untitled h1
untitled h2

TI T L E: P h a s e II St u d y of M G T A -1 4 5 i n c o m bi n ati o n wit h pl e ri x af o r i n t h e m o bili z ati o n of h e m at o p oi eti c st e m c ell s f o r a ut ol o g o u s t r a n s pl a nt ati o n i n p ati e nt s wit h m ulti pl e m y el o m a  
```
C o or di n ati n g C e nt er

St a nf or d C a nc er I nstit ut e

8 7 5 Bl a k e Wil b ur Dri v e

St a nf or d, C A 9 4 3 0 5


Pr ot oc ol Dir e ct or

N a m e : S ur b hi Si d a n a, M D

A d dr ess : 3 0 0 P ast e ur Dri v e H 0 1 0 1c, St a nf or d, C A, 9 4 3 0 5

T el e p h o n e : 6 5 0-7 2 3 -0 8 2 2

F a x : 6 5 0-7 2 5 -9 5 9 0

e -m ail a d dr ess : sur b hi.si d a n a @st a nf or d. e d u


C o -I n v esti g at ors

J u dit h S hiz ur u, M D, P h D

E v er ett M e y er, M D, P h D

L ori M uffl y, M D

D a vi d Mi kl os M D, P h D

P ar v e e n S hir a z, M D

M att h e w Fr a n k, M D, P h D

R o b ert L o ws k y, M D

A n dr e w R e z v a ni, M D

W e n -K ai W e n g , M D, P h D

L a ur a J o h nst o n, M D

S all y Ar ai, M D


Bi ost atistici a n s

N a m e s: J o h n T a m ar esis, P h D a n d Yi n g L u, P h D

A d dr ess :

e -m ail a d dr ess :

```  
  
  
P h ar m a c e utic al P art n er: M a g e nt a T h er a p e utics  
  
V e rsi o n 1. 4 / V e rsi o n D at e: 2 1 A p ril 2 0 2 1  
|  TABLE OF CONTENTS                                                                                              |                                                                              |           |
|-----------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------|-----------|
| PROTOCOL DIRECTOR                                                                                               |                                                                              |           |
| CO-INVESTIGATORS .                                                                                              |                                                                              |           |
| BIOSTATISTICIANS                                                                                                |                                                                              |           |
| STUDY COORDINATOR                                                                                               |                                                                              |           |
| TABLE OF CONTENTS                                                                                               |                                                                              |           |
| TABLE OF TABLES                                                                                                 |                                                                              |           |
| PROTOCOL SYNOPSIS                                                                                               |                                                                              |           |
| E XPLORATORY OBJECTIVES                                                                                         |                                                                              |           |
| 1.1                                                                                                             |                                                                              |           |
| 1.2                                                                                                             | EXPLORATORY E NDPOINTS .                                                     |           |
| STUDY SCHEMA                                                                                                    |                                                                              |           |
| TABLE OF ABBREVIATIONS                                                                                          |                                                                              |           |
| 1                                                                                                               | OBJECTIVES/ENDPOINTS                                                         |           |
| PRIMARY OBJECTIVE                                                                                               |                                                                              |           |
| 1.1                                                                                                             |                                                                              |           |
| 1.2                                                                                                             | PRIMARY ENDPOINT:                                                            |           |
| 1.3                                                                                                             | SECONDARY OBJECTIVES                                                         |           |
| 1.4                                                                                                             | SECONDARY ENDPOINTS                                                          |           |
| 1.5                                                                                                             | EXPLORATORY OBJECTIVES                                                       |           |
| 1.6                                                                                                             | E E XPLORATORY E NDPOINTS                                                    |           |
| 2                                                                                                               | BACKGROUND .                                                                 |           |
| 2.1                                                                                                             | A A TOLOGOUS TRANSPLANT AND S TEM C ELL M OBILIZATION IN M ULTIPLE M ELOMA . |           |
| 2.1.1                                                                                                           | Multiple Myeloma and Role of Transplant:                                     |           |
| 2.1.2                                                                                                           | Stem Cell Mobilization for ASCT: .                                           |           |
| Rationale for proposed study:                                                                                   |                                                                              |           |
| 2.1.3                                                                                                           |                                                                              |           |
| 2.2                                                                                                             | MM                                                                           |           |
| 2.3                                                                                                             | RATIONALE                                                                    |           |
| 2.4                                                                                                             | STUDY DESIGN                                                                 |           |
| 2.5                                                                                                             | CORRELATIVE STUDIES BACKGROUND .                                             |           |
| PATIENT REPORTED OUTCOME MEASURES: BACKGROUND AND EVALUATION ................................................30 |                                                                              |           |
| 2.6                                                                                                             |                                                                              |           |
| 3                                                                                                               | PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES                              |           |
| I I NCLUSION C RITERIA                                                                                          |                                                                              |           |
| 3.1                                                                                                             | E EXCLUSION C RITERIA                                                        |           |
| 3.2                                                                                                             |                                                                              |           |
| Protocol Version 1.4, 21 April 2021                                                                             | 3                                                                            | IRB-57056 |  
| INFORMED CONSENT PROCESS                                                                                                                              |                                                                                                                                             |                                                                                     |
|-------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| 3.3                                                                                                                                                   | STUDY TIMELINE                                                                                                                              |                                                                                     |
| 3.4                                                                                                                                                   |                                                                                                                                             |                                                                                     |
| 4                                                                                                                                                     | TREATMENT PLAN .                                                                                                                            |                                                                                     |
| STUDY TREATMENT AND FOLLOW-UP                                                                                                                         |                                                                                                                                             |                                                                                     |
| 4.1                                                                                                                                                   | Pre-mobilization phase:                                                                                                                     |                                                                                     |
| 4.1.1                                                                                                                                                 |                                                                                                                                             |                                                                                     |
| 4.1.2                                                                                                                                                 | Study Treatment: stem cell mobilization/apheresis: .                                                                                        |                                                                                     |
| 4.1.3.                                                                                                                                                | Event Monitoring/Follow-up:                                                                                                                 |                                                                                     |
| 4.2                                                                                                                                                   | CRITERIA FOR PATIENT WITHDRAWAL                                                                                                             |                                                                                     |
| 4.3                                                                                                                                                   | STUDY DISCONTINUATION                                                                                                                       |                                                                                     |
| 4.4                                                                                                                                                   | A A TERNATIVES                                                                                                                              |                                                                                     |
| 5                                                                                                                                                     | INVESTIGATIONAL AGENT INFORMATION                                                                                                           |                                                                                     |
| 5.1                                                                                                                                                   | INVESTIGATIONAL AGENT MGTA-145                                                                                                              |                                                                                     |
| 5.2                                                                                                                                                   | AVAILABILITY .                                                                                                                              |                                                                                     |
| 5.3                                                                                                                                                   | A A G E N T  O R D E R I N G .                                                                                                              |                                                                                     |
| AGENT ACCOUNTABILITY/PREPARATION/ADMINISTRATION                                                                                                       |                                                                                                                                             |                                                                                     |
| 5.4                                                                                                                                                   | DOSE MODIFICATIONS                                                                                                                          |                                                                                     |
| 6                                                                                                                                                     |                                                                                                                                             |                                                                                     |
| 7                                                                                                                                                     | ADVERSE EVENTS AND REPORTING PROCEDURES                                                                                                     |                                                                                     |
| POTENTIAL ADVERSE EVENTS                                                                                                                              |                                                                                                                                             |                                                                                     |
| 7.1                                                                                                                                                   | MM                                                                                                                                          |                                                                                     |
| 7.1.1                                                                                                                                                 | Plerixafor:                                                                                                                                 |                                                                                     |
| 7.1.2                                                                                                                                                 | ADVERSE EVENT AND SERIOUS ADVERSE EVENT REPORTING .......................................................................................43 |                                                                                     |
| 7.2                                                                                                                                                   | DEFINITIONS                                                                                                                                 |                                                                                     |
| 7.2.1                                                                                                                                                 | Serious Adverse Event Reporting.                                                                                                            |                                                                                     |
| 7.2.2                                                                                                                                                 | Baseline and Follow-up Adverse Event Evaluations:                                                                                           |                                                                                     |
| 7.2.3                                                                                                                                                 |                                                                                                                                             |                                                                                     |
| LABORATORY CORRELATIVE/SPECIAL STUDIES .                                                                                                              |                                                                                                                                             |                                                                                     |
| 8                                                                                                                                                     | 8.1                                                                                                                                         | (APHERESIS PRODUCT COMPOSITION - LABORATORY CORRELATIVE STUDY #1A AND #1B) …………….47 |
| (CFU ASSAY- LABORATORY CORRELATIVE STUDY #2) ......................................................................................................48 |                                                                                                                                             |                                                                                     |
| 8.2                                                                                                                                                   |                                                                                                                                             |                                                                                     |
| 8.3                                                                                                                                                   | (IMMUNE RECONSTITUTION AT DAY 28 AND 100 BY FLOW CYTOMETRY AND AT DAY 100 BY CYTOF -                                                        |                                                                                     |
| LABORATORY CORRELATIVE STUDY #3A AND 3B)                                                                                                              |                                                                                                                                             |                                                                                     |
| STUDY CALENDAR                                                                                                                                        |                                                                                                                                             |                                                                                     |
| 9                                                                                                                                                     |                                                                                                                                             |                                                                                     |
| 10 MEASUREMENTS                                                                                                                                       |                                                                                                                                             |                                                                                     |
| 10.1                                                                                                                                                  | HSC YIELD IN APHERESIS PRODUCT (PRIMARY AND SECONDARY OUTCOME MEASURES) .........................56                                         |                                                                                     |
| OTHER SECONDARY OUTCOME MEASURES                                                                                                                      |                                                                                                                                             |                                                                                     |
| 10.2                                                                                                                                                  | Infusion related toxicities with MGTA-145; Adverse events with mobilization of HSCs                                                         |                                                                                     |
| 10.2.1                                                                                                                                                |                                                                                                                                             |                                                                                     |  
Protocol Version 1.4, 21 April 2021 IRB-57056  
| with MGTA-145 and plerixafor .                       |                                                                                                                                                          |
|------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|
| 10.2.2                                               | Neutrophil and platelet engraftment                                                                                                                      |
| 10.2.3                                               | Transplant related mortality                                                                                                                             |
| 10.2.4                                               | Non-relapse related mortality                                                                                                                            |
| 10.2.5                                               | Progression Free Survival (PFS): .                                                                                                                       |
| Overall Survival (OS): .                             |                                                                                                                                                          |
| 10.2.6                                               |                                                                                                                                                          |
| 10.2.7                                               | Response Assessment to Determine Progression:                                                                                                            |
| 11                                                   | REGULATORY CONSIDERATIONS                                                                                                                                |
| 11.1                                                 | INSTITUTIONAL REVIEW OF PROTOCOL                                                                                                                         |
| 1.2                                                  | D DATA AND SAFETY M ONITORING P LAN                                                                                                                      |
| 1.2.1                                                | Principal Investigator and Study Research Team                                                                                                           |
| 11.2.2                                               | Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) ........................ 59                                                        |
| 11.2.3                                               | DATA MANAGEMENT Plan .                                                                                                                                   |
| 12                                                   | COLLABORATIVE AGREEMENTS .                                                                                                                               |
| STATISTICAL CONSIDERATIONS                           |                                                                                                                                                          |
| 13                                                   | STATISTICAL DESIGN                                                                                                                                       |
| 13.1                                                 |                                                                                                                                                          |
| 13.2                                                 | SAFETY RUN-IN/FUTILITY RULE                                                                                                                              |
| DESCRIPTIVE STATISTICS AND EXPLORATORY DATA ANALYSIS |                                                                                                                                                          |
| 13.3                                                 | PRIMARY ANALYSIS .                                                                                                                                       |
| 13.4                                                 | SECONDARY ANALYSIS                                                                                                                                       |
| 13.5                                                 | Secondary Endpoint #1: .                                                                                                                                 |
| 13.5.1                                               | Secondary Endpoint #2:                                                                                                                                   |
| 13.5.2                                               |                                                                                                                                                          |
| 13.5.3                                               | Secondary Endpoint #3:                                                                                                                                   |
| Secondary Endpoint #4:                               |                                                                                                                                                          |
| 13.5.4                                               | Secondary Endpoint #5: .                                                                                                                                 |
| 13.5.5                                               |                                                                                                                                                          |
| 13.6                                                 | SAMPLE SIZE                                                                                                                                              |
| Accrual estimates.                                   |                                                                                                                                                          |
| 13.6.1                                               |                                                                                                                                                          |
| 13.6.2                                               | Sample size justification                                                                                                                                |
| 13.6.3                                               | Effect size justification                                                                                                                                |
| 13.7                                                 | CRITERIA FOR FUTURE STUDIES                                                                                                                              |
| 14 REFERENCES                                        |                                                                                                                                                          |
| 15                                                   | APPENDICES .                                                                                                                                             |
| 15.1                                                 | APPENDIX A: PARTICIPANT ELIGIBILITY CHECKLIST ........................................................................................................70 |  
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1 5. 2 7 2

1 5. 3 7 2

1 5. 4 7 2

A P P E N DI X B ............................................................................................................................................................ 7 3


```  
T a bl e of T a bl e s  
T a bl e 1: A d v ers e eff e cts wit h M G T A a n d pl eri x af or i n a p h as e 1 st u d y of h e alt h y v ol u nt e ers ............. 2 3  
T a bl e 2: Fl o w C yt o m etr y P a n el wit h A nti b o di es f or H S C a n d pr o g e nit or c ell st ai ni n g ............................ 2 6  
T a bl e 3: C y T O F P a n el wit h A nti b o di es f or p eri p h er al bl o o d m o n o n ucl e ar c ell i m m u n o p h e n ot y pi n g  
.......................................................................................................................................................................................................... 2 6  
T a bl e 4: Fl o w C yt o m etr y P a n el wit h A nti b o di es f or T a n d N K c ell st ai ni n g .................................................. 2 9  
T a bl e 5: Fl o w C yt o m etr y P a n el wit h A nti b o di es f or B c ell st ai ni n g .................................................................. 2 9  
T a bl e 6: Tr e at m e nt Pl a n ....................................................................................................................................................... 3 3  
T a bl e 7: S u m m ar y of Ac ut e B a c k P ai n ( T a bl e s o urc e: I n v esti g at or's Br oc h ur e) ......................................... 3 9  
T a bl e 8: A d v ers e R e a cti o ns i n ≥ 5 % of N o n -H o d g ki n's L y m p h o m a a n d M ulti pl e M y el o m a P ati e nts  
R e c ei vi n g Pl eri x af or a n d M or e Fr e q u e nt t h a n Pl a c e b o d uri n g H S C M o bili z ati o n a n d A p h er esis ........ 4 3  
T a bl e 9: A d v ers e E v e nt Ass ess m e nt ................................................................................................................................ 4 6  
T a bl e 1 0 A: Sc h e d ul e of St u d y Ass ess m e nts ................................................................................................................. 5 0  
T a bl e 1 1: St e m c ell m o bili z ati o n d at a fr o m pri or st u di es of G -C S F a n d G C S F + / -pl eri x af or i n  
m y el o m a ...................................................................................................................................................................................... 6 4
untitled h1
p r o t o

TI T L E: P h as e II St u d y of M G T A -1 4 5 i n c o m bi n ati o n wit h pl eri x af or i n t h e m o bili z ati o n of h e m at o p oi etic st e m c ells ( H S Cs) f or a ut ol o g o us tr a ns pl a nt ati o n i n p ati e nts wit h m ulti pl e m y el o m a S T U D Y P H A S E: P h as e 2, o p e n l a b el , pr o of of c o nc e pt st u d y S T U D Y C E N T E R: Si n gl e C e nt er, St a nf or d C a nc er I nstit ut e I N V E S TI G A TI O N A L P R O D U C T: M G T A -1 4 5 (i ntr a v e n o us dr u g)  
I N DI C A TI O N: H e m at o p oi etic s t e m c ell ( H S C) c oll e cti o n f or a ut ol o g o us st e m c ell tr a ns pl a nt ati o n i n m ulti pl e m y el o m a  
P RI M A R Y O BJ E C TI V E( S)  
1. T o ass ess t h e effic a c y of M G T A -1 4 5 i n c o m bi n ati o n wit h pl eri x af or i n m o bili zi n g a d e q u at e n u m b er of h e m at o p oi etic st e m c ells (> 2 x 1 0 C D 3 4 + c ells / k g) i n p ati e nts wit h m ulti pl e m y el o m a ( M M ) i n pr e p ar ati o n f or a ut ol o g o us st e m c ell tr a ns pl a nt ati o n ( A S C T).  
S E C O N D A R Y O BJ E C TI V E( S)  
1. T o ass ess t h e effic a c y of M G T A -1 4 5 a n d pl eri x af or i n m o bili zi n g diff er e nt H S Cs t ar g et g o als i n p ati e nts wit h M M i n pr e p ar ati o n f or A S C T.  
2. T o ass ess t h e s af et y a n d t ol er a bilit y of M G T A -1 4 5 a n d pl eri x af or f or m o bili zi n g H S Cs i n p ati e nts wit h M M.  
3. T o ass ess t h e e n gr aft m e nt r at e a n d ti m e t o e n gr aft m e nt f oll o wi n g A S C T aft er H S C  
m o bili z ati o n wit h M G T A -1 4 5 a n d pl eri x af or i n p ati e nts wit h M M u n d er g oi n g u pfr o nt A S C T.  
4. T o ass ess r at e of o n g oi n g e n gr aft m e nt at d a y 3 0 a n d 1 0 0 aft er st e m c ell i nf usi o n i n p ati e nts wit h M M w h o ar e m o bili z e d wit h M G T A -1 4 5 a n d pl eri x af or u n d er g oi n g u pfr o nt A S C T.  
5. T o ass ess tr a ns pl a nt a n d dis e as e -r el at e d o utc o m es aft er m o bili z ati o n of H S Cs wit h M G T A -  
1 4 5 a n d pl eri x af or i n p ati e nts wit h M M u n d er g oi n g u pfr o nt A S C T.  
```
P RI M A R Y E N D P OI N T( S)

1. T o e v al u at e t h e r at e of s ucc essf ul c oll e cti o n i n p ati e nts wit h M M of ≥ 2 . 0 x 1 0 C D 3 4

c ells / k g i n u p t o t w o d a ys of a p h er esis aft er M G T A-1 4 5 + pl eri x af or d osi n g .


```  
S E C O N D A R Y E N D P OI N T( S)  
1. T o ass ess t h e r at e of s ucc essf ul c oll e cti o n of ( a) ≥ 4. 0 x 1 0 C D 3 4 c ells / k g i n u p t o t w o a p h er esis s essi o ns aft er M G T A -1 4 5 a n d pl eri x af or d osi n g i n p ati e nts wit h M M ( K e y S e c o n d a r y E n d p oi nt) ( b) ≥ 6. 0 x 1 0 C D 3 4 c ells / k g wit h u p t o t w o a p h er esis s essi o ns a ft er M G T A -1 4 5 a n d pl eri x af or d osi n g i n p ati e nts wit h M M ( c) ≥ 2. 0 x 1 0 C D 3 4 a n d  
≥ 4. 0 x 1 0 C D 3 4 c ells / k g wit h o n e a p h er esis s essi o n aft er M G T A -1 4 5 a n d pl eri x af or d osi n g .  
2. T o ass ess i nf usi o n r el at e d t o xiciti es wit h M G T A -1 4 5 a n d a d v ers e e v e nts wit h m o bili z ati o n of H S Cs wit h M G T A -1 4 5 a n d pl eri x af or.  
3. T o ass ess ti m e t o n e utr o p hil ( d efi n e d as t h e first d a y of A N C ≥ 0. 5 x 1 0 / L f or 3 d a ys f oll o wi n g st e m c ell i nf usi o n) a n d pl at el et e n gr aft m e nt ( d efi n e d as first d a y of pl at el et c o u nt m or e t h a n or e q u al t o 2 0 x 1 0 / L wit h o ut tr a nsf usi o n i n t h e l ast 7 d a ys a n d wit h pl at el et c o u nt  
≥ 2 0 x 1 0 / L o n 2 s e p ar at e, s u bs e q u e nt d a ys ), a n d t o als o d et er mi n e ti m e t o first d a y of pl at el et c o u nt > 5 0 x 1 0 / L, wit h o ut n e e d f or pl at el et tr a nsf usi o n i n 4 8 h o urs i n p ati e nts u n d er g oi n g u pfr o nt A S C T.  
4. T o ass ess r at es of o n g oi n g s ucc essf ul e n gr aft m e nt at 3 0 - a n d 1 0 0 -d a ys p ost -tr a ns pl a nt aft er s ucc essf ul pri m ar y e n gr aft m e nt i n p ati e nts u n d er g oi n g u pfr o nt A S C T.  
5. T o ass ess r at e of tr a ns pl a nt r el at e d m ort alit y, n o n -r el a ps e m ort alit y, pr ogr essi o n fr e e s ur vi v al a n d o v er all s ur vi v al at 1 0 0 d a ys i n p ati e nts wit h u n d er g oi n g u pfr o nt A S C T.  
E x pl o r at o r y O bj e cti v e s 1. Ass ess t h e c o m p ositi o n of t h e a p h er esis pr o d uct wit h m o bili z ati o n wit h M G T A -1 4 5 a n d pl eri x af or i n p ati e nts wit h M M.  
2. Ass ess pr olif er ati o n a n d diff er e nti ati o n p ot e nti al of H S Cs c oll e ct e d wit h M G T A -1 4 5 a n d pl eri x af or vi a c ol o n y -f or mi n g u nit ass a ys.  
3. T o ass ess i m m u n ol o gic al r e c o v er y i n p ati e nts wit h M M u n d er g oi n g u pfr o nt tr a ns pl a nt ati o n aft er i nf usi o n of H S Cs c oll e ct e d wit h M G T A -1 4 5 a n d pl eri x af or m o bili z ati o n.  
4. T o ass ess p ati e nt r e p ort e d s y m pt o ms wit h st e m c ell m o bili z ati o n wit h M G T A -1 4 5 a n d pl eri x af or i n p ati e nts wit h M M.  
E x pl o r at o r y E n d p oi nt s 1. T o ass ess t h e c o m p ositi o n of t h e a p h er esis pr o d uct o bt ai n e d aft er M G T A-1 4 5 a n d pl eri x af or m o bili z ati o n t hr o u g h e n u m er ati o n C D 3 4 C D 9 0 C D 4 5 R A c ells i n t h e pr o d uct a n d i m m u n ol o gic al c h ar a ct eriz ati o n of t h e T c ell s u bs ets, B c ell s u bs ets, N K c ells, n e utr o p hils, a n d m y el oi d / m o n oc ytic c ells i n t h e pr o d uct usi n g fl o w c yt o m etr y a n d C y T O F ( C yt o m etr y b y Ti m e of Fli g ht) a n d mi ni m al r esi d u al dis e as e ( M R D) ass ess m e nt usi n g n e xt g e n er ati o n fl o w c yt o m etr y ( N G F) .  
2. Ass ess pr olif er ati o n a n d diff er e nti ati o n p ot e nti al of H S Cs c oll e ct e d wit h M G T A-1 4 5 a n d pl eri x af or vi a c ol o n y -f or mi n g u nit ass a ys fr o m t h e a p h er esis a ut o gr aft.  
3. T o ass ess i m m u n ol o gic al c h ar a ct eriz ati o n of w hit e c ell p o p ul ati o n s u bs ets ( T c ell s u bs ets, B  
c ell s u bs ets, N K c ells, n e utr o p hils, a n d m y el oi d / m o n oc ytic c ells) i n p ati e nt's p eri p h er al bl o o d at d a y 2 8 usi n g fl o w c yt o m etr y a n d at d a y 1 0 0 usi n g fl o w c yt o m etr y a n d m ass c yt o m etr y / C y T O F a n d ass ess i m m u n ol o gic al c h ar act eriz ati o n of w hit e c ell p o p ul ati o n s u bs ets i n t h e b o n e m arr o w micr o e n vir o n m e nt at d a y 1 0 0 f oll o wi n g t r a ns pl a nt.  
4. T o ass ess p ati e nt r e p ort e d s y m pt o ms, usi n g it e ms f or i nf usi o n r e a cti o n a n d p ai n a d a pt e d fr o m t h e p ati e nt r e p ort e d o utc o m es 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) as w ell as t h e bri ef p ai n i n v e nt or y t o ol f oll o wi n g pl eri x af or a n d M G T A -1 4 5 i nf usi o n.
untitled h1
b a c k g

A ut ol o g o us st e m c ell tr a ns pl a nt is a n eff e cti v e t h er a p y f or m ulti pl e m y el o m a a n d r e m ai ns a st a n d ar d of c ar e f or eli gi bl e p ati e nts. W hil e m ost p ati e nts u n d er g o u pfr o nt tr a ns pl a nt s o o n aft er st e m c ell c oll e cti o n, s o m e p ati e nts m a y o pt t o d el a y tr a ns pl a nt u ntil r el a ps e. C oll e cti o n of C D 3 4 +  
h e m at o p oi etic st e m c ells ( H S Cs) t o r esc u e t h e b o n e m arr o w fr o m eff e cts of hi g h -d os e c h e m ot h er a p y i n A S C T is m ost c o m m o nl y d o n e t hr o u g h m o bili z ati o n a n d c oll e cti o n of H S Cs fr o m t h e p eri p h er al bl o o d. T h e t w o c o m m o n str at e gi es t o a c hi e v e t his ar e c h e m ot h er a p y -b as e d m o bili z ati o n al o n g wit h gr a n ul oc yt e c ol o n y sti m ul ati n g f a ct or ( G-C S F ) or G-C S F m o bili z ati o n wit h or wit h o ut pl eri x af or.  
W hil e t h es e m et h o ds ar e effic a ci o us, t h e pr oc ess c a n b e l o n g a n d is ass oci at e d wit h s o m e a d v ers e eff e cts. F or e x a m pl e, c h e m ot h er a p y -b as e d m o bili z ati o n c a n t a k e t w o t o t hr e e w e e ks a n d r es ult i n  
```
c o m plic ati o ns li k e n e utr o p e nic f e v er a n d si g nific a nt c yt o p e ni as.

2 -4
G -C S F i nj e cti o ns c a n r es ult i n


```  
si g nific a nt b o n e p ai n. R ar e s eri o us a d v ers e eff e cts wit h G -C S F i ncl u d e s pl e nic r u pt ur e a n d p ul m o n ar y t o xicit y. E v e n wit h G -C S F a n d pl eri x af or us e, at l e ast 4 d a ys of G C S F i nj e cti o ns ar e n e e d e d e v e n b ef or e m o bili z ati o n c a n b e gi n , r e q uiri n g 5-8 d a ys f or c oll e cti o n .  
T h e i d e al st e m c ell m o bili z ati o n a n d c oll e cti o n m et h o d s h o ul d r es ult i n r a pi d a n d r eli a bl e c oll e cti o n of a d e q u at e C D 3 4 + H S Cs , wit h mi ni m al a d v ers e eff e cts. A mi ni m u m of 2. 0 x 1 0 C D 3 4 c ells / k g ar e r e c o m m e n d e d t o pr oc e e d wit h tr a ns pl a nt p er St a nf or d B M T Di visi o n i nstit uti o n al pr ot oc ol a n d I nt er n ati o n al M y el o m a W or ki n g Gr o u p g ui d eli n es. C oll e cti o n of a n a d diti o n al 2. 0 x 1 0 C D 3 4 c ells / k g is pr ef err e d as a b a c k -u p st e m c ell i nf usi o n p er i nstit uti o n al pr ot oc ol.  
I n n o v ati o n i n t h e st e m c ell m o bili z ati o n m et h o d t o r e d uc e t h e ti m e t a k e n t o c oll e ct st e m c ells a n d d e cr e as e a d v ers e eff e cts will b e b e n efici al fr o m b ot h p ati e nt s a n d h e alt h c ar e r es o urc e utiliz ati o n .  
M G T A -1 4 5 is a C X C R 2 a g o nist , whic h h as s h o w n pr o misi n g a cti vit y f or r a pi d m o bili z ati o n of C D 3 4 +  
H S Cs i n pr e-cli nic al m o d els . Its a cti vit y w as s y n er gistic wit h pl eri x af or, a C X C R 4 a nt a g o nist, i n a ni m al m o d els a n d i n a p h as e I st u d y of h e alt h y v ol u nt e ers, wit h r a pi d m o bili z ati o n of st e m c ells.  
Gi v e n t h e pr o misi n g r es ults s e e n i n pr e-cli nic al m o d els a n d a p h as e 1 st u d y of h e alt h y v ol u nt e ers , w e e x p e ct t his a g e nt t o r es ult i n f ast, eff e cti v e a n d s af e st e m c ell m o bili z ati o n i n p ati e nts wit h m ulti pl e m y el o m a, i n c o m bi n ati o n wit h pl eri x af or. T his p h a s e II p r o of of c o n c e pt st u d y will e v al u at e st e m c ell m o bili z ati o n i n p ati e nts wit h m y el o m a wit h a c o m bi n ati o n of M G T A -1 4 5 a n d pl eri x af or. T h e d os e of M G T A -1 4 5 ( 0. 0 3 m g / k g) i n c o m bi n ati o n wit h pl eri x af or h as b e e n i d e ntifi e d i n a p h as e I st u d y of h e alt h y v ol u nt e ers. T h er e w er e mi ni m al a d diti o n al si d e eff e cts o bs er v e d wit h M G T A -1 4 5 i n t h at st u d y, wit h m ost p ati e nts r e p orti n g tr a nsi e nt b ac k p ai n l asti n g l ess t h a n 2 0 mi n ut es i n t h e M G T A -  
1 4 5 vs. pl a c e b o ar m. A d diti o n al e x p e ct e d si d e eff e cts, i ncl u di n g di arr h e a , w er e n ot e d i n t h e M G T A -  
1 4 5 + pl eri x af or ar m. Wit h t his r e gi m e n, p ati e nts will u n d er g o s a m e d a y m o bili z ati o n aft er a d mi nistr ati o n of M G T A -1 4 5 a n d pl eri x af or f or a m a xi m u m of 2 a p h er esis s essi o ns.
untitled h1
t r e a t

T his is a p h as e 2 st u d y t o e v al u at e s af et y a n d effic a c y of st e m c ell m o bili z ati o n (f or hi g h -d os e t h er a p y a n d a ut ol o g o us st e m c ell r esc u e) wit h a c o m bi n ati o n of M G T A -1 4 5 a n d pl eri x af or, f oll o w e d b y s a m e d a y a p h er esis i n p ati e nts wit h m ulti pl e m y el o m a. T h e d os e of M G T A -1 4 5 i n c o m bi n ati o n wit h pl eri x af or h as b e e n d et er mi n e d i n a p h as e 1 st u d y o f h e alt h y v ol u nt e ers. P ati e nts will u n d er g o u p t o 2 d a ys of m o bili z ati o n f oll o w e d b y s a m e d a y a p h er esis s essi o ns.  
T h e pri m ar y e n d p oi nt is s ucc essf ul c oll e cti o n of at l e ast ≥ 2 . 0 x 1 0 C D 3 4 c ells / k g wit h u p t o t w o d a ys o f a p h er esis s essi o n s aft er M G T A -1 4 5 a n d pl eri x af or d osi n g. K e y s e c o n d ar y e n d p oi nt is t h e c oll e cti o n of ≥ 4. 0 x 1 0 C D 3 4 c ells / k g i n u p t o t w o d a ys of a p h er esis . Ot h er se c o n d ar y e n d p oi nts i ncl u d e c oll e cti o n of ≥ 2. 0 x 1 0 C D 3 4 c ells / k g a n d ≥ 4. 0 x 1 0 C D 3 4 c ells / k g o n d a y o n e of a p h er esis a n d of  
≥ 4. 0 x 1 0 C D 3 4 c ells / k g a n d ≥ 6. 0 x 1 0 C D 3 4 c ells / k g i n u p t o t w o d a ys of a p h er esis aft er M G T A -1 4 5 a n d pl eri x af or d osi n g, ass ess m e nt of a d v ers e e v e nts a n d s ucc essf ul e n gr aft m e nt as d escri b e d a b o v e.
untitled h1
t h e st u

1. Pr e -m o bili z ati o n p h as e :
P ati e nts will u n d er g o scr e e ni n g pr oc e d ur es aft er si g ni n g i nf or m e d c o ns e nt. T h e y will u n d er g o b as eli n e e v al u ati o n d uri n g t h e pr e -m o bili z ati o n p h as e u p t o 3 0 d a ys b ef or e m o bili z ati o n a n d b e  
```
e nr oll e d if t h e y m e et eli gi bilit y crit eri a .

2. St e m c ell m o bili z ati o n / a p h er esis p h as e :

P ati e nts will u n d er g o s e q u e nti al a d mi nistr ati o n of pl eri x af or 0. 2 4 m g / k g ( d os e 0. 1 6 m g / k g f or

cr e ati ni n e cl e ar a nc e < 5 0 ml / mi n ut e) s u bc ut a n e o usl y f oll o w e d 2 h o urs l at er b y M G T A -1 4 5 at a

d os e of 0. 0 3 m g / k g i ntr a v e n o usl y. T his will b e f oll o w e d b y a p h er esis . A p h er esis s h o ul d b e gi n as

s o o n as f e asi bl e aft er M G T A -1 4 5 i nf usi o n is c o m pl et e.

E a c h s essi o n of a p h er esis will b e st a n d ar diz e d t o p r oc e s s 3 bl o o d v ol u m e s, wit h a m a r gi n of + / -

1 0 % o r 4. 5 h o u r s, w hi c h e v e r i s l o n g e r.


```  
A s e c o n d d a y of m o bili z ati o n a n d a p h er esis will b e p urs u e d i n p ati e nts w h o h a v e n ot c oll e ct e d 6. 0 x 1 0 C D 3 4 c ells / k g i n o n e s essi o n.  
A mi ni m u m of 2 . 0 x 1 0 C D 3 4 c ells / k g ar e r e c o m m e n d e d t o pr oc e e d wit h tr a ns pl a nt p er St a nf or d B M T Di visi o n i nstit uti o n al pr ot oc ol a n d I nt er n ati o n al M y el o m a W or ki n g Gr o u p g ui d eli n es. C oll e cti o n of a n a d diti o n al 2. 0 x 1 0 C D 3 4 c ells / k g is pr ef err e d as a b ac k -u p st e m c ell i nf usi o n p er i nstit uti o n al pr ot oc ol.  
If t h e mi ni m u m g o al of 2. 0 x 1 0 C D 3 4 c ells / k g is n ot m et aft er 2 d a ys of c oll e cti o n , p ati e nts m a y pr oc e e d wit h w as h o ut pr ot o c ol a n d alt er n ati v e st e m c ell m o bili z ati o n str at e g y at t h e discr eti o n of t h e tr e ati n g p h ysici a n .  
F or p ati e nts c oll e cti n g b et w e e n 2. 0 a n d 4. 0 x 1 0 C D 3 4 c ells / k g , p ati e nts m a y pr oc e e d t o tr a ns pl a nt or c oll e ct a d diti o n al st e m c ells wit h alt er n ati v e str at e gi es t o m e et t h e t ot al g o al of 4. 0 x 1 0 C D 3 4 c ells / k g p er tr e ati n g p h ysici a n discr eti o n . If a n a d diti o n al c oll e cti o n is s o u g ht at t h e discr eti o n of t h e tr e ati n g ph ysici a n, it is r e c o m m e n d e d n ot t o c o m bi n e t h e st a n d ar d of c ar e m o bili z e d gr aft a n d t h e M G T A -1 4 5 + pl eri x af or m o bili z e d gr aft f or o n e tr a ns pl a nt.  
3. E v e nt M o nit ori n g / F oll o w -u p:  
a. A p ati e nt will b e c o nsi d er e d t o h a v e f ail e d m o bili z ati o n a n d will disc o nti n u e t h er a p y o n tri al a n d g o t o E v e nt M o nit ori n g if t h e y f ail t o c oll ect t h e mi ni m u m of 2. 0 milli o n  
C D 3 4 c ells / k g aft er t w o a p h er esis s essi o ns.  
b. P ati e nts w h o ar e n ot pr oc e e di n g wit h u pfr o nt A S C T (i. e p ati e nts w h o c oll e ct a n d st or e st e m c ells a n d o p t f or d el a y e d tr a ns pl a nt) will b e f oll o w e d i n E v e nt M o nit ori n g u ntil 3 0 d a ys aft er c o m pl eti o n of tr e at m e nt. Aft er t h at n o, f urt h er f oll o w -u p is r e q uir e d.  
c. If p ati e nts ar e pr oc e e di n g wit h u pfr o nt tr a ns pl a nt, t h e y will b e f oll o w e d u ntil d a y 1 0 0 f or s e c o n d ar y o utc o m es of e n gr aft m e nt, dis e as e pr o gr essi o n a n d s ur vi v al. Aft er t h at, n o f urt h er f oll o w -u p is r e q uir e d. P ati e nts will b e off er e d p artici p ati o n i n a n i nstit uti o n al tr a ns pl a nt r e gistr y st u d y f or l o n g er t er m f oll o w u p.
d. A d v ers e E v e nts occ urri n g aft er t h e p ati e nt c o m pl et es st u d y i nt er v e nti o n ( M G T A-1 4 5 a n d pl eri x af or) will b e c oll e ct e d o n t h e E v e nt M o nit ori n g F or m if t h e y ar e > / = gr a d e 3, at l e ast p ossi bl y r el at e d t o st u d y tr e at m e nt a n d h a v e n ot b e e n pr e vi o usl y r e p ort e d.  
e. F or p ati e nts pr oc e e di n g wit h u pfr o nt tr a ns pl a nt ( d efi n e d u p t o 6 0 d a ys aft er H S C  
m o bili z ati o n), m y el o a bl ati v e m el p h al a n c o n diti o ni n g ( m el p h al a n 1 4 0 - 2 0 0 m g / m )  
o n d a y -2 f oll o w e d b y i nf usi o n of c oll e ct e d H S Cs c ells o n d a y 0 p er i nstit uti o n al st a n d ar d of pr a ctic e pr ot oc ol. T h e m a xi m u m i nt er v a l b et w e e n st e m c ell c oll e cti o n a n d tr a ns pl a nt o n t his st u d y is 6 0 d a ys. Wit hi n 6 0 d a ys, t h e ti mi n g of tr a ns pl a nt is at t h e discr eti o n of t h e tr e ati n g p h ysici a n.  
f. If t h es e p ati e nts u n d er g o r esc u e m o bili z ati o n f or a n y r e as o n (i ncl u di n g p h ysici a n discr eti o n t o c oll e ct m or e t h a n 2 milli o n C D 3 4 + c ell s / k g) a n d pr oc e e d t o u pfr o nt tr a ns pl a nt wit h M G T A-1 4 5 a n d pl eri x af or m o bili z e d gr aft, t h e y will b e f oll o w e d f or s e c o n d ar y tr a ns pl a nt r el at e d o utc o m es. O n t h e ot h er h a n d, if t h e y u n d er g o u pfr o nt tr a ns pl a nt wit h t h e st e m c ell gr aft o bt ai n e d fr o m r esc u e m o bili z ati o n o nl y, t h e y will n ot b e f oll o w e d f or s e c o n d ar y o utc o m es. It is r e c o m m e n d e d n ot t o c o m bi n e gr afts  
```
fr o m diff er e nt m o bili z ati o n pr ot oc ols

Eli gi bilit y C rit e ri a:

I n cl u si o n C rit e ri a

1. Di a g n osis of m ulti pl e m y el o m a p er t h e I nt er n ati o n al M y el o m a W or ki n g Gr o u p (I M W G)

crit eri a

2. A g e: 1 8 t o 7 0 y e ars

3. Eli gi bl e f or A S C T p er i nstit uti o n al g ui d eli n es

4. Wit hi n o n e y e ar of st art of m y el o m a t h er a p y

5. C ar di a c a n d p ul m o n ar y st at us s uffici e nt t o u n d er g o a p h er esis a n d tr a ns pl a nt ati o n p er

i nstit uti o n al tr a ns pl a nt g ui d eli n es.

6. C alc ul at e d cr e ati ni n e cl e ar a nc e > 3 0 m L / mi n a cc or di n g t o t h e M o dific ati o n of Di et i n R e n al

Dis e as e ( M D R D) f or m ul a.

7. A bs ol ut e n e utr o p hil c o u nt > 1 5 0 0 x 1 0 / L a n d pl at el ets > 1 0 0, 0 0 0 x 1 0 / L

8. A bilit y t o u n d erst a n d a n d t h e willi n g n ess t o si g n a writt e n i nf or m e d c o ns e nt d oc u m e nt.

9. A gr e e m e nt t o us e a n a p pr o v e d f or m of c o ntr ac e pti o n f or m al e p ati e nts or f e m al e p ati e nts of

c hil d b e ari n g p ot e nti al.

E x cl u si o n C rit e ri a

1. Hist or y of pri or st e m c ell tr a ns pl a nt f or m ulti pl e m y el o m a or ot h er i n dic ati o ns

2. Pl a n n e d t a n d e m st e m c ell tr a ns pl a nt

3. Pri or hist or y of f ail ur e t o c oll e ct H S Cs.

4. Li v er f u ncti o n t ests: T ot al bilir u bi n > 1. 5 x u p p er li mit of n or m al ( U L N) i n t h e a bs e nc e of a

d oc u m e nt e d hist or y of Gil b ert's s y n dr o m e a n d / or A S T / A L T > 3 x U L N.

5. K n o w n all er g y t o M G T A -1 4 5 or pl eri x af or .

6. Lif eti m e e x p os ur e t o l e n ali d o mi d e or a n ot h er i m m u n o m o d ul at or y dr u g gr e at er t h a n 6

c u m ul ati v e m o nt hs of tr e at m e nt i. e m or e t h a n si x 2 8 -d a y c ycl es or m or e t h a n ei g ht 2 1 -d a y

c ycl es.

```
untitled h1
7. pr e g n

S af et y M o nit o ri n g of t h e R es e a r c h : T h e PI will r e vi e w t h e st u d y p eri o dic all y t o r e vi e w t h e pr o gr ess of t his pr ot o c ol a n d b e k e pt a w ar e of effic a c y a n d t o xicit y iss u es. T his st u d y will b e m o nit or e d a cc or di n g t o t h e St a nf or d C a nc er I nstit ut e D at a S af et y M o nit ori n g Pl a n t h at is c urr e ntl y i n pla c e f or i n v esti g at or-i niti at e d cli nic al tri als a n d will r e p ort t o t h e St a nf or d C a nc er I nstit u t e D at a S af et y M o nit ori n g C o m mitt e e ( D S M C).  
T o xicit y will b e c a pt ur e d a s p er N CI C T C A E versi o n 5. 0, w h er ei n t h e t er m t o xicit y is d efi n e d as a d v ers e e v e nts t h at ar e cl assifi e d as eit h er p ossi bl y, pr o b a bl y, or d efi nit el y r el at e d t o st u d y tr e at m e nt. N o n-h e m at ol o gic t o xiciti es will b e e v al u at e d vi a t h e or di n al C T C st a n d ar d t o xicit y gr a di n g. D ur ati o n of t o xicit y e v e nts c a n b e i nc or p or at e d i nt o ass ess m e nts of t o xicit y gr a di n g.  
H e m at ol o gic t o xicit y m e as ur es of t hr o m b oc yt o p e ni a, n e utr o p e ni a, a n d l e u k o p e ni a will b e ass ess e d usi n g c o nti n u o us v ari a bl es as t h e o utc o m e m e as ur es as w ell as c at e g oriz ati o n vi a C T C st a n d ar d t o xicit y gr a di n g. O v er all t o xicit y i nci d e nc e will b e e x pl or e d a n d s u m m ariz e d. Fr e q u e nc y distri b uti o ns, gr a p hic al t e c h ni q u es a n d ot h er d escri pti v e m e as ur es will f or m t h e b asis of t h es e a n al ys es .
untitled h1
d r u g a

C O M M E R CI A L A G E N T: Pl eri x af or P H A R M A C E U TI C A L C O M P A N Y S U P P LI E D: M G T A -1 4 5 S A M P L E SI Z E : 2 5 p ati e nts
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s t a ti s

S a m pl e Si z e: F or t his si n gl e -ar m tri al wit h a bi n o mi al pri m ar y e n d p oi nt, t h e m a xi m u m s a m pl e si z e is 2 5 e v al u a bl e p ati e nts.  
```
B as e d o n hist oric al d at a wit h H S C m o bili z ati o n wit h pl eri x af or a n d G -C S F

5, 8 -1 0
, w e h y p ot h esi z e t h at


```  
at l e ast 9 5 % of s u bj e cts w h o u n d er g o m o bili z ati o n wit h t his n o v el r e gi m e n of M G T A -1 4 5 a n d pl eri x af or will m e et t h e pri m ar y e n d -p oi nt of c oll e cti n g ≥ 2 . 0 x 1 0 C D 3 4 c ells / k g i n t w o d a ys of a p h er esi s. W e m o d el t h e pri m ar y e n d p oi nt as a bi n o mi al r a n d o m v ari a bl e.  
T h e tri al will b e c o n d uct e d i n t w o s e q u e nti al s e g m e nts : t h e first f or e v al u ati o n of s af et y a n d f e asi bilit y, a n d t h e n if s ucc essf ul, t h e n u m b er will b e e x p a n d e d t o f urt h er e v al u at e s af et y a n d f e asi bilit y. I n t h e first s e g m e nt, 1 5 p ati e nts will b e e v al u at e d f or t h e pri m ar y e n d p oi nt. I n t h e s e c o n d s e g m e nt, w hic h will b e c o nti n g e nt u p o n a c hi e vi n g s ucc ess i n t h e first s e g m e nt, 1 0 p ati e nts will b e e nr oll e d t o g ai n a d diti o n al s af et y a n d f e asi bilit y e x p eri e nc e wit h t his r e gi m e n a n d t o e v al u at e t h e k e y s e c o n d ar y e n d p oi nt. Acc o u nti n g f or b ot h s e g m e nts, t h e t ot al s a m pl e si z e is 2 5 p ati e nts.  
A r es p o n d er is d efi n e d as a p ati e nt m e eti n g t h e pri m ar y e n d p oi nt. T h e st atistic al d esi g n f or t h e pri m ar y e n d p oi nt is b as e d o n a bi n o mi al e x a ct t est f or t h e n ull h y p ot h esis of a r es p o n d er r at e b ei n g 7 0 % or l ess a n d t h e alt er n ati v e h y p ot h esis of a r es p o n d er of 9 5 % or m or e. T h e crit eri o n f or s uc c ess of t h e tri al is at l e ast 1 3 o ut of 1 5 p ati e nts ar e r es p o n d ers. T h e t y p e I err or r at e is 5 % a n d st atistic al p o w er is 8 5 %. T his d esi g n f e at ur es a n i m plicit f utilit y st o p pi n g r ul e. P ati e nts will b e e nr oll e d c o nti n u o usl y t o t h e first s e g m e nt aft er i niti al s af et y r u n-i n. T h e crit eri o n f or s uc c ess is t h at at l e ast 1 3 o ut of 1 5 p ati e nts ar e r es p o n d ers. T hi s i m pli e s t h at if 3 o r m o r e p ati e nt s a r e n o n -r e s p o n d e r s at a n y p oi nt, t h e n t h e t ri al will b e st o pp e d f o r f utilit y .  
T h e c oll e cti o n of ≥ 4. 0 x 1 0 ^ 6 C D 3 4 + wit hi n 2 d a ys a k e y s e c o n d a r y e n d p oi nt of t his tri al. W e h y p ot h esi z e t h at at l e ast 7 5 % of t h e 2 5 p ati e nts will m e et t his s e c o n d ar y e n d p oi nt . T h e st atistic al d esi g n f or t h e s e c o n d ar y e n d p oi nt is b as e d o n e nr olli n g e n o u g h p ati e nts i n t h e s e c o n d s e g m e nt s uc h t h at t h e t ot al s a m pl e si z e will pr o d uc e a pr e cisi o n esti m at e wit h a l o w er bi n o mi al c o nfi d e nc e li mit t h at e xcl u d es t h e r es p o ns e r at e of t h e hist oric al c o ntr ols (i. e., 5 0 %). F or t his s e c o n d ar y e n d p oi nt, w e c o m p ut e a pr e cisi o n esti m at e of o ur h y p ot h esi z e d r es p o ns e r at e f or t h e sc e n ari o t h at b ot h s e g m e nts ar e c o m pl et e d. W e m o d el t h e s e c o n d ar y e n d p oi nt as a bi n o mi al r a n d o m v ari a bl e. W e d efi n e pr e cisi o n t o b e t h e l e n gt h of t h e bi n o mi al c o nfi d e nc e i nt erv al f or t h e h y p ot h esi z e d r es p o ns e r at e of 7 5 %. W e c o m p ut e pr e cisi o n usi n g t h e m et h o d of Wils o n at t h e si g nific a nc e l e v el of 9 0 % w hic h is a p pr o pri at e f or a n e arl y-p h as e tri al. B as e d o n t h es e s p e cific ati o ns, t h e pr e cisi o n is 2 6. 8 %.  
E a rl y S af et y R u n -i n: T h e first si x p ati e nts a ccr u e d t o t his st u d y will b e p ati e nts w h o ar e pl a n n e d f or u pfr o nt tr a ns pl a nt f oll o wi n g c oll e cti o n. A d diti o n al p ati e nts will n ot b e gi n m o bili z ati o n u ntil t h es e si x p ati e nts h a v e c o m pl et e d st e m c ell m o bili z ati o n a n d ar e at l e a st 2 1 d a ys f oll o wi n g i nf usi o n of st e m c ells aft er m y el o a bl ati v e m el p h al a n c o n diti o ni n g. S af et y r e vi e w will b e d o n e t o e v al u at e st u d y dr u g -  
r el at e d a d v ers e e v e nts, i n p artic ul ar a n y u n e x p e ct e d gr a d e 3 or hi g h er tr e at m e nt r el at e d a d v ers e e v e nts d uri n g t his p e ri o d. E n gr aft m e nt d at a will als o b e r e vi e w e d. If a n y u n e x p e ct e d gr a d e 3 or hi g h er a d v ers e e v e nts p ossi bl y, pr o b a bl y or d efi nit el y r el at e d t o t h e st u d y dr u g ar e n ot e d i n t h e first t hr e e p ati e nts, e nr oll m e nt will p a us e w hil e t h e PI r e vi e ws t h e st u d y wit h t h e F D A t o d et er mi n e w h et h er st u d y c a n c o nti n u e.  
I N D N u m b e r: 1 5 1 8 7 4
untitled h1
study schema

Study Treatment: Plerixafor 0.24 mg/kg (0.16 mg/kg for CrCl ≤50 ml/min) SC + MGTA-145 IV 0.03 mg/kg IV (after 2 hours) → followed  
  
  
  
END OF STUDY FOLLOW-
UP/EVENT MONITORING  
| T A B L E O F A B B R E VI A TI O N S  A E   | A d v ers e e v e nt                                                 |
|----------------------------------------------|----------------------------------------------------------------------|
| A L T                                        | Al a ni n e a mi n otr a nsf er as e                                 |
| A S C T                                      | A ut ol o g o us st e m c ell tr a ns pl a nt                        |
| A S T                                        | As p art at e a mi n otr a nsf er as e                               |
| C X C R 2                                    | C h e m o ki n e r e c e pt or 2                                     |
| C X C R 4                                    | C h e m o ki n e r e c e pt or 4                                     |
| C X C L 2                                    | C h e m o ki n e ( C -X -C m otif) li g a n d 2                      |
| C B C                                        | C o m pl et e bl o o d c o u nt                                      |
| C D 3 4                                      | Cl ust er of diff er e nti ati o n 3 4                               |
| C F U                                        | C ol o n y f or mi n g u nit                                         |
| C R F                                        | C as e r e p ort f or m                                              |
| C R                                          | C o m pl et e r es p o ns e                                          |
| 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 T O F                                    | C yt o m etr y b y ti m e of fli g ht                                |
| D L T                                        | D os e li miti n g t o xicit y                                       |
| D S M B                                      | D at a s af et y m o nit ori n g b o ar d                            |
| E C G                                        | El e ctr 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                 |
| E D C                                        | El e ctr o nic d at a c a pt ur e                                    |
| E O S                                        | E n d of St u d y                                                    |
| G -C S F                                     | Gr a n ul oc yt e - c ol o n y-sti m ul ati n g f a ct or            |
| G C P                                        | G o o d cli nic al pr a ctic e                                       |
| H S Cs                                       | H e m at o p oi etic st e m c ells                                   |
| I B                                          | I n v esti g at or's br oc h ur e                                    |
| I C F                                        | I nf or m e d c o ns e nt f or m                                     |
| 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                                                   |
| M D R D                                      | M o difi c ati o n of di et i n r e n al dis e as e                  |
| M M                                          | M ulti pl e m y el o m a                                             |
| M R D                                        | Mi ni m al r esi d u al dis e as e                                   |
| N H L                                        | N o n -H o d g ki n l y m p h o m a                                  |  
| N K c ells   | N at ur al kill er c ells                    |
|--------------|----------------------------------------------|
| O S          | O v er all s ur vi v al                      |
| P B          | P eri p h er al bl o o d                     |
| P F S        | Pr o gr essi o n fr e e s ur vi v al         |
| P K          | p h ar m a c o ki n etics                    |
| Q o L        | Q u alit y of lif e                          |
| S A E        | S eri o us a d v ers e e v e nt              |
| S C          | S u bc ut a n e o us                         |
| U L N        | U p p er li mit of t h e n or m al r a n g e |
untitled h1
1 o bj e c

```
1. 1 P ri m a r y O bj e cti v e

1. T o ass ess t h e effic a c y of M G T A -1 4 5 i n c o m bi n ati o n wit h pl eri x af or i n m o bili zi n g a d e q u at e

n u m b er of h e m at o p oi etic st e m c ells ( H S Cs) i n p ati e nts wit h m ulti pl e m y el o m a ( M M) i n

pr e p ar ati o n f or a ut ol o g o us st e m c ell tr a ns pl a nt ati o n ( A S C T).


1. 2 P ri m a r y E n d p oi nt :

1. T o ass ess t h e r at e of s ucc essf ul c oll e cti o n of ≥ 2 . 0 x 1 0 C D 3 4 c ells / k g i n u p t o t w o d a ys of

a p h er esis aft er M G T A -1 4 5 + pl eri x af or d osi n g i n p ati e nts wit h M M. 1. 3 S e c o n d a r y O bj e cti v e s

1. T o ass ess t h e effic a c y of M G T A -1 4 5 i n c o m bi n ati o n wit h pl eri x af or i n m o bil izi n g diff er e nt

H S Cs t ar g et g o als i n p ati e nts wit h M M i n pr e p ar ati o n f or A S C T .


```  
2. T o ass ess t h e s af et y a n d t ol er a bilit y of M G T A -1 4 5 a n d pl eri x af or f or m o bili zi n g H S Cs i n p ati e nts wit h M M .  
3. T o ass ess t h e r at e a n d ki n etics of e n gr aft m e nt f oll o wi n g A S C T aft er H S C m o bili z ati o n wit h M G T A -1 4 5 + pl eri x af or i n p ati e nts wit h M M u n d er g oi n g u pfr o nt A S C T.  
4. T o ass ess r at e of o n g oi n g e n gr aft m e nt at d a y 2 8 a n d 1 0 0 aft er A S C T wit h H S Cs wit h M G T A -  
1 4 5 a n d pl e ri x af or i n p ati e nts wit h M M u n d er g oi n g u pfr o nt A S C T.  
5. T o ass ess tr a ns pl a nt a n d dis e as e -r el at e d o utc o m es aft er m o bili z ati o n of H S Cs wit h M G T A -  
1 4 5 a n d pl eri x af or i n p ati e nts wit h M M u n d er g oi n g u pfr o nt A S C T.  
```
1. 4 S e c o n d a r y E n d p oi nt s

1. T o ass ess t h e r at e of s ucc essf ul c oll e cti o n of ( a) ≥ 4. 0 x 1 0 C D 3 4 c ells / k g i n u p t o t w o

a p h er esis s essi o ns aft er M G T A -1 4 5 a n d pl eri x af or d osi n g i n p ati e nts wit h M M. ( K e y

S e c o n d a r y E n d p oi nt) ( b) ≥ 6. 0 x 1 0 C D 3 4 c ells / k g wit h u p t o t w o a p h er esis s essi o ns aft er

M G T A -1 4 5 a n d pl e ri x af or d osi n g i n p ati e nts wit h M M. ( c) ≥ 2. 0 x 1 0 C D 3 4 a n d

≥ 4. 0 x 1 0 C D 3 4 c ells / k g wit h o n e a p h er esis s essi o n aft er M G T A -1 4 5 a n d pl eri x af or d osi n g .


```  
2. T o ass ess i nf usi o n r el at e d t o xiciti es wit h M G T A -1 4 5 a n d a d v ers e e v e nts wit h m o bili z ati o n of H S Cs wit h M G T A -1 4 5 a n d pl eri x af or.  
3. T o ass ess ti m e t o n e utr o p hil ( d efi n e d as t h e first d a y of A N C ≥ 0. 5 x 1 0 / L f or 3 d a ys f oll o wi n g st e m c ell i nf usi o n) a n d pl at el et e n gr aft m e nt ( d efi n e d as first d a y of pl at el et c o u nt m or e t h a n or e q u al t o 2 0 x 1 0 / L wit h o ut tr a nsf usi o n i n t h e l ast 7 d a ys a n d wit h pl at el et c o u nt ≥ 2 0 x 1 0 / L o n 2 s e p ar at e, s u bs e q u e nt d a ys a n d t o als o d et er mi n e ti m e t o first d a y of pl at el et c o u nt > 5 0 x 1 0 / L (wit h o ut tr a nsf usi o n i n 4 8 h o urs ) i n p ati e nts u n d er g oi n g u pfr o nt A S C T.  
4. T o ass ess r at es of o n g oi n g s ucc essf ul e n gr aft m e nt at 3 0 - a n d 1 0 0 -d a ys p ost -tr a ns pl a nt aft er s ucc essf ul pri m ar y e n gr aft m e nt i n p ati e nts u n d er g oi n g u pfr o nt A S C T.  
5. T o ass ess r at e of tr a ns pl a nt r el at e d m ort alit y, n o n -r el a ps e m ort alit y, pr o gr essi o n fr e e s ur vi v al a n d o v er all s ur v i v al at 1 0 0 d a ys i n p ati e nts u n d er g oi n g u pfr o nt A S C T.  
```
1. 5 E x pl o r at o r y O bj e cti v e s

1. Ass ess t h e c o m p ositi o n of t h e a p h er esis pr o d uct wit h m o bili z ati o n wit h M G T A -1 4 5 a n d

pl eri x af or i n p ati e nts wit h M M .


```  
2. Ass ess pr olif er ati o n a n d diff er e nti ati o n p ot e nti al of H S Cs c oll e ct e d wit h M G T A -1 4 5 a n d pl eri x af or vi a c ol o n y -f or mi n g u nit ass a ys.  
3. T o ass ess i m m u n ol o gic al r e c o v er y i n p ati e nts wit h M M u n d er g oi n g u pfr o nt tr a ns pl a nt ati o n aft er i nf usi o n of H S Cs c oll e ct e d wit h M G T A -1 4 5 a n d pl eri x af or m o bili z ati o n.  
4. T o ass ess p ati e nt r e p ort e d s y m pt o ms wit h st e m c ell m o bili z ati o n wit h M G T A -1 4 5 a n d pl eri x af or i n p ati e nts wit h M M.  
```
1. 6 E x pl o r at o r y E n d p oi nt s

1. T o a ss ess t h e c o m p ositi o n of t h e a p h er esis pr o d uct o bt ai n e d aft er M G T A -1 4 5 a n d pl eri x af or

m o bili z ati o n t hr o u g h e n u m er ati o n C D 3 4 C D 9 0 C D 4 5 R A c ells i n t h e pr o d uct a n d

i m m u n ol o gic al c h ar a ct eriz ati o n of t h e T c ell s u bs ets, B c ell s u bs ets, N K c ells, n e utr o p hils, a n d

m y el oi d / m o n oc ytic c ells i n t h e pr o d uct usi n g fl o w c yt o m etr y a n d C y T O F ( C yt o m etr y b y

Ti m e of Fli g ht) .


```  
2. Ass ess pr olif er ati o n a n d diff er e nti ati o n p ot e nti al of H S Cs c oll e ct e d wit h M G T A -1 4 5 a n d pl eri x af or vi a c ol o n y -f or mi n g u nit ass a ys fr o m t h e a p h er esis a ut o gr aft.  
3. T o a ss ess i m m u n ol o gic al c h ar a ct eriz ati o n of w hit e c ell p o p ul ati o n s u bs ets (T c ell s u bs ets, B  
c ell s u bs ets, N K c ells, n e utr o p hils, a n d m y el oi d / m o n oc ytic c ells) i n p ati e nt's p eri p h er al bl o o d at d a y 2 8 usi n g fl o w c yt o m etr y a n d at d a y 1 0 0 usi n g fl o w c yt o m etr y a n d m ass c yt o m etr y / C y T O F a n d ass ess i m m u n ol o gic al c h ar act eriz ati o n of w hit e c ell p o p ul ati o n s u bs ets i n t h e b o n e m arr o w micr o e n vir o n m e nt at d a y 1 0 0 f oll o wi n g tr a ns pl a nt.  
4. T o ass ess p ati e nt r e p ort e d s y m pt o ms, usi n g it e ms f or i nf usi o n r e a cti o n a n d p ai n a d a pt e d fr o m t h e p ati e nt r e p ort e d o utc o m es 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) as w ell as t h e bri ef p ai n i n v e nt or y t o ol f oll o wi n g pl eri x af or a n d M G T A -1 4 5 i nf usi o n. ( Q u esti o n n air e i n A p p e n di x B )
untitled h1
2 b a c k

A n n u all y, o v er 3 0, 0 0 0 p ati e nts ar e di a g n os e d wit h m ulti pl e m y el o m a i n t h e U nit e d St at es ( N CI S E E R  
```
pr o gr a m) .

1 1
A ut ol o g o us st e m c ell tr a ns pl a nt ( A S C T) f or t h e tr e at m e nt of m y el o m a w as first d escri b e d i n 1 9 8 0s.

1 2
S u bs e q u e nt st u di es, i ncl u di n g l ar g e r a n d o miz e d cli nic al tri als d e m o nstr at e d cl e ar


```  
e vi d e nc e of s ur vi v al b e n efit of tr a ns pl a nt a n d it b e c a m e a st a n d ar d of c ar e tr e at m e nt f or p ati e nts wit h m y el o m a. A S C T is t y pic all y p urs u e d aft er a f e w c ycl es of i n d ucti o n t h er a p y. It i n v ol v es a d mi nistr ati o n of hi g h -d os e m el p h al a n c h e m ot h er a p y f oll o w e d b y r esc u e of t h e b o n e m arr o w wit h H S Cs c oll e ct e d fr o m t h e p ati e nt pri or t o c h e m ot h er a p y a d mi nistr ati o n. O v er t h e p ast t w o d e c a d es, s e v er al n e w dr u gs h a v e b e e n a p pr o v e d f or t h e tr e at m e nt of m ulti pl e m y el o m a a n d h a v e r es ult e d i n dr a m atic  
```
i m pr o v e m e nt of p ati e nt o utc o m es.

1 3, 1 4
E v e n t h o u g h tr e at m e nt of m y el o m a h as e v ol v e d si g nific a ntl y


```  
wit h t h e a v ail a bilit y of n o v el a g e nts i n t h e p ast t w o d e c a d es, A S C T still r e m ai ns a c or n erst o n e of  
```
tr e at m e nt i n eli gi bl e p ati e nts.

1 5


```  
T h e I F M -2 0 0 9 r a n d o miz e d cli ni c al tri al e v al u at e d o utc o m es of p ati e nts wit h e arl y vs. d el a y e d tr a ns pl a nt f oll o wi n g i n d ucti o n c h e m ot h er a p y wit h b ort e z o mi b, l e n ali d o mi d e a n d d e x a m et h as o n e.  
E arl y tr a ns pl a nt w as ass oci at e d wit h i m pr o v e d pr o gr essi o n fr e e s ur vi v a l ( P F S) a n d hi g h er mi ni m al  
```
r esi d u al dis e as e n e g ati vit y c o m p ar e d wit h d el a y e d A S C T at t h e ti m e of first r el a ps e .

1, 1 6
O v er all


```  
s ur vi v al o utc o m es w er e si mil ar i n p ati e nts pr oc e e di n g wit h e arl y tr a ns pl a nt vs. p ati e nts d el a y i n g tr a ns pl a nt u ntil t h e ti m e of first r el a ps e. Si mil arl y, t h e F O R T E tri al c o m p are d p ati e nts pr oc e e di n g wit h e arl y A S C T vs. n ot aft er in d ucti o n wit h c arfil z o mi b, l e n ali d o mi d e a n d d e x a m et h as o n e . I nt eri m r es ults s h o w t h at p ati e nts wit h hi g h -ris k m y el o m a u n d er g oi n g tr a ns pl a nt h a d hi g h er p ersist e nt M R D  
```
n e g ati vit y r at es a n d l o w er ris k of r el a ps e.

1 7
F oll o w -u p f or s ur vi v al o utc o m es is still o n g oi n g. A m et a -


```  
a n al ysis of r a n d o miz e d cli nic al tri als fr o m 2 0 0 0 -2 0 1 7 s h o w e d t h at hi g h -d os e t h er a p y / A S C T w as  
```
ass oci at e d wit h s u p eri or P F S a n d mi ni m al t o xic eff e cts c o m p ar e d t o st a n d ar d d os e t h er a p y.

1 8


```  
T h er ef or e, all eli gi bl e p ati e nts wit h m ulti pl e m y el o m a s h o ul d b e c o nsi d er e d f or tr a ns pl a nt. E arl y tr a ns pl a nt is pr ef err e d, es p e ci all y i n i nt er m e di at e or hi g h-ris k p ati e nts. St a n d ar d ris k p ati e nts m a y  
```
c h o os e t o d el a y tr a ns pl a nt u ntil first-r el a ps e.

1 5
I n s uc h p ati e nts, st e m c ell c oll e cti o n a n d st or a g e is


```  
r e c o m m e n d e d aft er a f e w c ycl es of i n d ucti o n t h er a p y , as l o n g-t er m l e n ali d o mi d e m ai nt e n a nc e  
```
t h er a p y c a n i m p air f ut ur e st e m c ell c oll e cti o n.

1 5, 1 9


```
untitled h1
2. 1. 2 st e

C oll e cti o n of C D 3 4 + H S Cs t o r esc u e t h e b o n e m arr o w fr o m eff e cts of hi g h -d os e c h e m ot h er a p y i n A S C T  
is m ost c o m m o nl y d o n e t hr o u g h m o bili z ati o n a n d c oll e cti o n of st e m c ells fr o m t h e p eri p h er al bl o o d.  
A mi ni m u m of 2 x 1 0 C D 3 4 c ells / k g ar e r e c o m m e n d e d f or tr a ns pl a nt, a n d ma n y i nstit uti o n al  
```
pr ot oc ols c oll e ct u p t o 4 x 1 0 C D 3 4 c ells / k g.

2 0
At b as eli n e, o nl y a s m all n u m b er of H S Cs, i d e ntifi e d


```  
b y pr es e nc e of C D 3 4 p ositi vit y o n s urf a c e, ar e circ ul ati n g i n p eri p h er al bl o o d. B ef or e st e m c ells c a n b e c oll e ct e d, sti m ul ati o n a n d m o bili z ati o n of st e m c ells fr o m t h e b o n e m arr o w is r e q uir e d. It w as i niti all y a c hi e v e d wit h m y el os u p pr essi v e c h e m ot h er a p y li k e c ycl o p h os p h a mi d e a n d et o p osi d e, w h er e r e b o u n d of t h e m arr o w fr o m t h e m y el os u p pr essi v e eff e cts of c h e m ot h er a p y w as ass oci at e d  
```
wit h i ncr e as e d H S Cs i n t h e p eri p h er al bl o o d.

2 0
T h e i ntr o d u cti o n of G -C S F f urt h er i ncr e as e d t h e H S Cs


```  
i n t h e circ ul ati o n aft er m y el o s u p pr essi v e t h er a p y a n d s h ort e n e d t h e ti m e n e e d e d f or a c hi e vi n g a d e q u at e st e m c ell c o u nts i n t h e bl o o d. G -C S F w as als o e x pl or e d as a si n gl e a g e nt f or H S C c oll e cti o n.  
Pr ot oc ol V ersi o n 1. 4 , 2 1 A pril 2 0 2 1 1 9 I R B-5 7 0 5 6  
```
H o w e v er, f ail ur e r at es wit h G -C S F al o n e w er e as hi g h as 4 0 -5 0 %.

2 1
Pl eri x af or, a C X C R -4 i n hi bit or w as


```  
st udi e d i n a d diti o n t o G -C S F , wit h e xc ell e nt o utc o m es f or m o bili z ati o n. It h as n o w b e c o m e a st an d ar d  
```
of c ar e r e gi m e n.

3, 5, 2 0
Pr ot oc ols wit h G -C S F a n d pl eri x af or m a y i ncl u d e us e of pl eri x af or o n d a y 4 of G-

```  
C S F i n all p ati e nts or us e of pl eri x af or i n a ris k-a d a pt e d m a n n er b as e d o n p eri p h er al bl o o d C D 3 4  
```
c o u nt aft er 4 d a ys of G -C S F.

2 2, 2 3
A li mit ati o n i n t h e us e of pl eri x af or is t h e n e e d t o c o m bi n e it wit h


```  
s e v er al d a ys of G -C S F i nj e cti o ns. Pl eri x af or al o n e h as b e e n st u di e d f or st e m c ell m o bili z ati o n i n  
```
h e alt h y v ol u nt e ers a n d b y its elf h as li mit e d f e asi bilit y f or a r a pi d c oll e cti o n.

2 4
Gi v e n t h e l a c k of r o b ust


```  
r es p o ns e wit h si n gl e a g e nt pl eri x af or i n h e alt h y d o n ors, it h as n ot b e e n e v al u at e d i n l ar g e st u di es f or st e m c ell m o bili z ati o n i n p ati e nts wit h h e m at ol o gic m ali g n a nci es u n d er g oi n g A S C T.  
  
T h er ef or e, t he t w o c o m m o n str at e gi es t o a c hi e v e H S C c oll e cti o n i n t h e c urr e nt er a ar e c h e m ot h er a p y -  
b as e d m o bili z ati o n (t ypi c all y c ycl o p h os p h a mi d e) al o n g wit h G -C S F or G -C S F m o bili z ati o n wit h pl eri x af or, i n all p ati e nts or i n a ris k-a d a pti v e al g orit h m .  
2 0 W hil e t h es e m et h o ds ar e effic a ci o us, t h e pr oc ess c a n b e l o n g as s h o w n i n Fi g u r e 1 a n d c a n b e ass oci at e d wit h a d v ers e eff e cts.  
C ycl o p h os p h a mi d e m o bili z ati o n c a n t a k e t w o t o t hr e e w e e ks a n d r es ult i n c o m plic ati o ns li k e n e utr o p e nic f e v er a n d si g nific a nt c yt o p e ni as.  
2 -4 G -C S F a n d pl eri x af or m o bili z ati o n r e q uir es u p t o 4 d a ys of G -C S F i nj e cti o ns b ef or e m o bili z ati o n c a n b e gi n ( Fi gu r e 1) . I nj e cti o ns ar e c o nti n u e d t hr o u g h c oll e cti o n, w hi c h c a n b e as l o n g as 4 s essi o ns, t h er ef or e r e q uiri n g 5 -8 d a ys f or c oll e ct i o n. G -C S F m a y r es ult i n si g nific a nt b o n e p ai n , f ati g u e, h e a d a c h e, a n d f e v er. R ar e s eri o us a d v ers e eff e cts wit h G-C S F  
i ncl ud e s pl e nic r u pt ur e a n d p ul m o n ar y t o xicit y.
untitled h1
2. 1. 3 r ati

T h e o pti m al st e m c ell m o bili z ati o n a n d c oll e cti o n m et h o d s h o ul d r es ult i n r a pi d a n d r eli a bl e c oll e cti o n of a d e q u at e C D 3 4 + H S Cs wit h mi ni m al a d v ers e eff e cts. T h er e is a n e e d f or i n n o v ati o n t o r e d uc e t h e ti m e t a k e n f or st e m c ell m o bili z ati o n a n d f urt h er d e cr e as e t h e a d v ers e eff e cts ass oci at e d wit h st e m c ell c oll e cti o n i n p ati e nts wit h m ulti pl e m y el o m a. T his will b e b e n efici al t o p ati e nts a n d als o i m pr o v e h e alt hc ar e r es o urc e utiliz ati o n . W e a r e p r o p o si n g a st u d y of a n o v el a g e nt f o r st e m c ell m o bili z ati o n, M G T A -1 4 5 i n c o m bi n ati o n wit h pl e ri x af o r f o r r a pi d, s a m e d a y st e m c ell m o bili z ati o n i n p ati e nt s wit h m ulti pl e m y el o m a ( Fi g u r e 1).
untitled h1
2. 2 m g t

M G T A -1 4 5 ( als o k n o w n as Gr o -b et a tr u nc at e; G R O β T) is a s y nt h eticall y m a n uf a ct ur e d n at ur all y occ urri n g f o ur a mi n o a ci d tr u nc at e d pr ot ei n v ari a nt of C X C L 2, a n d h as a 6 9 a mi n o a ci d pr ot ei n pri m ar y str uct ur e as list e d b el o w .  
T E L R C Q C L Q T L Q GI H L K NI Q S V K V K S P G P H C A Q T E VI A T L K N G Q K A C L N P A S P M V K KII E K M L K N G K S N  
M G T A -1 4 5 h as t w o dis ulfi d e bri d g es: C 5 t o C 3 1 a n d C 7 t o C 4 7, a n d is c o m pris e d of a n al p h a h eli x a n d a b et a -s h e et.  
C X C L 2 pr ef er e nti all y bi n d s t o th e c ell -s urf a c e c h e m o ki n e r e c e pt or C X C R 2 , w hi c h is e x pr ess e d pr e d o mi n a ntl y o n n e utr o p hils a n d e n d ot h eli al c ells. G R O β T bi n ds t o t h e C X C R 2 r e c e pt or a n d wit h  
```
gr e at er p ot e nc y t h a n f ull -l e n gt h G R O β.

2 5


```  
P h a r m a c e uti c al P r o p e rti e s: M G T A -1 4 5 bi n ds t o t h e c ell -s urf a c e c h e m o ki n e r e c e pt or C X C R 2, w hic h is e x pr ess e d pr e d o mi n a ntl y o n n e utr o p hils a n d e n d ot h eli al c ells t o i n d uc e m o bili z ati o n of H S Cs i nt o t h e p eri p h er al bl o o d. H S C m o bili z ati o n is d e p e n d e nt o n t h e e q uili bri u m of M M P-9 a n d tiss u e i n hi bit or of m et all o pr ot ei n as e-1 ( TI M P -1) s hifti n g t o w ar ds M M P -9 f oll o wi n g M M P -9 r el e as e b y n e utr o p hils u p o n C X C R 2 bi n di n g. St u di es s h o w e d t h at t h e a d diti o n of A M D 3 1 0 0 ( pl eri x af or) i n hi bits cr oss -c o m m u nic ati o n b et w e e n C X C R 4 a n d C X C R 2 r e c e pt ors w hic h n or m all y f u ncti o n t o di mi nis h t h e C X C R 2 r es p o ns e. T h e a d diti o n of pl eri x af or h el ps e n h a nc e t h e r el e as e of M M P -9, l e a d i n g t o i ncr e as e d m o bili z ati o n of h e m at o p oi etic c ells.
untitled h1
m g t a -1

| M ol e c ul ar F or m ul a ( n et)   | C 3 2 5 H 5 5 7 N 9 7 O 9 5 S 6   |
|--------------------------------------|-----------------------------------|
| M ol e c ul ar M ass ( a v er a g e) | 7 5 3 6. 0                        |
| S ol u bilit y                       | > 1 0 0 m g / m L                 |  
M ol e c ul ar M ass ( a v er a g e) 7 5 3 6. 0  
A p p e ar a nc e of S ol uti o n Cl e ar, c ol orl ess s ol uti o n, ess e nti all y fr e e of visi bl e p articl es  
S ol u bilit y > 1 0 0 m g / m L  
F o r m ul ati o n: M G T A -1 4 5 is f or m ul at e d at 2 0 m g / m L i n 2 0 m M s o di u m a c et at e, 1 5 0 m M s o di u m c hl ori d e, 0. 0 2 % ( w / v) P ol ys or b at e 8 0 at p H 4. 0. M G T A -1 4 5 is s u p pli e d i n a si n gl e -d os e 2 m L T y p e I  
a m b er gl ass vi al. E a c h vi al c o nt ai ns n ot l ess t h a n 1 m L.
untitled h1
st o r a g

Vi als of M G T A -1 4 5 s h o ul d b e st or e d at -2 0° C ± 5° C i n t h e c art o n t o pr ot e ct fr o m li g ht.
untitled h1
i n st r u

M G T A -1 4 5 (i nj e cti o n) is a st eril e s ol uti o n f or I V us e s u p pli e d as a si n gl e -d os e vi al p a c k a g e d i n a c art o n.  
Vi als of M G T A -1 4 5 s h o ul d b e t h a w e d o v er ni g ht at 4° C pri or t o us e a n d ar e st a bl e at 4° C f or u p t o 3 0 d a ys. O nc e t h a w e d, M G T A -1 4 5 s h o ul d n ot b e r efr oz e n.  
M G T A -1 4 5 s h o ul d b e dil ut e d i n 0. 9 % s ali n e i n a cc or d a nc e wit h t h e st u d y pr ot oc ol a n d p h ar m a c y m a n u al. S ol uti o ns of M G T A -1 4 5 ( 0. 0 3 6 t o 1. 4 4 m g / m L) pr e p ar e d i n 0. 9 % s ali n e m a y b e st or e d f or n o m or e t h a n 8 h o urs at r o o m t e m p er at ur e pri or t o a d mi nistr ati o n. M G T A -1 4 5 s h o ul d b e a d mi nist er e d as a n I V i nf usi o n o v er 3 -1 0 mi n ut es , as cli nic all y i n dic at e d.  
P r e cli ni c al d at a: Pr e cli nic al st u di es d e m o nstr at e d t h at G R O β T ( M G T A-1 4 5) , w h e n a d mi nist er e d si m ult a n e o usl y wit h pl eri x af or, l e d t o a s y n er gistic i ncr e as e i n m o bili z ati o n of hi g hl y e n gr aft a bl e H S Cs i n mic e. M o bili z ati o n w as r a pi d, occ urri n g wit hi n mi n ut es of a d mi nistr ati o n of G R O β T, a n d r o b ust, m o bili zi n g si g nific a ntl y m or e H S Cs t h a n eit h er G R O β T or pl eri x af or al o n e. I n a d diti o n t o t h e e v al u ati o n of mic e i n t his st u d y, s af et y a n d p h ar m a c o ki n etic st u di es of M G T A -1 4 5 h a v e b e e n d o n e i n r ats a n d n o n-h u m a n pri m at es as d escri b e d i n t h e a cc o m p a n yi n g I n v e sti g at o r' s Br o c h u r e .  
Cli ni c al d at a : I n a p h as e 1 st u d y , a d ult h e alt h y m al es r e c ei v e d esc al ati n g d os es of pl a c e b o i nj e cti o n f oll o w e d b y M G T A -1 4 5 f o ur w e e ks l at er. M ost c o m m o n si d e eff e ct w as a c ut e l u m b ar b a c k p ai n, w hic h l ast e d 1 0 mi n ut es or l ess a n d di d n ot r e q uir e tr e at m e nt. B a c k p ai n w as s ee n is s u bj e cts w h o r e c ei v e d i nf usi o ns of 0. 0 9 m g / k g or hi g h er a n d w as s e e n i n 2 9. 7 % of s u bj e cts r e c ei vi n g M G T A -1 4 5 vs. 5. 3 %  
r e c ei vi n g pl a c e b o. Si n gl e a g e nt M G T A -1 4 5 r es ult e d i n C D 3 4 m o bili z ati o n at hi g h er d os es, b ut it w as n ot f elt t o b e s uffici e nt f or a d e q u at e st e m c ell c oll e cti o n wit h M G T A -1 4 5 us e d as a si n gl e a g e nt.  
A p h as e 1 st u d y of M G T A -1 4 5, wit h or wit h o ut pl eri x af or w as c o n d uct e d i n h e alt h y v ol u nt e ers t o d et er mi n e t h e s af et y a n d d os e of M G T A -1 4 5. M G T A -1 4 5 w as a d mi nist er e d t o 7 9 h e alt h y v ol u nt e ers.  
T h e st u d y h a d f o ur p arts. I n P art A, s u bj e cts r e c ei v e d si n gl e d os e of M G T A -1 4 5 al o n e ( 0. 0 0 7 5 -0. 3 m g / k g). I n P art B , s u bj e cts r e c ei v e d si n gl e d os e of M G T A-1 4 5 ( 0. 0 1 5 -0. 1 5 m g / k g) wit h pl eri x af or. I n P art C, s u bj e cts r e c ei v e d 2 d ail y d os es of M G T A -1 4 5 ( 0. 0 3 a n d 0. 0 7 m g / k g) a n d pl eri x af or. I n P art D,  
s u bj e cts r e c ei v e d si n gl e d os e of M G T A -1 4 5 ( 0. 0 1 5 a n d 0. 0 3 m g / k g) a n d pl eri x af or , f oll o w e d b y s a m e d a y a p h er esis. M G T A -1 4 5 w as f o u n d t o h a v e a g o o d s af et y pr ofil e, wit h m ost c o m m o n si d e eff e ct of tr a nsi e nt b ac k p ai n l asti n g l ess t h a n 2 0 mi n ut es i n m ost p ati e nts. I n P art A, b a c k p ai n w as s e e n i n 7 9 % ( 1 9 / 2 4) of v ol u nt e ers r e c ei vi n g si n gl e a g e nt M G T A -1 4 5 vs. 0 % ( 0 / 1 2) of v ol u nt e ers r e c ei vi n g pl eri x af or. T h er e w er e n o ot h er tr e at m e nt e m er g e nt a d v er s e eff e cts ( T E A E) i n s u bj e cts i n P art A  
r e c ei vi n g M G TA -1 4 5 ( 0. 0 0 7 5 t o 0. 3 m g / k g). W h e n M G T A -1 4 5 ( 0. 0 1 5 t o 0. 1 5 m g / k g) w as c o m bi n e d wit h pl eri x af or i n P art -B , T E A E w er e s e e n i n 8 1 % ( 2 6 / 3 2) of s u bj e cts c o m p ar e d t o 5 8 % ( 7 / 1 2) of p ati e nts r e c ei vi n g pl eri x af or al o n e. T E A E i n t h e M G T A -1 4 5 a n d pl eri x af or ar m i ncl u d e d b ac k p ai n / m usc ul os k el et al p ai n i n 6 2. 5 % ( n = 2 0), di arr h e a, n a us e a a n d diz zi n ess i n 1 5. 6 % s u bj e cts e a c h  
( n = 5 e a c h), r es p e cti v el y, a b d o mi n al p ai n i n 1 2. 5 % ( n = 4), v o miti n g a n d h e a d a c h e i n 9. 4 % ( n = 3 e a c h)  
of s u bj e cts e a c h, r es p e cti v el y a n d p ar est h esi a i n 6. 3 % of s u bj e cts . T his d at a is s h o w n i n t h e T a bl e 1 b el o w ( s o urc e: Di Persi o et al T C T 2 0 1 9 or al pr es e nt ati o n )  
| Table 1: Adverse effects with MGTA and plerixafor in a phase 1 study of healthy volunteers                                            |                    |                    |                     |              |            |              |
|---------------------------------------------------------------------------------------------------------------------------------------|--------------------|--------------------|---------------------|--------------|------------|--------------|
| Part D                                                                                                                                |                    |                    |                     |              |            |              |
| MGTA-145                                                                                                                              | MGTA-145           | MGTA-145           |                     |              |            |              |
| MGTA-145                                                                                                                              | Placebo            | ✦ plerixafor       | Plerixafor          | + plerixafor | Plerixafor | ✦ plerixafor |
| 075 - 0.3 mg/kg                                                                                                                       | 1.015 - 0.15 mgikg | 0.03 - 0.07 mg'kg) | 0.015 - 0.03 mg/kg) |              |            |              |
| n=24                                                                                                                                  | n=12               | n=38               | n=14                | n=8          | n=2        | n=8'         |
| n (%)                                                                                                                                 | n (%)              | n (%)              | n (%)               | n (%)        | n (%)      | n (%)        |
| Subjects with any drug related                                                                                                        | 19 (79.2)          | 31 (81.6)          | 8 (57.1)            | 6 (75.0)     | 8 (88.9)   |              |
| TEAE                                                                                                                                  | 6 (15.8)           | 5 (35.7)           | 1 (12.5)            | 1 (11.1)     |            |              |
| Diarrhea                                                                                                                              |                    |                    |                     |              |            |              |
| Nausea                                                                                                                                | 7 (18.4)           | 2 (14.3)           | 1 (12.5)            | 4 (44.4)     |            |              |
| Abdominal discomfort/pain                                                                                                             | 5 (13.2)           | 4 (28.6)           | 3 (33.3)            |              |            |              |
| Vomiting                                                                                                                              | 3 (7.9)            | 1 (7.1)            | 1 (11.1)            |              |            |              |
| Back pain / Musculoskeletal pain 2                                                                                                    | 19 (79.2)          | 24 (63.2)          | 2 (14.3)            | 4 (50.0)     | 3 (33.3)   |              |
| Dizziness / Lightheadedness                                                                                                           | 5 (15.6)           | 1 (7.1)            | 4 (44.4)            |              |            |              |
| Headache                                                                                                                              | 4 (10.5)           | 1 (7.1)            | 2 (25.0)            | 2 (22.2)     |            |              |
| Dysgeusia                                                                                                                             | 2 (14.3)           | 1 (12.5)           | 1 (11.1)            |              |            |              |
| Paraesthesia                                                                                                                          | 2(5.3)             |                    |                     |              |            |              |
| There was no dose response in AEs, so data are aggregated.                                                                            |                    |                    |                     |              |            |              |
| 1 All AEs are grade 1 except for grade 2 abdominal pain (1), nausea (1), and back pain (1) in the plenxafor + MGTA-145 0.075 mgfkg 2h |                    |                    |                     |              |            |              |
| stagger cohort (Part B) and grade 2 headache (1) in the plerixafor + MGTA-145 0.015 mg/kg cohort (Part D).                            |                    |                    |                     |              |            |              |
| 2 Back pain was associated with MGTA-145 infusion, lasted <20 minutes in most cases and did not require medical therapy.              |                    |                    |                     |              |            |              |  
- A 9 h subject enrolled in Part D but did not undergo leukapheresis.  
Source: Dipersio et al. TCT 2020 oral presentation At the 0.03 mg/kg dose the median CD34+ cell count in peripheral following MGTA-145 and plerixafor administration was 40 cells/microL (range 18-63), which was higher than that observed with plerixafor alone (median 24, range: 13-78). The dose of 0.03 mg/kg was determined to be safe and effective, with predictable, dose linear pharmacokinetics that are not affected by the coadministration of plerixafor. Administration of plerixafor followed by MGTA-145 after a 2-hour interval was associated with the best stem cell mobilization outcomes, as determined by peripheral blood CD34 counts and will be the regimen used in this trial.  
A study of MGTA-145 in subjects with renal impairment is ongoing. The primary objective of that study is to establish the effect of renal impairment on MGTA-145 pharmacokinetics. A single, monotherapy dose 0.07 mg/kg was used for this study. Twenty-three adult subjects were enrolled into 1 of the following 3 groups based on eGFR, determined by the Modification of Diet in Renal Disease Study (MDRD) equation: 1. normal ≥ 90; 2. mild 60 to 89; and 3. moderate 30 to 59 mL/min/1.73 m2). Overall, the results demonstrate that MGTA-145 was well tolerated in subjects with normal kidney function and in subjects with renal impairment. Renal impairment had no impact on the PK of MGTA-145. MGTA-145 is not excreted in urine.  
Non-clinical pharmacokinetics: Please refer to accompanying Investigator's Brochure for pharmacokinetic studies in mice, rats and non-human primates. Clinical pharmacokinetics: In a phase 1 study®, adult healthy males received escalating doses of placebo injection followed by MGTA-145  weeks later. The maximum tolerated dose was determined to be 0.2 mg/kg.  
In the Magenta Therapeutics phase 1 study of healthy volunteers, pharmacokinetic studies of different doses of MGTA-145, with or without plerixafor were done. MGTA-145 plasma drug concentration increased proportionally with the infused dose and was not affected by plerixafor. The Cmax of MGTA-145 increased along with dose linearly and AUC increased in a supra proportional manner in the dosing range of 0.0075 mg/kg to 0.3 mg/kg. In Part A, the mean Cmax of MGTA-145 ranged from 35.12 µg/L to1461.55 µg/L, and the mean area under the concentration-time curve from time zero to time of last measurable concentration (AUClast) of MGTA-145 ranged from 20.1 h*µg/L
t o 2 1 4 9. 9 h* μ g / L. M e a n h alf-lif e (t 1 / 2) r a n g e d fr o m 0. 5 1 t o 1. 9 7 h o urs. C o-a d mi nistr ati o n of pl eri x af or of 1 0 mi n ut es or 2 h o urs h a d n o i m p a ct o n t h e P K pr ofil e of M G T A -1 4 5. F oll o wi n g t h e a d mi nistr ati o n of a s e c o n d d os e o n D a y 2 i n P art C, mi ni m al a cc u m ul ati o n w as o bs er v e d.  
Acc u m ul ati o n w as hi g h er wit h t h e 0. 0 7 m g / k g d os e t h a n wit h t h e 0. 0 3 m g / k g d os e. Uri n e e xcr eti o n of M G T A -1 4 5 w as ass ess e d fr o m 4 h o urs t o 1 6 d a ys aft er d osi n g, a n d M G T A -1 4 5 is n ot e xcr et e d i n uri n e.  
T h e i nf usi o n ti m e i n t h e st u d y of h e alt h y v ol u nt e ers w as s et at 1 0 mi n ut es. S u bs e q u e nt p h ar m a c o ki n etic m o d eli n g d o n e b y M a g e nt a T h er a p e utics s u p p orts a n i nf usi o n ti m e of 1 t o 1 0 mi n ut es as d e e m e d a cc e pt a bl e i n f ut ur e st u di es.  
Pl e as e r ef er t o t h e a cc o m p a n yi n g I n v esti g at o r's B r o c h u r e a n d a d diti o n al P o p ul ati o n P h a r m ac o ki n etic A n al ysis of M G T A -1 4 5 ( D R-2 0 -0 0 2) V e rsi o n 0 0 d at e d 1 4 J ul y 2 0 2 0 f or a d diti o n al d et ails.  
R e g ul at o r y C o m pli a n c e: Pl eri x af or is F D A a p pr o v e d f or st e m c ell m o bili z ati o n i n c o m bi n ati o n wit h G -C S F i n p ati e nts wit h m ulti pl e m y el o m a. M G T A -1 4 5 is n ot F D A a p pr o v e d. T h er ef or e, a n I n v esti g ati o n al N e w Dr u g a p plic ati o n (I N D) is r e q uir e d a n d will b e s u b mitt e d.
untitled h1
2. 3 r ati o

M G T A -1 4 5 ( G R O β T) a cti v at es t h e C X C R 2 p at h w a y i n n e utr o p hils. It h as s h o w n pr o misi n g a cti vit y f or r a pi d m o bili z ati o n of C D 3 4 + H S Cs i n pr e-cli nic al e v al u ati o n i n mic e. W h e n us e d i n c o m bi n ati o n wit h pl eri x af or, a C X C R 4 i n hi bit or, M G T A -1 4 5 h as t h e p ot e nti al t o r a pi dl y a n d r eli a bl y m o bili z e a d e q u at e n u m b ers of H S Cs f or st e m c ell tr a ns pl a nt ati o n. It h as b e e n e v al u at e d wit h pl eri x af or i n a p h as e I st u d y of h e alt h y v ol u nt e ers , w h er e it w as f o u n d t o b e s af e a n d r es ult e d i n r a pi d m o bili z ati o n of st e m c ells o n t h e s a m e d a y. T h es e H S Cs w er e tr a ns pl a nt e d i nt o s u bl et h all y irr a di at e d ( 2 0 0 c G y) N S G mic e at li mit dil uti o n ( 3 c ell d os es). E n gr aft m e nt of h u m a n C D 4 5 ( h C D 4 5 ) i n peri p h er al bl o o d w as m e as ur e d at w e e k 4 w e e ks p ost -tr a ns pl a nt b y fl o w c yt o m etr y. E n gr aft m e nt w as m or e r o b ust i n mic e i nj e ct e d h u m a n H S Cs o bt ai n e d fr o m M G T A-1 4 5 a n d pl eri x af or vs. t h os e o bt ai n e d wit h G -C S F al o n e.  
Gi v e n t h e pr o misi n g r es ults s e e n i n p r e-cli nic al m o d els a n d p h as e 1 d at a , w e e x p e ct t h at t h e c o m bi n ati o n of M G T A -1 4 5 a n d pl eri x af or will r es ult i n f ast, eff e cti v e a n d s af e st e m c ell m o bili z ati o n i n p ati e nts wit h m ulti pl e m y el o m a. M G T A -1 4 5 is a p ot e nti al alt er n ati v e t o G -C S F w h e n us e d i n c o m bin ati o n wit h pl eri x af or t o a c hi e v e s a m e d a y d osi n g a n d a p h er esis, r es ulti n g i n p ati e nt c o n v e ni e nc e, i m pr o v e d h e alt h c ar e r es o urc e utiliz ati o n a n d p ot e nti all y f e w er a d v ers e eff e cts t h a n ass oci at e d wit h m ulti -d a y G -C S F b as e d r e gi m e ns .  
T h er ef or e, t o e v al u at e t h e effic a c y a n d s af et y of t his n o v el m o bili z ati o n r e gi m e n, w e ar e p r o p osi n g a p h a s e II , p r o of of c o n c e pt st u d y of M G T A -1 4 5 a n d pl e ri x af o r i n p ati e nt s wit h m y el o m a . P ati e nts will r e c ei v e pl eri x af or at 0. 2 4 m g / k g ( 0. 1 6 m g / k g f or cr e ati ni n e cl e ar a nc e < 5 0 ml / mi n) S C f oll o w e d b y M G T A -1 4 5 at 0. 0 3 m g / k g I V aft er a t w o-h o ur i nt er v al. T his will b e f oll o w e d b y s a m e d a y a p h er esis.  
D osi n g m a y b e r e p e at e d o n d a y 2 b as e d o n C D 3 4 + yi el d of a p h er esis pr o d uct. T his st u d y will als o i ncl u d e c orrel ati v e st u di es t o u n d erst a n d t h e gr aft c o m p ositi o n, pr olif er ati o n of H S Cs i n vitr o wit h c ol o n y f or mi n g u nit (C F U ) ass a ys, e n gr aft m e nt ki n etics a n d i m m u n e r e c o nstit uti o n f oll o wi n g i nf usi o n of st e m c ells m o bili z e d wit h t his n o v el r e gi m e n.  
```
2. 4 St u d y D esi g n

- T h is is a p h as e II, o p e n l a b el , pr o of of c o nc e pt st u d y t o e v al u at e t h e s af et y a n d effic a c y

of H S C m o bili z ati o n wit h a n o v el dr u g, M G T A -1 4 5 at a fi x e d d os e l e v el i n c o m bi n ati o n

wit h pl eri x af or i n p ati e nts wit h M M f or st e m c ell m o bili z ati o n i n pr e p ar ati o n of

a ut ol o g o us st e m c ell tr a ns pl a nt.

- P ri m ar y p ur p os e of t h e st u d y i nt er v e nti o n : I nt e r v e nti o n al ( H S C m o bili z ati o n)

- Si n gl e c o h ort, si n gl e c e nt er, o p e n l a b el st u d y wit h o n e i nt er v e nti o n ar m

- R a n d o miz ati o n: N o n -r a n d o miz e d

- P ri m ar y o utc o m e: Effic a c y

- S e c o n d ar y O utc o m es: Effic a c y, s af et y, e n gr aft m e nt, s ur vi v al


```
untitled h1
2. 5 c o r

C o r r el ati v e St u d y \# 1: A s s e s s m e nt of g r aft c o m p o siti o n of st e m c ell p o p ul ati o n s a n d ot h e r w hit e bl o o d c ell s u b s et s b y fl o w c yt o m et r y a n d C y T O F .  
Ai m: T o ass ess t h e c o m p ositi o n of t h e a p h er esis pr o d uct o bt ai n e d aft er M G T A -1 4 5 a n d pl eri x af or m o bili z ati o n t hr o u g h e n u m er ati o n C D 3 4 C D 9 0 C D 4 5 R A c ells i n t h e pr o d uct a n d i m m u n ol o gic al c h ar a ct eriz ati o n of t h e T c ell s u bs ets, B c ell s u bs ets, N K c ells, n e utr o p hils, a n d m y el oi d / m o n oc ytic c ells i n t h e pr o d uct usi n g a c o m bi n ati o n of fl o w c yt o m etr y a n d C y T O F .  
C D 9 0 + C D 3 4 + st e m c ells h a v e b e e n s h o w n t o b e tr u e s elf -r e n e wi n g pl uri p ot e nt H S Cs a m o n g t h e C D 3 4 + c ells, w h er e as C D 9 0( -) C D 3 4 + c ells h a v e b e e n s h o w n t o b e diff er e nti at e d c o m mitt e d  
```
pr o g e nit or c ells .

2 6
W hil e d at a is li mit e d, t h er e is e vi d e nc e t h at C D 9 0 + C D 3 4 + c ells i n t h e gr aft dri v e


```  
t h e e n gr aft m e nt effici e nc y of st e m c ell gr afts. M G T A-1 4 5 w as ass oci at e d wit h pr ef er e nti al  
```
m o bili z ati o n of C D 9 0 + C D 3 4 + st e m c ells i n pr e -cli nic al m o d els vs. gr afts m o bili z e d b y G -C S F.

6, 7
I n


```  
t h e p h as e 1 st u d y of M G T A-1 4 5 wit h pl eri x af or, t h e m e di a n C D 9 0 + C D 3 4 + st e m c ell pr o p orti o n w as 3 3 %, hi g h er t h a n t h at o bs er v e d i n a s m all s u bs et of p ati e nts ( n = 2) m o bili z e d wit h G -C S F. T his c orr el ati v e st u d y will pr o vi d e d at a o n t h e C D 9 0 + C D 3 4 + c ells fr a cti o n fr o m a p h er esis pr o d ucts c oll e ct e d wit h t his n o v el m o bili z ati o n r e gi m e n (T a bl e 2 ).  
S e c o n dl y, w e will e v al u at e gr aft c o m p ositi o n of T, B a n d N K c ells a n d t h eir s u bs ets usi n g v ali d at e d fl o w c yt o m etr y/ C y T O F p a n els (T a bl e 3 ). It h as b e e n s h o w n t h at hi g h er l y m p h oc yt e s u bs et pr o p orti o ns i n t h e st e m c ell gr aft ar e ass oci at e d wit h b ett er p ost -tr a ns pl a nt i m m u n e r e c o nstit uti o n a n d s ur vi v al.  
Ass ess m e nt of gr aft c o m p ositi o n will b e d o n e b y fl o w c yt o m etr y i n t h e l a b of Dr. J u dit h S hiz ur u at St a nf or d U ni v ersit y a n d b y C y T O F i n t h e H u m a n Im m u n e M o nit ori n g C e nt er at St a nf or d U ni v ersit y .  
C orr el ati o n of fr a cti o n of C D 9 0 + C D 3 4 + c ells wit h e n gr aft m e nt ki n etics will b e e x pl or e d. T his d at a will b e c o m p ar e d wit h d at a fr o m a c o nt e m p or a n e o us c o h ort of p ati e nts wit h m ulti pl e m y el o m a u n d er g oi n g H S C c oll e cti o n wit h c urr e ntl y a p pr o v e d r e gi m e ns . S a m pl es will b e o bt ai n e d u n d er a s e p ar at e I R B a p pr o v e d bi or e p osit or y pr ot oc ol.  
T hir dl y, w e will e v al u at e gr aft c o nt a mi n ati o n usi n g n e xt g e n er ati o n fl o w c yt o m etr y ass a y mi ni m al r esi d u al dis e as e n e g a ti vit y t esti n g. M R D N G F will b e b as e d o n t h e E ur o -Fl o w st a n d ar diz e d al g orit h m a n d will b e d o n e at M a y o Cli nic.  
2 7 -2 9 T h e s e nsiti vit y of t h e ass a y is 1 i n 1 x 1 0 t o 1 x 1 0 6 c ells. It is a 2 t u b e, 8 c ol or ass a y a n d t h e f oll o wi n g p a n els ar e us e d:
Pr ot oc ol V ersi o n 1. 4 , 2 1 A pril 2 0 2 1 2 5 I R B-5 7 0 5 6 T u b e \# 1: C D 3 8 / C D 5 6 / C D 4 5 / C D 1 9 / C D 1 1 7 / C D 8 1 / C D 1 3 8 / C D 2 7 T u b e \# 2: C D 3 8 / C D 5 6 / C D 4 5 / C D 1 9 / K a p p a / L a m b d a / C D 1 3 8 / C D 2 7  
| Fl u or oc hr o m e   | T ar g et                   | Cl o n e   | V e n d or          | C at al o g N o.                      | Fi n al  Dil uti o n   |
|-----------------------|-----------------------------|------------|---------------------|---------------------------------------|------------------------|
| FI T C                | h C D 4 5 R A               | HI 1 0 0   | e Bi osci e nc es   | 1 1 -0 4 5 8 -4 2                     | 1: 1 0 0               |
| P E                   | h C D 9 0  ( 2 0  g / m L) | P R 1 3    | P a cific G M P     | l ot # 1 0 2- 1 4 P / N 7 0 - 0 0 3 1 | 1: 1 0                 |
| A P C -C y 7          | h C D 1 2 3                 | 6 H 6      | e Bi osci e nc es   | 4 7 -1 2 3 9 -4 2                     | 1: 1 0 0               |
| A P C                 | h C D 3 4                   | 5 6 1      | Bi o L e g e n d    | 3 4 3 6 0 8                           | 1: 1 0 0               |
| P E -C y 7            | h C D 3 8                   | HI T 2     | e Bi osci e nc es   | 2 5 -0 3 8 9 -4 2                     | 1: 1 0 0               |
| B V 5 1 0             | h C D 1 0                   | HI 1 0 a   | Bi o L e g e n d    | 3 1 2 2 1 9                           | 1: 1 0 0               |
| P a c Bl u e          | h C D 1 1 7                 | 1 0 4 D 2  | e Bi osci e nc es   | 4 8 -1 1 7 8 -4 2                     | 1: 1 0 0               |
| P er C P -C y 5. 5    | h C D 1 9                   | HI B 1 9   | B D Bi osci e nc es | 5 6 1 2 9 5                           | 1: 1 0 0               |  
1: 1 0  
1 0  
T a bl e 3 : C y T O F P a n el wit h A nti b o di e s f o r p e ri p h e r al bl o o d m o n o n u cl e a r c ell  
| P B M C p h e n ot y pi n g   |                  |                             |                       |
|-------------------------------|------------------|-----------------------------|-----------------------|
| M et al l a b el              | S p e cifi cit y | Cl o n e                    | C o nj u g at e d b y |
| 1 0 2 -1 1 0 P d  1 1 3I n    | C D 5 7          | H C D 5 7, Bi o L e g e n d | HI M C                |
| 1 1 5I n                      | li v e / d e a d |                             |                       |
| 1 3 9 L a  1 4 1 P r          |                  |                             |                       |  
| 1 4 2 N d                                        | C D 1 9     | SJ 2 5 C 1, S o ut h er n Bi o T ec h         | HI M C                        |        |
|--------------------------------------------------|-------------|-----------------------------------------------|-------------------------------|--------|
| 1 4 3 N d                                        | C D 4       | S K 3, Bi o L e g e n d                       | HI M C                        |        |
| 1 4 4 N d                                        | C D 8       | S K 1, Bi o L e g e n d                       | HI M C                        |        |
| 1 4 5 N d                                        | C D 3 9 B   | Bi o L e g e n d                              | HI M C                        |        |
| 1 4 6 N d                                        | I g D       | I A 6-2, Bi o L e g e n d                     | HI M C                        |        |
| 1 4 7 S                                          | m           | C D 8 5j                                      | 2 9 2 3 1 9, R & D S yst e ms | HI M C |
| 1 4 8 N d                                        | C D 1 1c    | B u 1 5, Bi o L e g e n d                     | HI M C                        |        |
| 1 4 9 S                                          | m           | C D 1 6                                       | 3 G 8, Bi o L e g e n d       | HI M C |
| 1 5 0 N d                                        | C D 3       | U C H T 1, B D                                | HI M C                        |        |
| 1 5 1 E u                                        | C D 3 8     | H B -7, B D                                   | HI M C                        |        |
| 1 5 2 S                                          | m           | C D 2 7                                       | L 1 2 8, B D                  | HI M C |
| 1 5 3 E u                                        | C D 1 1 b   | I C R F 4 4, Bi o L e g e n d                 | HI M C                        |        |
| 1 5 4 S                                          | m           | C D 1 4                                       | M 5 E 2, Bi o L e g e n d     | HI M C |
| 1 5 5 G d                                        | C C R 6     | 1 1 A 9, B D or G 0 3 4 E 3, Bi o L e g e n d | HI M C                        |        |
| 1 5 6 G d                                        | C D 9 4     | H P -3 D 9, B D                               | HI M C                        |        |
| 1 5 7 G d                                        | C D 8 6     | I T 2. 2, Bi o L e g e n d                    | HI M C                        |        |
| 1 5 8 G d                                        | C X C R 5   | R F 8 B 2, B D                                | HI M C                        |        |
| 1 5 9 T b                                        | C X C R 3   | G 0 2 5 H 7, Bi ol e g e n d                  | HI M C                        |        |
| 1 6 0 G d                                        | C C R 7     | 1 5 0 5 0 3, R & D S yst e ms                 | HI M C                        |        |
| 1 6 1 D y  1 6 2 D y                             | C D 4 5 R A | HI 1 0 0, Bi o L e g e n d                    | HI M C                        |        |
| 1 6 3 D y  1 6 4 D y                             | C D 2 0     | 2 H 7, Bi o L e g e n d                       | HI M C                        |        |
| 1 6 5 H o                                        | C D 1 2 7   | A 0 1 9 D 5, Bi o L e g e n d                 | HI M C                        |        |
| 1 6 6 E r                                        | C D 3 3     | P 6 7. 8, B D                                 | HI M C                        |        |
| Pr ot oc ol V ersi o n 1. 4 , 2 1 A pril 2 0 2 1 | 2 7         | I R B-5 7 0 5 6                               |                               |        |  
| 1 6 7 E r   | C D 2 8    | L 2 9 3, B D            | HI M C       |        |
|-------------|------------|-------------------------|--------------|--------|
| 1 6 8 E r   | C D 2 4    | M L 5, Bi o L e g e n d | HI M C       |        |
| 1 6 9 T     | m          | I C O S                 | D X 2 9, B D | HI M C |
| 1 7 0 E r   | C D 1 6 1  | D X 1 2, B D            | HI M C       |        |
| 1 7 1 Y b   | T C R g d  | B 1, Bi o L e g e n d   | HI M C       |        |
| 1 7 2 Y b   | P D -1     | E H 1 2. 1, B D         | HI M C       |        |
| 1 7 3 Y b   | C D 1 2 3  | 9 F 5, B D              | HI M C       |        |
| 1 7 4 Y b   | C D 5 6    | N C A M 1 6. 2, B D     | HI M C       |        |
| 1 7 5 L u   | H L A -D R | G 4 6 -6, B D           | HI M C       |        |
| 1 7 6 Y b   | C D 2 5    | M -A 2 5 1, B D         | HI M C       |        |  
C o r r el ati v e St u d y \# 2: A s s e s s p r olif e r ati o n a n d diff e r e nti ati o n p ot e nti al of H S C s c oll e ct e d wit h M G T A -1 4 5 a n d pl e ri x af o r vi a c ol o n y -f o r mi n g u nit ( C F U) a s s a y s f r o m t h e a p h e r e si s a ut o g r aft.  
C F U ass a ys ar e d o n e t o e v al u at e t h e pr olif er ati o n a n d diff er e nti ati o n p ot e nti al of H S Cs.  
3 0 -3 2 T h e y pr o vi d e i n-vitr o f u ncti o n al d at a of c oll e cte d H S Cs, w hic h c o m pl e m e nts t h e d at a o bt ai n e d fr o m fl o w c yt o m etric e v al u ati o n of t h e a p h er esis pr o d uct . T h e a p h er esis pr o d uct c o nt ai ni n g t h e H S Cs is pl at e d o n a c ult ur e m e di u m. C ult ur es ar e gr o w n f or a fi x e d d ur ati o n of ti m e ( 1 0 -1 4 d a ys) a n d pr o g e nit or c ol oni es gr o wi n g i n t h e c ult ur e m e di a ar e t h e n q u a ntifi e d. T h e y i ncl u d e: c ol o n y f or mi n g u nit er yt hr oc yti c ( C F U -E), bl ast f or mi n g u nit er yt hr oc ytic ( B F U -E), c ol o n y f or mi n g u nit gr a n ul oc ytic a n d m o n oc ytic ( C F U -G M), c ol o n y f or mi n g u nit gr a n ul oc ytic, er yt hr oc yti c, m o n oc yti c a n d m e g a k ar y oc ytic  
( C F U-G E M M), a n d hi g hl y pr olif er ati v e pr o g e nit ors ( H P P).  
C F U ass a ys will b e d o n e p er St a nf or d B M T C ell ul ar T h er a p y F a cilit y st a n d ar d pr ot oc ol, w hi c h is s u m m ariz e d b el o w:  
o D esir e d pl ati n g c o nc e ntr ati o n f or u n m a ni p ul at e d fr es h or t h a w e d p eri p h er all y c oll e ct e d  
```
a ut ol o g o us H S Cs: St arti n g Pr o d uct: 1 -5 x 1 0

5
c ells


```  
o R e q uir e d v ol u m e of fr es h or t h a w e d c ell s us p e nsi o n a n d Isc o v e is a d d e d t o C F U m e di a t u b e o F oll o wi n g t h e a d diti o n c ells a n d Isc o v e ar e a d d e d t o m et h y ell ul os e tiss u e c ult ur e m e di u m, t h e c ells ar e v ort e x e d o O nc e t h e c ell - m et h y ell ul os e tiss u e c ult ur e s ol uti o n s ettl es, 2 w ells of a 2 4 -w ell pl at e ar e e a c h s e e d e d wit h 0. 2 5 m L of t h e s ol uti o n o T h e r e m ai ni n g w ells ar e fill e d wit h ~ 0. 5 m L P B S t o pr e v e nt e v a p or ati o n o Pl at e is i nc u b at e d f or 1 4 d a ys, t h e n r e a d f or C F Us.  
C o r r el ati v e St u d y \# 3: T o a s s e s s i m m u n ol o gi c al c h a r a ct e ri z ati o n of w hit e c ell p o p ul ati o n s u b s et s ( T c ell s u b s et s, B c ell s u b s et s, N K c ell s, n e ut r o p hil s, a n d m y el oi d / m o n o c yti c c ell s) i n p ati e nt's p e ri p h e r al bl o o d at d a y 2 8 u si n g fl o w c yt o m et r y a n d at d a y 1 0 0 u si n g fl o w c yt o m et r y a n d C y T O F  
H S Cs i nf us e d aft er hi g h -d os e c h e m ot h er a p y r e p o p ul at e t h e h ost h e m at o p oi esis a n d l e a d t o gr a d u al i m m u n e r e c o nstit uti o n. T h e ti m e t a k e n f or r e c o v er y of diff er e nt i m m u n e c ell s u bs ets c a n v ar y.  
I m m u n e r e c o nstit uti o n n ot o nl y i m p a cts i nf e cti o us dis e as e o utc o m es, b ut als o h as b e e n s h o w n t o h a v e a n i m p a ct o n s ur vi v al o utc o m es. E arl y l y m p h oc yt e c o u nt r e c o v er y is ass oci at e d wit h b ett er  
```
s ur vi v al aft er A S C T i n p ati e nts wit h m ulti pl e m y el o m a a n d n o n -H o d g ki n's l y m p h o m a.

3 3, 3 4
It h as b e e n


```  
s h o w n t h at hi g h er l y m p h oc yt e s u bs et pr o p orti o ns i n t h e st e m c ell gr aft ar e ass oci at e d wit h p ost -  
```
tr a ns pl a nt l y m p h oc yt e c o u nt, w hic h i n t ur n h as a str o n g c orr el ati o n wit h s ur vi v al o utc o m es.

3 3, 3 5


```  
W hit e c ell s u bs ets will b e e v al u at e d b y fl o w c y t o m etr y a n d ( C y T O F (C yt o m etr y b y Ti m e -Of -Fli g ht) at d a y 2 8 a n d d a y 1 0 0 (T a bl e 4 a n d T a bl e 5 ). M ass c yt o m etr y all o ws si m ult a n e o us t esti n g of s e v er al a nti g e ns a n d is a d v a nt a g e o us t o pr o vi d e a d et ail e d o v er vi e w of diff er e nt c ell p o p ul ati o ns a n d w h e n  
```
st u d yi n g s m all tr a nsiti o n al i m m u n e p o p ul ati o ns.

3 6, 3 7
T h e pr oc ess is w ell -est a blis h e d at t h e h u m a n i m m u n e m o nit ori n g c or e l a b or at or y f a ciliti es at St anf or d U ni v ersit y.

3 8 -4 3


```  
| Fl u or oc hr o m e   | T ar g et     | Cl o n e      | V e n d or          | C at al o g  N o.   |             |          |    |
|-----------------------|---------------|---------------|---------------------|---------------------|-------------|----------|----|
| FI T C                | h C D 1 0 3   | B er -A C T 8 | B D Bi osci e nc es | 5 5 0 2 5 9         | 1: 1 0 0    | 1        |    |
| P E                   | h C D 6 2 L   | D R E G -5 6  | B D Bi osci e nc es | 5 5 5 5 4 4         | 1: 1 0 0    | 1        |    |
| P er C P -C y 5. 5    | h C D 4       | R P A -T 4    | B D Bi osci e nc es | 5 6 0 6 5 0         | 1: 1 0 0    | 1        |    |
| A P C -H 7            | h C D 8       | S K 1         | B D Bi osci e nc es | 5 6 0 1 7 9         | 1: 1 0 0    | 1        |    |
| A P C                 | h C D 5 6     | B 1 5 9       | B D Bi osci e nc es | 5 5 5 5 1 8         | 1: 5 0      | 2        |    |
| P E -C y 7            | h C D 4 5 R A | HI 1 0 0      | B D Bi osci e nc es | 5 6 0 6 7 5         | 1: 1 0 0    | 1        |    |
| B V 5 1 0             | h C D 3 1     | W M 5 9       |                     | B D Bi osci e nc es | 5 6 3 4 5 4 | 1: 1 0 0 | 1  |
| A P C -R 7 0 0        | h C C R 7     | 3 D 1 2       | B D Bi osci e nc es | 5 6 5 8 6 7         | 1: 1 0 0    | 1        |    |
| B V 4 2 1             | h C D 3       | S K 7         | B D Bi osci e nc es | 5 6 3 7 9 8         | 1: 1 0 0    | 1        |    |  
| Fi n al  Dil uti o n   |
|------------------------|  
T a bl e 5 : Fl o w C yt o m et r y P a n el wit h A nti b o di e s f o r B c ell st ai ni n g  
Fl u or oc hr o m e T ar g et Cl o n e V e n d or C at al o g  
N o.  
µ L A b /  
1 0 0 µ L  
c oc kt ail  
FI T C hI g M G 2 0 -1 2 7 B D Bi osci e nc es 5 5 5 7 8 2 1: 1 0 0 1  
P E h C D 2 4 M L 5 B D Bi osci e nc es 5 5 5 4 2 8 1: 1 0 0 1  
P er C P -C y 5. 5 h C D 1 9 HI B 1 8 B D Bi osci e nc es 5 6 1 2 9 5 1: 1 0 0 1  
A P C -H 7 h C D 2 0 2 H 7 e Bi osci e nc es 5 6 1 1 7 2 1: 1 0 0 1  
A P C h C D 3 8 HI T 2 B D Bi osci e nc es 5 5 5 4 6 2 1: 1 0 0 1  
P E -C y 7 h C D 2 7 M -T 2 7 1 B D Bi osci e nc es 5 6 0 6 0 9 1: 1 0 0 1  
B V 5 1 0 hI g D I A 6-2 B D Bi osci e nc es 5 6 3 0 3 4 1: 1 0 0 1  
B V 4 2 1 h C D 3 S K 7 B D Bi osci e nc es 5 6 3 7 9 8 1: 1 0 0 1  
Pr ot oc ol V ersi o n 1. 4 , 2 1 A pril 2 0 2 1 2 9 I R B-5 7 0 5 6  
| Fi n al  Dil uti o n   |
|------------------------|
untitled h1
2. 6 p ati e

A c o m bi n e d q u esti o n n air e i nc or p or ati n g it e ms a d a pt e d f or i nf usi o n sit e r e a cti o n fr o m t h e P ati e nt R e p ort e d O utc o m es 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) as w ell as t h e Bri ef P ai n I n v e nt or y will b e us e d t o m e as ur e p ati e nt r e p ort e d o utc o m es. P ati e nts will b e as k e d t o c o m pl et e q u esti o n n air es o n e a c h d a y of c oll e cti o n a n d wit hi n o n e w e e k f oll o wi n g st e m c oll e cti o n.  
P R O -C T C A E is a s elf-r e p orti n g t o ol, w hic h h as b e e n pr e vi o usl y v ali d at 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.

4 4, 4 5
It c o v ers v ari o us s y m pt o ms a n d ass ess es t h e pr es e nc e,


```  
fr e q u e nc y a n d s e v erit y of t h es e s y m pt o ms. W e will ass ess t h e f oll o wi n g s y m pt o m ati c A Es : 'p ai n a n d s w elli n g at i nj e cti o n sit e '  
T h e B ri ef P ai n I n v e nt o r y ( B PI) c o nsists of 2 d o m ai ns: p ai n s e v erit y a n d p ai n i nt erf er e nc e wit h a  
```
r e c all of 2 4 h o urs.

4 6
W e will us e t h e s h ort -f or m B PI wit h 9 it e ms, w hic h r e q uir es a b o ut 5 mi n ut es t o


```  
c o m pl et e, o n a v er a g e. P ati e nts ar e as k e d if t h e y h a v e p ai n a n d t h e l oc ati o n of p ai n, P ai n s e v erit y is sc or e d o n a sc al e of 0 -1 0 wit h 0 = n o p ai n a n d 1 0 = p ai n as b a d as y o u c a n i m a gi n e. T h e B PI p ai n s e v erit y q u esti o ns ass ess p ai n at its " w orst," "l e ast," " a v er a g e," a n d " n o w" (c urr e n t p ai n). A c o m p osit e m e a n s e v erit y sc or e of t h es e f o ur it e ms m a y b e c alc ul at e d. P ai n i nt erf er e nc e is esti m at e d b y 7 q u esti o ns t h at as k p ati e nts h o w p ai n h as i nt erf er e d wit h s e v e n d ail y a cti viti es: w al ki n g, w or k, m o o d, e nj o y m e nt of lif e, r el ati o ns wit h ot h e rs, a n d sl e e p. P ai n i nt erf er e nc e is sc or e d as a m e a n of t h e 7 i nt erf er e nc e it e ms. I m p ut ati o n f or missi n g d at a m a y b e us e d if at l e ast 5 0 % ( 4 of 7 it e ms h a v e b e e n c o m pl et e d at a gi v e n ti m e p oi nt). Q u esti o ns a b o ut p ai n m e dic ati o ns a n d t h eir eff e cti v e n ess ar e als o i ncl u d e d.  
A c o p y of t h e i nstr u m e nt is pr o vi d e d i n t h e A P P E N DI X B : P R O Q u esti o n n air e . It is als o a v ail a bl e i n ot h er l a n g u a g es i ncl u di n g S p a nis h. It is v ali d at e d f or b ot h a c ut e a n d c hr o nic p ai n. It c a n b e s elf -  
r e p ort e d or as k e d i n a n i nt er vi e w f or m at. As d escri b e d a b o v e, t h er e is n o sc ori n g al g orit h m, b ut  
" w orst p ai n" or t h e arit h m etic m e a n of t h e f o ur s e v erit y it e ms c a n b e us e d as m e as ur es of p ai n s e v erit y; t h e arit h m etic m e a n of t h e s e v e n i nt erf er e nc e it e ms c a n b e us e d as a m e as ur e of p ai n i nt erf er e nc e.  
I nt er n al c o nsist e nc y f or B PI r a n g es fr o m 0. 8 0 t o 0. 8 7 f or 4 it e ms f or p ai n s e v erit y as d e m o nstr at e d  
```
i n n u m er o us st u di es, i ncl u di n g c a nc er p ati e nts

4 7, 4 8
. T est-r et est ( 1 d a y t o 1 w e e k) r eli a bilit y f or


```  
r ati n gs of p ai n as w orst ( 0. 9 3) a n d u s u al or a v er a g e p ai n ( 0. 7 8) i n p ati e nts wit h m et ast atic c a nc er  
```
w er e a cc e pt a bl e
4 6. F a ct or str uct ur e a n d t h e vali dit y of B PI h as b e e n s ucc essf ull y t est e d

4 9
. T h e


```  
v ali dit y of B PI w as ass ess e d usi n g k n o w n -gr o u p m et h o ds wit h m e a n sc or es c o m p ar e d a cr oss c a nc er p ati e nts t a ki n g diff er e nt t y p es of p ai n m e dic ati o n ( n arc otic v ers us n o n -n arc otic p ai n r eli e v ers). T h e B PI m e a n sc or es si g nific a ntl y dif f er e d b et w e e n t h e 2 gr o u ps, d e m o nstr ati n g str o n g e vi d e nc e of  
```
v ali dit y

4 7
. F or c o n diti o ns s uc h as b o n e m et ast asis a n d fi br o m y al gi a, t h e mi ni m u m cli nic all y i m p ort a nt diff er e nc e f or B PI is a p pr o xi m at el y a 2-p oi nt c h a n g e fr o m b as eli n e

5 0, 5 1
. A n ot h er st u d y o n


```  
b u pr e n or p hi n e us e d i n l o w er b a c k p ai n us e d a m i ni m al cli nic all y im p ort a nt d iff er e nc e of 2 p oi nts f or  
```
B PI

5 2
.


```  
P R O q u esti o n n air es will b e d esi g n e d i n a p a p er f or m at t o b e fill e d b y t h e p ati e nt or st u d y t e a m m e m b er i nt er vi e wi n g t h e p ati e nt. D at a will b e u pl o a d e d i n t h e E D C t o ol.
untitled h1
3 p a r ti

P ati e nt eli gi bilit y will b e r e vi e w e d. I ncl usi o n a n d e xcl usi o n crit eri a ar e list e d b el o w. Eli gi bl e p ati e nts will b e i n vit e d t o e nr oll o n t o t h e st u d y a n d will si g n i nf or m e d c o ns e nt as d escri b e d i n S e cti o n 3. 3 . R ef er t o t h e P artici p a nt Eli gi bilit y C h e c klist i n A P P E N DI X B : P R O Q u esti o n n air e .
untitled h1
3. 1 i n clu

3. 1. 1 Di a g n osis of m ulti pl e m y el o m a p er t h e I nt er n ati o n al M y el o m a W or ki n g Gr o u p (I M W G)  
crit eri a .  
3. 1. 2 A g e: 1 8 t o 7 0 y e ars 3. 1. 3 Eli gi bl e f or A S C T p er i nstit uti o n al g ui d eli n es 3. 1. 4 Wit hi n o n e y e ar of st art of m y el o m a t h er a p y 3. 1. 5 C ar di a c a n d p ul m o n ar y st at us s uffici e nt t o u n d er g o a p h er esis a n d tr a ns pl a nt ati o n p er  
i nstit uti o n al tr a ns pl a nt g ui d eli n es.  
3. 1. 6 C alc ul at e d cr e ati ni n e cl e ar a nc e > 3 0 m L / mi n a cc or di n g t o t h e M o dific ati o n of Di et i n R e n al Dis e as e ( M D R D) f or m ul a  
3. 1. 7 A bs ol ut e n e utr o p hil c o u nt > 1 5 0 0 x 1 0 / L a n d pl at el ets > 1 0 0, 0 0 0 x 1 0 / L  
3. 1. 8 A bilit y t o u n d erst a n d a n d t h e willi n g n ess t o si g n a writt e n i nf or m e d c o ns e nt d oc u m e nt.  
3. 1. 9 A gr e e m e nt t o us e a n a p pr o v e d f or m of c o ntr ac e pti o n f or m al e p ati e nts or f e m al e p ati e nts of c hil d b e ari n g p ot e nti al.
untitled h1
3. 2 e x cl

3. 2. 1 Hist or y of pri or st e m c ell tr a ns pl a nt f or m ulti pl e m y el o m a or ot h er i n dic ati o ns 3. 2. 2 Pl a n n e d t a n d e m st e m c ell tr a ns pl a nt 3. 2. 3 Pri or hist or y of f ail ur e t o c oll e ct H S Cs .  
3. 2. 4 Li v er f u ncti o n t ests: T ot al b ilir u bi n > 1. 5 x u p p er li mit of n or m al ( U L N) i n t h e a bs e nc e of a d oc u m e nt e d hist or y of Gil b ert's s y n dr o m e a n d / or A S T / A L T > 3 x U L N  
3. 2. 5 K n o w n all er g y t o M G T A -1 4 5 or pl eri x af or 3. 2. 6 Lif eti m e e x p os ur e t o l e n ali d o mi d e gr e at er t h a n 6 c u m ul ati v e m o nt hs of tr e at m e nt , i. e. m or e  
t h a n si x 2 8 -d a y c ycl es or m or e t h a n ei g ht 2 1 -d a y c ycl es 3. 2. 7 Pr e g n a nt or l a ct ati n g w o m e n .
untitled h1
3. 3 i nf o

All p artici p a nts will b e pr o vi d e d a c o ns e nt f or m d escri bi n g t h e st u d y wit h s uffici e nt i nf or m ati o n f or p artici p a nts t o m a k e a n i nf or m e d d e cisi o n r e g ar di n g t h eir p artici p ati o n. P artici p a nts will si g n t h e I R B a p pr o v e d i nf or m e d c o ns e nt pri or t o p artici p ati o n i n a n y st u d y s p e cific pr oc e d ur e. T h e p artici p a nt will r e c ei v e a c o p y of t h e si g n e d a n d d at e d c o ns e nt d oc u m e nt. T h e ori gi n al si g n e d c o p y of t h e c o ns e nt d oc u m e nt will b e r et ai n e d i n t h e m e dic al r e c or d or r es e arc h fil e.
untitled h1
3. 4 st u d

P ri m a r y C o m pl eti o n: T h e st u d y is a ntici p at e d t o r e a c h pri m ar y c o m pl eti o n 1 5 m o nt hs fr o m t h e ti m e t h e st u d y o p e ns t o a ccr u al. W e a ntici p at e a ccr u al t o b e c o m pl et e d i n 9 -1 2 m o nt hs a n d t h e r e m ai n d er of t h e ti m e is r e q uir e d t o c o m pl et e i nt er v e nti o n a n d f oll o w -u p f or pri m ar y e n d p oi nt.  
St u d y C o m pl eti o n: T h e st u d y is a ntici p at e d t o r e a c h st u d y c o m pl eti o n 1 8 m o nt hs fr o m t h e ti m e t h e st u d y o p e ns t o a ccr u al.
untitled h1
4 t r e a

T his is a n o p e n l a b el, pr o of of c o nc e pt, p h as e 2 st u d y t o e v al u at e s af et y a n d effic a c y of st e m c ell m o bili z ati o n (f or hi g h -d os e t h er a p y a n d a ut ol o g o us st e m c ell r esc u e) wit h a c o m bi n ati o n of M G T A -  
1 4 5 a n d pl eri x af or, f oll o w e d b y s a m e d a y a p h er esis i n p ati e nts wit h m ulti pl e m y el o m a.  
T h e pri m ar y e n d p oi nt is s ucc essf ul c oll e cti o n ≥ 2 . 0 x 1 0 C D 3 4 c ells / k g wit h u p t o t w o a p h er esis s essi o ns aft er M G T A -1 4 5 / pl eri x af or d osi n g. S e c o n d ar y e n d p oi nts i ncl u d e c oll e cti o n of  
≥ 2. 0 x 1 0 C D 3 4 c ells / k g a n d ≥ 4. 0 x 1 0 C D 3 4 c ells / k g o n d a y o n e of a p h er esis a n d ≥ 4. 0 x 1 0 C D 3 4 c ells / k g a n d ≥ 6. 0 x 1 0 C D 3 4 c ells / k g i n u p t o t w o d a ys of a p h er esis aft er M G T A-1 4 5 / pl eri x af or d osi n g, ass ess m e nt of a d v ers e e v e nts a n d s ucc essf ul e n gr aft m e nt as d escri b e d a b o v e.
untitled h1
4. 1 st u d

```
T h e st u d y i s di vi d e d i nt o t h r e e p h a s e s:

4. 1. 1 P r e -m o bili z ati o n p h a s e :

a. P ati e nts w h o ar e eli gi bl e will b e i n vit e d t o p artici p at e i n t h e st u d y. P ati e nts will

u n d er g o scr e e ni n g a n d b as eli n e e v al u ati o n .

b. If p ati e nts d o n ot m e et eli gi bilit y crit eri a aft er si g ni n g c o ns e nt o n t h e st u d y, t h e y will

b e d e e m e d scr e e n f ail ur es a n d m a y b e r e pl a c e d t o m e et a ccr u al g o al. P ati e nts m a y b e

r escr e e n e d at t h e discr eti o n of t h e pri nci p al i n v esti g at or. P ati e nts will b e e nr oll e d

aft er t h e y m e et eli gi bilit y crit eri a .

c. C h e m ot h er a p y, i ncl u di n g i m m u n o m o d ul at or y dr u gs (I Mi Ds) t o b e st o p p e d 1 4 d a ys

pri or t o st art of m o bili z ati o n.


```
untitled h1
4. 1. 2 s tu

All p ati e nts will r e c ei v e M G T A -1 4 5 a n d pl eri x af or at si n gl e, w ei g ht-b as e d d os es. D os e of M G T A -1 4 5 h as b e e n d et er mi n e d fr o m a p h as e 1 st u d y. P ati e nts will u n d er g o s e q u e nti al a d mi nistr ati o n of pl eri x af or 0. 2 4 m g / k g s u bc ut a n e o usl y f oll o w e d 2 h o urs l at er b y M G T A -1 4 5 at 0. 0 3 m g / k g i ntr a v e n o usl y (3 t o 1 0 mi n ut e i nf usi o n) as s h o w n i n T a bl e 6 . F or p ati e nts wit h cr e ati ni n e cl e ar a nc e  
< 5 0 ml / mi n ut e, pl eri x af or d os e will b e r e d uc e d t o 0. 1 6 m g / k g p er p a c k a g e i ns ert. T his will b e f oll o w e d b y a p h er esis.  
| M G T A -1 4 5   | Pl e ri x af o r                                                                                                   |                                   |            |
|------------------|--------------------------------------------------------------------------------------------------------------------|-----------------------------------|------------|
| D o s e          |                                                                                                                    |                                   |            |
| (                | m g / k g)                                                                                                         | T ot al D o s e s                 | R o ut e   |
| A d              | mi ni st e r e d                                                                                                   |                                   |            |
| 0. 0 3           | 1 p er d a y f or 1 t o  2 d a ys  T ot al D o s e s                                                               | D o s e                           |            |
| R o ut e         |                                                                                                                    |                                   |            |
| A d              | mi ni st e r e d                                                                                                   | (                                 | m g / k g) |
| I V              | 0. 2 4 0 or  0. 1 6*                                                                                               | 1 p er d a y f or 1  t o 2 d a ys | S C        |
|                  | I V =i ntr a v e n o us; S C =s u bc ut a n e o us. * Pl eri x af or d os e r e d uc e d t o 0. 1 6 m g / k g p er |                                   |            |  
p a c k a g e i ns ert f or cr e ati ni n e cl e ar a nc e < 5 0 ml / mi n ut e
untitled h1
- d r u g

T h er e ar e n o d os e m o dific ati o ns f or t h e i n v esti g ati o n al a g e nt ( M G T A-1 4 5). If a n y p ati e nt e x p eri e nc e gr a d e 3 or hi g h er n o n -h e m at ol o gic al t o xicit y, n ot a p pr o pri at el y c o ntr oll e d b y a p pr o pri at e i nt er v e nti o ns, a n d c o nsi d er e d p ossi bl y, pr o b a bl y or d efi nit el y r elat e d t o M G T A -1 4 5, t h e st u d y dr u g will b e disc o nti n u e d a n d p ati e nt will g o t o e v e nt m o nit ori n g.
untitled h1
- i nf u si

P ati e nts s h o ul d b e c ar ef ull y m o nit or e d d uri n g M G T A -1 4 5 i nf usi o n. If a n i nf usi o n-r el at e d r e a cti o n d e v el o ps, t h e n t h e i nf usi o n s h o ul d b e t e m p or aril y i nt err u pt e d or sl o w e d d o w n. S u bj e cts w h o e x p eri e nc e a d v ers e e v e nts d uri n g t h e i nf usi o n m ust b e tr e at e d a cc or d i n g t o t h e i n v esti g at or's j u d g m e nt a n d b est cli nic al pr a ctic e. As d escri b e d a b o v e, if p ati e nt e x p eri e nc es a gr a d e 3 or hi g h er i nf usi o n r e a cti o n wit h M G T A-1 4 5 t h at is n ot a d e q u at el y c o ntr ol l e d b y a p pr o pri at e i nt er v e nti o ns, tr e at m e nt wit h M G T A-1 4 5 will b e disc o nti n u e d.
untitled h1
- a p h e

A p h er esis c oll e cti o n will b e gi n as s o o n as f e asi bl e aft er M G T A -1 4 5 i nf usi o n. A p h er esis s h o ul d c o m m e nc e (i. e. i nl et fl o w i niti at e d) n o l at er t h a n 3 0 mi n ut es aft er t h e st art of M G T A-1 4 5 i nf usi o n.  
A p h er esis pr oc e d ur e , i ncl u di n g t h e m a c hi n e, c oll e cti o n pr oc e d ur e a n d s u p p orti v e c ar e will b e i n a cc or d a nc e wit h st a n d ar diz e d pr oc e d ur es of St a nf or d B l o o d a n d m arr o w tr a nspl a nt ati o n  
( B M T) /A p h er esis pr o gr a m. E a c h s essi o n of a p h er esis will b e st a n d ar diz e d t o p r o c e s s at l e a st 3 bl o o d v ol u m e s, wit h a m a r gi n of + / -1 0 % o r 4. 5 h o u r s, w hi c h e v e r i s l o n g e r . T h e pr oc essi n g a n d cr y o pr es er v ati o n of t h e a p h er esis pr o d uct will b e i n a cc or d a nc e wit h St a nf or d B M T / C ell T h er a p y F a cilit y ( C T F) st a n d ar d iz e d pr oc e d ur es.  
A s e c o n d d a y of m o bili z ati o n a n d a p h er esis will b e p urs u e d i n p ati e nts w h o h a v e n ot c oll e ct e d 6. 0 x 1 0 C D 3 4 c ells / k g i n o n e s essi o n.  
A mi ni m u m of 2 . 0 x 1 0 C D 3 4 c ells / kg s h o ul d b e c oll ect e d i n o n e t o t w o a p h er esis s essi o ns. If t his g o al is n ot m et, p ati e nt m a y pr oc e e d wit h w as h o ut pr ot oc ol a n d alt er n ati v e st e m c ell m o bili z ati o n str at e g y as r o uti n e cli nic al c ar e at discr eti o n of tr e ati n g p h ysici a n .  
```
P ati e nts w h o h a v e c oll e ct e d b et w e e n 2. 0 t o 3. 9 x 1 0

6
C D 3 4 c ells / k g m a y pr oc e e d t o tr a ns pl a nt at


```  
t h e discr eti o n of t h e tr e ati n g p h ysici a n p er c urr e nt i nstit uti o n al g ui d eli n es. Alt er n ati v el y, t h e y c a n pr oc e e d wit h w as h o ut pr ot oc ol a n d alt er n ati v e st e m c ell m o bili z ati o n str at e g y as r o uti n e cli nic al c ar e . T his d e cisi o n will b e m a d e b y t h e tr e ati n g p h ysici a n i n c o ns ult ati o n wit h t h e PI. A mi ni m u m of 2. 0 x 1 0 C D 3 4 c ells / k g ar e r e c o m m e n d e d f or s ucc essf ul e n gr aft m e nt f or tr a ns pl a nt a n d w hil e a b ac k -u p is pr ef err e d, it is n ot m a n d at or y. T his is i n a cc or d a nc e wit h c urr e nt i nstit uti o n al st a n d ar d of pr a ctic e. If a n a d diti o n al c oll e cti o n is s o u g ht at t h e discr eti o n of t h e tr e ati n g p h ysici a n, it is r e c o m m e n d e d n ot t o c o m bi n e t h e st a n d ar d of c ar e m o bili z e d gr aft a n d t h e M G T A -1 4 5 + pl eri x af or m o bili z e d gr aft f or o n e tr a ns pl a nt.
untitled h1
- p ati e nt

P ati e nt r e p ort e d o utc o m es will b e ass ess e d as d escri b e d i n S e cti o n 2. 6 a b o v e usi n g a p ati e nt r e p ort e d q u esti o n n air e i nc or p or ati n g it e ms fr o m P R O -C T C A E, as w ell as t h e Bri ef P ai n I n v e nt or y.  
El e ctr o nic q u esti o n n air es will b e d esi g n e d t h at will b e a d mi nist er e d usi n g a t a bl et. P a p er c o pi es will b e a v ail a bl e as b ac k -u p a n d m a y b e us e d if u n a bl e t o c o m pl et e t h e el e ctr o nic q u esti o n n air es.  
El e ctr o nic q u esti o n n air es will b e dir e ctl y u pl o a d e d i nt o t h e M e d ri o d at a b as e. If p a p er c o pi es ar e us e d, t h e y will b e h a n d e d t o t h e st u d y c o or di n at or a n d st or e d i n a l oc k e d r o o m at St a nf or d H e alt h C ar e. P a p er a ns w ers will b e e nt er e d i nt o el e ctr o nic f or m at b y t h e st u d y st aff.  
P R O q u esti o n n air e is d esi g n e d t o b e s elf-a d mi nist er e d b y t h e p ati e nt ( assist a nc e c a n b e pr o vi d e d b y st u d y /cli nic al st aff, as n e e d e d) o n e a c h d a y of a p h er esis a n d at t h e p ost -a p h er esis cli nic visit ( wit hi n 7 d a ys of a p h er esis). O n t h e d a y of a p h er esis, t h e q u esti o n n air e s h o ul d b e gi v e n t o t h e p at i e nt aft er at l e ast 3 0 mi n ut es f oll o wi n g M G T A -1 4 5 i nf usi o n. It is r e c o m m e n d e d t o gi v e it t o t h e p ati e nt t o w ar ds t h e e n d of t h e a p h er esis s essi o n.
untitled h1
g e n e r

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T r e at m e nt

- Ot h er gr o wt h f a ct or m e d ic ati o ns (e. g. , G-C S F, gr a n ul oc yt e -m a cr o p h a g e c ol o n y -

sti m ul ati n g f a ct or) ar e pr o hi bit e d u p t o 7 d a ys pri or t o a n d d uri n g t h e

m o bili z ati o n a n d a p h er esis p h as e of t h e st u d y.

- P ati e nts e nr oll e d o n t his st u d y will r efr ai n fr o m p artici p ati o n i n a n y ot h er

i n v esti g ati o n al st u d y dr u g i n w hic h t h e y will r e c ei v e a n i n v esti g ati o n al st u d y dr u g

f or at l e ast f o ur w e e ks b ef or e d osi n g of M G T A -1 4 5 a n d pl eri x af or.

- I m m u n o m o d ul at or y dr u gs (I Mi Ds) t o b e st o p p e d 1 4 d a ys pri or t o st art of

m o bili z ati o n. Ot h er c a nc er dir e ct e d t h er a p y t o b e st o p p e d at l e ast 1 0 d a ys pri or

t o st art of m o bili z ati o n.

- P ati e nts s h o ul d r e c ei v e f ull s u p p orti v e c ar e w hil e o n t his st u d y. T his i ncl u d es

bl o o d pr o d u ct s u p p ort, a nti bi otic tr e at m e nt, a n d tr e at m e nt of ot h er n e wl y

di a g n os e d or c o nc urr e n t m e dic al c o n diti o ns. All bl o o d pr o d ucts a n d c o nc o mit a nt

m e dic ati o ns s uc h as a nti di arr h e als, a n al g esics, a n d / or a nti e m etics r e c ei v e d fr o m

t h e first d a y of st u d y tr e at m e nt a d mi nistr ati o n u ntil 3 0 d a ys aft er t h e fi n al d os e

of M G T A -1 4 5 or u ntil st art of tr a ns pl a nt c o n diti o ni n g ( w hic h e v er c o m es first) will

b e r e c or d e d i n t h e m e dic al r e c or ds.

4. 1. 3. E v e nt M o nit o ri n g / F oll o w -u p :

a. A p ati e nt will b e c o nsi d er e d t o h a v e f ail e d m o bili z ati o n a n d will disc o nti n u e st u d y

dr u g a n d g o t o E v e nt M o nit ori n g if t h e y f ail t o c oll e ct t h e mi ni m u m of 2. 0 milli o n C D 3 4

c ells / k g aft er t w o a p h er esis s essi o ns .


```  
b. If p ati e nts u n d er g o r esc u e m o bili z ati o n f or a n y r e as o n (i ncl u di n g p h ysici a n discr eti o n t o c oll e ct m or e t h a n 2 milli o n C D 3 4 + c ells / k g) a n d pr oc e e d t o u pfr o nt tr a ns pl a nt wit h M G T A-1 4 5 a n d pl eri x af or m o bili z e d gr aft, t h e y will b e f oll o w e d f or s e c o n d ar y tr a ns pl a nt r el at e d o utc o m es. O n t h e ot h er h a n d, if t h e y u n d er g o u pfr o nt tr a ns pl a nt wit h t h e st e m c ell gr aft o bt ai n e d fr o m r esc u e m o bili z ati o n o nl y , t h e y will n ot b e f oll o w e d f or s e c o n d ar y o utc o m es. It is r e c o m m e n d e d n ot t o c o m bi n e gr afts fr o m diff er e nt m o bili z ati o n pr ot oc ols c. P ati e nts w h o ar e n ot pr oc e e di n g wit h u pfr o nt A S C T will b e f oll o w e d i n E v e nt M o nit ori n g u ntil 3 0 d a ys aft er c o m pl eti o n of st u d y dr u g. Aft er t h at n o, f urt h er f oll o w -  
u p is r e q uir e d i n p ers o n or vi a p h o n e visits. P ati e nts ' el e ctr o nic m e dic al r e c or ds m a y b e p eri o dic all y r e vi e w e d t o f oll o w -u p o n m y el o m a tr e at m e nt, r es p o ns e a n d l a b or at or y v al u es f or u p t o 5 y e ars or w h e n t h e y u n d er g o A S C T l at er i n dis e as e c o urs e, w hic h e v er is l at er.  
d. If p ati e nts ar e pr oc e e di n g wit h u pfr o nt tr a ns pl a nt, t h e y will b e f oll o w e d u ntil d a y 1 0 0 f or s e c o n d ar y o ut c o m es of e n gr aft m e nt, dis e as e pr o gr essi o n a n d s ur vi v al. Aft er t h at, n o f urt h er f oll o w -u p is r e q uir e d i n p ers o n or vi a p h o n e visits. P ati e nts el e ctr o nic m e dic al r e c or ds m a y b e p eri o dic all y r e vi e w e d t o f oll o w -u p o n m y el o m a tr e at m e nt, r es p o ns e a n d l a b or at or y v al u es f or u p t o 5 y e ars e. A d v ers e E v e nts occ urri n g aft er t h e p ati e nt c o m pl et es st u d y dr u g ( M G T A-1 4 5 a n d pl eri x af or) will b e c oll e ct e d o n t h e E v e nt M o nit ori n g F or m if t h e y ar e > / = gr a d e 3, at l e ast p ossi bl y r el at e d t o st u d y dr u gs a n d h a v e n ot b e e n pr e v i o usl y r e p ort e d.  
f. F or p ati e nts pr oc e e di n g wit h u pfr o nt tr a ns pl a nt ( d efi n e d u p t o 6 0 d a ys aft er H S C  
m o bili z ati o n), m y el o a bl ati v e m el p h al a n c o n diti o ni n g ( m el p h al a n 1 4 0- 2 0 0 m g / m )  
o n d a y -2 f oll o w e d will b y i nf usi o n of c oll e ct e d H S Cs c ells o n d a y 0 p er i nst it uti o n al st a n d ar d of pr a ctic e pr ot oc ol. T h e m a xi m u m i nt er v al b et w e e n st art of st e m c ell c oll e cti o n o n st u d y a n d tr a ns pl a nt o n t his st u d y is 6 0 d a ys. Wit hi n 6 0 d a ys, t h e ti mi n g of tr a ns pl a nt is at t h e discr eti o n of t h e tr e ati n g p h ysici a n. If tr a ns pl a nt is n ot pl a n n e d or is pl a n n e d aft er 6 0 d a ys of c oll e cti o n, t h es e p ati e nts will b e c o nsi d er e d i n t h e d el a y e d tr a ns pl a nt gr o u p a n d tr a ns pl a nt r el at e d o utc o m es will n ot b e f oll o w e d.
untitled h1
4. 2 c rit e

P ati e nts m a y b e wit h dr a w n fr o m t h e st u d y f or t h e f oll o wi n g r e as o ns:
a. If a p ati e nt si g ns t h e c o ns e nt f or m, b ut h as n ot r e c ei v e d t h e st u d y dr u g, t h e p ati e nt will b e r e g ar d e d as n o n -e v al u a bl e a n d will b e r e pl a c e d . T his i ncl u d es p ati e nts u n a bl e t o pr oc e e d wit h pl a n n e d st e m c ell c oll e cti o n f or a n y r e as o n, i ncl u di n g m e dic al iss u es t h at pr e cl u d e f urt h er p artici p ati o n or r e q uir e a pr o hi bit e d c o nc o mit a nt tr e at m e nt , or a c h a n g e of pl a n . S uc h p ati e nts will b e wit h dr a w n fr o m t h e st u d y. W h e n s uc h a n e v e nt h a p p e ns b ef or e t h e st u d y dr u g is gi v e n, t h e n p ati e nt will n ot b e f oll o w e d f or e v e nts / o utc o m es. T his p ati e nt will b e d e e m e d a 'c a nc el' a n d n o f urt h er d at a s u b missi o n is n e c ess ar y. P ati e nts m a y b e r e pl a c e d t o  
```
m e et a ccr u al g o al.

b. P ati e nts w h o r e q u est t o wit h dr a w fr o m t h e st u d y at a n y p oi nt will b e r e m o v e d.


```  
c. P ati e nts w h o ar e l ost t o f oll o w -u p b ef or e e n d of st u d y ( d efi n e d as t h e i n a bilit y t o c o nt a ct t h e p ati e nt o n 3 s e p ar at e d oc u m e nt e d occ asi o ns) will b e wit h dr a w n fr o m t h e st u d y.  
d. P ati e nts w h o pr oc e e d t o r esc u e m o bili z ati o n a n d u n d er g o tr a ns pl a nt d uri n g t h e st u d y wit h a st a n d ar d of c ar e m o bili z e d H S C gr aft.
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4. 3 st u d

T h e f oll o wi n g ar e s p e cific st u d y st o p pi n g r ul es. E nr oll m e nt will b e p a us e d p e n di n g disc ussi o ns wit h t h e F D A, a g e nt m a n uf a ct ur er a n d St a nf or d I R B s h o ul d a n y of t h e f oll o wi n g st u d y st o p pi n g r ul es occ ur:  
( 1) A n y p ati e nt wit h a st u d y a g e nt r el at e d Gr a d e 4 or Gr a d e 5 e v e nt  
( 2) M or e t h a n 1 ( o n e) p ati e nt e x p eri e nc es f ail e d / d el a y e d e n gr aft m e nt d u e t o n e utr o p hil r e c o v er y b e y o n d D a y 4 2  
( 3) M or e t h a n 1 ( o n e) p ati e nt d e v el o ps s y m pt o m atic h y p erl e u k oc yt osis .  
S y m pt o m ati c h y p e rl e u k o c yt o si s is d efi n e d as a w hit e bl o o d c ell ( W B C) c o u nt of o v er 1 0 0 x 1 0 / L  
( 1 0 0, 0 0 0 / micr o L) ass oci at e d wit h s y m pt o ms t h o u g ht t o b e d u e t o tiss u e h y p o xi a . m ost c o m m o n s y m pt o ms i ncl u d e r es pir at or y (s uc h as d ys p n e a a n d h y p o xi a wit h or wit h o ut diff us e i nt erstiti al or al v e ol ar i nfiltr at es o n i m a gi n g st u di es ) or n e ur ol o gic al distr ess (s uc h as vis u al c h a n g es, h e a d a c h e, diz zi n ess, ti n nit us, g ait i nst a bilit y, c o nf usi o n, s o m n ol e nc e, a n d c o m a ). L ess c o m m o n si g ns or s y m pt o ms i ncl ud e el e ctr oc ar di o gr a p hic si g ns of m y oc ar di al isc h e mi a or ri g ht v e ntric ul ar o v erl o a d, w ors e ni n g r e n al i ns uffici e nc y, pri a pis m, a c ut e li m b isc h e mi a, or b o w el i nf arcti o n .  
I n a d diti o n t o t h e a b o v e r ul es, th e st u d y m a y b e t e m p or aril y or p er m a n e ntl y disc o nti n u e d at a n y ti m e. R e as o ns f or st u d y disc o nti n u ati o n m a y i ncl u d e, b ut ar e n ot li mit e d t o, t h e f oll o wi n g:  
a. S af et y c o nc er ns b. P o or e nr oll m e nt c. R e q u est t o disc o nti n u e t h e tri al b y a r e g ul at or y or h e alt h a ut h orit y or a n I R B  
d. M a n uf a ct uri n g diffic ulti es / c o nc er ns
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4. 4 alt e r

If p ati e nts d o n ot p artici p at e i n t his st u d y, t h e y m a y u n d er g o H S C m o bili z ati o n wit h t h e t w o c o m m o n st a n d ar d of c ar e str at e gi es t o a c hi e v e H S C c oll e cti o n as d escri b e d i n S e cti o n 2. 1. 2. T h es e i ncl u d e c h e m ot h er a p y -b as e d m o bili z ati o n (t y pic all y c ycl o p h os p h a m i d e) al o n g wit h G-C S F or G -C S F  
m o bili z ati o n wit h pl eri x af or, i n all p ati e nts or i n a ris k -a d a pti v e al g orit h m.  
2 0 C ycl o p h os p h a mi d e m o bili z ati o n c a n t a k e t w o t o t hr e e w e e ks a n d r es ult i n c o m plic ati o ns li k e n e utr o p e nic f e v er a n d si g nific a nt c yt o p e ni as.  
2 -4 G -C S F a n d pl eri x af or m o bili z ati o n r e q uir es u p t o 4 d a ys of G -C S F i nj e cti o ns b ef or e m o bili z ati o n c a n b e gi n ( Fi g u r e 1). I nj e cti o ns ar e c o nti n u e d t hr o u g h c oll e cti o n, w hic h c a n b e as l o n g as 4 s essi o ns, t h er ef or e r e q uiri n g 5 -8 d a ys f or c oll e cti o n.
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5 i n v e

C o m pl et e i nf or m a ti o n o n i n v esti g ati o n al st u d y a g e nt is pr o vi d e d i n t h e a cc o m p a n yi n g I n v e sti g at o r' s B r o c h u r e. T his i ncl u des t h e m e c h a nis m of a cti o n, s u m m ari es of a ni m al a n d cli nic al st u di es, n o n -cli nic al a n d cli nic al p h ar m a c o ki n etics, m aj or r o ut e of eli mi n ati o n, s af et y pr o fil e, a n d t h e r ati o n al e f or t h e st arti n g d os e a n d r e gi m e n c h os e n. T his als o i ncl u d es i nf or m ati o n o n t h e m et a b olis m of M G T A -1 4 5 i n h u m a ns.  
5. 2 A v ail a bilit y M G T A -1 4 5 i n v esti g ati o n al a g e nt will b e pr o vi d e d b y M a g e nt a T h er a p e utics. Pl eri x af or will b e a c q uir e d c o m m erci all y b as e d o n st a n d ar d i nstit uti o n al pr oc ur e m e nt f or p ati e nts u n d er g oi n g st e m c ell m o bili z ati o n.
untitled h1
5. 3 a g e

M G T A -1 4 5 will b e d eli v er e d t o St a nf or d H e alt h C ar e I n v esti g ati o n al Dr u g P h ar m a c y b y M a g e nt a T h er a p e utics. T w o d os es of M G T A -1 4 5 m ust b e a v ail a bl e b ef or e att e m pt e d m o bili z ati o n f or a gi v e n p ati e nt o n t his pr ot oc ol. Pl eri x af or will b e o bt ai n e d c o m m erci all y p er i nstit uti o n al st a n d ar d pr oc e d ur es.  
```
S hi p pi n g a d dr ess of t h e i n v esti g ati o n al p h ar m a c y:

St a nf or d H e alt h C ar e

Att e nti o n: I n v esti g ati o n al P h ar m a c y


```
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5. 4 a g e

T h e i n v esti g ati o n al a g e nt will b e s e c ur e d b y t h e St a nf or d H e alt h C ar e i n v esti g ati o n al p h ar m a c y p er st a n d ar d pr oc e d ur es.  
a. F o r m ul ati o n: M G T A -1 4 5 is f or m ul at e d at 2 0 m g / m L i n 2 0 m M s o di u m a c et at e, 1 5 0 m M  
s o di u m c hl ori d e, 0. 0 2 % ( w / v) P ol ys or b at e 8 0 at p H 4. 0. M G T A -1 4 5 is s u p pli e d i n a si n gl e -  
d os e 2 m L T y p e I a m b er gl ass vi al. E a c h vi al c o nt ai ns n ot l ess t h a n 1 m L. M G T A -1 4 5  
(i nj e cti o n) is a st eril e s ol uti o n f or I V us e s u p pli e d as a si n gl e -d os e vi al p a c k a g e d i n a c art o n.  
b. St o r a g e: Vi als of M G T A -1 4 5 s h o ul d b e st or e d at -2 0° C ± 5° C i n t h e c art o n t o pr ot e ct fr o m li g ht. Vi als of M G T A-1 4 5 s h o ul d b e t h a w e d o v er ni g ht at 4° C pri or t o us e a n d ar e st a bl e at 4° C  
f or u p t o 3 0 d a ys. O nc e t h a w e d, M G T A-1 4 5 s h o ul d n ot b e r efr oz e n.  
c. T h a wi n g: T h e t h a wi n g will b e c o n d uct e d p er i n v esti g ati o n al p h ar m a c y st a n d ar d pr oc e d ur es a n d dr u g h a n d off t o St a nf or d H e alt h C ar e a p h er esis u nit at 8 7 5 Bl a k e Wil b ur Dri v e will occ ur i n t h e m or ni n g b ef or e a d mi nistr ati o n p er i nstit uti o n al pr oc e d ur es.  
d. P r e p a r ati o n: M G T A -1 4 5 will b e dil ut e d i n 0. 9 % s ali n e i n a cc or d a nc e wit h t h e p h ar m a c y m a n u al. S ol uti o ns of M G T A -1 4 5 ( 0. 0 3 6 t o 1. 4 4 m g / m L) pr e p ar e d i n 0. 9 % s ali n e m a y b e st or e d f or n o m or e t h a n 8 h o urs at r o o m t e m p er at ur e pri or t o a d mi nistr ati o n.  
e. A d mi ni st r ati o n: M G T A -1 4 5 will b e a d mi nist er e d as a n I V i nf usi o n o v er 3 t o 1 0 mi n ut es , as cli nic all y i n dic at e d.
untitled h1
6 d o s e

T h er e ar e n o pr o p os e d d os e m o dific ati o ns of M G T A -1 4 5 or pl eri x af or as d escri b e d i n s e cti o n 4 u n d er tr e at m e nt pl a n. If a n y p ati e nt e x p eri e nc es gr a d e 3 or hi g h er n o n -h e m at ol o gic al t o xicit y, n ot r e v ersi bl e t o gr a d e 1 or b as eli n e usi n g st a n d ar d of c ar e i nt er v e nti o ns wit hi n 2 4 h o urs , a n d is c o nsi d er e d p ossi bl y, pr o b a bl y or d efi nit el y r el at e d t o M G T A -1 4 5, t h e st u d y dr u g will b e disc o nti n u e d a n d p ati e nt will g o t o e v e nt m o nit ori n g. T h e p ati e nt c a n c o nti n u e t o r e c ei v e pl eri x af or if t h at is f elt a p pr o pri at e b y t h e tr e ati n g p h ysici a n. T h e p ati e nts will b e f oll o w e d f or 3 0 d a ys fr o m l ast d os e of M G T A -1 4 5 or till st art of tr a ns pl a nt c o n diti o ni n g, w hic h e v er c o m es first.
untitled h1
7 a d v e

St u d y 1 4 5 -H V -1 0 1, P h a s e 1 st u d y wit h M G T A -1 4 5 a n d pl e ri x af o r i n h e alt h y v ol u nt e e r s: O v er all, 7 7 o ut of 1 0 7 s u bj e cts ( 6 5 w h o r e c ei v e d M G T A -1 4 5 a n d 1 2 w h o r e c ei v e d pl a c e b o) e x p eri e nc e d at l e ast 1 A E d uri n g t h e st u d y. T h e m ost fr e q u e nt tr e at m e nt-e m er g e nt a d v ers e e v e nts ( T E A Es) ( occ urri n g i n > 5 s u bj e cts) a m o n g s u bj e cts r a n d o miz e d t o r e c ei v e M G T A-1 4 5 w er e b ac k p ai n ( 4 8 s u bj e cts), n a us e a ( 1 3 s u bj e cts),  
diz zi n ess ( 1 3 s u bj e cts), di arr h e a ( 8 s u bj e cts), a n d h e a d a c h e ( 8 s u bj e cts). A t ot al of 6 3 s u bj e cts e x p eri e nc e d a T E A E c o nsi d er e d b y t h e I n v esti g at or t o b e r el at e d t o M G T A -1 4 5.  
The most frequent TEAEs (occurring in > 1 subject) were back pain, diarrhea, nausea, vomiting, fatigue, abdominal discomfort, abdominal pain, injection site pruritus, headache, paresthesia, musculoskeletal chest pain, and dizziness. The majority of all AEs reported were described as mild (grade 1) in NCI CTCAE severity, without an apparent trend across dose levels or study part. The consistent observation associated with MGTA-
145 infusion was grade 1 bone pain in the back that begins during the 10-minute infusion and generally approximately 10 minutes later (Table 7: Summary of Acute Back Pain ).  
All of the reported AEs of back pain were considered by the Investigator to be related to study treatment.  
| MGTA-145                                                                      | All   |        |        |        |        |        |       |         |        |
|-------------------------------------------------------------------------------|-------|--------|--------|--------|--------|--------|-------|---------|--------|
| 0.0075                                                                        | 0.015 | 0.030  | 0.070  | 0.075  | 0.15   | 0.30   | MCTA- | Pooled  |        |
| mg/kg                                                                         | mg/dg | mg/kg  | mg/kg  | mg/    | mg/    | mg/    | 145   | Placebo |        |
| Parameter                                                                     | (N=4) | (N=14) | (N=25) | (N=10) | (N=12) | (N=10) | (N=4) | (N=79)  | (N=28) |
| Duration (min)                                                                |       |        |        |        |        |        |       |         |        |
| n                                                                             | 4     | 8      | 13     | S      | 10     | 5      | 3     | 48      | 2      |
| Mean                                                                          | 9.5   | 10.3   | 17.2   | 14     | 28.6   | 12.8   | 125   | 23.7    | 15.5   |
| 3.74                                                                          | 37.07 | 201.79 | 52.90  | 13.44  |        |        |       |         |        |
| Standard Deviation                                                            | 4.51  | 3.69   | 14.63  | 3.90   |        |        |       |         |        |
| Median                                                                        | 1.0   | 9.5    | 1.0    | 21.0   | 1.0    | 10.0   | 1.0   | 15.5    |        |
| 14.0                                                                          |       |        |        |        |        |        |       |         |        |
| Minimum                                                                       | 3     | 5      | 4      | 10     | 9      | 7      | 3     | 6       |        |
| 6                                                                             |       |        |        |        |        |        |       |         |        |
| Maximum                                                                       | 13    | 17     | 555    | 20     | 132    | 17     | 358   | 358     | 25     |
| Note: Acute back pain is defined as back pain that occurs on the dosing date, |       |        |        |        |        |        |       |         |        |
untitled h1
table 7 summary of acute

The known toxicities of plerixafor were observed and generally assessed as mild. For this study, a dose-limiting toxicity (DLT) was defined as a grade 2 or higher TEAE based on the NCI CTCAE v5.0 that is not a commonly expected TEAE associated with plerixafor
(≥5% of plerixafor administrations) (see below in Section 7.1.2).  
There were no grade 3 or grade 4 TEAEs in the study. A DLT of 1 event of grade 2 back pain was observed at 0.075 mg/kg MGTA-145 mg/kg, administered 2 hours after plerixafor (Part B). After dose reduction to 0.070 mg/kg, no DLTs were observed at that dose or at subsequent doses of 0.030 mg/kg or 0.015 mg/kg when MGTA-145 was administered 2 hours after plerixafor. Notably, grade 2 back pain was not reported for subjects administered MGTA-145 at 0.075 and 0.150 mg/kg immediately following plerixafor in Part B, or for subjects administered MGTA-145 at 0.070 mg/kg on 2 days in Part C.  
Seventy-seven subjects (65 in a MGTA-145 group and 12 in the placebo group) reported at least 1 grade 1 TEAE; 4 subjects experienced a moderate (grade 2) event, and no ≥
grade 3 events were observed. One subject (Subject 101-393) experienced an AE that led Protocol Version 1.4, 21 April 2021 IRB-57056 39 t o st u d y tr e at m e nt wit h dr a w al. T his gr a d e 2 e v e nt of b ac k p ai n occ urr e d f oll o wi n g a d mi nistr ati o n of 0. 0 7 5 m g / k g M G T A -1 4 5 w hi c h w as gi v e n 2 h o urs aft er pl eri x af or a n d m et t h e crit eri a f or a D L T p er t h e pr ot oc ol. As s uc h, a m a xi m u m d os e of 0. 0 7 m g / k g M G T A -1 4 5 T a bl e i n c o m bi n ati o n wit h pl eri x af or w as us e d as t h e hi g h est d os e f or t h e r e m ai n d er of t h e st u d y d osi n g. N o s u bj e ct i n t h e st u d y w as disc o nti n u e d fr o m a n M G T A -  
1 4 5 st u d y d u e t o a n A E, a n d n o s eri o us a d v ers e e v e nts ( S A Es) or d e at hs w er e r e p ort e d.  
T h er e w er e n o c h a n g es i n a n y l a b or at or y i n v esti g ati o n t h at w er e ass ess e d as cli nic all y si g nific a nt. Is ol at e d el e v ati o ns i n bilir u bi n fr o m 1. 4 t o 3. 2 m g / d L ( n or m al 0 t o 1. 2 m g / d L)  
w er e s e e n o n D a ys 1 t o 3 i n 8 s u bj e cts ( 6 r e c ei v e d M G T A -1 4 5 + pl eri x af or, 1 r e c ei v e d pl a c e b o + pl eri x af or, 1 r e c ei v e d M G T A -1 4 5 al o n e). El e v ati o ns i n bilir u bi n ar e k n o w n t o b e ass oci at e d wit h pl eri x af or d osi n g. N o el e v ati o n w as ass ess e d as cli nic all y si g nific a nt, a n d all v al u es r et ur n e d t o n or m al b ef or e st u d y c o m pl eti o n. T h e 1 s u bj e ct w h o r e c ei v e d M G T A -1 4 5 al o n e i n P art A w h o h a d a n el e v at e d bilir u bi n t o 1. 4 m g / d L o n D a y 2 als o h a d a n el e v at e d l e v el of 1. 3 m g / d L at b as eli n e. T h us, t h e el e v ati o n o n D a y 2 w as n ot attri b ut e d t o st u d y dr u g. El e v ati o ns i n W B Cs a n d W B C s u bs ets ar e e x p e ct e d as p art of t h e P D a cti o n of M G T A -1 4 5 + pl eri x af or. Pr ot hr o m bi n ti m e / a cti v at e d p arti al t hr o m b o pl asti n ti m e  
( a P T T), fi bri n o g e n, a n d d-di m er t ests w er e a d d e d t o t h e l a b or at or y i n v esti g ati o ns f or t h e fi n al s u bj e cts i n t h e st u d y (s u bj e cts r e c ei vi n g M G T A-1 4 5 0. 0 1 5 m g / k g 2 h o urs aft er pl eri x af or i n P art B a n d P art D) aft er a s u bj e ct at t h e 0. 0 3 m g / k g d os e l e v el i n P art D f ail e d t o est a blis h a d e q u at e v e n o us fl o w f or a p h er esis aft er m o bili z ati o n. F or t h es e s u bj e cts r e c ei vi n g t h e M G T A-1 4 5 0. 0 1 5 m g / k g d os e 2 h o urs aft er pl eri x af or, tr a nsi e nt el e v ati o ns w er e s e e n i n d -di m er t o 0. 5 9 t o 1. 4 4 m g / L i n 5 of 9 s u bj e cts ( n or m al r a n g e 0 t o 0. 4 9 m g / L)  
6 h o urs aft er M G T A -1 4 5 i nf usi o n. D -di m er r et ur n e d t o n or m al i n all s u bj e cts at t h e n e xt o bs er v ati o n at 4 8 h o urs. Tr a nsi e nt c h a n g es i n d -di m er ar e c o nsist e nt wit h w h at is o bs er v e d d uri n g ot h er m o bili z ati o n r e gi m e ns. T h er e w as n o cli nic all y si g nific a nt c h a n g e i n vit al si g ns wit h M G T A-1 4 5 d osi n g. Tr a nsi e nt el e v ati o ns i n s yst olic bl o o d pr ess ur e ≥  
1 4 0 m m H g w er e n ot e d i n 1 0 s u bj e cts w h o e x p eri e nc e d b ac k p ai n.  
C h a n g es i n el e ctr oc ar di o gr a m ( E C G) m e as ur e m e nts w er e c o nsi d er e d n ot cli nic all y si g nific a nt, a n d n o cli nic all y i m p ort a nt i ncr e as e i n t h e fr e q u e nc y of Q Tc a b n or m aliti es aft er i niti ati o n of tr e at m e nt w as o bs er v e d.  
O v er all, t h e i nci d e nc e of A Es w as si mil ar b et w e e n t h e tr e at m e nt c o h orts. N o i ncr e as e i n s e v erit y or fr e q u e nc y of a d v ers e eff e cts ass oci at e d wit h pl eri x af or w as o bs er v e d w h e n it w as gi v e n i n c o m bi n ati o n wit h M G T A -1 4 5.  
Pl e as e r ef er t o a cc o m p a n yi n g I n v esti g at or's Br oc h ur e f or a d et ail e d d escripti o n of a d v ers e e v e nts i n e a c h of t h e 4 ar ms of t h e st u d y as w ell as A Es s e e n i n t h e o n g oi n g st u d y of M G T A -  
1 4 5 i n p ati e nts wit h r e n al i m p air m e nt.
untitled h1
7. 1. 2 pl e

T h e p ot e nti al a d v ers e e v e nt ass oci at e d wit h pl eri x af or as o bt ai n e d fr o m t h e F D A a p pr o v e d p a c k a g e i n s e rt ar e as f oll o ws:  
Cli ni c al T ri al s E x p e ri e n c e: T h e m ost c o m m o n a d v ers e r e a cti o ns ( ≥ 1 0 %) r e p ort e d i n p ati e nts w h o r e c ei v e d pl eri x af or i n c o nj u ncti o n wit h G -C S F r e g ar dl ess of c a us alit y a n d m or e fr e q u e nt wit h pl eri x af or t h a n pl a c e b o d uri n g H S C m o bili z ati o n a n d a p h er esis w er e di arr h e a, n a us e a, f ati g u e, i nj e cti o n sit e r e a cti o ns, h e a d a c h e, art hr al gi a, diz zi n ess, a n d v o miti n g.  
S af et y d at a f or pl eri x af or i n c o m bi n ati o n wit h G -C S F w er e o bt ai n e d fr o m t w o r a n d o miz e d pl a c e b o -c o ntr oll e d st u di es ( 3 0 1 p ati e nts) a n d 1 0 u nc o ntr oll e d st u di es ( 2 4 2 p ati e nts).  
P ati e nts w er e pri m aril y tr e at e d wit h Pl eri x af or at d ail y d os es of 0. 2 4 m g / k g S C. M e di a n e x p os ur e t o Pl eri x af or i n t h es e st u di es w as 2 d a ys (r a n g e 1 t o 7 d a ys).  
I n t h e t w o r a n d o miz e d st u di es i n p ati e nts with N H L a n d M M, a t ot al of 3 0 1 p ati e nts w er e tr e at e d i n t h e Pl eri x af or a n d G-C S F gr o u p a n d 2 9 2 p ati e nts w er e tr e at e d i n t h e pl a c e b o a n d G -C S F gr o u p. P ati e nts r e c ei v e d d ail y m or ni n g d os es of G -C S F 1 0 micr o gr a ms / k g f or 4 d a ys pri or t o t h e first d os e of Pl eri x a f or 0. 2 4 m g / k g S C or pl a c e b o a n d o n e a c h m or ni n g pri or t o a p h er esis. T h e a d v ers e r e a cti o ns t h at occ urr e d i n ≥ 5 % of t h e p ati e nts w h o r e c ei v e d Pl eri x af or r e g ar dl ess of c a us alit y a n d w er e m or e fr e q u e nt wit h Pl eri x af or t h a n pl a c e b o d uri n g H S C m o bili z ati o n a n d a p h er esis ar e s h o w n i n T a bl e 8 .  
I n t h e r a n d o miz e d st u di es, 3 4 % of p ati e nts wit h N H L or M M h a d mil d t o m o d er at e i nj e cti o n sit e r e a cti o n s at t h e sit e of s u bc ut a n e o us a d mi nistr ati o n of pl eri x af or. T h es e i ncl u d e d er yt h e m a, h e m at o m a, h e m orr h a g e, i n d ur ati o n, i nfl a m m ati o n, irrit ati o n, p ai n, p ar est h esi a, pr urit us, r as h, s w elli n g, a n d urtic ari a.  
Mil d t o m o d e r at e all e r gi c r e a cti o n s w er e o bs er v e d i n l ess t h a n 1 % of p ati e nts wit hi n a p pr o xi m at el y 3 0 mi n aft er Pl eri x af or a d mi nistr ati o n, i ncl u di n g o n e or m or e of t h e f oll o wi n g: urtic ari a ( n = 2), p eri or bit al s w elli n g ( n = 2), d ys p n e a ( n = 1) or h y p o xi a ( n = 1).  
S y m pt o ms g e n er all y r es p o n d e d t o tr e at m e nts ( e. g., a nti hist a mi n es, c ortic ost er oi ds, h y dr ati o n or s u p pl e m e nt al o x y g e n) or r es ol v e d s p o nt a n e o usl y.  
V a s o v a g al r e a cti o n s, o rt h o st ati c h y p ot e n si o n, a n d / o r s y n c o p e c a n occ ur f oll o wi n g s u bc ut a n e o us i nj e cti o ns. I n pl eri x af or o nc ol o g y a n d h e alt h y v ol u nt e er cli nic al st u di es, l ess t h a n 1 % of s u bj e cts e x p eri e nc e d v as o v a g al r e a cti o ns f oll o wi n g s u bc ut a n e o us a d mi nistr ati o n of Pl eri x af or d os es ≤ 0. 2 4 m g / k g. T h e m aj orit y of t h es e e v e nts occ urr e d wit hi n 1 h o ur of Pl eri x af or a d mi nistr ati o n. B e c a us e of t h e p ot e nti al f or t h es e r e a cti o ns, a p pr o pri at e pr e c a uti o ns s h o ul d b e t a k e n.  
Ot h er a d v ers e r e a cti o ns i n t h e r a n d o miz e d st u di es t h at occ urr e d i n < 5 % of p ati e nts b ut w er e r e p ort e d as r el at e d t o pl eri x af or d uri n g H S C m o bili z ati o n a n d a p h er esis i ncl u d e d a b d o mi n al p ai n, h y p er hi dr osis, a b d o mi n al dist e nti o n, dr y m o ut h, er yt h e m a, st o m a c h disc o mf ort, m al ais e, h y p o est h esi a or al, c o nsti p ati o n, d ys p e psi a, a n d m usc ul os k el et al p ai n.  
H y p e rl e u k o c yt o si s: I n cli ni c al tri als, w hit e bl o o d c ell c o u nts of 1 0 0, 0 0 0 / mc L or gr e at er w er e o bs er v e d, o n t h e d a y pri or t o or a n y d a y of a p h er esis, i n 7 % of p ati e nts r e c ei vi n g pl eri x af or a n d i n 1 % of p ati e nts r e c ei vi n g pl a c e b o. N o c o m plic ati o ns or cli nic al s y m pt o ms of l e u k ost asis w er e o bs er v e d.  
P o st -m a r k eti n g E x p e ri e n c e: I n a d diti o n t o a d v ers e r e a cti o ns r e p ort e d fr o m cli nic al tri als, t h e f oll o wi n g a d v ers e r e a cti o ns h a v e b e e n r e p ort e d fr o m p ost m ar k eti n g e x p eri e nc e wit h Pl eri x af or. B e c a us e t h es e r e a cti o ns ar e r e p o rt e d v ol u nt aril y fr o m a p o p ul ati o n of u nc ert ai n si z e, it is n ot al w a ys p ossi bl e t o r eli a bl y esti m at e t h eir fr e q u e nc y  
```
or est a blis h a c a us al r el ati o ns hi p t o dr u g e x p os ur e.

- Bl o o d a n d L y m p h atic S yst e m: S pl e n o m e g al y a n d s pl e nic r u pt ur e

- I m m u n e S yst e m Dis or d ers: A n a p h yl a ctic r e a cti o ns, i ncl u di n g a n a p h yl a ctic s h oc k

- Ps yc hi atric Dis or d ers: A b n or m al dr e a ms a n d ni g ht m ar es

```  
Table 8: Adverse Reactions in ≥5% of Non-Hodgkin's Lymphoma and Multiple Myeloma Patients Receiving Plerixafor and More Frequent than Placebo during HSC
Mobilization and Apheresis  
| Percent of Patients (%)                                           |                   |         |            |         |         |    |
|-------------------------------------------------------------------|-------------------|---------|------------|---------|---------|----|
| Mozobil and G-CSF                                                 | Placebo and G-CSF |         |            |         |         |    |
| (n=301)                                                           | (=292)            |         |            |         |         |    |
| All                                                               | Grade 3           | Grade 4 | AII Grades | Grade 3 | Grade 4 |    |
| Grades                                                            |                   |         |            |         |         |    |
| Gastrointestinal                                                  |                   |         |            |         |         |    |
| disorders                                                         |                   |         |            |         |         |    |
| Diarrhea                                                          | 37                | <1      | 0          | 17      | o       | 0  |
| Nausea                                                            | 34                | 1       | 0          | 22      | 0       | 0  |
| Vomiting                                                          | 10                | <1      | 0          | 6       | 0       | 0  |
| Flatulence                                                        | 7                 | 0       | 0          | 3       | o       | 0  |
| General disorders and                                             |                   |         |            |         |         |    |
| administration site                                               |                   |         |            |         |         |    |
| conditions                                                        |                   |         |            |         |         |    |
| Injection site reactions                                          | 34                | 0       | 0          | 10      | 0       | 0  |
| Fatigue                                                           | 27                | 0       | 0          | 25      | 0       | 0  |
| Musculoskeletal and                                               |                   |         |            |         |         |    |
| connective tissue                                                 |                   |         |            |         |         |    |
| disorders                                                         |                   |         |            |         |         |    |
| Arthralgia                                                        | 13                | 0       | o          | 12      | 0       | 0  |
| Nervous system                                                    |                   |         |            |         |         |    |
| disorders                                                         |                   |         |            |         |         |    |
| Headache                                                          | 22                | <1      | o          | 21      | 1       | 0  |
| Dizziness                                                         | 11                | 0       | 0          | 6       | o       | 0  |
| Psychiatric disorders                                             |                   |         |            |         |         |    |
| Insomnia                                                          | 7                 | 0       | 0          | 5       | 0       | o  |
| Grades based on criteria from the World Health Organization (WHO) |                   |         |            |         |         |    |
untitled h1
adverse event and serious adverse

An adverse event (AE) is defined as any reaction, side effect, or untoward event that occurs during the course of the clinical trial associated with the use of a drug in humans, whether or not the event is considered related to the treatment or clinically significant.  For this study, AEs will include events reported by the subject, as well as clinically significant abnormal findings on physical examination or laboratory evaluation.  A new illness, symptom, sign or clinically significant laboratory abnormality or worsening of a pre-existing condition or abnormality is considered an AE.  All adverse events will be graded according to NCI CTCAE v5.0. Toxicities present at the initiation of study drug will be considered baseline conditions.  
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S e ri o u s A d v e r s e E v e nt

A n A E or s us p e ct e d a d v ers e r e a cti o n is c o nsi d er e d s eri o us if i n t h e vi e w of t h e i n v esti g at or or t h e

s p o ns or, it r es ults i n a n y of t h e f oll o wi n g:

- D e at h,

- A lif e -t hr e at e ni n g a d v ers e dr u g e x p eri e nc e

- I n-p ati e nt h os pit ali z ati o n or pr ol o n g ati o n of e xisti n g h os pit ali z ati o n [ N ot e: H os pit ali z ati o ns

r el at e d t o sc h e d uli n g iss u es ( e. g. e v e ni n g or w e e k e n d e v al u ati o ns) a n d c o n v e ni e nc e

c o nsi d er ati o ns d o n ot c o nstit ut e a s eri o us a d v ers e e v e nt.]

- P ersist e nt or si g nific a nt i nc a p a cit 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

- A c o n g e nit al a n o m al y / birt h d ef e ct.

- I mp 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 ali z ati o n m a y b e c o nsi d er e d a s eri o us a d v ers e dr u g e x p eri e nc e 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 s u bj e ct or s u bj e ct a n d m a y r e q ui r 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.


```
untitled h1
7. 2. 2 s e

A d v ers e e v e nts a n d S eri o us A d v ers e E v e nts i n t his st u d y will b e gr a d e d f or s e v erit y a cc or di n g t o N ati o n al C a nc er I nstit ut 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 v ersi o n 5. 0 ( C T C A E  
v 5. 0 ).  
B ot h S eri o us a n d N o n -S eri o us A d v ers e E v e nts will b e cl e arl y n ot e d i n s o urc e d oc u m e nt ati o n a n d list e d o n st u d y s p e cific C as e R e p ort F or ms ( C R Fs). T h e Pr ot oc ol Dir e ct or ( P D) or d esi g n e e will ass ess e a c h S eri o us A d v ers e E v e nt ( S A E) t o d et er mi n e w h et h er it is u n e x p e ct e d a cc or di n g t o t h e R ef er e nc e S af et y I nf or m ati o n s e cti o n of t h e I n v esti g at or's Br oc h ur e f or MG T A -1 4 5 or t h e p a c k a g e i ns ert f or pl eri x af or .  
All S eri o us A d v ers e E v e nts ( S A Es) will b e tr ac k e d fr o m pr e-m o bili z ati o n e v al u ati o n ( b as eli n e A E  
ass ess m e nt, c a n occ ur u p t o 7 d a ys b ef or e m o bili z ati o n as d escri b e d i n sc h e d ul e of e v e nts) u ntil r es ol uti o n, or u ntil 3 0 d a ys aft er t h e l ast d os e of t h e st u d y i nt er v e nti o n i. e. m o bili z ati o n a g e nts . St u d y i nt er v e nti o n r el at e d A Es / S A Es s h o ul d c o nti n u e t o b e f oll o w e d u ntil r es ol uti o n or st a bili z ati o n. A n y S A E occ urri n g aft er t h e r e p orti n g p eri o d m ust b e pr o m ptl y r e p ort e d if a c a us al r el ati o ns hi p t o t h e i n v esti g ati o n al dr u g is s us p e ct e d.  
W h e n ass essi n g w h et h er a n a d v ers e e v e nt is r el at e d t o t h e i n v esti g ati o n al i nt er v e nti o n, t h e f oll o wi n g attri b uti o n c at e g ori es ar e utiliz e d:  
D efi nit e - T h e a d v ers e e v e nt is cl e arl y r el at e d t o t h e a g e nt(s).  
Pr o b a bl e - T h e a d v ers e e v e nt is li k el y r el at e d t o t h e a g e nt(s).  
P ossi bl e - T h e a d v ers e e v e nt m a y b e r el at e d t o t h e a g e nt(s).  
Pr ot oc ol V ersi o n 1. 4 , 2 1 A pril 2 0 2 1 4 4 I R B-5 7 0 5 6 U nli k el y - T h e a d v ers e e v e nt is d o u btf ull y r el at e d t o t h e a g e nt(s).  
U nr el at e d - T h e a d v ers e e v e nt is cl e arl y N O T r el at e d t o t h e a g e nt(s).  
F or t h e p ur p os e of r e g ul at or y r e p orti n g r e q uir e m e nts, c a us al r el ati o ns hi ps of d efi nit e, pr o b a bl e, a n d p ossi bl e will b e c o nsi d er e d tr e at m e nt r el at e d, w hil e u nli k el y a n d u nr el at e d will b e c o nsi d er e d n ot tr e at m e nt r el at e d.  
S A Es C T C A E Gr a d e 3 a n d a b o v e, a n d all s u bs e q u e nt f oll o w -u p r e p orts will b e r e p ort e d t o t h e St a nf or d C a nc er I nstit ut 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) usi n g t h e st u d y s p e cific C R F  
r e g ar dl ess of t h e e v e nt's r el at e d n ess t o t h e i n v esti g ati o n al pr o d uct . F oll o wi n g r e vi e w b y t h e D S M C,  
e v e nts m e eti n g t h e I R B d efi niti o n of ' U n a ntici p at e d Pr o bl e m' will b e r e p ort e d t o t h e I R B usi n g e Pr ot oc ol wit hi n 1 0 w or ki n g d a ys of D S M C r e vi e w, or wit hi n 5 w or ki n g d a ys f or d e at hs or lif e -  
t hr e at e ni n g e x p eri e nc es.  
All S A Es occ urri n g d uri n g st e m c ell m o bili z ati o n a n d u p t o p ost -m o bili z ati o n visit , r e g ar dl ess of r el ati o ns hi p t o st u d y tr e at m e nt, m ust b e r e p ort e d i m m e di at el y t o M a g e nt a T h er a p e utics wit h t h e ti m efr a m e n ot t o e xc e e d 2 4 h o urs of t h e I n v esti g at or b ec o mi n g a w ar e of t h e e v e nt. I niti al S A E  
n otific ati o n s h o ul d b e m a d e b y e m aili n g or f a xi n g t h e S A E r e p ort f or m t o M a g e nt a T h er a p e utics at t h e e m ail or f a x n u m b er pr o vi d e d b y M a g e nt a T h er a p e utics. A n y pr e g n a nc y i n a f e m al e p ati e nt or p art n er of a m al e p ati e nt m ust als o b e r e p ort e d t o M a g e nt a T h er a p e utics , wit hi n 2 4 h o urs of t h e i n v esti g at or b e c o mi n g a w ar e of t h e e v e nt usi n g a Pr e g n a nc y R e p ort F or m.  
S A Es occ urri n g aft er t h e p ati e nt disc o nti n u es M G T A -1 4 5, i. e. b e y o n d t h e p ost -m o bili z ati o n visit, will b e c oll e ct e d a n d r e p ort e d a cc or di n g t o a b o v e pr ot oc ol if t h e y ar e at l e ast p ossi bl y r el at e d t o st u d y a g e nt, a n d h a v e n ot b e e n pr e vi o usl y r e p ort e d ( u n e x p ect e d).  
As st u d y s p o ns or, th e I n v esti g at or is r es p o nsi bl e f or all c o m m u nic ati o ns wit h t h e F D A. T h e I n v esti g at or will r e p ort t o t h e F D A, a n y s eri o us a d v ers e e v e nt t h at m e ets t h e F D A's crit eri a f or e x p e dit e d r e p orti n g f oll o wi n g r e p orti n g r e q uir e m e nts a n d ti m eli n es s et b y t h e F D A.  
M a g e nt a will n otif y I n v esti g at ors of all s us p e ct e d u n e x p e ct e d s eri o us a d v ers e r e a cti o ns ( S U S A Rs 7 / 1 5 D a y S af et y R e p orts) t h at occ ur d uri n g a n y cli nic al st u di es t h at ar e usi n g t h e i n v esti g ati v e c o m p o u n d. E a c h sit e is r es p o nsi bl e f or n otif yi n g t h eir I R B / E C of t h es e a d diti o n al S U S A Rs i n a cc or d a nc e wit h l oc al r e g ul ati o ns.
untitled h1
7. 2. 3 b a

a. A d v ers e e v e nts t o b e gr a d e d at b as eli n e, aft er e a c h d os e of M G T A -1 4 5, i n a ti m el y m a n n er of st u d y i nt er v e nti o n f or st e m c ell m o bili z ati o n a n d 3 0 d a ys aft er t h e l ast d os e of st u d y i nt er v e nti o n, or u ntil i niti ati o n of tr a ns pl a nt pr oc e d ur es, w hic h e v er is first. If t h e A E occ urs aft er i niti ati o n of tr a ns pl a nt pr oc e d ur es b ut b ef or e t h e c o ncl usi o n of t h e 3 0 d a ys, A Es will b e c oll e ct e d if t h e y ar e s eri o us a n d p ossi bl y, pr o b a bl y or d efi nit el y r el at e d t o t h e st u d y a g e nt. Tr a ns pl a nt r el at e d A Es will N O T b e c oll e ct e d o n t his st u d y.  
b. D e at h wit hi n 3 0 d a ys of l ast i n v esti g ati o n al a g e nt a n d d e at h at a n y ti m e at l e ast p ossi bl y r el at e d t o st u d y a g e nt will als o b e r e p ort e d o n t h e E v e nt M o nit ori n g F or m a n d r e p ort e d t o D S M C, M a g e nt a T h er a p e utics usi n g a n S A E F or m a n d t h e F D A .  
c. A d v ers e e v e nts will b e gr a d e d a cc or di n g t o 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 n ts  
( C T C A E) v ersi o n 5. 0 gr a di n g u nl ess ot h er wis e st at e d.  
d. T h e f oll o wi n g pr e -tr e at m e nt s y m pt o ms / c o n diti o ns (T a bl e 9 ) ar e t o b e gr a d e d at b as eli n e a n d a d v ers e e v e nts ar e t o b e gr a d e d at e a c h e v al u ati o n usi n g C T C A E v 5. 0 gr a di n g ( d oc u m e nt 0 if a bs e nt) .  
| C T C A E S Y S T E M /  O R G A N / C L A S S   | A d v ers e e v e nt / S y m pt o ms   | B as eli n e   | M o bili z ati o n  D a ys   | P ost -   |
|--------------------------------------------------|----------------------------------------|----------------|------------------------------|-----------|
| m o bili z ati o n                               |                                        |                |                              |           |
| I n v esti g ati o ns                            | Cr e ati ni n e i ncr e as e d         | X              | X                            | X         |
| N e utr o p hil c o u nt                         | X                                      | X              | X                            |           |
| N e utr o p hil c o u nt                         | X                                      | X              | X                            |           |
| Pl at el et c o u nt d e cr e as e d             | X                                      | X              | X                            |           |
| A L T i ncr e as e d                             | X                                      | X              | X                            |           |
| A S T i ncr e as e d                             | X                                      | X              | X                            |           |
| Bilir u bi n i ncr e as e d                      | X                                      | X              | X                            |           |
| G e n er al dis or d ers a n d                   | F ati g u e                            | X              | X                            | X         |
| Fl u li k e s y m pt o ms                        | X                                      | X              | X                            |           |
| P ai n                                           | X                                      | X              | X                            |           |
| I nj e cti o n sit e r e a cti o n               | X                                      | X              | X                            |           |
| Pr oc e d ur al                                  | I nf usi o n r el at e d r e a cti o n | X              | X                            | X         |
| G astr oi nt esti n al  Dis or d ers             | N a us e a                             | X              | X                            | X         |
| V o miti n g                                     | X                                      | X              | X                            |           |
| A b d o mi n al P ai n                           | X                                      | X              | X                            |           |
| B as eli n e n u m b er of st o ols              | X                                      |                |                              |           |  
Pr ot oc ol V ersi o n 1. 4 , 2 1 A pril 2 0 2 1 4 6 I R B-5 7 0 5 6  
| Bl o o d a n d l y m p h atic    M usc ul os k el et al   | B o n e P ai n   | X   | X   | X   |
|-----------------------------------------------------------|------------------|-----|-----|-----|
| N er v o us S yst e m  Dis or d ers                       |                  |     |     |     |  
P ar est h esi as X X X  
H e a d a c h e X X X  
Diz zi n ess X X X  
e. T h e f oll o wi n g A Es e x p eri e nc e d b y a p ati e nt a n d n ot s p e cifi e d i n S e cti o n 7. 2. 2 will b e  
r e c or d e d i n t h e st u d y d at a b as e usi n g C as e R e p ort F or ms .  
o Gr a d e 2 A Es d e e m e d p ossi bl y, pr o b a bl y, or d efi nit el y r el at e d t o t h e st u d y tr e at m e nt or pr oc e d ur e at a b o v e d efi n e d ti m e p oi nts.  
o Gr a d e 3 a n d 4 A Es r e g ar dl ess of attri b uti o n t o t h e st u d y tr e at m e nt or pr oc e d ur e at a b o v e d efi n e d ti m e p oi nts.  
o Gr a d e 5 A Es ( D e at hs). A n y d e at h wit hi n 3 0 d a ys of t h e p ati e nt's l ast st u d y i nt er v e nti o n r e g ar dl ess of attri b uti o n t o t h e st u d y a g e nt . A n y d e at h m or e t h a n 3 0 d a ys aft er t h e p ati e nt's l ast st u d y a g e nt t h at is f elt t o b e at l e ast p ossi bl y r el at e d t o t h e st u d y a g e nt m ust als o b e r e p ort e d as a Gr a d e 5 A E, wit h t h e r e as o n f or d e at h, a n d attri b uti o n assi g n e d.
untitled h1
8 l a b o

8. 1 ( A p h er esis Pr o d uct C o m p ositi o n - L a b or at or y C orr el ati v e St u d y \# 1 a , \# 1 b , \# 1c)  
8. 1. 1 C oll e cti o n of S p e ci m e n(s) : T w o 2 -4 m L s a m pl e s of cr y o pr es er v e d p eri p h er all y m o bili z e d a p h er esis pr o d uct will t a k e n fr o m t h e m o bili z e d fr es h pr o d uct fr o m t h e first d a y of a p h er esis d eli v er e d t o t h e St a nf or d B M T C ell ul ar T h er a p y F a cilit y ( C T F) . A t hir d fr es h s a m pl e ( 2-3 m L) will b e c oll e ct e d f or mi ni m al r esi d u al dis e as e a n al ysis .  
8. 1. 2 H a n dli n g of S p e ci m e ns(s) : S a m pl es will b e pr oc ess e d , ali q u ot e d a n d cr y o pr es er v e d i n t h e C ell ul ar T h er a p y F a cilit y at St a nf or d a n d st or e d i n li q ui d nitr o g e n u ntil r e a d y f or b atc h e d a n al ysis . F or M R D t esti n g (st u d y \# 1c), fr es h s a m pl e will b e ali q u ot e d i n a E D T A ( p ur pl e t o p) t u b e t o b e s hi p p e d t o M a y o Cli nic f or pr oc essi n g a n d a n al ysis.  
8. 1. 3 S hi p pi n g of S p e ci m e n(s) : C r y o pr es er v e d s a m pl es will b e h a n d d eli v er e d Dr. S hiz ur u's l a b f or a n al ysis f or fl o w c yt o m etr y a n d H u m a n I m m u n e M o nit ori n g Ce nt er at St a nf or d f or C y T O F a n al ysis. S a m pl es will b e t h a w e d p er l a b or at or y pr ot oc ol pri or t o b atc h e d t esti n g.  
Fr es h s a m pl e ( d e -i d e ntifi e d) f or M R D t esti n g will b e s hi p p e d o v er ni g ht i n a st yr of o a m c o nt ai n er wit h c hill e d or a m bi e nt p a c ks.  
8. 1. 4 Sit e(s) P erf or mi n g C orr el ati v e St u d y : St a nf or d U ni v ersit y ( S hiz ur u l a b a n d H u m a n I m m n u e M o nit ori n g Ce nt er - HI M C ), M a y o Cli nic ( S h aji K u m ar l a b) f or M R D t esti n g.  
8. 1. 5 C o di n g of s p e ci m e ns f or pri v a c y pr ot e cti o n : F or s p e ci m e ns b ei n g t est e d i nt er n all y at St a nf or d U ni v ersit y: s p e ci m e ns m a y b e l a b el e d wit h p ati e nt's n a m e, m e dic al r e c or d n u m b er a n d st u d y I D. F or s a m pl es t o b e t o b e s e nt o utsi d e of St a nf or d U ni v ersit y, P HI  
i nf or m ati o n will b e r e m o v e d a n d s a m pl es will b e l a b el e d wit h p ati e nts i niti als a n d St u d y I D o nl y. T h e l att er c o n v e nti o n (st u d y I D a n d i niti als) m a y b e a d o pt e d f or all i nt er n al s a m pl es as w ell.  
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8. 2 ( C F U a s s a y– L a b o r at o r y C o r r el ati v e St u d y # 2)

8. 2. 1 C oll e cti o n of S p e ci m e n(s) : S a m pl es of p eri p h er all y m o bili z e d a p h er esis pr o d uct will t a k e n

fr o m t h e m o bili z e d pr o d uct d eli v er e d t o t h e C T F fr o m a p h er esis u nit. C F U c a n b e d o n e o n

b ot h fr es h a n d t h a w e d s a m pl es. Fr es h s a m pl es will b e us e d. C F U t esti n g p er St a nf or d B M T

C T F F a cilit y.

8. 2. 2 H a n dli n g of S p e ci m e ns(s) : Pr oc essi n g a n d t esti n g will b e d o n e i n t h e St a nf or d B M T C T F

l a b p er i nstit uti o n al S O P.

8. 2. 3 S hi p pi n g of S p e ci m e n(s) : N o n e

8. 2. 4 Sit e(s) P erf or mi n g C orr el ati v e St u d y : St a nf or d B M T C ell ul ar T h er a p y F a cilit y

8. 2. 5 C o di n g of s pe ci m e ns f or pri v a c y pr ot e cti o n: S p e ci m e ns will b e l a b el e d wit h p ati e nt's n a m e,

m e dic al r e c or d n u m b er a n d st u d y I D. S a m pl es will b e a n al y z e d wit hi n St a nf or d U ni v ersit y.

I n c as e s a m pl es n e e d t o b e s e nt o utsi d e of St a nf or d U ni v ersit y, P HI i nf or m ati o n will be

r e m o v e d a n d s a m pl es will b e l a b el e d wit h p ati e nts i niti als a n d St u d y I D o nl y. T h e l att er

c o n v e nti o n (st u d y I D a n d i niti als) m a y b e a d o pt e d f or all i nt er n al s a m pl es as w ell.


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