................................................................................
0
1
2
3
4
G E 2
I a m s atisfi e d wit h h o w I a m c o pi n g wit h m y 
ill n ess
.......................................................................................................
0
1
2
3
4
G E 3
I a m l osi n g h o p e i n t h e fi g ht a g ai nst m y 
ill n ess
.......................................................................................................
0
1
2
3
4
G E 4
I f e el n er v o us
.......................................................................................................
0
1
2
3
4
G E 5
I w orr y a b o ut d yi n g
.......................................................................................................
0
1
2
3
4
........................................................................................................
G S 5
I a m satisfie d wit h fa mil y c o m m u nicati o n a b o ut 
m y ill ness
........................................................................................................
0
1
2
3
4
G S 6
I feel cl ose t o m y part ner ( or t he pers o n w h o is 
m y mai n s u p p ort)
........................................................................................................
0
1
2
3
4
Q 1
Re g ar dless of y o ur c urre nt level of sex u al activity, 
ple ase a ns wer t he f oll o wi n g q uesti o n. If y o u 
prefer n ot t o a ns wer it, ple ase m ark t his b ox           
a n d g o t o t he next secti o n.
G S 7
I a m satisfie d wit h m y se x life
........................................................................................................
0
1
2
3
4

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 8 0 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
G E 6
I w orr y t h at m y c o n diti o n will g et w ors e
.......................................................................................................
0
1
2
3
4
F U N C TI O N AL W ELL- B EI N G
N ot 
at all
A littl e 
bit
S o m e-
w h at
Q uit e
a bit
V er y 
m uc h
G F 1
I a m a bl e t o w or k (i ncl u d e w or k at h o m e)
.......................................................................................................
0
1
2
3
4
G F 2
M y w or k (i ncl u d e w or k at h o m e) is f ulfilli n g
.......................................................................................................
0
1
2
3
4
G F 3
I a m a bl e t o e nj o y lif e
.......................................................................................................
0
1
2
3
4
G F 4
I h a v e acc e pt e d m y ill n ess
.......................................................................................................
0
1
2
3
4
G F 5
I a m sl e e pi n g w ell
.......................................................................................................
0
1
2
3
4
G F 6
I a m e nj o yi n g t h e t hi n gs I us u all y d o f or f u n
.......................................................................................................
0
1
2
3
4
G F 7
I a m c o nt e nt wit h t h e q u alit y of m y lif e ri g ht 
n o w
.......................................................................................................
0
1
2
3
4

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 8 1 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X G  
H os pit al A n xi et y a n d D e pr essi o n Sc al e ( H A D S)

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 8 2 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3
A P P E N DI X H  
P R O- C T C A E F O R M

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 8 3 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 8 4 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3

Titl e :  A n O p e n-L a b el P h as e 2 Tri al of Ac al a br uti ni b pl us O bi n ut uz u m a b i n P ati e nts wit h U ntr e at e d, L o w 
T u m or B ur d e n F ollic ul ar L y m p h o m a a n d Ot h er I n d ol e nt N o n- H o d g ki n L y m p h o m as 
P a g e 8 5 of 8 5 
Pr ot oc ol V ersi o n: 3. 0; 1 1/ 1 5/ 2 0 2 3