A Phase II Trial Evaluating the Efficacy of Polatuzumab Vedotin With Rituximab, Gemcitabine, Dexamethasone, and Cisplatin (PV-RGDP) Chemotherapy for Relapsed or Refractory Diffuse Large B-cell Lymphoma
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Sponsor: UNC Lineberger Comprehensive Cancer Center

LINEBERGER COMPREHENSIVE CANCER CENTER 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
LCCC 2033 
PI: Dittus 
November 27, 2023 
SUMMARY OF CHANGES 
Protocol Amendment #2 
LCCC2033: A phase II trial evaluating the efficacy of polatuzumab vedotin with 
rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) chemotherapy for 
relapsed or refractory diffuse large B-cell lymphoma 
AMENDMENT INCORPORATES: 
__  Editorial, administrative changes 
_X_  Scientific changes  
__  Therapy changes  
_X_   Eligibility Changes  
Rationale for amendment: The purpose of this amendment is to clarify that subjects who 
are enrolled on this study do not have to be in their first relapse. Therefore, inclusion criteria 
and study plan language have been updated accordingly.  
Administrative changes: 
Section 8.1 
___ 
T&E table footnotes corrected for consistency. 
Scientific changes: 
Section 
5.1.1___ 
Study design language updated to clarify that subjects who have had at least 
one prior treatment regimen are eligible for study participation. 
Eligibility changes: 
Section 
4.1.2_ 
Language that mandated subjects must be in first relapse was removed. 
THE ATTACHED VERSION DATED November 27, 2023 INCORPORATES THE 
ABOVE REVISIONS 

LINEBERGER COMPREHENSIVE CANCER CENTER 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
LCCC 2033 
PI: Dittus 
November 27, 2023 
 
 
SUMMARY OF CHANGES 
 
 
Protocol Amendment #1 
 
LCCC2033: A phase II trial evaluating the efficacy of polatuzumab vedotin with 
rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) chemotherapy for 
relapsed or refractory diffuse large B-cell lymphoma 
AMENDMENT INCORPORATES: 
_X_  Editorial, administrative changes 
_X_  Scientific changes  
__  Therapy changes  
__   Eligibility Changes  
Rationale for amendment: The purpose of this amendment is to rectify inconsistencies that 
were observed between the protocol and the time and events table. 
Editorial, administrative changes: 
Grammer and mechanical edits throughout 
Scientific changes: 
Section 7.1.5 Audiometry language updated to specify that audiometric monitoring will be 
performed during physical examination prior to initiation of therapy, and then if 
clinically indicated by formal assessment per physician’s discretion. 
Section 7.1.7 
and 
T&E 
Footnote 
4 
___ 
Timing updated so that PET/CT imaging should be obtained within 28 days 
of initiating study treatment. Language also added to Section 7.1.7 to 
specify the exact time response assessment will be measured.  
Section 7.2.2 
and Section 
8.0 
Time and events table and Blood Chemistry Profile updated to ensure that 
both sections are consistent with the testing that will be completed.  
Section 8.0  
Coagulation profile added to T&E table to correspond with Section 7.2.3 
of the protocol.  
Section 8.3 
Language corrected to specify that a CT scan (and not a PET scan) will be 
conducted during the follow up period. 
THE ATTACHED VERSION DATED June 22, 2023 INCORPORATES THE ABOVE 
REVISIONS  
 
 
 

LINEBERGER COMPREHENSIVE CANCER CENTER 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
LCCC 2033 
PI: Dittus 
November 27, 2023 
 
LCCC2033: A phase II trial evaluating the efficacy of polatuzumab vedotin with 
rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) chemotherapy for 
relapsed or refractory diffuse large B-cell lymphoma 
 
Short Title: Polatuzumab vedotin with R-GDP in relapsed/refractory diffuse large B-cell 
lymphoma 
 
Principal Investigator 
Christopher Dittus, DO, MPH 
 
 
 
 
 
Email: chris_dittus@med.unc.edu 
 
 
Biostatistician 
Xianming Tan, PhD 
 
 
 
 
E-mail: xianming@email.unc.edu 
 
 
Clinical Protocol Office 
Lineberger Comprehensive Cancer Center 
The University of North Carolina at Chapel Hill 
450 West Drive, 3rd Floor, CB# 7295 
Chapel Hill, NC 27599-7295 
 
University of North Carolina Multicenter Project Manager: 
Email: CPOMulticenter@med.unc.edu  
 
Sponsor: Lineberger Comprehensive Cancer Center 
 
IND: 161215 
Funding Source: Genentech 
Version #: Amendment 2 
Version Date: November 27, 2023, Version 2.1 

LINEBERGER COMPREHENSIVE CANCER CENTER 
CLINICAL ONCOLOGY RESEARCH PROGRAM 
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
LCCC 2033 
PI: Dittus 
November 27, 2023 
 
LCCC2033: A phase II trial evaluating the efficacy of polatuzumab vedotin with 
rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) chemotherapy for 
relapsed or refractory diffuse large B-cell lymphoma 
 
 
 
Principal Investigator 
Christopher Dittus, DO, MPH 
 
 
 
 
 
 
 
 
 
 
 
Signature Page 
 
The signature below constitutes the approval of this protocol and the attachments and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable U.S. federal regulations 
and ICH guidelines. 
 
Principal Investigator (PI) Name:  
 
 
PI Signature:  
 
 
Date:  
 
 
Version #: Amendment 2 
Version Date: November 27, 2023, Version 2.1 

LCCC 2033 
PI: Dittus 
Amendment 2 
CONFIDENTIAL 
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November 27, 2023 
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LIST OF ABBREVIATIONS 
 
ADC 
ADCC 
Antibody-drug conjugate 
Antibody dependent cellular cytotoxicity 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BID 
Bis in die (twice daily) 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
CAP 
College of American Pathologists 
CBCD 
Complete blood count with differential 
CBR 
Clinical benefit rate 
cfDNA 
Circulating free deoxyribonucleic acid 
CL 
Clearance 
CLL 
Chronic Lymphocytic Leukemia 
Cmax 
Maximum plasma drug concentration 
CMP 
Comprehensive metabolic panel 
CPO 
Clinical Protocol Office 
CR 
Complete response 
CrCl 
Creatinine Clearance 
CT 
Computer tomography 
DEL 
Double-expressor lymphomas 
DHL 
Double hit lymphoma 
DLBCL 
Diffuse large B-cell lymphoma 
DLT 
Dose limiting toxicity 
DNA 
Deoxyribonucleic acid 
DSMC 
Data safety monitoring committee 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GC 
Germinal Center 
GCP 
Good Clinical Practice 
GPA 
Granulomatosis with Polyangiitis 
HBs-Ag 
Hepatitis B surface antigen 
HBc 
Hepatitis B core 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
IDS 
Investigational drug service 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IMIDs 
Immunomodulators 
INR 
International normalized ratio 
IV 
Intravenous 
LCCC 
Lineberger Comprehensive Cancer Center 
LDH 
Lactate dehydrogenase 
MRI 
Magnetic resonance Imaging 
MPA 
Microscopic Polyangiitis 
NCI-CTCAE 
National Cancer Institute – Common Terminology Criteria for 
Adverse Events 
NHL 
Non-Hodgkin’s lymphoma 
NK 
Natural killer 
OAT 
Organic anion transporter 

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OATP 
Organic anion transporter polypeptide 
ORR 
Objective response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cells 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 
PE 
Polyethylene 
PET 
Positron Emission Tomography 
PFS 
Progression free survival 
PFT 
Pulmonary function test 
Pgp 
P-glycoprotein 
PI 
Principal investigator 
PK 
Pharmacokinetic(s) 
PR 
Partial response 
PRC 
Protocol review committee 
PT 
Prothrombin time 
PTT 
PV 
Partial thromboplastin time 
Polatuzumab vedotin or Pemphigus Vulgaris 
PVC 
Polyvinylchloride 
PV-RGDP 
Rituximab, gemcitabine, dexamethasone, and cisplatin 
RA 
Rheumatoid arthritis 
RECIST 
Response evaluation criteria in solid tumors 
RNA 
Ribonucleic acid 
rrDLBCL 
Relapse-refractory diffuse large B-cell lymphoma 
SAE 
Serious adverse event 
s.c. 
Subcutaneous 
SD 
Stable disease 
SAR 
Serious adverse reaction 
t½ 
Half-life 
TBNK 
T or B-cell natural killer 
THL 
Triple hit lymphoma 
ULN 
Upper limit of normal 
UNC 
University of North Carolina 
USP 
United States Pharmacopeia 
 
 

LCCC 2033 
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TABLE OF CONTENTS 
 
SUMMARY OF CHANGES .............................................................................................. 1 
SUMMARY OF CHANGES .............................................................................................. 2 
LIST OF ABBREVIATIONS ............................................................................................. 1 
1.0 
BACKGROUND AND RATIONALE .................................................................... 1 
1.1 
Study Synopsis........................................................................................................ 1 
1.2 
Disease Background ............................................................................................... 1 
1.3 
Current Standard of Care ........................................................................................ 2 
1.4 
Polatuzumab ........................................................................................................... 2 
1.5 
Rationale for Clinical Study ................................................................................... 4 
1.6 
Correlative Studies ................................................................................................. 5 
2.0 
STUDY OBJECTIVES ............................................................................................ 6 
2.1 
Primary Objectives ................................................................................................. 6 
2.2 
Secondary Objectives ............................................................................................. 6 
2.3 
Exploratory Objectives ........................................................................................... 6 
3.0 
Criteria for Evaluation / Study Endpoints ............................................................. 7 
3.1 
Primary Endpoint .................................................................................................... 7 
3.2 
Secondary Endpoints .............................................................................................. 7 
3.3 
Exploratory Endpoints ............................................................................................ 7 
4.0 
SUBJECT ELIGIBILITY........................................................................................ 9 
4.1 
Inclusion Criteria .................................................................................................... 9 
4.2 
Exclusion Criteria ................................................................................................. 11 

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5.0 
TREATMENT PLAN ............................................................................................ 13 
5.1 
Schema ................................................................................................................. 13 
5.2 
Treatment Dosage and Administration ................................................................. 14 
5.3 
Toxicities and Dosing Delays/Dose Modifications ............................................... 15 
5.4 
Concomitant Medications/Treatments/Supportive Care Allowed ........................ 20 
5.5 
Medications/Treatment Precautions ..................................................................... 20 
5.6 
Other Modalities or Procedures ............................................................................ 21 
5.7 
Duration of Therapy ............................................................................................. 21 
5.8 
Duration of Follow Up.......................................................................................... 21 
5.9 
Study Withdrawal ................................................................................................. 22 
5.10 
Off-Study Criteria ................................................................................................. 22 
6.0 
DRUG INFORMATION........................................................................................ 23 
6.1 
Polatuzumab ......................................................................................................... 23 
6.2 
Dexamethasone ..................................................................................................... 26 
6.3 
Rituximab ............................................................................................................. 28 
6.4 
Rituxan Hycela ..................................................................................................... 30 
6.5 
Gemcitabine: ......................................................................................................... 31 
6.6 
Cisplatin ................................................................................................................ 33 
7.0   CLINICAL ASSESSMENTS ................................................................................ 37 
7.1 
List of Assessments .............................................................................................. 37 
7.2 
Clinical Laboratory Assessments ......................................................................... 38 
7.3 
Virus Testing ........................................................................................................ 38 
7.4 
Correlative Studies ............................................................................................... 38 
8.0 
EVALUATIONS AND ASSESSMENTS .............................................................. 39 

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8.1 
Time and Events Table ......................................................................................... 39 
8.2 
Assessment of Safety ............................................................................................ 43 
8.3 
Assessment of Efficacy ......................................................................................... 43 
9.0 
ADVERSE EVENTS .............................................................................................. 44 
9.1 
Definitions ............................................................................................................ 44 
9.2 
Documentation of non-serious AEs or SARs ....................................................... 45 
9.3 
SAEs or Serious SARs .......................................................................................... 46 
9.4 
Adverse Event Reporting ...................................................................................... 46 
9.5 
Data and Safety Monitoring Plan .......................................................................... 59 
10.0 
STATISTICAL CONSIDERATIONS .................................................................. 60 
10.1 
Study Design ......................................................................................................... 60 
10.2 
Sample Size, Accrual and Duration of Accrual .................................................... 60 
10.3 
Data Analysis Plans .............................................................................................. 61 
11.0 
STUDY MANAGEMENT ..................................................................................... 62 
11.1 
Institutional Review Board (IRB) Approval and Consent .................................... 62 
11.2 
Required Documentation ...................................................................................... 62 
11.3 
Registration Procedures ........................................................................................ 62 
11.4 
Data Management and Monitoring/Auditing ........................................................ 63 
11.5 
Adherence to the Protocol ..................................................................................... 63 
11.6 
Amendments to the Protocol................................................................................. 65 
11.7 
Record Retention .................................................................................................. 66 
11.8 
Obligations of Investigators .................................................................................. 66 
12.0 
REFERENCES ....................................................................................................... 67 
13.0 
APPENDICES ........................................................................................................ 69 

LCCC 2033 
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13.1 
Appendix A. Revised response criteria for lymphoma ......................................... 69 
13.2 
Appendix B. ECOG Performance Status .............................................................. 72 
13.3 
Appendix C. Child-Pugh Score ............................................................................ 73 
13.4 
Appendix D: Strong Inhibitors and Inducers of CYP3A Strong inhibitors .......... 74 
 

LCCC 2033 
PI: Dittus 
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November 27, 2023 
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1.0 
BACKGROUND AND RATIONALE 
1.1 
Study Synopsis 
LCCC 2033 is a multicenter, open-label, single arm, phase 2 study to evaluate the 
efficacy of a novel regimen consisting of polatuzumab vedotin in combination with 
rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) for the 
treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). RGDP 
is a standard regimen for rrDLBCL and PV is a novel antibody-drug conjugate 
targeting CD79b. PV has shown efficacy in the setting of rrDLBCL and we feel it 
can improve the response rates of standard salvage therapy. This is particularly 
important because, although there is a cure rate with salvage treatment of rrDLBCL, 
there is significant room for improvement. This study will focus on subjects in 
relapse (who have had at least one prior regimen) and will include both subjects 
who are transplant eligible and those who are transplant ineligible. Subjects who are 
transplant eligible may proceed to autologous stem cell transplant after a minimum 
of 2 cycles as long as they achieve a complete or partial remission. 
 
The primary endpoint will be the overall response rate (ORR), with complete 
response (CR) rate, progression free survival (PFS), and overall survival (OS) being 
secondary endpoints. The study will use a Simon two-stage design. In the first stage, 
27 evaluable subjects will be recruited. If there are at least 13 (≥ 13) subjects with a 
partial or complete response after at least 2 cycles, another 17 evaluable subjects 
will be enrolled and treated in the second stage of the trial, for a total of 44 evaluable 
subjects. We will reject the null hypothesis if and only if there are ≥ 13 subjects 
with an ORR from the first stage and ≥ 23 subjects with an ORR out of the 44 
subjects. We hypothesize that this regimen will be more effective than the historical 
standard of care, salvage regimens which includes RGDP. 
 
1.2 
Disease Background 
DLBCL is the most common type of non-Hodgkin lymphoma (NHL) in the United 
States and is the prototype for aggressive B-cell lymphomas. Based on 2013-2017 
SEER data, the estimated number of new cases of DLBCL in the United States is 
around 18,000 per year [1]. Standard frontline therapy leads to a cure in 
approximately 60% of patients [2]. Cure rates are highly variable based on multiple 
factors, 
including 
the 
international 
prognostic 
index 
(IPI), 
stage, 
immunohistochemical findings, and chromosomal abnormalities. Of the 40% who 
will relapse, the standard approach is to proceed with salvage chemotherapy 
followed by an autologous stem cell transplant (autoSCT) in eligible patients who 
have chemosensitive disease. This approach was initially described in the seminal 
PARMA study comparing salvage chemotherapy alone to salvage chemotherapy 
consolidated with autoSCT [3]. The group that received consolidation autoSCT had 
an overall survival benefit (53% vs. 32%; p = 0.038), setting the new standard of 
care for relapsed aggressive B-cell lymphoma. The salvage regimen used in the 
PARMA study was high-dose cytarabine, dexamethasone, and cisplatin (DHAP), 
which had a response rate of 64% in those who relapsed after frontline 
chemotherapy and 21% in those who relapsed during frontline chemotherapy. 

LCCC 2033 
PI: Dittus 
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Despite an improvement in the approach to salvage therapy, significant room for 
improvement remains. 
 
1.3 
Current Standard of Care 
Since the PARMA study, the standard of care for relapsed DLBCL has been salvage 
chemoimmunotherapy followed by autoSCT. Multiple studies have compared 
standard salvage regimens for DLBCL, including the CORAL study, which 
compared R-ICE to R-DHAP, and the LY.12 study, which compared (R)-DHAP to 
(R)-GDP [4, 5]. Each of these studies failed to show a superior regimen, but they 
did report unique toxicity profiles. The CORAL study had response rates for R-ICE 
of 63% (ORR) and 36% (CR), while the responses for the R-DHAP arm were 64% 
(ORR) and 40% (CR). The LY.12 study found that R-DHAP and R-GDP were 
similar in terms of responses, but with less toxicity in the R-GDP arm. This study 
described a CR rate of 13.8% and an ORR of 46.1% in the R-GDP arm, and 14.6% 
and 44.7% in the R-DHAP arm. Although these studies clearly show an effective 
approach for a proportion of subjects, approximately half of subjects will not 
achieve a suitable remission for transplant. A follow-up of the CORAL study 
evaluated subjects who could not proceed to autoSCT, and found that they had an 
ORR of 39% to third-line chemotherapy (OS of 4.4 months) [2, 6]. Thus, 
improvements in second-line salvage therapies are tantamount to improved DLBCL 
survival rates. 
 
One study has evaluated the use of a newer CD20 monoclonal antibody, 
ofatumumab, in the hope that this would improve the response rate in subjects who 
had received prior rituximab [7]. Unfortunately, this study showed low response 
rates in general, including an ORR of 38% in the O-DHAP group and 42% in the 
R-DHAP group. Other novel agents have been successfully combined with standard 
salvage regimens in pilot studies, including lenalidomide with R-ICE and ibrutinib 
with R-ICE [8, 9]. Although response rates seem promising, these studies require 
further evaluation. 
 
1.4 
Polatuzumab 
Polatuzumab vedotin (PV) is a novel antibody-drug conjugate (ADC) that contains 
a humanized monoclonal antibody portion combined with monomethyl auristatin E 
(MMAE). The monoclonal antibody targets the B-cell antigen receptor complex- 
associated protein beta chain (CD79b), while the MMAE component is an 
antimitotic agent that blocks the polymerization of tubulin. PV has been studied in 
relapsed and frontline DLBCL. This agent was first studied as monotherapy in 
relapsed B-cell NHL in a phase 1 study and found to have significant activity in 
subjects with NHL [10]. Specifically, this study showed an ORR of 56% in 
DLBCL. This study established the recommended phase 2 dose for NHL as 2.4 
mg/kg every 21 days. At this dose, investigators found the most common adverse 
events to be grade 3-4 neutropenia (40%) and grade 1-2 neuropathy (27%). 
 
PV has also been evaluated in the relapsed DLBCL setting in combination with 
bendamustine and rituximab (PV-BR) [11]. This study found a CR rate of 40% in 
a heavily pretreated population and compared very well to the CR rate of 15% seen 

LCCC 2033 
PI: Dittus 
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with bendamustine rituximab alone. Median PFS and OS were also appreciably 
higher in the PV-BR arm, leading to FDA accelerated approval in 2019. The dose 
of PV used in this study was 1.8 mg/kg every 21 days, with common adverse 
reactions including neutropenia, thrombocytopenia, anemia, peripheral neuropathy, 
fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia [11]. 
 
1.4.1.1 Clinical Studies [12] 
 
Polatuzumab vedotin is currently being investigated in ongoing clinical trials in 
subjects with B-cell hematological malignancies. 
 
1.4.1.2 Pharmacokinetics 
 
Distribution 
The antibody conjugated (acMMAE) central volume of distribution estimated 
based on population pharmacokinetic analysis is 3.15 L. For human, MMAE 
plasma protein binding is 71% to 77% and the blood to plasma ratio is 0.79 to 
0.98, in vitro. 
 
Elimination 
After the first 1.8 mg/kg polatuzumab vedotin dose, the acMMAE mean ( ± 
standard deviation) Cmax was 803 ( ± 233) ng/mL and AUCinf was 1860 ( ± 
966) day*ng/mL; the terminal half-life is 5.05 ( ± 1.60) days for acMMAE and 
6.59 (± 2.08) days for total antibody. 
 
Metabolism 
PV catabolism has not been studied in humans; however, it is expected to undergo 
catabolism to small peptides, amino acids, unconjugated MMAE, and 
unconjugated MMAE-related catabolites. 
 
Specific Populations 
No clinically significant differences in the pharmacokinetics of PV were observed 
based on age (20 to 89 years), sex, or race/ethnicity (Asian and non-Asian). Mild 
renal impairment did not result in clinically significant differences in the 
pharmacokinetics of acMMAE or unconjugated MMAE. There was a 40% 
increase in MMAE exposure with mild hepatic impairment that was not clinically 
significant. The effect of severe renal or hepatic impairment are unknown. 
 
Drug Interaction Studies 
No dedicated clinical drug–drug interaction studies with PV in humans have been 
conducted. In vitro studies indicate MMAE is a substrate for CYP3A4/5. MMAE 
is a weak time-dependent inhibitor of CYP3A4/5 but does not competitively 
inhibit CYP3A4/5 at clinically relevant concentrations. MMAE does not inhibit 
CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6. MMAE is not 
an inducer of major CYP enzymes. 

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1.4.1.3 Clinical Safety [12] 
In addition to the study mentioned above, GO29044 is an ongoing Phase Ib/II 
study investigating polatuzumab vedotin in combination with rituximab (375 
mg/m2 IV), cyclophosphamide (750 mg/m2 IV), doxorubicin (50 mg/m2 IV) and 
prednisone/prednisolone (100 mg/day PO on Days 1 – 5 of each cycle) (R-CHP), 
or in combination with obinutuzumab (1000 mg IV) plus CHP (G-CHP), for 6-8 
treatment cycles in B-cell lymphoma subjects. 
 
The most common AEs (occurring in ≥ 10% of subjects) included fatigue (50%), 
nausea (50%), diarrhea (48%), neutropenia (40%), anemia (27%), alopecia and 
constipation (24% each), and thrombocytopenia (20%). 
 
Grade 3-4 AEs regardless of relationship to study drugs were reported in 33/53 
subjects (62%) receiving polatuzumab vedotin plus R-CHP. Grade 3-4 AEs 
reported in more than two subjects in this group (all doses) included neutropenia 
(14/53 [26%]), febrile neutropenia (6/53 [11%]), leukocytosis and leukopenia 
(5/53 [9%] each), thrombocytopenia (4/53 [8%]), and hyperglycemia (3/53 [6%]). 
 
In the polatuzumab vedotin plus G-CHP group (all doses), Grade 3-4 AEs 
reported in more than two patients included neutropenia (12/29 [41%]), febrile 
neutropenia (8/29 [28%]), anemia (4/29 [14%]), thrombocytopenia (4/29 [14%]), 
and leukocytosis (3/29 [10%]). 
 
Grade 5 AEs were reported in two subjects (1 septic shock event in the 
polatuzumab vedotin 1.8 mg/kg plus G-CHP group and 1 atrial fibrillation event 
in the polatuzumab vedotin 1.8 mg/kg plus R-CHP group). 
 
Additional information on adverse events can be found in Section 6.1. 
 
1.5 
Rationale for Clinical Study 
Although the majority of patients will be cured in the frontline setting, 40% will 
still require salvage therapy [2]. These patients do poorly, with a 2-year survival 
rate estimated to be 20% [13]. As described above, the standard of care for relapsed 
DLBCL is an autoSCT. Once a patient is deemed eligible for a transplant in terms 
of underlying medical problems and performance status, the patient must meet two 
criteria: 1) they need a complete or good partial remission with salvage 
chemotherapy and 2) they need an adequate collection of stem cells. Given there 
are many salvage regimens, the overarching goal of treatment is to provide high 
response rates with low toxicities, specifically those related to myelosuppression. 
Recommended second-line regimens include R-ICE, R-DHAP (R-DHAX), and R- 
GDP. These regimens have ORRs that range from 38 to 64% and transplant rates 
that range from 33 to 55% [14]. As described above, based on current evidence, 
these regimens are all equal in efficacy, but R-GDP is better tolerated than R-DHAP 
[5]. 

LCCC 2033 
PI: Dittus 
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Several new agents have been developed to improve the response and survival rates 
of relapsed DLBCL. As described in Section 1.4, PV has been studied both as 
monotherapy and in combination with bendamustine-rituximab in relapsed DLBCL 
[10,11]. The combination of PV-BR found a CR rate of 40% in a heavily pretreated 
population compared very well to the CR rate of 15% seen with BR alone [15]. This 
CR rate also compares favorably to our current standard salvage regimens. 
Although the PV-BR data are very exciting, BR is not a regimen typically used in 
the first relapse setting. Based on these encouraging data, we propose a single-arm 
study evaluating PV in combination with a safe and effective standard salvage 
regimen consisting of rituximab, gemcitabine, cisplatin, and dexamethasone (R- 
GDP). Because only half of patients are able to proceed to transplant, our study will 
include both transplant eligible and ineligible subjects. If successful, this regimen 
could define a new standard for relapsed/refractory DLBCL. 
 
1.5.1 Dose Rationale 
The phase 1 study on PV established that the recommended phase 2 dose for NHL 
was 2.4 mg/kg every 21 days, with grade 3-4 neutropenia and grade 1-2 neuropathy 
as the most common adverse effects at rates of 40% and 27% respectively for this 
particular dose [10]. The dose of polatuzumab vedotin used in the GO29365 study, 
which led to FDA approval, was 1.8 mg/kg, given day 2 of cycle 1 and on day 1 of 
subsequent cycles every 21 days [11]. Additionally, the frontline randomized trial 
evaluating PV with CHP, used a dose of 1.8 mg/kg once every 21 days 
ClinicalTrials.gov NCT01992653. We plan to use PV dosed at 1.8 mg/kg once 
every 21 days. 
 
1.6 
Correlative Studies 
Genomic alterations and protein expression in DLBCL have also been found to be 
prognostically significant. Double-expressor lymphomas (DEL) have co- 
expression of MYC and BCL2 and have had worse responses to frontline 
chemotherapy [17]. Additionally, DLBCL that has MYC with BCL2 and/or BCL6 
rearrangements (i.e. double hit and triple hit lymphomas [DHL and THL, 
respectively]) have been found to have a worse prognosis and poorer outcomes 
with standard frontline regimens such as R-CHOP. We will compare response 
rates, progression free survival and overall survival between these more aggressive 
variants and standard DLBCL [18, 19]. 

LCCC 2033 
PI: Dittus 
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2.0 
STUDY OBJECTIVES 
2.1 
Primary Objectives 
 
2.1.1 To determine the overall response rate (ORR) rate for polatuzumab vedotin in 
combination with R-GDP in rrDBLCL. 
 
2.2 
Secondary Objectives 
 
2.2.1 To determine the complete response rate (CR) for polatuzumab vedotin in 
combination with R-GDP in rrDBLCL. 
 
2.2.2 To determine median progression free survival (PFS) for polatuzumab vedotin in 
combination with R-GDP in rrDBLCL. 
 
2.2.3 To determine median progression free survival (PFS) for polatuzumab vedotin in 
combination with R-GDP in rrDBLCL who receive autologous stem cell transplant 
(AutoSCT). 
 
2.2.4 To determine median progression free survival (PFS) for polatuzumab vedotin in 
combination with R-GDP in rrDBLCL who do not receive autologous stem cell 
transplant (AutoSCT). 
 
2.2.5 To determine the median overall survival (OS) for polatuzumab vedotin in 
combination with R-GDP in rrDBLCL. 
 
2.2.6 To determine the safety of polatuzumab vedotin in combination with R-GDP in 
subjects with rrDBLCL. 
 
2.3 
Exploratory Objectives 
 
2.3.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3.0 
Criteria for Evaluation / Study Endpoints 
3.1 
Primary Endpoint 
 
3.1.1 Overall response rate (ORR) defined as the proportion of subjects who achieve CR 
and PR responses by Lugano classification (Appendix A) in subjects with rrDLBCL 
after receiving at least 2 cycles of PV-RGDP. 
 
3.2 
Secondary Endpoints 
 
3.2.1 Complete response rate (CR) as defined by the Lugano classification (Appendix A) 
in subjects with rrDLBCL receiving at least 2 cycles of PV-RGDP. 
 
3.2.2 Progression free survival (PFS) defined as the time from the start of study treatment 
until progression or death in subjects with rrDLBCL receiving PV-RGDP who 
received autologous stem cell transplant (AutoSCT). 
 
3.2.3 Progression free survival (PFS) defined as the time from the start of study treatment 
until progression or death in subjects with rrDLBCL receiving at least 2 cycles of 
PV-RGDP who did not receive AutoSCT. 
 
3.2.4 Overall survival (OS) defined as the time from the start of treatment until death 
from any cause in subjects with rrDLBCL receiving at least 2 cycles of PV-RGDP. 
 
3.2.5 Toxicity/safety as defined in the CTCAE v5.0 in subjects with rrDLBCL receiving 
at least one treatment with PV-RGDP. 
 
3.3 
Exploratory Endpoints 
 
3.3.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3.3.5.2 
, 
 
 
 

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4.0 
SUBJECT ELIGIBILITY 
In order to participate in this study a subject must meet ALL of the eligibility 
criteria outlined below. 
 
4.1 
Inclusion Criteria 
 
4.1.1 Written informed consent obtained to participate in the study and HIPAA 
authorization for release of personal health information. 
 
4.1.2 Biopsy proven diffuse large B-cell lymphoma (DLBCL) who have had at least one prior 
treatment regimen (biopsy can be from initial diagnosis). The study will allow high-
grade B cell lymphoma, but not including Burkitt’s lymphoma. Per the 2016 WHO 
criteria, the following histologies are eligible to participate in this study:  
• Diffuse large B-cell lymphoma (DLBCL), NOS  
• Germinal center B-cell type  
• Activated B-cell type  
• T-cell/histiocyte-rich large B-cell lymphoma  
• EBV+ DLBCL, NOS 
• DLBCL associated with chronic inflammation  
• Primary mediastinal (thymic) large B-cell lymphoma  
• Intravascular large B-cell lymphoma  
• ALK+ large B-cell lymphoma  
• HHV8+DLBCL, NOS  
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 
rearrangements  
• High-grade B-cell lymphoma, NOS 
• B-cell lymphoma, unclassifiable, with features intermediate between 
DLBCL and classical Hodgkin lymphoma 
 
4.1.3 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 
(Appendix B). 
 
4.1.4 Age > 18 at the time of consent. 
 
4.1.5  Radiologic evidence of active disease per Lugano criteria (Appendix A) within 42 
days of starting trial therapy. 
 
4.1.6 Subject must have at least one prior line of therapy. 
 
4.1.7 Prior cancer treatment or other investigational treatment must be completed at least 
21 days or 5 half-lives (whichever is longer) prior to start of treatment and the 
subject must have recovered from all reversible acute toxic effects of the regimen 
(other than alopecia) to ≤ Grade 1 at start of treatment. 
 
4.1.8 Subjects with a history of prior or concurrent second primary malignancy whose 
natural history or treatment does not have the potential to interfere with the safety 
or efficacy assessment of the study drugs are eligible for enrollment in the trial. 
This includes localized prostate cancer, bladder cancer, in situ breast cancer and 

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4.1.15 Females of childbearing potential must have a negative serum pregnancy test within 
72 hours prior to initiation of study treatment. NOTE: Females are considered of 
childbearing potential unless they are surgically sterile (have undergone a 
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are 
naturally postmenopausal for at least 12 consecutive months. Documentation of 
postmenopausal status must be provided. 
 
4.1.16 Females of childbearing potential must be willing to abstain from heterosexual 
activity or to use 2 forms of effective methods of contraception from the time of 
informed consent until 12 months after rituximab discontinuation and 9 months 
after last dose of polatuzumab vedotin. The two contraception methods can be 
comprised of two barrier methods, or a barrier method plus a hormonal method or 
an intrauterine device that meets < 1% failure rate for protection from pregnancy in 
the product label. 
 
4.1.17 Male subjects with female partners of childbearing potential must have had a prior 
vasectomy or agree to use an adequate method of contraception (i.e., double barrier 
method: condom plus spermicidal agent) starting with the first dose of study 
therapy and 6 months after the last dose of polatuzumab vedotin. 
 
4.1.18 Subjects are willing and able to comply with study procedures based on the 
judgement of the investigator. 
 
4.2 
Exclusion Criteria 
 
4.2.1 Known severe, active bacterial, viral, fungal, mycobacterial, parasitic, or other 
infections at study enrollment that may put the subject at undue risk as determined 
by the investigator. 
 
4.2.2 Subjective hearing loss interfering with daily activities or born with impaired or 
loss of hearing. 
 
4.2.3 Women who are pregnant or breastfeeding or who intend to become pregnant 
within a year of the last dose of study treatment (NOTE: breast milk cannot be 
stored for future use while the mother is being treated on study). 
 
4.2.4 History of severe allergic or anaphylactic reaction to humanized or murine 
monoclonal antibodies or known sensitivity or allergy to murine. 
 
4.2.5 Contraindication to gemcitabine or cisplatin, or dexamethasone or similar 
corticosteroid. 
 
4.2.6 Symptomatic cardiac disease including ventricular dysfunction, left ventricular 
ejection fraction < 40%, symptomatic coronary artery disease or symptomatic 
arrhythmias. 
 
4.2.7 Subjects with severe hepatic insufficiency Child-Pugh Score > 6 (see Appendix C). 

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4.2.8 Pre-existing ≥ grade 2 neuropathy. 
 
4.2.9 Active CNS disease. 
 
4.2.10 Subject is receiving prohibited medications or treatments, such as strong CYP3A 
inhibitors and inducers, as listed in Section 5.5 of the protocol that cannot be 
discontinued/replaced by an alternative therapy. 

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5.1.1 Study Design 
This will be an open-label, single-arm phase II study meant to examine the efficacy 
of polatuzumab vedotin with rituximab, gemcitabine, cisplatin, and dexamethasone 
(PV-RGDP) in subjects with relapsed/refractory diffuse large B-cell lymphoma 
(DLBCL). We will enroll subjects with biopsy-proven diffuse large B-cell 
lymphoma (DLBCL) who have had at least one prior treatment regimen. Using a 
Simon two-stage design, we will plan to enroll 27 eligible and evaluable subjects 
to receive treatment in the first stage. If there are at least 13 (≥ 13) subjects with an 
overall response (PR or CR), another 17 evaluable subjects will be enrolled and 
treated in the second stage of the trial, for a total of 44 evaluable subjects. We will 
reject the null hypothesis if and only if there are ≥ 13 subjects with an ORR from 
the first stage and ≥ 23 subjects with an ORR out of the 44 subjects. 
 
Subjects enrolled in the study will be treated with PV-RGDP. Transplant eligible 
patients will be assessed for response every two cycles of PV-RGDP with a PET- 
CT (PET1, PET2 and PET3). If the subject has a complete response (CR) they may 
go to transplant or CAR-T at any time after 2 cycles have been completed (per 
investigator discretion). If the subject has a partial response (PR), they may go to 
transplant or CAR-T at any time after 4 cycles have been completed. If the subject is 
not transplant eligible, and has CR, PR, or SD on imaging, the subject will continue 
for six total cycles of therapy.  
 
Safety data on adverse events will be recorded. Specifically, Grade 3 + toxicities as 
described in Section 5.3.2, unacceptable toxicities will be monitored, and the study 
will be halted if per the stopping rules in Toxicities and Dosing Delays/Dose 
Modifications. 

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5.2 
Treatment Dosage and Administration  
Table 2  Regimen Description 
 
1. Biosimilars is allowed in this study. 
2. Other corticosteroids may be used at equivalent dose 
3. Treatment visits may have a window of +/- 2 days. 
4. SC dosing may start after cycle 1. All subjects must receive at least 1 full dose of rituximab by IV 
prior to starting SC treatment. 
5. If a subject is clinically high-risk they may receive PJP prophylaxis per institutional standards.  
 
            5.2.1 Order of Dosing 
On treatment cycles where PV and rituximab are scheduled on the same day, PV will be 
administered first, followed by rituximab. On Cycle 1 Day1, the initial dose of PV will be 
administered over 90 minutes (+/- 30 minutes). Monitor subject for infusion-related 
reaction during the infusion and for a minimum of 90 minutes (+/- 30 minutes) following 
completion of the initial dose and prior to administration of rituximab. If the previous 
treatments were well tolerated, the subsequent dose of PV will be administered as a 30 (+/- 
15 min) infusion and subject should be monitored during the infusion and for at least 30 
minutes after completion of the infusion and prior to administration of rituximab. 
 
REGIMEN DESCRIPTION5 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule3 
Cycle 
Length 
Polatuzumab 
vedotin (PV) 
Administer an 
antihistamine 
and antipyretic at 
least 30 to 60 
minutes prior to 
PV for potential 
infusion-related 
reactions 
1.8 mg/kg 
IV 
Day 1 
3 weeks 
(21 days) 
Rituximab1 
375 mg/m2 
IV 
Day 1 or Day 2 
1,400 
mg/23,400 
units hyaluronidase 
SC4 
SC administration 
may start at cycle 
2. 
Gemcitabine 
1,000 mg/m2 
IV 
Days 1 and 8 
Cisplatin 
75 mg/m2 
IV 
Day 1 
Dexamethasone2 
40 mg 
IV, 
PO 
Day 1: IV 
Days 2-4: PO 
GCSF (e.g. 
neupogen,  
Neulasta, 
biosimilar or 
Onpro) 
Required for all subjects. Agent choice per institutional standard 

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Subjects must receive a full dose of rituximab by IV prior to starting Rituxan Hycela or a 
biosimilar by SC (see section 6.4). Previous research has demonstrated that IV and SC 
rituximab have equivalent safety and efficacy, with a patient preference for SC 
administration. After initial IV treatment of rituximab, subjects can receive SC rituximab 
for all subsequent doses. Subjects will not be allowed to resume IV administration once 
they have transitioned to SC administration. Cisplatin and gemcitabine will be 
administered via IV on Day1, and gemcitabine will be administered again on Day 8. 
Dexamethasone will be administered via IV on Day 1 and PO on days 2-4.  
 
5.3 
Toxicities and Dosing Delays/Dose Modifications 
 
5.3.1 General Considerations 
 
5.3.1.1 Subjects may have one agent (with the exception of polatuzumab) discontinued 
and remain on the study and be evaluable for efficacy. However, if polatuzumab 
or more than one drug is discontinued, then the subject should be removed from 
the study treatment but will still be followed for disease progression (Section 
5.10). If subjects are otherwise responding to therapy and given that R-GDP is a 
standard salvage regimen, patients will be given the opportunity to continue to 
receive R-GDP off study per SOC. 
 
5.3.1.2 If there is a delay for D1, then all drugs will be delayed. This delay can be 
extended for a maximum of 3 weeks or the subject should be permanently 
discontinued. If the subject doesn’t meet treatment parameters for D8 
gemcitabine, then the dose of gemcitabine should be skipped. 
 
5.3.1.3 Tumor lysis prophylaxis (administer aggressive intravenous hydration, anti- 
hyperuricemic agents, and monitor renal function, Section 6.3.8) will be 
administered prior to cycles 1 per institutional standards. Prophylaxis is not 
needed after cycle 1 since the bulk of disease would be controlled at cycle 1.  
 
5.3.2 Definition of a Treatment Related Unacceptable Toxicity 
≥ Grade 3 myelosuppression resulting in study discontinuation and ≥ Grade 3 
peripheral neuropathy or any Grade 4 toxicity, except for electrolyte abnormalities, 
resulting in discontinuation of polatuzumab by CTCAE v5.0. 
5.3.3 Considerations for Peripheral Neuropathy 
 
  Table 3.  Modifications for Peripheral Neuropathy (Cisplatin, Gemcitabine and PV) 
Peripheral Neuropathy 
NCI CTC Grade 
Cisplatin 
Gemcitabine 
Polatuzumab* 
0-1 
No reduction 
No reduction 
No reduction 

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2-3 
Hold until resolved to 
< Grade 1, then 
reduce to 50 mg/m2 
 
 
No reduction 
Hold polatuzumab dosing until improvement to 
Grade 1 or lower. 
If recovered to Grade 1 or lower on or before 
Day 14, restart polatuzumab with the next cycle 
at a permanently reduced dose of 1.4 mg/kg. 
If a prior dose reduction to 1.4 mg/kg has 
occurred, discontinue polatuzumab. 
If not recovered to Grade 1 or lower on or 
before Day 14, discontinue polatuzumab. 
Grade 4 
Discontinue 
No reduction 
Discontinue 
* For polatuzumab there should be no dose reduction to a dose below 1.4 mg/kg. 
Note: Grade 2-3 Neuropathy: consider providing gabapentin (or similar agent) as supportive care 
per institutional standards. 
 
             5.3.4 Considerations for Hematological Toxicity (neutropenia and thrombocytopenia) 
 
 Table 4.  Modifications for Cisplatin, Gemcitabine and Polatuzumab vedotin 
 
Hematological toxicity 
(Neutropenia and 
Thrombocytopenia) 
NCI CTC 
Grade 
Cisplatin 
Gemcitabine 
PV 
0 
No reduction 
No reduction 
No reduction 
1 
No reduction 
No reduction 
No reduction 
2 
Thrombocytopenia:  
• 
Hold until PLT are at least 
75,000/mm3 
• 
Reduce cisplatin dose by 
25%  
 
• 
For second occurrence of 
grade 2 or higher 
thrombocytopenia: 
o Reduce cisplatin dose 
by 50% 
• 
For third occurrence of 
grade 2 or higher 
thrombocytopenia 
o 
Reduce cisplatin 
by 75% 
• 
Discontinue for any 
subsequent occurrences of 
grade 2 or higher 
thrombocytopenia 
 
Thrombocytopenia:  
• 
Hold until platelets recover to 
at least 75,000/mm3  
• 
Reduce subsequent cycles 
gemcitabine 800 mg/m2 on 
day 1 and day 8 
• 
For second occurrence of 
grade 2 or higher 
thrombocytopenia:  
o 
Reduce gemcitabine 
to 800 mg/m2 and 
administer on day 1 
only 
o 
Day 8 should be 
discontinued. 
• 
For third occurrence of grade 
2 or higher thrombocytopenia 
o 
Reduce gemcitabine 
to 400 mg/m2 day 1 
only 
• 
Discontinue for any 
subsequent occurrences of 
grade 2 or higher 
Thrombocytopenia:  
• 
Hold until platelets 
recover to greater than 
75.0 × 109/L. 
• 
If platelets recover to 
greater than 75.0 × 109/L 
on or before Day 14, 
resume all treatment 
without any additional 
dose reductions. 
• 
If platelets recover to 
greater than 75.0 × 109/L 
after Day 14: 
o 
restart all 
treatment dose 
reduction of 
polatuzumab to 
1.4 

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thrombocytopenia 
3a.b 
Neutropenia:  
• 
Hold until ANC recovers to 
greater than 1.0 × 109/L, 
and  
• 
Reduce cisplatin dose by 
25%  
• 
For second occurrence of 
grade 3 or higher 
neutropenia:  
o 
Reduce cisplatin 
dose by 50%  
• 
For third occurrence of 
grade 3 or higher 
neutropenia: 
o 
Reduce cisplatin 
dose by 75% 
• 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher 
neutropenia 
Thrombocytopenia:  
• 
Hold until PLT are at least 
75,000/mm3 
• 
Reduce cisplatin dose by 
25%  
• 
For second occurrence of 
grade 3 or higher 
thrombocytopenia:  
o 
Reduce cisplatin 
dose by 50%  
• 
For third occurrence of 
grade 3 or higher 
thrombocytopenia: 
o 
Reduce cisplatin 
dose by 75% 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher 
thrombocytopenia 
Neutropenia:  
• 
Hold until ANC recovers to 
greater than 1.0 × 109/L, and  
• 
Reduce subsequent cycles 
day 1 and day 8 to 
gemcitabine 800 mg/m2 
• 
For second occurrence of 
grade 3 or higher 
neutropenia:  
o Reduce gemcitabine to 
800 mg/m2 and 
administer on day 1 
only 
• 
For third occurrence of grade 
3 or higher neutropenia: 
o 
Reduce gemcitabine 
to  400 mg/m2 on 
day 1 only 
• 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher neutropenia 
 
 
 
Thrombocytopenia:  
• 
Hold until PLT are at least 
75,000/mm3  
• 
Reduce subsequent cycles 
gemcitabine 800 mg/m2 on 
day 1 and day 8 
• 
For second occurrence of 
grade 3 or higher 
thrombocytopenia: Reduce 
gemcitabine to 800 mg/m2 
and administer on day 1 only; 
Day 8 should be 
discontinued. 
• 
For third occurrence of grade 
3 or higher 
thrombocytopenia: 
• 
Reduce 
gemcitabine to 
400 mg/m2 on 
day 1 only 
• 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher neutropenia 
 
Neutropenia:  
• 
Hold all treatment until 
ANC recovers to greater 
than 1.0 × 109/L. 
• 
If ANC recovers to 
greater than 1.0 × 109/L 
on or before Day 14, 
resume 
all 
treatment 
without any additional 
dose 
reductions. 
Consider 
granulocyte 
colony 
stimulating 
factor prophylaxis for 
subsequent cycles, if not 
previously given. 
• 
If ANC recovers to 
greater than 1.0 × 109/L 
after Day 14: 
o 
restart 
all 
treatment dose 
reduction 
of 
polatuzumab 
to 1.4 mg/kg. 
Thrombocytopenia:  
• 
Hold until platelets 
recover to greater than 
75.0 × 109/L. 
• 
If platelets recover to 
greater than 75.0 × 109/L 
on or before Day 14, 
resume all treatment 
without any additional 
dose reductions. 
• 
If platelets recover to 
greater than 75.0 × 109/L 
after Day 14: 
o 
restart all 
treatment dose 
reduction of 
polatuzumab to 
1.4 mg/kg 
4a,b  
Neutropenia:  
• 
Hold until ANC recovers to 
greater than 1.0 × 109/L, 
and  
• 
Reduce cisplatin dose by 
25%  
Neutropenia:  
• 
Hold until ANC recovers to 
greater than 1.0 × 109/L, 
and  
• 
Reduce subsequent cycles 
day 1 and day 8 to 
Neutropenia:  
• 
Hold all treatment until 
ANC recovers to greater 
than 1.0 × 109/L. 
• 
If ANC recovers to 
greater than 1.0 × 109/L 

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• 
For second occurrence of 
grade 3 or higher 
neutropenia:  
o Reduce cisplatin dose 
by 50%  
• 
For third occurrence of 
grade 3 or higher 
neutropenia: 
o 
Reduce cisplatin 
dose by 75% 
• 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher 
neutropenia 
 
Thrombocytopenia:  
• 
Hold until PLT are at 
least 75,000/mm3 
• 
Reduce cisplatin dose by 
25%  
• 
For second occurrence of 
grade 3 or higher 
thrombocytopenia:  
o Reduce cisplatin dose 
by 50%  
• 
For third occurrence of 
grade 3 or higher 
thrombocytopenia: 
Reduce cisplatin dose by 
75% 
• 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher 
thrombocytopenia 
 
gemcitabine 800 mg/m2 
• 
For second occurrence of 
grade 3 or higher 
neutropenia:  
o 
Reduce 
gemcitabine to 800 
mg/m2 and 
administer on day 1 
only; Day 8 should 
be discontinued.  
• 
For third occurrence of 
grade 3 or higher 
neutropenia: 
o 
Reduce gem dose 
by to 400 mg/m2 
on day 1 only 
• 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher 
neutropenia 
Thrombocytopenia:  
• 
Hold until PLT are at least 
75,000/mm3 
• 
Reduce subsequent cycles 
gemcitabine 800 mg/m2 on 
day 1 and day 8 
• 
For second occurrence of 
grade 3 or higher 
thrombocytopenia:  
o 
Reduce 
gemcitabine to 800 
mg/m2 and 
administer on day 1 
only; Day 8 should 
be discontinued. 
• 
For third occurrence of 
grade 3 or higher 
thrombocytopenia: 
o 
Reduce 
gemcitabine  to 400 
mg/m2 day 1 only 
• 
Discontinue for any 
subsequent occurrences of 
grade 3 or higher 
thrombocytopenia 
 
on or before Day 14, 
resume all treatment 
without any additional 
dose reductions. 
Consider granulocyte 
colony stimulating factor 
prophylaxis for 
subsequent cycles, if not 
previously given. 
• 
If ANC recovers to 
greater than 1.0 × 109/L 
after Day 14: 
o restart all 
treatment dose 
reduction of 
polatuzumab to 
1.4 mg/kg. 
Thrombocytopenia:  
• 
Hold all treatment until 
platelets recover to greater 
than 75.0 × 109/L. 
• 
If platelets recover to 
greater than 75.0 × 109/L 
on or before Day 14, 
resume all treatment 
without any additional 
dose reductions. 
• 
If platelets recover to 
greater than 75.0 × 109/L 
after Day 14: 
o 
restart all 
treatment dose 
reduction of 
polatuzumab to 
1.4 mg/kg 
a Severity on Day 1 of any cycle. 
b If primary cause is due to lymphoma, dose delay or reduction may not be needed at discretion of investigator 
5.3.5 Considerations for Non-Hematological Toxicities 
Table 5. Considerations for Non-Hematological Toxicities 
Non-Hematological Toxicities 
NCI CTC 
Grade 
Cisplatin2,3 
Gemcitabine2 
Polatuzumab4 

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0-1 
No reduction 
 
No reduction 
 
No reduction 
2 
No reduction except for renal toxicity: 
CrCl 46 to 50 mL/min: Reduce dose by 
25%. 
CrCl 31 to 45 mL/min: reduce dose by 
50%. 
No Reduction 
No reduction 
Grade 3-4 
Reduce dose of Cisplatin by 50% for 
other Grade 3 or 4 non-hematological 
adverse reactions until resolved to ≤ 
Grade 2. 
For grade 3-4 Renal toxicity:  
(CrCl<30mL/min): 
Discontinue cisplatin 
Permanently discontinue for any 
recurrent Grade 3 or 4 non-
hematological adverse reaction possibly 
related to cisplatin. 
Reduce dose of gemcitabine by 50% for 
Grade 3 or 4 non-hematological adverse 
reactions at least possibly related to 
gemcitabine until resolved to ≤ Grade 2. 
• 
If resolved – return to full dose.  
Permanently discontinue for any recurrent 
Grade 3 or 4 non-hematological adverse 
reaction possibly related to gemcitabine1. 
Discontinue 
1.  Permanently discontinue gemcitabine for any of the following: 
• 
Unexplained dyspnea or evidence of severe pulmonary toxicity 
• 
Hemolytic uremic syndrome (HUS) or severe renal impairment 
• 
Severe hepatic toxicity 
• 
Capillary leak syndrome (CLS) 
• 
Posterior reversible encephalopathy syndrome (PRES) 
• 
Recurrent grade 3 or 4 non-hematologic adverse reactions possibly related to gemcitabine 
 2.   No dose modifications are recommended for alopecia, nausea, or vomiting. 
3.   Permanently discontinue Cisplatin for any of the following: 
• Severe hypersensitivity reactions 
4.   For polatuzumab: New-onset symptoms suggestive of progressive multifocal leukoencephalopathy (PML) and 
permanently discontinue if diagnosis is confirmed. 
 
5.3.6 Dose Modifications for Rituximab 
Dosage adjustments for rituximab are not recommended. 
  Table 6.   Dose Modifications for IRR 
 
Event 
Dose Modification 
Grade 1–3 Infusion-Related Reaction 
Interrupt polatuzumab infusion and give supportive treatment. 
For the first instance of Grade 3 wheezing, bronchospasm, or generalized 
urticaria, permanently discontinue polatuzumab. For recurrent Grade 2 
wheezing or urticaria permanently discontinue polatuzumab. 
For any other recurrent grade 3 symptoms, permanently discontinue 
polatuzumab. 
Otherwise, upon complete resolution of symptoms, infusion may be resumed 
at 50% of the rate achieved prior to interruption. In the absence of infusion 
related symptoms, the rate of infusion may be escalated in increments of 50 
mg/hour every 30 minutes. 

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For the next cycle, infuse polatuzumab over 90 minutes. If no infusion related 
reaction occurs, subsequent infusions may be administered over 30 
minutes. Administer premedication for all cycles. 
Grade 4 Infusion-Related Reaction 
Stop polatuzumab infusion immediately. Give supportive treatment. 
Permanently discontinue polatuzumab 
 
 
5.4 
Concomitant Medications/Treatments/Supportive Care Allowed 
The following concomitant medications/treatment and supportive cares are 
allowed: 
• G-CSF (all formulations, including long and short acting and biosimilars) 
is mandatory for all subjects. 
Subjects on the trial are allowed to receive all supportive care therapy needed 
to alleviate symptoms related to their cancer diagnosis or other medical 
problems at the investigator’s discretion. No treatments should be withheld due 
to a subject’s participation in this study. Prophylaxis for infusion-related 
reactions should be employed per institutional guidelines. 
 
Transfusion of blood products allowable for subjects with symptomatic or at 
risk for symptomatic anemia and/or thrombocytopenia per Investigator’s 
discretion and per institution guidelines.   
 
Medications or vaccinations specifically prohibited in the exclusion criteria are 
not allowed during the ongoing trial. If there is a clinical indication for one of 
these or other medications or vaccinations specifically prohibited during the 
trial, discontinuation from trial therapy or vaccination may be required. 
 
5.5 
Medications/Treatment Precautions 
The following medications/treatments are required precautions or are prohibited 
• 
 Warfarin/coumarin anticoagulants: increased or fluctuating anticoagulant 
effects. Avoid, if possible, consider switching subject to a low molecular 
weight heparin or DOAC during treatment or if the subject continues taking 
an oral anticoagulant monitor the INR at least once a week and adjust dose 
accordingly. 
• Concomitant use of strong CYP3A inhibitors or inducers has the potential 
to affect the exposure to unconjugated monomethyl auristatin E (MMAE) 
(Appendix D). 
• Aminoglycoside antibiotics: increased risk of nephrotoxicity and 
ototoxicity when given within 2 weeks of cisplatin. 
• Diuretics: increased risk of nephrotoxicity and ototoxicity, monitor fluid 
status and creatine closely if given 
• Nephrotoxic drugs 
• Ototoxic drugs 
• Phenytoin: cisplatin reduces absorption and efficacy of phenytoin, monitor 
levels and adjust dose as necessary 
• Anti-gout agents: cisplatin may increase plasma concentration of uric acid 
therefore dose adjustments may be required to control hyperuricemia and 
gout. 

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• Lithium: cisplatin may affect lithium plasma levels – monitor 
5.6 
Other Modalities or Procedures 
AutoSCT may be performed for eligible subjects as early as Cycle 2 in subjects that 
demonstrate CR and 4 cycles in subjects that demonstrate PR or CAR-T at any time after 2 
cycles have been completed (per investigator discretion). If the subject has a partial response 
(PR), they may go to transplant or CAR-T at any time after 4 cycles have been completed. 
Transplant ineligible subjects may be eligible for CAR-T therapy  
 
5.7 
Duration of Therapy 
Treatment may continue until: 
• Disease progression 
• Inter-current illness that prevents further administration of treatment 
• Unacceptable adverse event(s) 
• Pregnancy 
• Subject decides to withdraw from study treatment. 
• General or specific changes in the subject’s condition render the subject 
unacceptable for further treatment in the judgment of the investigator. 
• Subject completes maximum number (6 cycles) of treatment cycles 
allowed per protocol. 
• Subject is lost to follow-up. 
• If polatuzumab or more than one drug is discontinued for treatment. Note: 
subjects may continue to receive the remaining regimen off study.  
5.7.6 Off-treatment Status: 
• Survival and progression follow- up. 
o If subject achieves a CR at completion of therapy (after transplant 
in transplant eligible group, or after 6 cycles of PV-RGDP in 
transplant ineligible group). 
o If subject achieves a PR or stable disease at the completion of 
therapy (but have not started a new treatment). 
 
• Survival follow-up only 
o Subject develops PD at any point in the study. 
o If the subject starts a new treatment. 
o If polatuzumab or more than one drug is discontinued for treatment. 
5.8 
Duration of Follow Up 
All subjects will be followed for up to 5 years, or until death, whichever occurs first 
after removal from study treatment for determination of study endpoints. Follow- 
up for progression and survival is at least every 6 months (more frequently if 
needed per Investigator discretion) with CT imaging for 2 years and every 6 months 
with survival assessment for 5 years. Subjects removed from study treatment for 
unacceptable AEs will be followed for resolution or stabilization of the adverse 
event(s). All subjects (including those withdrawn for AEs and non-evaluable 
subjects) should be followed after removal from study treatment for survival as 
stipulated in the protocol. 
 

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5.9 
Study Withdrawal 
If a subject decides to withdraw from the study (and not just from protocol therapy) 
an effort should be made to complete and report study assessments as thoroughly 
as possible. At the time of withdrawal, the investigator should attempt to establish 
as completely as possible the reason for the study withdrawal. 
• 
The subject should be asked if they are willing to allow for the abstraction 
of relevant information from their medical record in order to meet the long 
term follow up (e.g., survival) objectives outlined in the protocol. 
• 
A complete final evaluation at the time of the subject’s study withdrawal 
should be obtained with an explanation of why the subject is withdrawing 
from the study. 
• 
If the subject is noncompliant and does not return for an end of study follow 
up assessment, this should be documented in the eCRF. 
• 
If the reason for removal of a subject from the study is an adverse event, the 
principal specific event will be recorded on the eCRF. 
 
Excessive subject withdrawals from protocol therapy or from the study can render 
the study un-interpretable; therefore, unnecessary withdrawal of subjects should be 
avoided. 
 
5.10 
Off-Study Criteria 
• Subject has completed all study activities including any needed follow-up 
activities and no further data collection from the subject is needed (Section 5.8). 
• Subject withdraws consent to be in the study (Section 5.9) 
• Death 
• Lost to follow-up. 
• Situations in which the treating physician feels it is in the best interest for the 
subject to not continue on the study. 

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6.0 
DRUG INFORMATION 
6.1 
Polatuzumab 
The information in this section is from the polatuzumab Investigator’s Brochure 
(IB), version 13.  For additional information, please refer to the IB.  
 
6.1.1 Description 
Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate (ADC) 
consisting of three components: 1) the humanized immunoglobulin G1 (IgG1) 
monoclonal antibody specific for human CD79b; 2) the small molecule anti-mitotic 
agent MMAE; and 3) a protease-cleavable linker maleimidocaproyl-valine- 
citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB) that covalently attaches 
MMAE to the polatuzumab antibody. 
 
Polatuzumab vedotin-piiq exhibits activity against dividing B cells. The small 
molecule, MMAE is an anti-mitotic agent covalently attached to the antibody via a 
cleavable linker. The antibody binds to a B-cell specific surface protein CD79b, a 
component of the B-cell receptor. Polatuzumab vedotin-piiq is then internalized, 
and lysosomal proteases cleave the linker enabling intracellular delivery of MMAE. 
MMAE inhibits cell division and induces apoptosis in dividing cells by binding to 
microtubules. 
 
6.1.2 How Supplied 
Polatuzumab vedotin-piiq (PV) is an investigation product provided by Genentech. 
PV for injection is a preservative-free, white to grayish-white lyophilized powder, 
which has a cake-like appearance, supplied in a single-dose vial. 
 
6.1.3 Preparation 
Reconstitute and further dilute PV prior to intravenous infusion. 
 
PV is a cytotoxic drug. Follow applicable special handling and disposal procedures. 
 
Parenteral drug products should be inspected visually for particulate matter and 
discoloration prior to administration, whenever solution and container permit. 
 
6.1.3.1 Reconstitution 
• Reconstitute immediately before dilution. 
• More than one vial may be needed for a full dose. Calculate the dose, the total 
volume of reconstituted PV solution required, and the number of PV vials 
needed. 
• Reconstitute each 140 mg PV vial by using a sterile syringe to slowly inject 
7.2 mL of Sterile Water for Injection, USP with the stream directed toward 
the inside wall of the vial to obtain a concentration of 20 mg/mL of 
polatuzumab vedotin-piiq. 

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• Swirl the vial gently until completely dissolved. Do not shake. 
• Inspect the reconstituted solution for discoloration and particulate matter. The 
reconstituted solution should appear colorless to slightly brown, clear to 
slightly opalescent, and free of visible particulates. Do not use if the 
reconstituted solution is discolored, is cloudy, or contains visible particulates. 
Do not freeze or expose to direct sunlight. 
• If needed, store unused reconstituted PV solution refrigerated at 2°C to 8°C 
(36°F to 46°F) for up to 48 hours or at room temperature (9°C to 25°C, 47°F 
to 77°F) up to a maximum of 8 hours prior to dilution. Discard vial when 
cumulative storage time prior to dilution exceeds 48 hours. 
 
6.1.3.2 Dilution 
• Dilute polatuzumab vedotin-piiq to a final concentration of 0.72–2.7 mg/mL 
in an intravenous infusion bag with a minimum volume of 50 mL containing 
0.9% Sodium Chloride Injection, USP, 0.45% Sodium Chloride Injection, 
USP, or 5% Dextrose Injection, USP. 
• Determine the volume of 20 mg/mL reconstituted solution needed based on 
the required dose. 
• Withdraw the required volume of reconstituted solution from the PV vial 
using a sterile syringe and dilute into the intravenous infusion bag. Discard 
any unused portion left in the vial. 
• Gently mix the intravenous bag by slowly inverting the bag. Do not shake. 
• Inspect the intravenous bag for particulates and discard if present. 
• If not used immediately, store the diluted PV solution as specified in Table 7. 
Discard if storage time exceeds these limits. Do not freeze or expose to direct 
sunlight. 
 
6.1.4 Storage and Handling 
Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from 
light. Do not use beyond the expiration date shown on the carton. Do not freeze. 
Do not shake. 
 
6.1.5 Stability 
 
Table 7 Diluted Polatuzumab Vedotin Solution Storage Conditions 
Diluent Used to Prepare 
Solution for Infusion 
Diluted Polatuzumab Vedotin Solution Storage 
Conditions* 
0.9% Sodium Chloride 
Injection, USP 
Up to 24 hours at 2°C to 8°C (36°F to 46°F) or up to 
4 hours at room temperature (9 to 25°C, 47 
0.45% Sodium Chloride 
Injection, USP 
Up to 18 hours at 2°C to 8°C (36°F to 46°F) or up to 
4 hours at room temperature (9 to 25°C, 47 
5% Dextrose Injection, USP 
Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 
6 hours at room temperature (9 to 25°C, 47 
* To ensure product stability, do not exceed specified storage durations. 

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Limit transportation to 30 minutes at 9°C to 25°C or 12 hours at 2°C to 8°C (refer 
to instructions below). The total storage plus transportation times of the diluted 
product should not exceed the storage duration specified in Table 7. 
 
Agitation stress can result in aggregation. Limit agitation of diluted product during 
preparation and transportation to administration site. Do not transport diluted 
product through an automated system (e.g., pneumatic tube or automated cart). If 
the prepared solution will be transported to a separate facility, remove air from the 
infusion bag to prevent aggregation. If air is removed, an infusion set with a vented 
spike is required to ensure accurate dosing during the infusion. 
 
No incompatibilities have been observed between PV and intravenous infusion 
bags with product contacting materials of polyvinyl chloride (PVC) or polyolefins 
such as polyethylene (PE) and polypropylene. No incompatibilities have been 
observed with infusion sets or infusion aids with product-contacting materials of 
PVC, PE, polyurethane, polybutadiene (PBD), acrylonitrile butadiene styrene, 
polycarbonate, 
polyetherurethane, 
fluorinated 
ethylene 
propylene, 
or 
polytetrafluorethylene, or with filter membranes composed of polyether sulfone or 
polysulfone. 
 
6.1.6 Route of Administration 
See Section 5.2. Administer only as an intravenous infusion. Do not administer as 
an intravenous push or bolus. 
 
6.1.7 Method of Administration 
IV 
 
Reconstitute and further dilute PV prior to intravenous infusion. 
 
PV must be administered using a dedicated infusion line equipped with a sterile, 
non-pyrogenic, low-protein binding in-line or add-on filter (0.2- or 0.22-micron 
pore size) and catheter. 
 
On treatment cycles where PV and rituximab are scheduled on the same day, PV 
will be administered first, followed by rituximab. On Cycle 1 Day1, the initial dose 
of PV will be administered over 90 minutes (+/- 30 minutes). Monitor subject for 
infusion-related reaction during the infusion and for a minimum of 90 minutes (+/- 
30 minutes) following completion of the initial dose and prior to administration of 
rituximab. If the previous treatments were well tolerated, the subsequent dose of 
PV will be administered as a 30 (+/- 15 min) infusion and subject should be 
monitored during the infusion and for at least 30 minutes after completion of the 
infusion and prior to administration of rituximab. 
 
Do not mix PV with or administer as an infusion with other drugs. 

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6.1.8 Drug Ordering and Accountability 
The investigator or designee is responsible for keeping accurate records of the 
clinical supplies received from the company sponsor or designee, the amount 
dispensed to the subjects and the amount remaining at the conclusion of the trial. 
An accurate and current accounting of the dispensing and return of investigational 
study drug for each subject will be maintained on an ongoing basis by a member of 
the study site staff. The amount of study drug dispensed and returned by the subject 
will be recorded in the Investigational Drug Accountability Record. 
 
6.1.9 Return and Retention of Study Drug 
Upon completion or termination of the study, all unused and/or partially used 
investigational product will be destroyed at the site per institutional policy (e.g., 
UNC IDS drug destruction policy). It is the Investigator’s responsibility to arrange 
for disposal of all empty containers, provided that procedures for proper disposal 
have been established according to applicable federal, state, local and institutional 
guidelines and procedures, and provided that appropriate records of disposal are 
kept. 
 
6.1.10 Adverse Events Associated with Polatuzumab Vedotin-piiq 
The 
most 
common 
adverse 
reactions 
(≥20%) 
included 
neutropenia, 
thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, 
decreased appetite, and pneumonia. 
 
6.1.11 Contraindications 
None 
 
6.1.12 There are no other known contraindications for polatuzumab vedotin. Other 
Significant AEs and Precautions 
Other significant adverse reactions include the following: 
• 
Peripheral neuropathy 
• 
Infusion-related reactions 
• 
Myelosuppression 
• 
Serious and opportunistic infections 
• 
Progressive multifocal leukoencephalopathy (PML) 
• 
Tumor lysis syndrome 
• 
Hepatotoxicity 
• 
Embryo-fetal toxicity 
 
6.1.13 Drug Interactions 
Strong CYP3A Inhibitors and Strong CYP3A Inducers are prohibited (Appendix 
D). MMAE is a substrate for CYP3A4/5. 
 
6.2 
Dexamethasone 
The following is a summary of dexamethasone information. Refer to package insert 
for complete dispensing instructions available at: 

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http://docs.boehringer- 
ingelheim.com/Prescribing%20Information/PIs/Roxane/Dexamethasone/Dexamet 
hasone%20Tablets%20Solution%20and%20Intensol.pdf 
 
6.2.1 Brief Description: 
Dexamethasone is a practically white or white, odorless, crystalline powder that is 
a synthetic glucocorticoid. Glucocorticoids produce varied metabolic effects. 
 
6.2.2 Dosage and Administration: 
See Section 5.2 
 
6.2.3 Storage and Stability: 
Store dexamethasone at 20℃-25℃ (68℉-77℉). 
 
6.2.4 Handling and Disposal: 
Local requirements for disposal of hazardous drugs should be followed at each 
participating clinical site. 
 
Please see UNC policy on hazardous drugs: 
https://unchealthcare-uncmc.policystat.com/policy/4734545/latest/ 
 
6.2.5 Adverse Events Associated with Dexamethasone 
Gastrointestinal: Nausea, vomiting, anorexia, increased appetite, weight gain; 
aggravation of peptic ulcers. 
 
Dermatologic: Rash, skin atrophy, facial hair growth, acne, facial erythema, 
ecchymoses. 
Genitourinary: 
Menstrual 
changes 
(amenorrhea, 
menstrual 
irregularities). 
 
Neurologic: Insomnia, euphoria, headache, vertigo, psychosis, depression, seizures, 
muscle weakness. 
 
Cardiovascular: Fluid retention and edema, hypertension; rarely, thrombophlebitis. 
Ocular: Cataracts, increased intraocular pressure, exophthalmos. 
 
Metabolic: Hyperglycemia, decreased glucose tolerance, aggravation or 
precipitation of diabetes mellitus, adrenal suppression (with Cushingoid features), 
hypokalemia. 
 
Hematologic: Leukocytosis. 
 
Other: Osteoporosis (and resulting back pain), appearance of serious infections 
including herpes zoster, varicella zoster, fungal infections, Pneumocystis carinii, 
tuberculosis; muscle wasting; delayed wound healing; suppression of reactions to 
skin tests. 

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6.2.6 Contraindications 
Contraindicated in systemic fungal infections. 
 
6.2.6.1 Use in Pregnancy 
Pregnancy Category C: Corticosteroids have been shown to be teratogenic in 
many species when given in doses equivalent to the human dose. 
 
6.2.6.2 Use in Nursing Women 
Systemically administered corticosteroids appear in human milk and could 
suppress growth, interfere with endogenous corticosteroid production, or cause 
other adverse effects on the nursing infant. 
 
6.2.6.3 Overdose 
Treatment of overdosage is by supportive and symptomatic therapy. In the case 
of acute overdosage, according to the subject's condition, supportive therapy may 
include gastric lavage or emesis. 
 
6.3 
Rituximab 
The following is a summary of rituximab details. For more information, please refer 
to the full prescribing package insert information. Importantly, biosimilars and 
subcutaneous dosing is allowed in this study (see Section 6.4 Rituxan Hycela). 
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b172773b-3905-4a1c- 
ad95-bab4b6126563 
 
6.3.1 Supplier/How Supplied 
Rituximab is commercially available. 
 
Rituximab injection is a sterile, preservative-free, clear, colorless solution for 
intravenous infusion). 
 
6.3.2 Brief Description: 
Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 
kappa antibody directed against the CD20 antigen. Rituximab has an approximate 
molecular weight of 145 kD. 
 
Rituximab is produced by mammalian cell (Chinese Hamster Ovary) suspension 
culture in a nutrient medium that may contain the antibiotic gentamicin. Gentamicin 
is not detectable in the final product. 
 
6.3.3 Dosage and Administration: 
See Section 5.2. Administer only as an intravenous infusion. Do not administer as 
an intravenous push or bolus. 
 
On days when PV and rituximab infusion are scheduled, rituximab would be 
administered following PV infusion (see section 6.1.7). 

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6.3.4 Storage and Stability: 
Store rituximab vials refrigerated at 2°C to 8°C (36°F to 46°F). Rituximab vials 
should be protected from direct sunlight. Do not freeze or shake. 
 
6.3.5 Handling and Disposal: 
Local requirements for disposal of hazardous drugs should be followed at each 
participating clinical site. 
 
Please see UNC policy on hazardous drugs: 
https://unchealthcare-uncmc.policystat.com/policy/4734545/latest/ 
 
6.3.6 Adverse Events Associated with Rituximab 
Most common adverse reactions in clinical trials were: 
• 
Non-Hodgkin’s Lymphoma (NHL) (≥ 25%): infusion-related reactions, 
fever, lymphopenia, chills, infection, and asthenia 
• 
Chronic Lymphocytic Leukemia (CLL) (≥ 25%): infusion-related reactions 
and neutropenia 
• 
Rheumatoid arthritis (RA) (≥ 10%): upper respiratory tract infection, 
nasopharyngitis, urinary tract infection, and bronchitis (other important 
adverse reactions include infusion-related reactions, serious infections, and 
cardiovascular events). 
• 
Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and 
Microscopic Polyangiitis (MPA) (≥15 %): infections, nausea, diarrhea, 
headache, muscle spasms, anemia, peripheral edema, infusion-related 
reactions. 
• 
Pemphigus Vulgaris (PV) (≥15%): infusion-related reactions, depression 
(other important adverse reactions include infections). 
 
6.3.7 Contraindications 
None 
 
6.3.8 Precautions 
Renal toxicity when used in combination with cisplatin. 
 
• 
Tumor lysis syndrome: Administer aggressive intravenous hydration, anti- 
hyperuricemic agents, monitor renal function. 
• 
Infections: Withhold rituximab and institute appropriate anti-infective therapy 
• 
Cardiac adverse reactions: Discontinue infusions in case of serious or life- 
threatening events. 
• 
Renal toxicity: Discontinue in subjects with rising serum creatinine or oliguria. 
• 
Bowel obstruction and perforation: Consider and evaluate for abdominal pain, 
vomiting, or related symptoms. 
• 
Immunizations: Live virus vaccinations prior to or during rituximab treatment 
not recommended 
• 
Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive 
potential of the potential risk to a fetus and use of effective contraception. 
 

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6.4 
Rituxan Hycela  
The following is a summary of Rituxan Hycela details. For more information, please 
refer to the full prescribing information.  
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e5b7e82-f018-4eaf-
ae78-d6145a906b20 
 
6.4.1 Supplier/How Supplied 
Rituxan Hycela is commercially available. Rituxan Hycela is a colorless to yellowish, clear 
to opalescent solution for subcutaneous injection 
 
6.4.2 Brief Description: 
Rituxan Hycela is indicated for the treatment of adult patients with previously untreated 
diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, 
vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens. 
 
6.4.3 Dosage and Administration: 
See Section 5.2.  
 
All patients must first receive at least one full dose of a rituximab product by intravenous 
infusion without experiencing severe adverse reactions before starting treatment with 
Rituxan Hycela. If patients are not able to receive one full dose by intravenous infusion, they 
should continue subsequent cycles with a rituximab product by intravenous infusion and not 
switch to Rituxan Hycela until a full intravenous dose is successfully administered. 
 
6.4.4 Storage and Stability: 
Store Rituxan Hycela vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original 
carton to protect from light. Do not freeze. 
 
6.4.5 Handling and Disposal: 
Local requirements for disposal of hazardous drugs should be followed at each 
participating clinical site. 
 
Please see UNC policy on hazardous drugs: 
https://unchealthcare-uncmc.policystat.com/policy/4734545/latest/ 
 
6.4.6 Adverse Events Associated with Rituximab 
Most common adverse reactions in clinical trials were: 
• Severe Mucocutaneous Reaction  
• Hepatitis B Virus Reactivation  
• Progressive Multifocal Leukoencephalopathy  
• Hypersensitivity and other Administration Reactions  
• Tumor Lysis Syndrome 
• Infections  
• Cardiovascular Adverse Reactions  
• Renal Toxicity  
• Bowel Obstruction and Perforation  

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6.4.7 Contraindications 
None 
 
6.4.8 Precautions 
Renal toxicity when used in combination with cisplatin. 
 
• 
Tumor lysis syndrome: Administer aggressive intravenous hydration, anti- 
hyperuricemic agents, monitor renal function. 
• 
Infections: Withhold rituximab and institute appropriate anti-infective therapy 
• 
Cardiac adverse reactions: Discontinue infusions in case of serious or life- 
threatening events. 
• 
Renal toxicity: Discontinue in subjects with rising serum creatinine or oliguria. 
• 
Bowel obstruction and perforation: Consider and evaluate for abdominal pain, 
vomiting, or related symptoms. 
• 
Immunizations: Live virus vaccinations prior to or during rituximab treatment 
not recommended 
• 
Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive 
potential of the potential risk to a fetus and use of effective contraception. 
 
6.5 
Gemcitabine: 
For more information on this drug please refer to the full prescribing information: 
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9dc35c59-f4f3-43b4- 
8251-0cf5c06cdc80 
 
6.5.1 Brief Description: 
Gemcitabine is a nucleoside metabolic inhibitor. Gemcitabine hydrochloride is 
soluble in water, slightly soluble in methanol, and practically insoluble in ethanol 
and polar organic solvents. Gemcitabine is a sterile white to off-white lyophilized 
powder and available as 200 mg and 1 g single-dose vials for intravenous use only. 
 
6.5.2 Supplier/How Supplied 
Gemcitabine is commercially available. 
 
Gemcitabine is a sterile white to off-white lyophilized powder available in single- 
dose vials individually packaged in a carton containing 200 mg or 1 g gemcitabine. 
 
6.5.3 Preparation 
 
6.5.3.1 Preparation and Administration Precautions 
Exercise caution and wear gloves when preparing gemcitabine solutions. 
Immediately wash the skin thoroughly or rinse the mucosa with copious amounts 
of water if gemcitabine contacts the skin or mucus membranes. Death has 
occurred in animal studies due to dermal absorption. 
 
6.5.3.2 Preparation for Intravenous Infusion Administration 
Reconstitute the vials with 0.9% Sodium Chloride Injection without 

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preservatives. Add 5 mL to the 200-mg vial or 25 mL to the 1-g vial. These 
dilutions each yield a gemcitabine concentration of 38 mg/mL. Complete 
withdrawal of the vial contents will provide 200 mg or 1 g of gemcitabine. Prior 
to administration the appropriate amount of drug must be diluted with 0.9% 
Sodium Chloride Injection. Final concentrations may be as low as 0.1 mg/mL. 
 
Reconstituted gemcitabine is a clear, colorless to light straw-colored solution. 
Inspect visually prior to administration and discard for particulate matter or 
discoloration. 
 
6.5.4 Dosage and Administration: 
See Section 5.2 
 
6.5.5 Storage and Stability: 
Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions 
permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room 
Temperature]. 
 
6.5.6 Handling and Disposal: 
Gemcitabine is a cytotoxic drug. Follow applicable special handling and disposal 
procedures. 
Local requirements for disposal of hazardous drugs should be followed at each 
participating clinical site. 
Please see UNC policy on hazardous drugs: 
https://unchealthcare-uncmc.policystat.com/policy/4734545/latest/ 
 
6.5.7 Adverse Events Associated with Gemcitabine 
The most common adverse reactions for the single agent (≥20%) are 
nausea/vomiting, anemia, increased aspartate aminotransferase (AST), increased 
alanine aminotransferase (ALT), neutropenia, increased alkaline phosphatase, 
proteinuria, fever, hematuria, rash, thrombocytopenia, dyspnea, and edema. 
 
6.5.8 Contraindications 
Gemcitabine is contraindicated in subjects with a known hypersensitivity to 
gemcitabine. Reactions include anaphylaxis. 
 
6.5.9 Other Significant AEs and Precautions with Gemcitabine 
Other significant adverse reactions include the follow (for more information please 
refer to the package insert or prescribing information): 
• 
Hypersensitivity 
• 
Schedule-Dependent Toxicity 
• 
Myelosuppression 
• 
Pulmonary Toxicity and Respiratory Failure 
• 
Hemolytic Uremic Syndrome 
• 
Hepatic Toxicity 
• 
Exacerbation of Radiation Therapy Toxicity 

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• 
Capillary Leak Syndrome 
• 
Posterior Reversible Encephalopathy Syndrome 
 
6.6 
Cisplatin 
 
6.6.1 Brief Description: 
Cisplatin Injection is a clear, colorless, sterile aqueous solution. Each 50 mL, 100 
mL or 200 mL amber vial of Cisplatin Injection contains: 1 mg/mL cisplatin, 9 
mg/mL sodium chloride, hydrochloric acid and/or sodium hydroxide to adjust pH, 
and water for injection to a final volume of 50 mL, 100 mL, or 200 mL, 
respectively. The pH range of Cisplatin Injection is 3.8 to 5.9. 
 
6.6.2 Supplier/How Supplied 
Cisplatin Injection (1 mg/mL) 
6.6.3 Preparation 
The 50 mg vials should be reconstituted with 50 mL of Sterile Water for 
Injection, USP. 
 
6.6.3.1 Preparation Precautions 
Caution should be exercised in handling the aqueous solution. Procedures for 
proper handling and disposal of anticancer drugs should be utilized. Several 
guidelines on this subject have been published. To minimize the risk of dermal 
exposure, always wear impervious gloves when handling vials and IV sets 
containing cisplatin. 
 
Skin reactions associated with accidental exposure to cisplatin may occur. The 
use of gloves is recommended. If cisplatin contacts the skin or mucosa, 
immediately and thoroughly wash the skin with soap and water and flush the 
mucosa with water. 
 
6.6.3.2 Instructions for Preparation 
The aqueous solution should be used intravenously only and should be 
administered by IV infusion over a 6- to 8-hour period. 
 
Parenteral drug products should be inspected visually for particulate matter and 
discoloration prior to administration, whenever solution and container permit. 
 
6.6.4 Dosage and Administration: 
See Section 5.2 
 
Cisplatin is administered by slow intravenous infusion. Cisplatin SHOULD NOT 
BE GIVEN BY RAPID INTRAVENOUS INJECTION. 
 
6.6.5 Storage and Stability: 
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Do 
not refrigerate. Protect from light. 
 

LCCC 2033 
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6.6.6 Handling and Disposal: 
Local requirements for disposal of hazardous drugs should be followed at each 
participating clinical site. 
 
Please see UNC policy on hazardous drugs: 
https://unchealthcare-uncmc.policystat.com/policy/4734545/latest/ 
 
6.6.7 Adverse Events Associated with Cisplatin 
 
6.6.7.1 Nephrotoxicity 
Dose-related and cumulative renal insufficiency, including acute renal failure, is 
the major dose-limiting toxicity of cisplatin. Renal toxicity has been noted in 28% 
to 36% of subjects treated with a single dose of 50 mg/m 2. It is first noted during 
the second week after a dose and is manifested by elevations in blood urea 
nitrogen (BUN) and creatinine, serum uric acid and/or a decrease in creatinine 
clearance. Renal toxicity becomes more prolonged and severe with repeated 
courses of the drug. Renal function must return to normal before another dose of 
cisplatin can be given. Elderly subjects may be more susceptible to 
nephrotoxicity. 
 
Impairment of renal function has been associated with renal tubular damage. The 
administration of cisplatin using a 6- to 8-hour infusion with intravenous 
hydration, and mannitol has been used to reduce nephrotoxicity. However, renal 
toxicity still can occur after utilization of these procedures. 
 
6.6.7.2   Anti-Emetics and Hydration Prior to and Post Cisplatin  
Appropriate pre- and post-hydration for cisplatin chemotherapy will be included 
according to 
institutional 
guidelines. Furosemide, mannitol, and electrolyte 
supplementation may be included according to local practices as well. Anti- emetic 
prophylaxis should be administered with cisplatin according to the following table and are 
recommended to include a corticosteroid and a 5-HT3 antagonist. Corticosteroids should 
only be used as pre- and post-medication for antiemetic prophylaxis for cisplatin therapy 
and should be dosed as delineated below. 
 
 
6.6.7.3     Ototoxicity 
Ototoxicity has been observed in up to 31% of subjects treated with a single dose 
of cisplatin 50 mg/m 2 and is manifested by tinnitus and/or hearing loss in the 
high frequency range (4,000 to 8,000 Hz). The prevalence of hearing loss in 
children is particularly high and is estimated to be 40 to 60%. Decreased ability 
to hear normal conversational tones may occur. Deafness after the initial dose of 
cisplatin has been reported. Ototoxic effects may be more severe in children 
Chemotherapy 
Premed Day 
Premeds 
Suggested Home Regimen 
Cisplatin  
Day 1  
Dexamethasone 8mg IV or 
po 
and 
5-HT3 antagonist 
and/or 
Lorazepam 
Dexamethasone 8mg po days 
2,3 9, and 10 
AND 
5-HT3 antagonist prn 
and/or 
Lorazepam prn 

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receiving cisplatin. 
 
Hearing loss can be unilateral or bilateral and tends to become more frequent and 
severe with repeated cisplatin doses. It is unclear whether cisplatin-induced 
ototoxicity is reversible. Vestibular toxicity has also been reported. Ototoxic 
effects may be related to the peak plasma concentration of cisplatin. Ototoxicity 
can occur during treatment or be delayed. Audiometric monitoring will be 
performed prior to initiation of therapy, and then if clinically indicated by formal 
assessment. 
 
The risk of ototoxicity may be increased by prior or simultaneous cranial 
irradiation and may be more severe in subjects less than 5 years of age, subjects 
being treated with other ototoxic drugs (e.g., aminoglycosides and vancomycin), 
and in subjects with renal impairment. 
 
Genetic factors (e.g., variants in the thiopurine S-methyltransferase [TPMT] 
gene) may contribute to cisplatin-induced ototoxicity; although this association 
has not been consistent across populations and study designs. 
 
6.6.7.4    Hematologic 
Myelosuppression occurs in 25% to 30% of subjects treated with cisplatin. The 
nadirs in circulating platelets and leukocytes occur between days 18 to 23 (range 
7.5 to 45) with most subjects recovering by day 39 (range 13 to 62). Leukopenia 
and thrombocytopenia are more pronounced at higher doses (>50 mg/m 2). 
Anemia (decrease of 2 g hemoglobin/100 mL) occurs at approximately the same 
frequency and with the same timing as leukopenia and thrombocytopenia. Fever 
and infection have also been reported in subjects with neutropenia. Potential 
fatalities due to infection (secondary to myelosuppression) have been reported. 
Elderly subjects may be more susceptible to myelosuppression. 
 
In addition to anemia secondary to myelosuppression, a Coombs’ positive 
hemolytic anemia has been reported. In the presence of cisplatin hemolytic 
anemia, a further course of treatment may be accompanied by increased 
hemolysis and this risk should be weighed by the treating physician. 
 
The development of acute leukemia coincident with the use of cisplatin has been 
reported. In these reports, cisplatin was generally given in combination with other 
leukemogenic agents. 
 
6.6.7.5  Gastrointestinal 
Marked nausea and vomiting occur in almost all subjects treated with cisplatin 
and may be so severe that the drug must be discontinued. Nausea and vomiting 
may begin within 1 to 4 hours after treatment and last up to 24 hours. Various 
degrees of vomiting, nausea and/or anorexia may persist for up to 1 week after 
treatment. 
 
Delayed nausea and vomiting (begins or persists 24 hours or more after 
chemotherapy) has occurred in subjects attaining complete emetic control on the 

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day of cisplatin therapy. 
 
Diarrhea has also been reported. 
 
6.6.8 Precautions 
 
6.6.8.1 Drug Interactions 
Plasma levels of anticonvulsant agents may become subtherapeutic during 
cisplatin therapy. 
 
6.6.8.2 Pregnancy 
Pregnancy Category D 
 
6.6.9 Nursing Mothers 
Cisplatin has been reported to be found in human milk; subjects receiving 
cisplatin should not breast-feed. 
 
6.6.10 Geriatric Use 
Insufficient data are available from clinical trials of cisplatin in the treatment of 
metastatic testicular tumors or advanced bladder cancer to determine whether 
elderly subjects respond differently than younger subjects. In four clinical trials 
of combination chemotherapy for advanced ovarian carcinoma, 1,484 subjects 
received cisplatin either in combination with cyclophosphamide or paclitaxel. Of 
these, 426 (29%) were older than 65 years. In these trials, age was not found to 
be a prognostic factor for survival. However, in a later secondary analysis for one 
of these trials, elderly subjects were found to have shorter survival compared with 
younger subjects. In all four trials, elderly subjects experienced more severe 
neutropenia 
than 
younger 
subjects. 
Higher 
incidences 
of 
severe 
thrombocytopenia and leukopenia were also seen in elderly compared with 
younger subjects, although not in all cisplatin-containing treatment arms. In the 
two trials where nonhematologic toxicity was evaluated according to age, elderly 
subjects had a numerically higher incidence of peripheral neuropathy than 
younger subjects. Other reported clinical experience suggests that elderly subjects 
may be more susceptible to myelosuppression, infectious complications, and 
nephrotoxicity than younger subjects. 
 
Cisplatin is known to be substantially excreted by the kidney and is 
contraindicated in subjects with pre-existing renal impairment. Because elderly 
subjects are more likely to have decreased renal function, care should be taken in 
dose selection, and renal function should be monitored. 
 
6.6.11 Contraindications 
Cisplatin is contraindicated in subjects with pre-existing renal impairment. 
Cisplatin should not be employed in myelosuppressed subjects, or in subjects with 
hearing impairment. 
 
Cisplatin is contraindicated in subjects with a history of allergic reactions to 
cisplatin or other platinum-containing compounds. 

LCCC 2033 
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CONFIDENTIAL 
UNIVERSITY OF NORTH CAROLINA 
November 27, 2023 
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7.0   CLINICAL ASSESSMENTS 
Clinical assessments outlined in this section will be performed as outlined in the 
Time and Events Table in Section 8.0. 
 
7.1 
List of Assessments 
 
7.1.1 Concomitant Medications 
All concomitant medication and concurrent therapies will be documented. Dose, 
route, unit frequency of administration, and indication for administration and dates 
of medication will be captured. 
 
7.1.2 Demographics 
Demographic information (date of birth, gender, race) will be recorded at 
Screening. 
 
7.1.3 Medical History 
Relevant medical history, including history of current disease, other pertinent 
history, and information regarding underlying diseases will be recorded at 
Screening and a focused medical history on symptoms/toxicity will be performed 
thereafter. 
 
7.1.4 Physical Examination 
A complete physical examination including height (at screening only), weight, 
Performance status ECOG and vital signs will be performed by either the 
investigator or a sub-investigator who is a physician at Screening. 
 
Qualified staff (MD, NP, RN, and PA) may complete the abbreviated physical exam 
at all other visits. 
 
New abnormal physical exam findings must be documented and will be followed 
by a physician or other qualified staff at the next scheduled visit. 
 
7.1.5 Audiometry 
Audiometric monitoring will be performed during physical examination prior to initiation 
of therapy, and then if clinically indicated by formal assessment per physician’s discretion. 
7.1.6 Adverse Events 
Events should be assessed per NCI-CTCAE criteria v5.0. Information regarding 
occurrence of adverse events will be captured throughout the study. Duration (start 
and stop dates), severity/grade, outcome, treatment, and relation to study drug will 
be recorded in the case report form (CRF). 
 
7.1.7 Disease Assessment 
Baseline disease assessment with PET/CT should be obtained within 28 days of 
initiating treatment through the study per the time and events calendar. Response 
assessment (C3D1 (-7 days), C5D1 (-7 days) and day 21 of cycle 6 (+/- 14 days)) 

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will require PET/CT imaging. During follow-up (every 6 months for 2 years), CT 
imaging will be used to evaluate progression. 
 
7.2 
Clinical Laboratory Assessments 
 
7.2.1 Hematology 
Blood will be obtained and sent to the clinical site hematology lab a complete blood 
count (hemoglobin, hematocrit, red blood cell count, white blood cell count, white 
blood cell differential, and platelet count). 
 
7.2.2 Blood Chemistry Profile 
Blood will be obtained and sent to the clinical site chemistry lab for determination 
of serum sodium, potassium, chloride, bicarbonate, glucose, BUN, creatinine, 
aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), 
alkaline phosphatase (ALP), total bilirubin, direct bilirubin, albumin, lactate 
dehydrogenase (LDH), calcium, magnesium, phosphorus, and total protein. 
 
7.2.3 Coagulation 
Coagulation profile: prothrombin time or INR and activated partial thromboplastin 
time. 
 
7.2.4 Pregnancy Test 
A urine or serum pregnancy test will be obtained from female subjects who are of 
childbearing potential within 72 hours of initiating study therapy. 
 
7.3 
Virus Testing 
Subjects must have been tested for HBV and HCV within 1 year of starting study 
therapy. Subjects positive for HBV may continue on the trial using prophylactic 
entecavir. Subjects positive for HCV may participate in the study with monitoring 
of liver function abnormalities. Subjects with HIV are allowed on study as long as 
they have a CD4+ count >200 cells/uL. 
 
7.4 
Correlative Studies 
PFS and OS of PV-RGDP will be examined in germinal center (GC) and post- 
germinal center (post-GC) tumor subtypes. 
 
PFS and OS will also be examined relative to double-expressor lymphomas (DEL, 
DEL vs Non-DEL) that have co-expression of MYC and BCL2, and MYC with 
BCL2 and/or BCL6 rearrangements (i.e., double hit and triple hit lymphomas [DHL 
and THL, respectively]). 

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8.0 
EVALUATIONS AND ASSESSMENTS 
8.1 
Time and Events Table 
TIME AND EVENTS TABLE1 
Assessments 
Screening2 
C1 
D1 
C1 
D8 
C2 
D1 
C2 
D8 
C3 
D1 
C3 
D8 
C4 
D1 
C4 
D8 
C5 
D1 
C5 
D8 
C6 
D1 
C6 
D8 
End of 
Treatment12 
Long- 
term 
Follow- 
up13 
Informed consent 
X 
History 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
X 
X 
X 
X 
X 
X 
X 
X 
Audiometry14 
X 
X14 
Eligibility 
verification 
X 
HIV Testing3 
X 
Coagulation Profile 
X 
ECOG 
performance status 
X 
X 
X 
X 
X 
X 
X 
X 
Radiographic 
tumor evaluation4,5 
X 
X 
X 
X 
X5 
Pregnancy test6 
X 
Hematology7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum 
chemistries8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hepatitis Testing9 
X 
Toxicity 
assessment10 
X 
X 
X 
X 
X 
X 
X 
X12 
X13 

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TIME AND EVENTS TABLE1 
Assessments 
Screening2 
C1 
D1 
C1 
D8 
C2 
D1 
C2 
D8 
C3 
D1 
C3 
D8 
C4 
D1 
C4 
D8 
C5 
D1 
C5 
D8 
C6 
D1 
C6 
D8 
End of 
Treatment12 
Long- 
term 
Follow- 
up13 
Concomitant med 
review 
X 
X 
X 
X 
X 
X 
X 
X 
Polatuzumab 
vedotin11 
X 
X 
X 
X 
X 
X 
Rituximab11 
X 
X 
X 
X 
X 
X 
Gemcitabine11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cisplatin11 
X 
X 
X 
X 
X 
X 
Dexamethasone11 
 
X 
X 
X 
X 
X 
X 
AutoSCT (transplant 
eligible subjects) 
                                             X  
Survival 
X13 

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UNIVERSITY OF NORTH CAROLINA 
November 27, 2023 
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Footnotes to Time and Events Table 
 
1 Unless otherwise noted, a window of +/- 14 days applies to all study visits. 
 
2 
Windows for the screening assessments are as follows: 
 
a. Complete history, physical exam and all imaging assessments should be 
performed within 42 days prior to day 1 of study treatment. Complete 
history is required at the screening visit only, thereafter focused history on 
symptoms/toxicity. 
 
b. All other screening evaluations (except for pregnancy test) must be 
performed within 21 days prior to cycle 1 day 1 unless otherwise stipulated. 
If screening hematology and chemistry labs are completed within 7 days 
hours prior to start of treatment on Day 1, Cycle 1 do not need to be repeated. 
 
3 For HIV positive subjects, HIV testing must include CD4 lymphocyte subset panel 
and HIV viral load. The testing must be completed within 28 days of starting trial 
therapy. 
 
4 Imaging with PET-CT should be obtained at screening within 28 days of initiating 
study treatment and at C3D1 (-7 days), C5D1 (-7 days) and day 21 of cycle 6 (+/- 
14 days) or as needed, if there are any clinical signs/symptoms of progression. If 
imaging studies are performed at other times after treatment on this study, the data 
will be collected, and information gained will be used for this study. 
 
5 Follow-up with CT imaging is every 6 months for 2 years. 
 
6 Pregnancy test is required 72 hours prior to initiating study treatment. 
 
7 Hematology includes a CBC with differential. 
 
8 Serum chemistries include sodium, potassium, chloride, bicarbonate, glucose, 
BUN, 
creatinine, 
aspartate 
aminotransferase 
(AST/SGOT), 
alanine 
aminotransferase (ALT/SGPT), alkaline phosphatase (ALP), total bilirubin, direct 
bilirubin, albumin, lactate dehydrogenase (LDH), calcium, magnesium, 
phosphorus, and total protein (See Section 7.2). 
 
9 HBV and HCV. Tests obtained within 1 year are acceptable. Subjects positive for 
HBV may continue on the trial using prophylaxis. Subjects positive for HCV may 
participate in the study if baseline bilirubin and transaminases are within normal 
limits. 
 
10 Cycles are 21 days. For subjects who are not transplant eligible, a total of 6 cycles 
should be completed as long as they have a CR, PR or SD. 
 
a. For subjects who are transplant eligible, they may proceed to transplant at 
any time after cycle 2 as long as they have achieved a CR. Subjects with  
PR must complete 4 cycles prior to proceeding to transplant. 

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11 See Section 5.2 
Treatment Dosage and Administration 
 
12 The end of treatment visit should only occur when subjects permanently stop study 
treatment and should be performed within 30 days (+/-7 days), ideally before 
transplant, after the last dose of study medication. Subjects who have an ongoing 
≥grade 2 or serious AE (SAE) at this visit will continue to be followed until the 
event is resolved or deemed irreversible by the investigator. Pregnancies and 
suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on study, or within 
12 months of the subject’s last dose of study should be recorded as SAEs. Follow- 
up for progression and survival is at least every 6 months (more frequently if needed 
per Investigator discretion) with CT imaging for 2 years and every 6 months with 
survival assessment for 5 years. The following conditions provide follow-up by 
Response Status: 
 
a. CR, Follow-up: 
• Every 6 months for 2 years (imaging for progression) 
• Every 6 months for 5 years (survival) 
 
b. PR/ SD Follow- up: 
• Relevant workup at investigator’s discretion. If a subject begins new 
treatment at any time, they will only be followed for survival and 
progression. 
13. All subjects will be followed for up to 5 years, or until death, whichever occurs 
first after removal from study treatment for determination of study endpoints. 
 
14.  Audiometric monitoring will be performed during physical examination prior to 
initiation of therapy, and then if clinically indicated by formal assessment per 
physician’s discretion. 

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UNIVERSITY OF NORTH CAROLINA 
November 27, 2023 
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8.2 
Assessment of Safety 
Any subject who receives at least one dose of study therapy on this protocol will be 
evaluable for toxicity. Each subject will be assessed periodically for the 
development of any toxicity according to the Time and Events table. Toxicity will 
be assessed according to the NCI CTCAEv5.0. Additionally, the adverse event 
severity grading scale for the NCI CTCAE (v5.0) will be used for assessing adverse 
event severity. Below Table should be used for assessing severity for adverse events 
that are not specifically listed in the NCI CTCAE. 
 
Adverse Event Severity Grading Scale for Events Not Specifically Listed in 
NCI CTCAE 
Grade 
Severity 
1 
Mild; asymptomatic or mild symptoms; clinical or 
diagnostic observations only; or intervention not 
indicated 
2 
Moderate; minimal, local, or non-invasive intervention 
indicated; or limiting age- appropriate instrumental 
activities of daily 
living a 
3 
Severe or medically significant, but not immediately 
life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; or limiting self-care 
activities of daily 
living b,c 
4 
Life-threatening 
consequences 
or 
urgent 
intervention indicated d 
5 
Death related to adverse event d 
NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events. 
Note: 
Based on the most recent version of NCI CTCAE (v5.0), which can be found at: 
http://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm 
a. 
Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using 
the telephone, managing money, etc. 
b. 
Examples of self-care activities of daily living include bathing, dressing and undressing, feeding oneself, 
using the toilet, and taking medications, as performed by patients who are not bedridden. 
c. 
If an event is assessed as a "significant medical event," it must be reported as a serious adverse event 
d. 
Grade 4 and 5 events must be reported as serious adverse events 
 
8.3 
Assessment of Efficacy 
All subjects should receive at least 2 cycles of the study therapy with PV-RGDP to 
be included in the efficacy analysis. However, if subjects proceed with stem cell 
transplant after 2 -3 cycles, they will still be eligible for the efficacy analysis. Any 
one drug may be held or discontinued during this time with the exception of 
polatuzumab and the subject will still be evaluable for efficacy. To assess disease 
response, a skull base to thigh (unless the subject has clinical suspicion for disease 
outside this area) PET/CT is used at the beginning of the study and while the subject 
is on treatment. During follow-up, a CT scan will be performed. Disease will be 
assessed using the Lugano classification (Appendix A) [20]. 

LCCC 2033 
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9.0 
ADVERSE EVENTS 
9.1 
Definitions 
 
9.1.1 Adverse Event (AE) 
An adverse event (AE) is any untoward medical occurrence (e.g., an abnormal 
laboratory finding, symptom, or disease temporally associated with the use of a 
drug) in a subject or clinical investigation subject administered a pharmaceutical 
product and which does not necessarily have a causal relationship with this 
treatment. An AE can, therefore, be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a medicinal product, whether or not related to the medicinal product. 
 
Hospitalization for elective surgery or routine clinical procedures that are not the 
result of an AE (e.g., surgical insertion of a central line) need not be considered 
AEs and should not be recorded as an AE. Disease progression should not be 
recorded as an AE, unless it is attributable by the investigator to the study therapy. 
 
9.1.2 Suspected Adverse Reaction (SAR) 
A suspected adverse reaction (SAR) is any AE for which there is a reasonable 
possibility that the pharmaceutical product is the cause. Reasonable possibility 
means that there is evidence to suggest a causal relationship between the drug and 
the AE. A suspected adverse reaction implies a lesser degree of certainty about 
causality than adverse reaction, which means any adverse event caused by a 
pharmaceutical product. 
 
Causality assessment to a study drug is a medical judgment made in consideration 
of the following factors: temporal relationship of the AE to study pharmaceutical 
product exposure, known mechanism of action or side effect profile of study 
treatment, other recent or concomitant drug exposures, normal clinical course of 
the disease under investigation, and any other underlying or concurrent medical 
conditions. Other factors to consider in considering drug as the cause of the AE: 
• Single occurrence of an uncommon event known to be strongly associated 
with pharmaceutical product exposure (e.g., angioedema, hepatic injury, 
Stevens-Johnson Syndrome) 
• One or more occurrences of an event not commonly associated with 
pharmaceutical product exposure, but otherwise uncommon in the 
population (e.g., tendon rupture); often more than one occurrence from one 
or multiple studies would be needed before the sponsor could determine that 
there is reasonable possibility that the pharmaceutical product caused the 
event. 
• An aggregate analysis of specific events observed in a clinical trial that 
indicates the events occur more frequently in the pharmaceutical product 
treatment group than in a concurrent or historical control group. 

LCCC 2033 
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9.1.3 Unexpected AE or SAR 
An AE or SAR is considered unexpected if the specificity or severity of it is not 
consistent with the applicable product information (e.g., Investigator’s Brochure 
(IB) for an unapproved investigational product or package insert/summary of 
product characteristics for an approved product). Unexpected also refers to AEs or 
SARs that are mentioned in the IB as occurring with a class of drugs product or as 
anticipated from the pharmacological properties of the drug product but are not 
specifically mentioned as occurring with the particular drug product under 
investigation. 
 
9.1.4 Serious AE or SAR 
An AE or SAR is considered serious if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes: 
• Death; 
• Is life-threatening (places the subject at immediate risk of death from 
the event as it occurred); 
• Requires inpatient hospitalization (>24 hours) or prolongation of 
existing hospitalization; * 
• Results in congenital anomaly/birth defect; 
• Results in a persistent or significant incapacity or substantial disruption 
of the ability to conduct normal life functions; 
• Important medical events that may not result in death, be life- 
threatening, or require hospitalization may be considered a serious 
adverse study treatment-related experience when, based upon 
appropriate medical judgment, they may jeopardize the subject or 
subject and may require medical or surgical intervention to prevent one 
of the outcomes listed in the definition. For reporting purposes, also 
consider the occurrences of pregnancy as an event which must be 
reported as an important medical event. 
 
*Hospitalization for anticipated or protocol specified procedures such as 
administration of chemotherapy, central line insertion, metastasis interventional 
therapy, resection of primary tumor, or elective surgery, will not be considered 
serious adverse events. 
 
Pregnancy that occurs during the study must also be reported as an SAE. 
 
9.2 
Documentation of non-serious AEs or SARs 
For non-serious AEs or SARs, documentation must begin from day 1 of study 
treatment and continue through the 30-day follow-up period after treatment is 
discontinued. 
 
Collected information should be recorded in the Case Report Forms (CRF) for that 
subject. Please include a description of the event, its severity or toxicity grade, onset 
and resolved dates (if applicable), and the relationship to the study drug. 
Documentation should occur at least monthly. 

LCCC 2033 
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9.3 
SAEs or Serious SARs 
 
9.3.1 Timing 
After informed consent but prior to initiation of study medications, only SAEs 
caused by a protocol-mandated intervention will be collected (e.g., SAEs related to 
invasive procedures such as biopsies, medication washout). 
 
For any other experience or condition that meets the definition of an SAE or a 
serious SAR, recording of the event must begin from day 1 of study treatment and 
continue through the 30-days follow-up period after treatment is discontinued. 
After this period, investigators should only report SAEs that are attributed to prior 
study treatment Subjects who have an ongoing ≥grade 2 or SAE at the EOT visit 
will continue to be followed until the event is resolved or deemed irreversible by 
the investigator. 
 
9.3.2 Documentation and Notification 
SAEs or Serious SARs must be recorded in the SAE console within OnCore® for 
that subject within 24 hours of learning of its occurrence. Additionally, the 
Multicenter Project Manager must also be notified via email of all SAEs within 24 
hours of learning of its occurrence. 
 
9.4 
Adverse Event Reporting 
 
9.4.1 IRB Reporting Requirements: 
UNC: 
• The UNC-IRB will be notified of all SAEs that qualify as an Unanticipated 
Problem as per the UNC IRB Policies using the IRB’s web-based reporting 
system within 7 days of the Investigator becoming aware of the problem. 
 
Multicenter sites: 
• For multicenter sites using a local IRB of record, please submit adverse 
events per local IRB policy. 
• For multicenter sites relying on the UNC-IRB, any SAEs that qualify as an 
Unanticipated Problem will be entered into OnCore® by the multicenter site 
and reported to the UNC IRB by the Multicenter Regulatory Associate using 
the IRB’s web-based reporting system within 7 days of the Investigator 
becoming aware of the problem. 
Pregnancy 
Pregnancies and suspected pregnancies (including a positive pregnancy test 
regardless of age or disease state) of a female subject occurring while the subject is 
on study, or within 12 months of the subject’s last dose of study should be recorded 
as SAEs. The subject is to be discontinued immediately from the study. 
 
For multicenter sites, the pregnancy, suspected pregnancy, or positive pregnancy 
test must be reported to the Multicenter Project Manager immediately (within 24 

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hours) via email (preferred) CPOMulticenter@med.unc.edu. The Multicenter 
Project Manager will then report the event to the Funding Source (see requirements 
below). The female subject should be referred to an obstetrician-gynecologist, 
preferably one experienced in reproductive toxicity for further evaluation and 
counseling. 
 
The Investigator will follow the female subject until completion of the pregnancy 
and must document the outcome of the pregnancy (either normal or abnormal 
outcome) and report the condition of the fetus or newborn to the Multicenter Project 
Manager. If the outcome of the pregnancy was abnormal (e.g., spontaneous or 
therapeutic abortion), the Investigator should report the abnormal outcome as an 
AE. If the abnormal outcome meets any of the serious criteria, it must be reported 
as an SAE. 
 
9.4.2 Funding Source (Genentech) Reporting Requirements: 
The investigator is responsible for ensuring that all AEs and SAEs that are observed 
or reported during the study are collected and reported to the FDA, appropriate 
IRB(s), and Genentech, Inc. in accordance with CFR 312.32 (IND Safety Reports) 
 
9.4.2.1 Adverse Event Reporting Period 
The study period during which AEs and SAEs as described in section 9.4.2.7 
where the subject has been exposed to Genentech product must be reported 
Reporting period begins after informed consent is obtained and initiation of study 
treatment and ends 30 days following the last administration of study treatment 
or study discontinuation/termination, whichever is earlier. After this period, 
investigators should only report SAEs that are attributed to prior study treatment. 
 
Assessment of Adverse Events 
All AEs and SAEs whether volunteered by the subject, discovered by study 
personnel during questioning, or detected through physical examination, 
laboratory test, or other means will be reported appropriately. Each reported AE 
or SAE will be described by its duration (i.e., start and end dates), regulatory 
seriousness criteria if applicable, suspected relationship to polatuzumab or 
rituximab (see following guidance), and actions taken. 
 
To ensure consistency of AE and SAE causality assessments, investigators should 
apply the following general guideline: 
 
Yes [Definite, Probable, Possible, Unlikely] 
 
There is a plausible temporal relationship between the onset of the AE and 
administration of the polatuzumab, and the AE cannot be readily explained by the 
subject’s clinical state, intercurrent illness, or concomitant therapies; and/or the 
AE follows a known pattern of response to the polatuzumab or with similar 
treatments; and/or the AE abates or resolves upon discontinuation of the 
polatuzumab or dose reduction and, if applicable, reappears upon re- challenge. 

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No [Unrelated, etc.]] 
 
Evidence exists that the AE has an etiology other than the polatuzumab (e.g., 
preexisting medical condition, underlying disease, intercurrent illness, or 
concomitant medication); and/or the AE has no plausible temporal relationship to 
polatuzumab administration (e.g., cancer diagnosed 2 days after first dose of 
study drug). 
 
Expected adverse events are those adverse events that are listed or characterized 
in the Package Insert (P.I) OR current Investigator Brochure (I.B). 
 
Unexpected adverse events are those not listed in the P.I or current I.B or not 
identified. This includes adverse events for which the specificity or severity is not 
consistent with the description in the P.I. or I.B. For example, under this 
definition, hepatic necrosis would be unexpected if the P.I. or I.B. only referred 
to elevated hepatic enzymes or hepatitis. 
 
For patients receiving combination therapy, causality will be assessed 
individually for each protocol-mandated therapy. 
 
PROCEDURES FOR ELICITING, RECORDING, AND REPORTING 
ADVERSE EVENTS 
 
Eliciting Adverse Events 
 
A consistent methodology for eliciting AEs at all subject evaluation time points 
should be adopted. Examples of non-directive questions include: 
● “How have you felt since your last clinical visit?” 
● “Have you had any new or changed health problems since you were last 
here?” 
 
Specific Instructions for Recording Adverse Events 
 
Investigators should use correct medical terminology/concepts when reporting 
AEs or SAEs. Avoid colloquialisms and abbreviations. 
 
a. Diagnosis vs. Signs and Symptoms 
 
If known at the time of reporting, a diagnosis should be reported rather than 
individual signs and symptoms (e.g., record only liver failure or hepatitis rather 
than jaundice, asterixis, and elevated transaminases). However, if a constellation 
of signs and/or symptoms cannot be medically characterized as a single diagnosis 
or syndrome at the time of reporting, it is acceptable to report the information that 
is currently available. If a diagnosis is subsequently established, it should be 
reported as follow-up information. 
 
b. Deaths 

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All deaths that occur during the protocol-specified AE reporting period (see 
Section I), regardless of attribution, will be reported to the appropriate parties. 
When recording a death, the event or condition that caused or contributed to the 
fatal outcome should be reported as the single medical concept. If the cause of 
death is unknown and cannot be ascertained at the time of reporting, report 
“Unexplained Death”. 
 
c. Preexisting Medical Conditions 
 
A preexisting medical condition is one that is present at the start of the study. 
Such conditions should be reported as medical and surgical history. A preexisting 
medical condition should be re-assessed throughout the trial and reported as an 
AE or SAE only if the frequency, severity, or character of the condition worsens 
during the study. When reporting such events, it is important to convey the 
concept that the preexisting condition has changed by including applicable 
descriptors (e.g., “more frequent headaches”). 
 
d. Hospitalizations for Medical or Surgical Procedures 
 
Any AE that results in hospitalization or prolonged hospitalization should be 
documented and reported as an SAE. If a subject is hospitalized to undergo a 
medical or surgical procedure as a result of an AE, the event responsible for the 
procedure, not the procedure itself, should be reported as the SAE. For example, 
if a subject is hospitalized to undergo coronary bypass surgery, record the heart 
condition that necessitated the bypass as the SAE. 
 
Hospitalizations for the following reasons do not require reporting: 
● Hospitalization or prolonged hospitalization for diagnostic or elective 
surgical procedures for preexisting conditions 
● Hospitalization or prolonged hospitalization required to allow efficacy 
measurement for the study or 
● Hospitalization or prolonged hospitalization for scheduled therapy of the 
target disease of the study 
 
9.4.2.2 Pregnancy 
If a female subject becomes pregnant while receiving polatuzumab or within [3 
months after the last dose of study drug, or if the female partner of a male study 
subject becomes pregnant while the study subject is receiving the study drug or 
within 5 months, a report should be completed and expeditiously submitted to 
Genentech, Inc. 
If a female subject becomes pregnant while receiving rituximab or within 12 
months after the last dose of the study, or if the female partner of a male study 
subject becomes pregnant while the study subject is receiving the study drug or 
within 5 months, a report should be completed and expeditiously submitted to 
Genentech, Inc. 
 

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Follow-up to obtain the outcome of the pregnancy should also occur. Abortion, 
whether accidental, therapeutic, or spontaneous, should always be classified as 
serious, and expeditiously reported as an SAE. Similarly, any congenital 
anomaly/birth defect in a child born to a female subject exposed to the study drug 
should be reported as an SAE. 
 
9.4.2.3 AEs of Special Interest (AESIs) 
AESIs are a subset of Events to Monitor (EtMs) of scientific and medical concern 
specific to the product, for which ongoing monitoring and rapid communication 
by the Investigator to the Sponsor is required. Such an event might require further 
investigation in order to characterize and understand it. Depending on the nature 
of the event, rapid communication by the trial Sponsor to other parties (e.g., 
Regulatory Authorities) may also be warranted. 
 
Adverse events of special interest for this study include the following: 
• Cases of potential drug-induced liver injury that include an elevated ALT 
or AST in combination with either an elevated bilirubin or clinical jaundice, 
as defined by Hy’s law: 
o Treatment-emergent ALT or AST > 3 × ULN in combination with 
total bilirubin > 2 × ULN 
o Treatment-emergent ALT or AST > 3 × ULN in combination with 
clinical jaundice 
• Data related to a suspected transmission of an infectious agent by the study 
drug (STIAMP), as defined below: 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, 
is considered an infectious agent. A transmission of an infectious agent may 
be suspected from clinical symptoms or laboratory findings that indicate an 
infection in a subject exposed to a medicinal product. This term applies 
only when a contamination of the study drug is suspected. 
 
The Polatuzumab Events of Special Interest are: 
● Infusion Associated Reactions, Hypersensitivity 
● PML (Progressive Multifocal Leukoencephalopathy) 
● Tumor lysis syndrome of any grade (irrespective of causality) 
● Second malignancies 
 
9.4.2.4 Other Special Situations Reports 
The following other Special Situations Reports should be collected even in the 
absence of an Adverse Event and transmitted to Genentech: 
• Data related to the Product usage during breastfeeding. 
• Data related to overdose, abuse, misuse, or medication error (including 
potentially exposed or intercepted medication errors) 
• In addition, reasonable attempts should be made to obtain and submit the 
age or age group of the subject, in order to be able to identify potential safety 
signals specific to a particular population. 
 
9.4.2.5 Product complaints 

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A Product Complaint is defined as any written or oral information received from 
a complainant that alleges deficiencies related to identity, quality, safety, strength, 
purity, reliability, durability, effectiveness, or performance of a product after it has 
been released and distributed to the commercial market or clinical trial. 
 
9.4.2.6 Post-Study Adverse Events 
For studies involving collection of survival data, the investigator after the end of 
the adverse event reporting period (defined as 30- days after the last dose of study 
drug) should report all deaths, (regardless of cause), and any serious adverse event 
including development of cancer or a congenital anomaly in a subsequently 
conceived offspring of a female subject -including pregnancy occurring in the 
partner of a male study subject who participated in the study that is believed to 
be related to prior exposure to study drug. 
 
Case Transmission Verification will be performed by both parties during this 
period (yearly) to ensure successful transmission of Single case reports. 
 
9.4.2.7 Exchange of Single Case Reports with Genentech 
UNC will be responsible for collecting all protocol-defined Adverse Events 
(AEs)/Serious Adverse Events (SAEs), pregnancy reports (including pregnancy 
occurring in the partner of a male study subject), other Special Situation reports, 
AESIs and Product Complaints with an AE where the subject has been exposed 
to the Product. The completed MedWatch form should be sent to the Genentech 
contact specified below. Transmission of these reports (initial and follow-up) will 
be either electronically via email or by fax and within the timelines specified 
below: 
 
Fax: 650-238-6067 
Email: usds_aereporting-d@gene.com 
 
All Product Complaints without an AE should call via: 
PC Hotline Number: (800) 334-0290 (M-F: 5 am to 5 pm PST) 
 
Transmission of these reports (initial and follow-up) will be either electronically 
or by fax and within the timelines specified below: 
 
 
Serious Adverse Drug Reactions 
(SADRs) 
15 calendar days of the awareness date 
Other SAEs 
30 calendar days of the awareness date. 
Special 
Situation 
Reports 
(Pregnancy) 
Special Situation Reports (Other) 
30 calendar days of the awareness date. 
30 calendar days of the awareness date. 
Product Complaints 
15 calendar days of the awareness date. 
AESIs 
15 calendar days of the awareness date. 
 
 

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• Serious Adverse Drug Reactions (SADRs) 
Serious AE reports that are related to the Product or where the causality 
is assessed as unknown or not provided shall be transmitted to Genentech 
within fifteen (15) calendar days of the awareness date. 
 
• Other SAEs 
Serious AE reports that are unrelated to the Product shall be transmitted 
to Genentech within thirty (30) calendar days of the awareness date. 
 
• Special Situation Reports 
o Pregnancy reports 
While such reports are not serious AEs or Adverse Drug Reactions 
(ADRs) per se, as defined herein, any reports of pregnancy 
(including pregnancy occurring in the partner of a male study 
subject), where the fetus may have been exposed to the Product, 
shall be transmitted to Genentech within thirty (30) calendar days 
of the awareness date. Pregnancies will be followed-up until the 
outcome of the pregnancy is known, whenever possible, based 
upon due diligence taken to obtain the follow-up information. 
 
• Pregnancies in Female Partners of Male Subjects 
Male subjects will be instructed through the Informed Consent Form to 
immediately inform the investigator if their partner becomes pregnant 
during the study or within 5 months after the last dose of polatuzumab. A 
Clinical Trial Pregnancy Reporting Form should be completed and 
submitted to Genentech within thirty (30) calendar days of the awareness 
date. 
o Other Special Situation Reports, as defined above, shall be 
transmitted to Genentech within thirty (30) calendar days of the 
awareness date. 
 
• Product Complaints 
All Product Complaints (with or without an AE) shall be forwarded to 
Genentech within fifteen (15) calendar days of the awareness date. 
• AESIs 
AESIs requiring expedited reporting (related or possibly related to Roche 
product or where the causality is assessed as unknown or not provided) 
shall be forwarded to Genentech within fifteen (15) calendar days of the 
awareness date. Others (non-related to Roche product) shall be sent within 
thirty (30) calendar days. 
 
9.4.2.8 Case Transmission Verification of Single Case Reports 
The Sponsor agrees to conduct the Case Transmission verification to ensure that 
all single case reports have been adequately received by Genentech via UNC 
emailing Genentech a Quarterly line-listing documenting single case reports sent 
by UNC to Genentech in the preceding time period. 
 

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The periodic line-listing will be exchanged within seven (7) calendar days of the 
end of the agreed time period. Confirmation of receipt should be received within 
the time period mutually agreed upon. 
 
If discrepancies are identified, the Sponsor and Genentech will cooperate in 
resolving the discrepancies. The responsible individuals for each party shall 
handle the matter on a case-by-case basis until satisfactory resolution. The 
sponsor shall receive reconciliation guidance documents within the ‘Activation 
Package’. 
 
Following Case Transmission Verification, single case reports which have not 
been received by Genentech shall be forwarded by UNC to Genentech within five 
(5) calendar days from request by Genentech. 
 
At the end of the study, a final cumulative Case Transmission Verification report 
will be sent to Genentech. 
 
MEDWATCH 3500A REPORTING GUIDELINES 
 
In addition to completing appropriate patient demographic (Section A) and 
suspect medication information (Section C & D), the report should include the 
following information within the Event Description (Section B.5) of the 
MedWatch 3500A form: 
● Protocol number and title description 
● Description of event, severity, treatment, and outcome if known 
● Supportive laboratory results and diagnostics (Section B.6) 
● Investigator’s assessment of the relationship of the adverse event to each 
investigational product and suspect medication 
 
Follow-Up Information 
● Additional information may be added to a previously submitted report by 
any of the following methods: 
● Adding to the original MedWatch 3500A report and submitting it as 
follow-up 
● Adding supplemental summary information and submitting it as follow- 
up with the original MedWatch 3500A form 
● Summarizing new information and faxing it with a cover letter including 
patient identifiers (i.e. D.O.B. initial, patient number), protocol 
description and number, if assigned, brief adverse event description, and 
notation that additional or follow-up information is being submitted (The 
patient identifiers are important so that the new information is added to 
the correct initial report) 
 
MedWatch 
3500A 
(Mandatory 
Reporting) 
form 
is 
available 
at 
https://www.fda.gov/media/69876/download 
 
Reporting to Regulatory Authorities, Ethics Committees and Investigators 

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UNC, as the Sponsor of the Study, will be responsible for the expedited reporting 
of safety reports originating from the Study to the Regulatory Authorities (FDA) 
where it has filed a clinical trial approval, in compliance with local regulations. 
 
UNC, as the Sponsor of the Study, will be responsible for the expedited reporting 
of safety reports originating from the study to the EMA through EudraVigilance 
Clinical Trial Module (EVCTM), where applicable. 
 
UNC, will be responsible for the expedited reporting of safety reports originating 
from the Study to the Ethics Committees and Institutional Review Boards (IRB), 
where applicable. 
 
UNC will be responsible for the distribution of safety information to its own 
investigators, where relevant, in accordance with local regulations. 
 
Additional Reporting Requirements for IND Holders: 
 
For Investigator-Initiated IND Studies, some additional reporting requirements 
for the FDA apply in accordance with the guidance set forth in 21 CFR § 
600.80. 
 
Events meeting the following criteria need to be submitted to the Food and Drug 
Administration (FDA) as expedited IND Safety Reports according to the 
following guidance and timelines: 
 
7 Calendar Day Email Report: 
The Investigator is required to notify the FDA of any fatal or life-threatening 
adverse event that is unexpected and assessed by the Investigator to be possibly 
related to the use of polatuzumab. An unexpected adverse event is one that is not 
already described in the polatuzumab Investigator Brochure. Such reports are to 
be emailed to the FDA and Genentech within 7 calendar days of first learning of 
the event. 
 
15 Calendar Day Written Report 
The Investigator is also required to notify the FDA and all participating 
investigators, in a written IND Safety Report, of any serious, unexpected AE that 
is considered reasonably or possibly related to the use of polatuzumab. An 
unexpected adverse event is one that is not already described in the polatuzumab 
investigator brochure. 
 
Written IND Safety reports should include an Analysis of Similar Events in 
accordance with regulation 21 CFR § 312.32. All safety reports previously filed 
by the investigator with the IND concerning similar events should be analyzed 
and the significance of the new report in light of the previous, similar reports 
commented on. 
 
Written IND safety reports with Analysis of Similar Events are to be submitted 

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to the FDA, Genentech, and all participating investigators within 15 calendar days 
of first learning of the event. The FDA prefers these reports on a MedWatch 3500 
form, but alternative formats are acceptable (e.g., summary letter). 
 
All written IND Safety Reports submitted to the FDA by the Investigator 
must also be emails to 
Genentech Drug Safety: 
 
Email: usds_aereporting-d@gene.com 
 
And UNC will be responsible for the distribution of safety information to Site 
IRB: 
 
CB 7097 
720 Martin Luther King Jr. Blvd. 
Bldg # 385, Second Floor 
Chapel Hill, NC 27599-7097 
Phone: 919-966-3113 
 
For questions related to safety reporting, please contact Genentech Drug 
Safety: 
Phone: (888) 835-2555 
9.4.2.9 Development Safety Update Report 
UNC, as the Sponsor of the Study, will be responsible for the preparation of an 
annual report for the Study and for the submission of the report to the regulatory 
authorities and Ethics Committees of the concerned Member States, where 
applicable. UNC, agrees to share a copy of their own annual report with 
Genentech as soon as reasonably possible after completion. 
 
Genentech agrees to forward to UNC an executive summary of the Genentech 
annual report upon request. Furthermore, Genentech agrees that UNC may cross- 
reference the executive summary of the Genentech DSUR, as applicable. 
 
9.4.2.10 Other Reports 
UNC will forward a copy of the Publication to Genentech upon completion of the 
Study. 
9.4.2.11 Study Close-Out 
Any study report submitted to the FDA by the Sponsor-Investigator should be 
copied to Genentech. This includes all IND annual reports and the Clinical Study 
Report (final study report). Additionally, any literature articles that are a result of 
the study should be sent to Genentech. Copies of such reports should be mailed 
to the assigned Clinical Operations contact for the study: 
Study mailbox: polatuzumab-gsur@gene.com 
And to Genentech Drug Safety CTV oversight mailbox at: 
ctvist_drugsafety@gene.com 

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9.4.2.12 Queries 
Queries related to the Study will be answered by UNC. However, responses to all 
safety queries from regulatory authorities or for publications will be discussed and 
coordinated between the Parties. The Parties agree that Genentech shall have the final 
say and control over safety queries relating to the Product. UNC agrees that it shall 
not answer such queries from regulatory authorities and other sources relating to the 
Product independently but shall redirect such queries to Genentech. 
9.4.2.13 Both Parties will use all reasonable effort to ensure that deadlines for 
responses to urgent requests for information or review of data are met. The 
Parties will clearly indicate on the request the reason for urgency and the 
date by which a response is required. Safety Crisis Management 
In case of a safety crisis, e.g., where safety issues have a potential impact on the 
indication(s), on the conduct of the Study, may lead to labeling changes or 
regulatory actions that limit or restrict the way in which the Product is used, or 
where there is media involvement, the Party where the crisis originates will contact 
the other Party as soon as possible. 
 
The Parties agree that Genentech shall have the final say and control over safety 
crisis management issues relating to the Product. UNC agrees that it shall not 
answer such queries from media and other sources relating to the Product but 
shall redirect such queries to Genentech. 
 
9.4.2.14 Compliance with Pharmacovigilance Agreement/Audit 
The Parties shall follow their own procedures for adherence to AE reporting 
timelines. 
 
Each Party shall monitor and, as applicable, request feedback from the other Party 
regarding AE report timeliness in accordance with its own procedures. The 
Parties agree to provide written responses in a timely manner to inquiries from 
the other Party regarding AE reports received outside the agreed upon Agreement 
timelines. If there is any detection of trends of increasing or persistent non- 
compliance to transmission timelines stipulated in this Agreement, both Parties 
agree to conduct ad hoc or institute a regular joint meeting to address the issue. 
 
In case of concerns related to non-compliance of processes, other than exchange 
timelines, with this Agreement, the Parties will jointly discuss and collaborate on 
clarifying and resolving the issues causing non-compliance. Every effort will be 
made by the non-compliant Party to solve the non-compliance issues and inform 
the other Party of the corrective and preventative actions taken. 
 
Upon justified request, given sufficient notice of no less than sixty (60) calendar 
days, an audit under the provisions of this Agreement can be requested by either 
Party. The Parties will then discuss and agree in good faith upon the audit scope, 
agenda and execution of the audit. The requesting Party will bear the cost of the 
audit. 
 

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9.4.3 FDA Expedited Reporting requirements for studies conducted under an 
IND: 
A sponsor must report any suspected adverse reaction that is both serious and 
unexpected to the FDA. The sponsor must report an adverse event as a suspected 
adverse reaction only if there is evidence to suggest a causal relationship between 
the drug and the adverse event, such as: 
• A single occurrence of an event that is uncommon and known to be strongly 
associated with drug exposure (e.g., angioedema, hepatic injury, Stevens- 
Johnson Syndrome); 
• One or more occurrences of an event that is not commonly associated with 
drug exposure, but is otherwise uncommon in the population exposed to 
the drug (e.g. tendon rupture); 
• An aggregate analysis of specific events observed in a clinical trial (such 
as known consequences of underlying disease or condition under 
investigation or other events that commonly occur in the study population 
independent of drug therapy) that indicates those events occur more 
frequently in the drug treatment group than in a concurrent or historical 
control group. 
The sponsor must submit each IND safety report on FDA Form 3500A. Each 
notification to FDA must bear prominent identification of its contents, i.e., “IND 
Safety Report,” and must be transmitted to the review division that has the 
responsibility for review of the IND. In each IND safety report, the sponsor must 
identify all IND safety reports previously submitted to FDA concerning a similar 
suspected adverse reaction and must analyze the significance of the suspected 
adverse reaction in light of previous, similar reports or any other relevant 
information. 
 
Timing 
FDA must be notified of potential serious risks within 15 calendar days after the 
sponsor determines the event requires reporting. FDA must be notified of 
unexpected fatal or life-threatening suspected adverse reactions as soon as possible 
but in no case later than 7 calendar days after the sponsor’s initial receipt of the 
information. For Multicenter trials, Lineberger is the sponsor, therefore, the UNC 
Multicenter Project Manager must be notified of the SAE within 24 hours of the 
event. If the results of a sponsor’s investigation show that an adverse event not 
initially determined to be reportable is reportable, the sponsor must report such 
suspected adverse reaction in an IND safety report as soon as possible, but in no 
case later than 15 calendar days after the determination is made. 
 
Follow-up 
The sponsor must promptly investigate all safety information it receives. Relevant 
follow-up information to an IND safety report must be submitted as soon as the 
information is available and must be identified as such, i.e., “Follow-up IND Safety 
Report.” Additionally, upon request from FDA, the sponsor must submit to FDA 
any additional data or information that the agency deems necessary, as soon as 
possible, but in no case later than 15 calendar days after receiving the request. 
 
Notification of Investigators 

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The sponsor must notify all participating investigators (i.e., all investigators to 
whom the sponsor is providing investigational product under its INDs or under any 
investigator’s IND) in an IND safety report of potential serious risks, from clinical 
trials or any other source, as soon as possible, but in no case later than 15 calendar 
days after the sponsor determines that the information qualifies for reporting. 
 
Process 
If the sponsor deems that an event is both a serious adverse reaction (SAR) AND 
unexpected, it must also (in addition to OnCore®) be recorded on the MedWatch 
Form 3500A as per 21 CFR 312.32. Unexpected adverse events or adverse reaction 
refers to an event or reaction that is not listed in the Investigator’s Brochure or is not 
listed at the specificity or severity that has been observed; or if an Investigator’s 
Brochure is not required or available, is not consistent with the risk information 
described in the general investigation plan or elsewhere in the current IND 
application. 
 
The MedWatch form and supporting documents defining the event and causality 
should be sent to the assigned Multicenter Project Manager and also to 
CPOMulticenter@med.unc.edu. The UNC Multicenter Project Manager will then 
send the report to the Funding Source and notify the Multicenter and CTO Regulatory 
Associate of the event. The MedWatch 3500a form can be accessed at: 
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm. 
 
(Please be sure and access form 3500A, and not form 3500). 
 
Once the UNC Principal Investigator determines an event is a serious SAR AND 
unexpected, the MedWatch 3500A form will be submitted to the FDA. If the event 
is serious, unexpected and considered to be possibly-, probably- or definitely-related 
to the study treatment, the UNC Project Manager will inform the Regulatory 
Associate at UNC and IND Specialist. The MedWatch form will be submitted 
according to LCCC SOP for safety reporting for a multi-site study. 
 
All IND safety reports must be submitted on Form 3500A and be accompanied by 
Form 1571. The FDA must be notified of any unexpected or life-threatening 
suspected adverse reactions as soon as possible, but no later than 7 calendar days of 
learning of the event. 
 
The UNC Multicenter Project Manager will also be responsible for informing each 
Affiliate site of all serious and unexpected SARs reported to the FDA via fax as soon 
as possible. 
 
Additional Reporting Requirements 
The following additional items must be reported via IND safety report: 
• Findings from other studies. The sponsor must report any findings from 
epidemiological studies, pooled analysis of multiple studies, or clinical 
studies, whether or not conducted under an IND, and whether or not 
conducted by the sponsor, that suggest a significant risk to humans exposed 
to the investigational product. 

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• Findings from animal or in vitro testing. The sponsor must report any 
findings from animal or in vitro testing, whether or not conducted by the 
sponsor, that suggest a significant risk in humans exposed to the 
investigational product, such as reports of mutagenicity, teratogenicity, or 
carcinogenicity, or reports of significant organ toxicity at or near the 
expected human exposure. 
• Increased rate of occurrence of serious suspected adverse reactions. 
Additional Guidance 
Please refer to 21CFR312.32 and “Guidance for Industry and Investigators: Safety 
Reporting Requirements for INDs and BA/BE Studies” for additional information 
and reporting requirements. All IND Safety Reports will be submitted in accordance 
with these regulations/guidances. 
 
9.5 
Data and Safety Monitoring Plan 
The Principal Investigator will provide continuous monitoring of subject safety in 
this trial with periodic reporting to the Data and Safety Monitoring Committee 
(DSMC). 
 
Meetings/teleconferences will be held at a frequency dependent on study accrual. 
These meetings will include the investigators as well as study coordinators, data 
coordinators, regulatory associates, clinical data management associates, and any 
other relevant personnel the principal investigators may deem appropriate. At these 
meetings, the research team will discuss all issues relevant to study progress, 
including enrollment, safety, regulatory, data collection, etc. 
 
The team will produce summaries or minutes of these meetings. These summaries 
will be available for inspection when requested by any of the regulatory bodies 
charged with the safety of human subjects and the integrity of data including, but 
not limited to, the oversight of Office of Human Research Ethics (OHRE) 
Biomedical IRB, the Oncology Protocol Review Committee (PRC) or the North 
Carolina TraCS Institute Data and Safety Monitoring Board (DSMB). 
 
The UNC LCCC Data and Safety Monitoring Committee (DSMC) will review the 
study on a regular (quarterly to annually) basis, with the frequency of review based 
on risk and complexity as determined by the UNC Protocol Review Committee. 
The UNC PI will be responsible for submitting the following information for 
review: 1) safety and accrual data including the number of subjects treated; 2) 
significant developments reported in the literature that may affect the safety of 
participants or the ethics of the study; 3) preliminary response data; and 4) 
summaries of team meetings that have occurred since the last report. Findings of 
the DSMC review will be disseminated by memo to the UNC PI, PRC, the UNC 
IRB and DSMB. 

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10.3 
Data Analysis Plans 
Analysis of efficacy will be conducted following pre-specified inference rule on 
rejecting the null hypothesis: H0: ORR <= 44%. Specifically, we will reject the null 
hypothesis if and only if there are >12 ORs in the 27 subjects accrued at stage 1, 
and there are > 23 ORs in 44 subjects (with 17 accrued at stage 2). 
 
For the primary outcome, ORR, there should be no missing data. We will replace 
non-evaluable cases with new subjects so that the total (maximal) sample size of 
44 is guaranteed. There is only one test for the primary endpoint and hence there is 
no multiplicity issue. 
 
Analyses of secondary endpoints will be descriptive. We will calculate rate of CR 
by sample proportion of complete response and associated 95% confidence interval 
using exact binomial method. Kaplan-Meier method will be used to examine PFS, 
OS of patients accrued. All toxicities and adverse events will be listed and tabulated 
by grade for all and by subgroups: GC vs post-GC, DEL vs non-DEL, DHL/THL 
vs non-DHL/THL. 
 
Per exploratory endpoints, we will compare PFS and OS in subjects with GC vs 
post-GC, DEL vs non-DEL, and DHL/THL vs non-DHL/THL, using log-rank tests, 
at 2-sided alpha level of 0.05. 
 
Also, among the subjects with rrDLBCL receiving PV-RGDP, the number of 
patients that complete stem cell harvest, the number of subjects that complete 
autoSCT, and median time to engraftment in these subjects will be summarized to 
describe the effect of PV-RGDP on stem cell transplant factors. 

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11.0 
STUDY MANAGEMENT 
11.1 
Institutional Review Board (IRB) Approval and Consent 
It is expected that the IRB will have the proper representation and function in 
accordance with federally mandated regulations. The IRB should approve the 
consent form and protocol. 
 
In obtaining and documenting informed consent, the investigator should comply 
with the applicable regulatory requirement(s) and should adhere to Good Clinical 
Practice (GCP) and to ethical principles that have their origin in the Declaration of 
Helsinki. 
 
Before recruitment and enrollment onto this study, the subject will be given a full 
explanation of the study and will be given the opportunity to review the consent 
form. Each consent form must include all the relevant elements currently required 
by the FDA Regulations and local or state regulations. Once this essential 
information has been provided to the subject and the investigator is assured that the 
subject understands the implications of participating in the study, the subject will 
be asked to give consent to participate in the study by signing an IRB-approved 
consent form. 
 
Prior to a subject’s participation in the trial, the written informed consent form 
should be signed and personally dated by the subject and by the person who 
conducted the informed consent discussion. 
 
11.2 
Required Documentation 
Before the study can be initiated at any site, the following documentation must be 
provided to the Clinical Trials Office (CTO) at the University of North Carolina. 
• A copy of the official IRB approval letter for the protocol and informed 
consent 
• IRB membership list or Federalwide Assurance (FWA) number 
• CVs and medical licensure for the principal investigator and any sub- 
investigators who will be involved in the study. 
• Form FDA 1572 appropriately filled out and signed with appropriate 
• Financial Disclosures 
• CAP and CLIA Laboratory certification numbers and institution lab 
normal values 
• Executed clinical research contract 
11.3 
Registration Procedures 
All subjects must be registered with the LCCC CTO Multicenter Office at the 
University of North Carolina before enrollment to study. To register a subject call 
the Multicenter office at 919-966-7359 Monday-Friday 8:30 am – 5:00 pm EST. 
Email the registration form, signed informed consents and all source documents to 
confirm  eligibility  to  the  assigned  Project  Manager  (if  unknown,  email 

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CPOMulticenter@med.unc.edu). All subjects must have final eligibility verified by 
the UNC Multicenter Project Manager on behalf of the UNC PI prior to starting 
treatment. When sending registration request with eligibility documentation, please 
allow 24 hours for source to be reviewed. 
 
11.4 
Data Management and Monitoring/Auditing 
The CTO Multicenter Office of the UNC LCCC will serve as the coordinating 
center for this trial. Data will be collected through a web based electronic data 
capture system, Advarra EDC. Other study institutions will be given a password to 
directly enter their own data onto the web site via electronic case report forms 
(eCRFs). Multicenter personnel will coordinate and manage data for quality control 
assurance and integrity. 
 
All data will be collected and entered into Advarra by the multicenter study teams 
at participating institutions. The investigators at each site will allow monitors to 
review all source documents supporting data entered into Advarra EDC. The 
Multicenter Data Coordinator can be reached at 919-843-2742 or 1-877-668-0683 
or LCCC_Oncore@unc.med.edu. 
 
All data will be monitored, and source data will be verified on selected subjects. 
Queries will be issued on an ongoing basis on all subjects. Participating sites should 
respond to data queries within 14 days of receipt. The LCCC compliance committee 
or their designee will audit trial sites every twelve months while still enrolling or 
subjects are still on treatment. Participating sites must send source and regulatory 
documents to LCCC upon request, for remote monitoring and/or audit review. 
 
11.5 
Adherence to the Protocol 
Except for an emergency situation in which proper care for the protection, safety, 
and well-being of the study subject requires alternative treatment, the study shall 
be conducted exactly as described in the approved protocol. 
 
11.5.1 Emergency Modifications 
UNC and multicenter investigators may implement a deviation from, or a change 
of, the protocol to eliminate an immediate hazard(s) to trial subjects without prior 
UNC or their respective institution’s IRB/IEC approval/favorable opinion. 
 
For any such emergency modification implemented, a UNC IRB modification form 
must be completed by UNC Research Personnel within five (5) business days of 
making the change. 
 
For Institutions Relying on UNC’s IRB: 
For any such emergency modification implemented, a UNC IRB modification form 
must be completed by UNC Research Personnel within five (5) business days of 
making the change. 
 
For Institutions Relying on Their Own IRB: 

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For multicenter investigators relying on their own institution’s IRB, as soon as 
possible after the modification has been made, the implemented deviation or change 
and the reasons for it should be submitted to: 
 
• To UNC Principal Investigator for agreement 
• The Multicenter institution’s IRB for review and approval. (Once 
IRB’s response is received, this should be forwarded to the 
Multicenter Regulatory Associate). 
 
11.5.2 Single Subject Exceptions 
Eligibility single subject exceptions are not permitted for Lineberger 
Comprehensive Cancer Center Investigator Initiated Trials under any 
circumstances. Other types of single subject exceptions may be allowed if proper 
regulatory review has been completed in accordance with Lineberger 
Comprehensive Cancer Center’s Single Subject Exceptions Policy. 
 
11.5.3 Other Protocol Deviations/Violations 
According to UNC’s IRB, a protocol deviation is any unplanned variance from an 
IRB approved protocol that: 
• Is generally noted or recognized after it occurs 
• Has no substantive effect on the risks to research participants. 
• Has no substantive effect on the scientific integrity of the research plan 
or the value of the data collected. 
• Did not result from willful or knowing misconduct on the part of the 
investigator(s). 
 
An unplanned protocol variance is considered a violation if the variance meets any 
of the following criteria: 
• Has harmed or increased the risk of harm to one or more research 
participants. 
• Has damaged the scientific integrity of the data collected for the study. 
• Results from willful or knowing misconduct on the part of the 
investigator(s). 
• Demonstrates serious or continuing noncompliance with federal 
regulations, State laws, or University policies. 
If a deviation or violation occurs, please follow the guidelines below: 
For Institutions Relying on UNC’s IRB: 
Protocol Deviations: UNC or multicenter personnel will record the deviation in 
OnCore®, and report to any sponsor or data and safety monitoring committee in 
accordance with their policies. Deviations should be summarized and reported to 
the IRB at the time of continuing review. 

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Protocol Violations: Violations should be reported by UNC personnel within one 
(1) week of the investigator becoming aware of the event using the same IRB online 
mechanism used to report Unanticipated Problems. 
 
For Institutions Relying on Their Own IRB: 
In addition to adhering to the policies regarding protocol compliance set forth by 
your institution’s IRB, the following is also required: 
 
Protocol Deviations: In the event a deviation from protocol procedures is 
identified, record the deviation in OnCore®. 
 
Protocol Violations: Any protocol violation that occurs must be reported to your 
IRB per institutional policies and reported to the UNC Multicenter Project Manager 
within 5 days. UNC will determine if the violation affects the safety of the subject 
and integrity of the data. Once your institution’s IRB response is received, please 
forward to the Multicenter Regulatory Associate. 
 
Unanticipated Problems: 
Any events that meet the criteria for “Unanticipated Problems” as defined by 
UNC’s IRB must be reported by the study personnel using the IRB’s web-based 
reporting system. 
 
Multicenter Sites: 
Any events that meet the criteria for “Unanticipated Problems (UPs)” as defined by 
UNC’s IRB must also be reported to the UNC Multicenter Project Manager. The 
Multicenter Regulatory Associate will report the event to the UNC IRB using the 
IRB’s web-based reporting system. Examples of such UPs include a lost or stolen 
laptop computer that contains sensitive study information. 
 
11.6 
Amendments to the Protocol 
Should amendments to the protocol be required, the amendments will be originated 
and documented by the Principal Investigator at UNC. It should also be noted that 
when an amendment to the protocol substantially alters the study design or the 
potential risk to the subject, a revised consent form might be required. 
 
For Institutions Relying on UNC’s IRB: 
The written amendment, and if required the amended consent form, must be sent to 
UNC’s IRB for approval prior to implementation. 
 
For Institutions Relying on Their Own IRB: 
Investigators must submit the amendment to their institution’s IRB for approval. 
For multicenter studies, any multicenter site must submit their informed consent 
revisions to the Multicenter Regulatory Associate for review and approval prior to 
submission to their IRB. 

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11.7 
Record Retention 
Study documentation includes all eCRFs, data correction forms or queries, source 
documents, Sponsor correspondence to Investigators, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and 
approval, signed subject consent forms). 
 
Source documents include all recordings of observations or notations of clinical 
activities and all reports and records necessary for the evaluation and reconstruction 
of the clinical research study. 
 
Government agency regulations and directives require that all study documentation 
pertaining to the conduct of a clinical trial must be retained by the study 
investigator. In the case of a study with a drug product seeking regulatory approval 
and marketing, these documents shall be retained for at least two years after the last 
approval of marketing application in an International Conference on Harmonization 
(ICH) region. In all other cases, study documents should be kept on file until three 
years after the completion and final study report of this investigational study. 
 
11.8 
Obligations of Investigators 
The Principal Investigator is responsible for the conduct of the clinical trial at the 
site in accordance with Title 21 of the Code of Federal Regulations and/or the 
Declaration of Helsinki. The Principal Investigator is responsible for personally 
overseeing the treatment of all study subjects. The Principal Investigator must 
assure that all study site personnel, including sub-investigators and other study staff 
members, adhere to the study protocol and all FDA/GCP/NCI regulations and 
guidelines regarding clinical trials both during and after study completion. 
 
The Principal Investigator at each institution or site will be responsible for assuring 
that all the required data will be collected and entered into the eCRFs. Periodically, 
auditing and monitoring of trials will be conducted, and the Principal Investigator 
will provide access to his/her original records to permit verification of proper entry 
of data. At the completion of the study, all eCRFs will be reviewed by the Principal 
Investigator and will require his/her final signature to verify the accuracy of the 
data. 

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12.0 
REFERENCES 
1. 
National Cancer Institute. Cancer stat facts: NHL - Diffuse Large B-Cell 
Lymphoma (DLBCL). https://seer.cancer.gov/statfacts/html/dlbcl.html. Accessed 
June 5. 
2. 
Coiffier, B., et al., Long-term outcome of patients in the LNH-98.5 trial, the first 
randomized study comparing rituximab-CHOP to standard CHOP chemotherapy 
in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. 
Blood, 2010. 116(12): p. 2040-5. 
3. 
Philip, T., et al., Autologous bone marrow transplantation as compared with 
salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's 
lymphoma. N Engl J Med, 1995. 333(23): p. 1540-5. 
4. 
Gisselbrecht, C., et al., Salvage regimens with autologous transplantation for 
relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol, 2010. 28(27): 
p. 4184-90. 
5. 
Crump, M., et al., Randomized comparison of gemcitabine, dexamethasone, and 
cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before 
autologous stem-cell transplantation for relapsed and refractory aggressive 
lymphomas: NCIC-CTG LY.12. J Clin Oncol, 2014. 32(31): p. 3490-6. 
6. 
Van Den Neste, E., et al., Outcome of patients with relapsed diffuse large B-cell 
lymphoma who fail second-line salvage regimens in the International CORAL 
study. Bone Marrow Transplant, 2016. 51(1): p. 51-7. 
7. 
van Imhoff, G.W., et al., Ofatumumab Versus Rituximab Salvage 
Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell 
Lymphoma: The ORCHARRD Study. J Clin Oncol, 2017. 35(5): p. 544-551. 
8. 
Feldman, T., et al., Addition of lenalidomide to rituximab, ifosfamide, carboplatin, 
etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell 
lymphoma. Br J Haematol, 2014. 166(1): p. 77-83. 
9. 
Sauter, C.S., et al., A phase 1 study of ibrutinib in combination with R-ICE in 
patients with relapsed or primary refractory DLBCL. Blood, 2018. 131(16): p. 
1805-1808. 
10. 
Palanca-Wessels, M.C., et al., Safety and activity of the anti-CD79B antibody- 
drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non- 
Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet 
Oncol, 2015. 16(6): p. 704-15. 
11. 
Sehn, L.H., et al., Addition of polatuzumab vedotin to bendamustine and 
rituximab (BR) improves outcomes in transplant-ineligible patients with 
relapsed/refractory (r/r) diffuse large b-cell lymphoma (DLBCL) versus BR 
alone: results from a randomized phase 2 study. Blood, 2017. 130. 
12. 
Polatuzumab vedotin (formerly DCDS4501A). Investigator's Brochure. 
R05541077 Version 9. July 2018. F. Hoffmann-La Roche LTD. . 
13. 
Crump, M., et al., Outcomes in refractory diffuse large B-cell lymphoma: results 
from the international SCHOLAR-1 study. Blood, 2017. 130(16): p. 1800-1808. 
14. 
Gisselbrecht, C. and E. Van Den Neste, How I manage patients with 
relapsed/refractory diffuse large B cell lymphoma. Br J Haematol, 2018. 182(5): 
p. 633-643. 

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15. 
Sehn, L.H., et al., Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large 
B-Cell Lymphoma. J Clin Oncol, 2020. 38(2): p. 155-165. 
16. 
Lenz, G., et al., Stromal Gene Signatures in Large-B-Cell Lymphomas. New 
England Journal of Medicine, 2008. 359(22): p. 2313-2323. 
17. 
Riedell, P.A. and S.M. Smith, Double hit and double expressors in lymphoma: 
Definition and treatment. Cancer, 2018. 124(24): p. 4622-4632. 
18. 
Petrich, A.M., et al., Impact of induction regimen and stem cell transplantation on 
outcomes in double-hit lymphoma: a multicenter retrospective analysis. Blood, 
2014. 124(15): p. 2354-2361. 
19. 
Sesques, P. and N.A. Johnson, Approach to the diagnosis and treatment of high- 
grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. 
Blood, 2017. 129(3): p. 280-288. 
20. 
Cheson, B.D., et al., Recommendations for initial evaluation, staging, and 
response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano 
classification. J Clin Oncol, 2014. 32(27): p. 3059-68. 
21. 
 Bartlett, N.L., et al., Retreatment with brentuximab vedotin in patients with CD30-
positive hematologic malignancies. J Hematol Oncol, 2014. 7: p. 24. 

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13.0 
APPENDICES 
13.1 
Appendix A. Revised response criteria for lymphoma 
 (Cheson, et al. J Clin Oncol. 2014;32(27):3059-68) 
Response and Site 
PET-CT-Based Response 
CT-Based Response 
Complete 
Complete metabolic response 
Complete radiologic response (all of 
the following) 
Lymph nodes and 
extra-lymphatic sites 
Score 1, 2, or 3* with or without 
a residual mass 5 PS† 
It is recognized that in 
Waldeyer’s ring or extranodal 
sites with high physiologic uptake 
or with activation within spleen 
or marrow (e.g., with 
chemotherapy or myeloid 
colony-stimulating factors), 
uptake may be greater than 
normal mediastinum and/or liver. 
In this circumstance, complete 
metabolic response may be 
interred if uptake at sites f initial 
involvement is no greater than 
surrounding normal tissue even if 
the tissue has high physiologic 
uptake 
Target nodes/nodal masses must 
regress to ≤ 1.5 cm in LDi 
No extralymphatic sites of disease 
Non-measured lesion 
Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone marrow 
No evidence of FDG-avid disease 
in marrow 
Normal by morphology; if 
indeterminate, IHC negative 
Partial 
Partial metabolic response 
Partial remission (all of the 
following) 
Lymph nodes and 
extra-lymphatic sites 
Score of 4 or 5† with reduced 
uptake compared with baseline 
and residual mass(es) of any size 
At interim, these findings indicate 
responding disease 
At end of treatment, these 
findings indicate residual disease 
≥50% decrease in SPD of up to 6 
target measurable nodes and 
extranodal sites 
When a lesion is too small to 
measure on CT, assign 5 mm X 5 mm 
as the default value 
When no longer visible, 0 x 0 mm 
For a node > 5 mm X 5 mm, but 
smaller than normal, use actual 
measurement for calculation 
Non-measured lesions 
Not applicable 
Absent/normal, regressed, but no 
increase 
Organ enlargement 
Not applicable 
Spleen must have regressed by > 
50% in length beyond normal 
New lesions 
None 
None 
Bone marrow 
Residual uptake higher than 
uptake in normal marrow but 
reduced compared w/ baseline 
(diffuse uptake compatible w. 
Not applicable 

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reactive changes from 
chemotherapy allowed). If there 
are persistent focal changes in 
the marrow in the context of a 
nodal response, consideration 
should be given to further 
evaluation w/ MRI or biopsy or 
an interval scan 
Revised Criteria for Response Assessment of Hodgkin and Non-Hodgkin 
Lymphoma (Lugano Criteria) 
Continued from previous page 
Response and Site 
PET-CT-Based Response 
CT-Based Response 
No response or stable 
disease 
No metabolic response 
Stable disease 
Target nodes/nodal 
masses, extranodal 
lesions 
Score 4 or 5 with no significant 
change in FDG uptake from 
baseline at interim or end of 
treatment 
< 50% decrease from baseline in 
SPD of up to 6 dominant, 
measurable nodes and extranodal 
sites; no criteria for progressive 
disease are met 
Non measure lesions 
Not applicable 
No increase consistent with 
progression 
Organ enlargement 
Not applicable 
No increase consistent with 
progression 
New lesions 
None 
None 
Bone marrow 
No change from baseline 
Not applicable 
Progressive disease 
Progressive metabolic disease 
Progressive disease requires at least 
1 of the following 
Individual target 
nodes/nodal masses 
Score 4 or 5 with an increase in 
intensity of uptake from 
baseline and/or 
PPD progression: 
Extranodal lesions 
New FDG-avid foci consistent 
with lymphoma at interim or 
end-of-treatment assessment 
An individual node/lesion must be 
abnormal with: 
LDi > 1.5 cm and 
Increase by ≥ 50% from PPD nadir 
and an increase in LDi or SDi from 
nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions > 2 cm 
In the setting of splenomegaly, the 
splenic length must increase by > 
50% of the extent of its prior 
increase beyond baseline (e.g., a 
15-cm spleen must increase to > 
16 cm). If no prior splenomegaly, 
must increase by at least 2 cm 
from baseline 
New or recurrent splenomegaly 
Non measured lesions 
None 
New or clear progression of 
preexisting non-measured lesions 
New lesions 
New FDG-avid foci consistent 
with lymphoma rather than 
Regrowth of previously resolved 
lesions 

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Bone marrow 
another etiology (e.g., 
infection, inflammation). If 
uncertain regarding etiology of 
new lesions, biopsy or interval 
scan may be considered 
A new node > 1.5 cm in any axis 
A new extranodal site > 1.0 cm in 
any axis; if < 1.0 cm in any axis, 
its presence must be unequivocal 
and must be attributable to 
lymphoma 
Assessable disease of any size 
unequivocally attributable to 
lymphoma 
New or recurrent FDG-avid foci 
New or recurrent involvement 
 
Revised Response Criteria (Table Key) 
Abbreviations: 5PS, 5-point scale, CT computed tomography; FDG, fluorodeoxyglucose; IHC, 
immunohistochemistry; LDi, longest transverse diameter of a lesion; MRI, magnetic resonance 
imaging; PET, positron emission tomography; PPD cross product of the LDi and perpendicular 
diameter; SDi, shortest axis perpendicular to the LDi; SPD, sum of the product of the perpendicular 
diameters for multiple lesions. 
*A score of 3 in many subjects indicates a good prognosis with standard treatment, especially if at 
the time of an interim scan. However, in trials involving PET where de-escalation is investigated, 
it may be preferable to consider a score of 3 as inadequate response (to avoid undertreatment). 
Measured dominant lesions: Up to 6 of the largest dominant nodes, nodal masses, and extranodal 
lesions selected to be clearly measurable in two diameters. Nodes should preferably be from 
disparate regions of the body and should include, where applicable, mediastinal and retroperitoneal 
areas. Non-nodal lesions include those preferably be from disparate regions of the body and should 
include, where applicable, mediastinal and retroperitoneal areas. Non-nodal lesions include those 
in solid organs (e.g., liver, spleen, kidneys, lungs), GI involvement, cutaneous lesions, or those 
noted on palpation. Non-measurable lesions: Any disease not selected as measure, dominant 
disease and truly assessable disease should be considered not measured. These sites include any 
nodes, nodal masses, and extranodal sites not selected as dominant or measurable or that do not 
meet the requirements for measurability but are still considered abnormal, as well as truly 
assessable disease, which is any site of suspected disease that would be difficult to follow 
quantitatively with measurement, including pleural effusions, ascites, bone lesions, leptomeningeal 
disease, abdominal masses, and other lesions that cannot be confirmed and followed by imaging. 
In Waldeyer’s ring or in extranodal sites (e.g., GI tract, liver, bone marrow), FDG uptake may be 
greater than in the mediastinum with complete metabolic response, but should be no higher than 
surrounding normal physiologic uptake (e.g., with marrow activation as a result of chemotherapy 
or myeloid growth factors). 
†PET 5 PS: 1, no uptake above background; 2 uptake ≤ mediastinum; 3, uptake > mediastinum but 
≤ liver; 4, uptake moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, 
new areas of uptake unlikely to be related to lymphoma. 
Reference: Cheson BD, et al. Recommendations for initial evaluation, staging, and response 
assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 
32:3059-3067. 

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13.2 
Appendix B. ECOG Performance Status 
 
Grade 
Description 
0 
Normal activity. Fully active, able to carry on all pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous 
activity, but ambulatory and able to carry out work of a light or 
sedentary nature (e.g., light housework, office work). 
2 
In bed <50% of the time. Capable of only limited self-care, 
confined to bed or chair more than 50% of waking hours. 
3 
In bed >50% of the time. Capable of only limited self-care, 
confined to bed or chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self- 
care. Totally confined to bed or chair. 
5 
Dead. 
* As published in Am. J. Clin. Oncol.: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., 
Davis, T.E., McFadden, E.T., Carbone, P.P. Toxicity and Response Criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982. The Eastern Cooperative 
Oncology Group, Robert Comis M.D., Group Chair. 

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13.3 
Appendix C. Child-Pugh Score 
 
Factor 
1 point 
2 points 
3 points 
Total 
bilirubin 
(μmol/L) 
<34 
34-50 
>50 
Serum 
albumin 
(g/L) 
>35 
28-35 
<28 
PT INR 
<1.7 
1.71-2.30 
>2.30 
Ascites 
None 
Mild 
Moderate to Severe 
Hepatic 
encephalopathy 
None 
Grade I-II (or 
suppressed with 
medication) 
Grade III-IV (or 
refractory) 
 
 
Class A 
Class B 
Class C 
Total points 
5-6 
7-9 
10-15 
1-year survival 
100% 
80% 
45% 

LCCC 2033 
PI: Dittus  
Amendment 2 
CONFIDENTIAL 
UNIVERSITY OF NORTH CAROLINA 
November 27, 2023 
74 
 
 
13.4 
Appendix D: Strong Inhibitors and Inducers of CYP3A 
Strong inhibitors 
Atazanavir 
Ceritinib 
Clarithromycin 
Cobicistat and cobicistat-containing coformulations 
Darunavir 
Idelalisib 
Indinavir 
Itraconazole 
Ketoconazole 
Lonafarnib 
Lopinavir 
Mifepristone 
Nefazodone 
Nelfinavir 
Ombitasvir-paritaprevir-ritonavir 
Ombitasvir-paritaprevir-ritonavir plus dasabuvir 
Posaconazole 
Ritonavir and ritonavir-containing coformulations 
Saquinavir 
Telithromycin 
Tucatinib 
Voriconazole 
 
Strong inducers 
Apalutamide 
Carbamazepine 
Enzalutamide 
Fosphenytoin 
Lumacaftor 
Lumacaftor-ivacaftor 
Mitotane 
Phenobarbital 
Phenytoin 
Primidone 
Rifampin (rifampicin)