A Phase 2 Study of Polatuzumab Vedotin With Rituximab, Ifosfamide, Carboplatin, and Etoposide (PolaR-ICE) as Initial Salvage Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma Unclassifiable, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma, Recurrent Transformed B-Cell Non-Hodgkin Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma, Refractory Transformed B-Cell Non-Hodgkin Lymphoma
Sponsor: City of Hope Medical Center

 
IRB #: 20148 
 
 
Packet: 09 
 
12/20/2021 
CITY OF HOPE 
1500 E. DUARTE ROAD 
DUARTE, CA 91010 
 
DEPARTMENT OF HEMATOLOGY AND HEMATOPOIETIC CELL TRANSPLANTATION                            
 
TITLE: A Phase 2 Study of Polatuzumab Vedotin with Rituximab, Ifosfamide, Carboplatin, and Etoposide 
(PolaR-ICE) as Initial Salvage Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma 
 
CITY OF HOPE PROTOCOL NUMBER: 
IRB #20148 
 
 
PROTOCOL DATE: 12/20/2021  
 
Initial Submission  
 
 
 
Protocol dated 09/17/2020 
 
 
 
Packet: 00 
COH Amendment 01   
 
 
Protocol dated 09/17/2020 (TP) 
 
 
Packet: 01 
COH Amendment 02   
 
 
Protocol dated 09/17/2020 (TP) 
 
 
Packet: 02 
COH Amendment 03   
 
 
Protocol dated 09/17/2020 (TP) 
 
 
Packet: 03 
COH Amendment 04   
 
 
Protocol dated 06/23/2021 
 
 
 
Packet: 04 
COH Amendment 05   
 
 
Protocol dated 06/23/2021 (TP) 
 
 
Packet: 05 
COH Amendment 06   
 
 
Protocol dated 06/23/2021 (TP) 
 
 
Packet: 06 
COH Amendment 07  
 
 
Protocol dated 12/20/2021 
 
 
 
Packet: 07 
COH Amendment 08  
 
 
Protocol dated 12/20/2021 (TP) 
 
 
Packet: 08 
COH Amendment 09 at Continuation 
Protocol dated 12/20/2021 (TP) 
 
 
Packet: 09 
 
 
SITE:  
 
 
STAGE (If applicable): 
 
 
 
 
 
MODALITY:  
 
 
 
 
 
 
TYPE:  
 
 
 
 
 
Phase II 
 
PRINCIPAL INVESTIGATOR: 
 
 
Alex Herrera, M.D. 
 
 
PARTICIPATING CLINICIANS: 
Elizabeth Budde, M.D., Ph.D., Alexey Danilov, M.D., Ph.D. 
 
Stephen Forman, M.D. 
 
Paul Koller, M.D. 
 
Larry Kwak, M.D., Ph.D. 
 
Matthew Mei, M.D. 
Liana Nikolaenko, M.D. 
Leslie Popplewell, M.D. 
Geoffrey Shouse, D.O. 
Tanya Siddiqi, M.D. 
Jasmine Zain, M.D. 
Ricardo Spielberger, M.D. 
Leonardo Farol, M.D. 
Joshua Mansour, M.D. 
Firoozeh Sahebi, M.D. 
James Godfrey. M.D. 
Nicole Karras, M.D. 
Swetha Kambhampati, M.D. 
John Baird, M.D. 

 
IRB #: 20148 
 
 
Packet: 09 
 
12/20/2021 
Steven Rosen, M.D. 
 
BIOSTATISTICIAN:  
 
 
 
Lu Chen, PhD 
 
PROTOCOL DEVELOPMENT SCIENTIST:  
Sandrine Puverel, PhD 
 
PARTICIPATING SITES: 
 
 
 
City of Hope, Duarte 
 
 
 
 
 
 
 
Stanford University 
 
 
 
 
 
 
 
Dana-Farber Cancer Institute 
 
 
 
 
 
 
 
Emory University 
 
 
 
 
 
 
 
Memorial Sloan Kettering Cancer Center 
 
 

This document is confidential and for research purposes only. Do not copy, redistribute, disclose or use except as 
authorized.  
 
 
 
 
 
 
City of Hope National Medical Center 
1500 E. Duarte Road 
Duarte, CA 91010 
Clinical Trial Protocol 
A Phase 2 Study of Polatuzumab Vedotin with Rituximab, Ifosfamide, Carboplatin, and 
Etoposide (PolaR-ICE) as Initial Salvage Therapy for Relapsed/Refractory Diffuse Large 
B-cell Lymphoma 
Version Date: 12/20/2021 
Protocol Version: 02  
 
City of Hope #: 20148 
Agents: Polatuzumab vedotin, Rituximab, Ifosfamide, Carboplatin, 
Etoposide 
IND Number: 152633 
Sponsor/ IND Holder: City of Hope 
Funding Support/ Industry Partner: Genentech 
Industry Partner Protocol ID: ML41673 
NCT Number: NCT04665765 
Participating Sites: City of Hope (Duarte), Stanford University, Dana-Farber 
Cancer Institute, Emory University, Memorial Sloan 
Kettering Cancer Center 
Short Title PolaR-ICE as initial salvage for R/R DLBCL 
 
 
Principal Investigator 
Alex Herrera, MD 
City of Hope National Medical Center 
Dept. of Hematology 
T: 626-256-4673 x 82405 
Email: aherrera@coh.org 
Coordinating Center 
Data Coordinating Center 
City of Hope National Medical Center 
Email: DCC@coh.org 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 2  
 
PROTOCOL TEAM 
Biostatistician 
Lu Chen, PhD 
City of Hope National Medical Center 
Dept. of Computational and 
Quantitative Medicine 
T: 626-256-4673 x 86626 
Email: lchen@coh.org 
Protocol Development Scientist 
Sandrine Puverel, PhD 
City of Hope National Medical Center 
Dept. of Hematology 
T: 626-256-4673 x 84220 
Email: spuverel@coh.org 
  
 
 
Participating non-COH sites 
Site Lead Investigator 
Ranjana Advani, MD 
Stanford University 
Dept. of Medicine 
Email: radvani@stanford.edu 
 
 
Site Lead Investigator 
Jennifer Crombie, MD 
Dana-Farber Cancer Institute 
Dept. of Medical Oncology 
Email: jlcrombie@partners.org 
 
 
Site Lead Investigator 
Jonathon Cohen, MD 
Emory University 
Dept. of Hematology and Medical 
Oncology 
Email: jonathon.cohen@emory.edu 
 
 
Site Lead Investigator 
Matthew Matasar, MD 
Memorial Sloan Kettering Cancer 
Center 
Dept. of Medicine 
T: 212-639-8889 
Email: matasarm@mskcc.org 
 
 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 3  
 
STUDY SCHEMA 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 4  
PROTOCOL SYNOPSIS 
Protocol Title 
A Phase 2 Study of Polatuzumab Vedotin with Rituximab, Ifosfamide, Carboplatin, and Etoposide (PolaR-ICE) as 
Initial Salvage Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma 
Study Detail 
Population/Indication(s): 
Relapsed/Refractory Diffuse Large B-cell Lymphoma 
Phase: 
2 
Sample Size: 
Expected: 40 evaluable patients; Maximum: 53 patients 
Estimated Accrual Duration: 
24 months 
Estimated Study Duration 
~ 4 years 
Participant Duration: 
~ 24 months 
Participating Sites: 
 City of Hope Duarte, CA 
 Stanford University 
 Dana-Farber Cancer Institute 
 Emory University 
 Memorial Sloan Kettering Cancer Center 
Study Agents: 
Polatuzumab vedotin, Rituximab, Ifosfamide, Carboplatin, Etoposide 
Sponsor: 
City of Hope 
Industry Partner:  Genentech 
 
 
 
 
Rationale for this Study 
Novel treatment strategies are needed to improve outcomes for relapsed/refractory (R/R), transplant-eligible DLBCL 
patients, where the goal is to achieve a high-quality remission that enables subsequent ASCT. The primary unmet need is 
the failure to achieve a high rate of CR, as achievement of a PET-negative CR following second-line salvage therapy has 
been associated with improvement in outcome in relapsed DLBCL patients who proceed to ASCT.[1-3] Pola is a potent anti-
CD79b ADC with demonstrated anti-tumor efficacy in R/R DLBCL and has been combined safely with chemotherapy 
resulting in higher response rates compared to chemotherapy alone.[4] Notably, Pola combined with BR in a population 
of heavily treated patients also resulted in improved PFS and OS compared to BR alone. Therefore, it has been 
demonstrated that Pola combined with chemotherapy can improve outcomes in patients with DLBCL. An important 
observation about the clinical use of Pola is that peripheral neuropathy has limited the therapeutic index of the drug, with 
the ultimate dose of the drug being 1.8 mg/kg as opposed to the 2.4 mg/kg dose initially chosen as the recommended 
phase 2 dose. In addition, the duration of Pola dosing has been limited to 6 doses, prior to the onset of dose-limiting 
neuropathy. Therefore, the ideal dosing of Pola may be as a short course to improve upon the efficacy of combination 
chemotherapy, as demonstrated with bendamustine and CHOP in other studies. With the need for more effective bridging 
therapy prior to ASCT in R-R DLBCL, there is an ideal opportunity to utilize Pola as part of salvage therapy to increase the 
CR rate prior to ASCT. The CR rate prior to transplant is an important prognostic factor for ASCT outcome; therefore, our 
hypothesis is that improving salvage therapy with Pola may increase the durable response rate with a salvage/ASCT 
approach.  
In addition, it has been demonstrated in Hodgkin lymphoma that the use of an effective ADC (brentuximab vedotin) after 
ASCT can improve progression-free survival. The AETHERA trial demonstrated that brentuximab vedotin consolidation 
treatment following ASCT prolongs PFS in patients with high risk relapsed or refractory classical Hodgkin lymphoma 
compared to placebo.[5] Like brentuximab vedotin in R/R Hodgkin lymphoma, Pola is an ADC that has potent anti-tumor 
activity in patients with R/R DLBCL. Pola has already been associated with improved survival in patients with R/R DLBCL 
receiving chemotherapy as compared to chemotherapy alone.[6] Therefore, we propose to use Pola as consolidation 
therapy after ASCT with the goal of increasing the proportion of patients with durable remission after ASCT. 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 5  
Objectives 
Primary Objectives 
 Safety Lead-in: Evaluate the safety and tolerability of polatuzumab vedotin (Pola) added to rituximab, ifosfamide, 
carboplatin, and etoposide (PolaR-ICE) as first salvage therapy for relapsed or refractory (R/R) diffuse large B-cell 
lymphoma (DLBCL). 
 Phase 2: Evaluate the anti-tumor activity of PolaR-ICE as first salvage therapy for R/R DLBCL as assessed by the complete 
response rate after 2 cycles. 
Secondary Objectives 
 Evaluate the overall response rate to PolaR-ICE as first salvage therapy for R/R DLBCL. 
 Evaluate the progression-free and overall survival of patients who received PolaR-ICE as first salvage therapy for R/R 
DLBCL followed by autologous stem cell transplantation (ASCT) and single-agent Pola consolidation after ASCT. 
 Evaluate the CR rate after Pola consolidation among those who were PR at ASCT. 
 Evaluate the toxicity of PolaR-ICE salvage therapy and that of Pola consolidation after ASCT. 
 Assess the rate of stem cell mobilization and collection failure in patients with R/R DLBCL who receive PolaR-ICE as first 
salvage therapy. 
Exploratory Objectives 
 Assess the kinetics of circulating tumor DNA after PolaR-ICE as first salvage therapy for R/R DLBCL followed by ASCT and 
single-agent Pola consolidation after ASCT. 
 Assess possible biomarkers of response to PolaR-ICE in patients with R/R DLBCL. 
 Examine the association between clinical outcomes (response, PFS) and pathological tumor characteristics. 
 Examine the association between clinical outcomes (response, PFS) and ctDNA characteristics (mutation profile, kinetics 
of clearance). 
Study Design 
This is a phase 2 study of PolaR-ICE followed by ASCT and Pola consolidation in patients with relapsed or refractory (R/R) 
DLBCL. Adult patients with pathologically documented relapsed or refractory DLBCL after induction therapy will be 
enrolled. Patients with subsets of DLBCL, including mediastinal large B-cell lymphoma, transformed DLBCL, and aggressive 
B-cell lymphoma unclassified will not be excluded. Patients must have received anthracycline- or anthracenedione-
containing induction chemotherapy. The Safety Lead-In will use a design that is slightly modified from the IQ rolling 6 
design.[7] Dose level 1 will use the standard doses of R-ICE (rituximab 375 mg/m2, ifosfamide 5000 mg/m2 or 3 x 1670 
mg/m2, carboplatin area under the curve 5 mg/mL x min; maximum dose, 750 mg, and etoposide 100 mg/m2 per day for 
3 days) with the approved dose of Pola (1.8 mg/kg). There will be a dose de-escalation dose level (dose level -1), only if 
necessary. Dose level -1 will use the standard doses of R-ICE with a reduced dose of Pola (1.4 mg/kg). The maximum number 
of PolaR-ICE cycles is 3. Patients who proceed to ASCT directly after PolaR-ICE and have achieved an objective response to 
PolaR-ICE will receive single-agent Pola consolidation after ASCT at the standard dose of Pola (1.8 mg/kg) every 21 days. 
The maximum number of Pola-containing cycles of therapy is 6. 
After the tolerable dose is confirmed the study will progress to the phase 2 portion of the study, which will employ a two-
stage design to evaluate the CR rate after 2 cycles of PolaR-ICE. Patients who were enrolled during the safety lead-in portion 
at the final dose level deemed tolerable for Phase 2 will also be included in the Phase 2 response evaluation if they are 
evaluable for response.  
Evaluation Criteria and Endpoints 
Toxicities will be will be graded using the NCI CTCAE v 5.0. 
Response/progression will be assessed per 2014 Lugano classification. 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 6  
Primary Endpoint(s):  
 Safety Lead-in: Unacceptable toxicity (defined in Section 11.2) during the first 2 cycles of PolaR-ICE therapy. 
 Phase 2: Complete response (CR) rate after 2 cycles of PolaR-ICE therapy. 
 
Secondary Endpoint(s):  
 Overall response rate (ORR) at the end of PolaR-ICE therapy. 
 Progression-free survival (PFS) and Overall survival (OS). 
 CR rate after Pola consolidation among patients who were PR at ASCT. 
 Toxicity of PolaR-ICE salvage therapy and toxicity of Pola consolidation after ASCT. 
 Stem cell mobilization rate and collection failure. 
Statistical Considerations 
Safety Lead-in: 
During the safety lead-in portion of the study, a design that is slightly modified from the IQ rolling 6 design will be used.[7] 
In this design, up to 8 evaluable patients may be treated at each dose level, and the highest dose level with <33% evaluable 
patients having unacceptable toxicities will be considered tolerable with respect to unacceptable toxicities. If DL 1 is not 
tolerable, DL -1 will be explored.  
Phase 2: 
The Phase 2 portion of the study adopts a two-stage design. Patients who were enrolled during the safety lead-in portion 
at the final dose level deemed tolerable for Phase 2 will also be included in the Phase 2 response evaluation if they are 
evaluable for response.  
At the first stage, 20 patients will be enrolled. If <8 complete responses are seen, the accrual will be terminated. If at least 
8 patients achieve a complete response, the trial will continue to the second stage. At the second stage, 20 additional 
patients will be entered. At the end of stage 2, if 21 or more patients out of the total 40 patients experience a complete 
response, the combination will be considered worthy of further study. If <21 patients experience a complete response 
then no further investigation of the combination is warranted. 
The 2-stage design aims to differentiate between the null hypothesis (disappointing rate) of 40% CR rate and an alternative 
hypothesis (promising rate) of 60% CR rate. The null hypothesis of 40% CR rate is based on a large randomized study 
comparing R-ICE with R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin) as salvage regimen followed by ASCT for 
relapsed/refractory DLBCL [8]. Similar complete response rates were observed after 3 cycles of R-ICE (37%, n=197) vs. 3 
cycles R-DHAP (40%, n=191). Therefore, we would consider a 40% CR rate a discouraging rate and 60% a promising CR rate 
for this regimen to merit further study. The design has a 1-sided type I error of 7.3% and a power of 87%. The expected 
sample size under the null hypothesis is 31.7, and the design has a 42% chance of early termination after Stage I if the true 
CR rate is 40%. 
Abbreviated Eligibility Criteria 
Main Inclusion Criteria 
 Age: ≥ 18 years 
 ECOG ≤ 2 
 Histologically confirmed diagnosis of diffuse large B-cell lymphoma according to the WHO classification, with 
hematopathology review at the participating institution. Subtypes of DLBCL including transformed indolent lymphomas 
(TIL), primary mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma not otherwise specified 
(HGBCL-NOS) are eligible. 
 Biopsy-proven relapsed or refractory disease after 1 line of frontline CD20-directed immunotherapy with anthracycline- 
or anthracenedione-based multi-agent chemotherapy. Monotherapy with rituximab or other CD20-directed 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 7  
immunotherapy prior to frontline chemotherapy or as maintenance therapy, and radiation therapy in a limited field or 
as a part of the frontline treatment plan are permitted. 
 Prior lymphoma therapy should be completed at least 2 weeks before start of protocol therapy. 
 Measurable disease by CT or PET/CT scan with one or more sites of disease ≥ 1.5 cm in longest dimension. 
 Considered eligible for high-dose chemotherapy followed by ASCT. 
 Fully recovered from the acute toxic effects (except alopecia) to ≤ Grade 1 to prior anti-cancer therapy. 
 Be willing to provide archival tissue of a biopsy that was performed after the frontline systemic therapy (if unavailable, 
exceptions may be granted with Study PI approval). 
 Adequate hematological, renal, and hepatic function. 
 Women of childbearing potential: negative urine or serum pregnancy test. 
 Agreement to use an effective method of contraception for both women of childbearing potential and male patients 
during the study and through at least 12 months post-last dose of pola or rituximab for women, 5 months post-last 
dose of pola or 3 months post-last dose of rituximab for men, and 6 months post-last dose of ifosfamide, carboplatin, 
or etoposide for both women and men. 
Main Exclusion Criteria 
 Patients who are not hematopoietic stem cell transplant candidates. 
 Prior solid organ transplantation. 
 Systemic steroid therapy or any other form of immunosuppressive therapy for lymphoma symptom control must be 
tapered down to ≤ 10 mg/day prednisone or equivalent. See exceptions in Section 3.2. 
 Peripheral neuropathy ≥ grade 2 or demyelinating form of Charcot-Marie-Tooth disease. 
 Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement. 
 Active infection requiring systemic therapy. 
 Other active malignancy requiring therapy. Exceptions include basal cell carcinoma of the skin or squamous cell 
carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 
 History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to study agents. 
 Recent major surgery (within 4 weeks) prior to start of protocol therapy, other than for diagnosis. 
 Symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, 
and symptomatic arrhythmias), cerebrovascular event/stroke or myocardial infarction within the past 6 months. 
 Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (See Section 3.2). 
 Known active human immunodeficiency virus (HIV) infection (Section 3.2). 
 History of or current progressive multifocal leukoencephalopathy (PML). 
 Females only: Pregnant or breastfeeding. 
Investigational Product Dosage and Administration 
The treatment plan for the Safety Lead-in and Phase 2 cohorts is as follows. 
Treatment may be given on an inpatient or outpatient basis. 
The maximum number of Pola-containing cycles of therapy is 6 (See Sections 5.6 and 5.7). 
Note: For the drugs that are given as standard of care (i.e. R-ICE), the schedule (e.g. day of drug administration), and order 
of drug administration may be modified for any component of R-ICE at the investigator’s discretion/ per institutional 
standards. In addition, dose modifications/ discontinuation of ifosfamide, carboplatin, and etoposide, whether or not they 
are due to toxicity are permitted at the investigator’s discretion/ per institutional standards. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 8  
 
 
 
 
SALVAGE - PolaR-ICE ‡ (Section 5.6) 
 
Agent 
Dose 
Route 
Schedule (Days 
within each 21-
day cycle) 
Maximum # 
Cycles 
 
R-ICE 
(Inpatient 
Schedule)** 
Rituximab 
375 mg/m2 
IV 
Day 1  
2-3 
 
Etoposide 
100 mg/m2 
IV 
Days 1-3 
Carboplatin 
AUC 5 (750 mg max) 
IV 
Day 2 
Ifosfamide ** 
5000 mg/m2 
IV 
Day 2  
 
Polatuzumab Vedotin 
(Pola) 
Safety Lead-in:  
 
*Dose Level 1: 1.8 mg/kg  
 
  Dose Level -1: 1.4 mg/kg 
(Section 5.4) 
IV 
Day 1  
2-3 
 
Phase 2:  
Tolerable dose from Safety 
Lead-in 
(Section 5.5) 
CONSOLIDATION - Pola ‡‡ (Section 5.7) 
Agent 
Dose 
Route 
Schedule (Days 
within each 21-
day cycle) 
Maximum # 
Cycles 
Polatuzumab Vedotin 
(Pola) 
1.8 mg/kg 
IV 
Day 1 
3-4 
 
* Starting dose is Dose Level 1. 
** Outpatient treatment is allowed and schedule is similar to Inpatient schedule, except for ifosfamide which 
will be given at a dose of 1670 mg/m2 on Days 1-3 (instead of 5000 mg/m2 on Day 2). Ifosfamide is always 
given with Mesna, according to institutional standards (Section 5.14). 
‡ G-CSF prophylaxis should be administered with each PolaR-ICE Salvage cycle. The schedule and G-CSF 
formulation are at the investigator’s discretion. 
‡‡ For participants with objective response (CR or PR).  
 
 
Clinical Observations and Tests to be Performed 
 Safety assessments (CBCs with differential, comprehensive chemistry panel) 
 Response assessments 
 CT/PET/MRI scans  
 Bone marrow biopsy/aspirate 
 Correlative tumor tissue 
 Correlative blood collection 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 9  
TABLE OF CONTENTS 
SECTION ....................................................................................................................................................................... PAGE 
Protocol Team ..................................................................................................................................................................... 2 
Study Schema ...................................................................................................................................................................... 3 
Protocol Synopsis ................................................................................................................................................................ 4 
Table of Contents ................................................................................................................................................................ 9 
Abbreviations .................................................................................................................................................................... 12 
1.0 
Objectives ............................................................................................................................................................ 13 
1.1 
Primary Objectives 
13 
1.2 
Secondary Objectives 
13 
1.3 
Exploratory Objectives 
13 
2.0 
Background .......................................................................................................................................................... 13 
2.1 
Introduction/Rationale for Development 
13 
2.2 
Rationale for Correlative Studies 
16 
2.3 
Overview and Rationale for Study Design 
17 
3.0 
Eligibility Criteria .................................................................................................................................................. 18 
3.1 
Inclusion Criteria 
18 
3.2 
Exclusion Criteria 
20 
4.0 
Participant Enrollment ......................................................................................................................................... 21 
4.1 
Pre-Enrollment Informed Consent and Screening Procedures 
21 
4.2 
Participant Enrollment 
21 
4.3 
Screen Failures and Registered Participants Who Do Not begin Study Treatment 
22 
5.0 
Treatment Program ............................................................................................................................................. 23 
5.1 
Treatment Program Overview 
23 
5.2 
Salvage and Consolidation: Treatment Cycle Definition 
23 
5.3 
Treatment Plan 
23 
5.4 
Safety Lead-In Cohort 
24 
5.5 
Phase 2 Cohort 
24 
5.6 
Salvage (PolaR-ICE) 
25 
5.7 
Consolidation (Polatuzumab Vedotin Single-Agent) 
25 
5.8 
Agent Administration 
27 
5.9 
Assessments and Special Monitoring 
28 
5.10 
Duration of Therapy and Criteria for Removal from Protocol Therapy 
28 
5.11 
Follow-Up 
28 
5.12 
Duration of Study Participation 
29 
5.13 
Prohibited and Concomitant Therapies/Medications 
29 
5.14 
Supportive care 
29 
6.0 
Anticipated Adverse Events ................................................................................................................................. 31 
6.1 
Polatuzumab vedotin 
31 
6.2 
Rituximab 
33 
6.3 
Ifosfamide 
34 
6.4 
Carboplatin 
34 
6.5 
Etoposide 
35 
7.0 
Dose Delay / Modification Guidelines .................................................................................................................. 36 
7.1 
Dose Delay / Modification 
36 
8.0 
Agent Information ............................................................................................................................................... 39 
8.1 
Polatuzumab vedotin 
39 
8.2 
Rituximab, Etoposide, Ifosfamide, and Carboplatin (R-ICE) 
41 
9.0 
Correlative/ Special Studies ................................................................................................................................. 42 
9.1 
Research Sample Collection and Dispensation 
42 
9.2 
Laboratory Studies Performed 
44 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 10  
10.0 
Study Calendar ..................................................................................................................................................... 45 
11.0 
Endpoint Definitions/Measurement of Effect ...................................................................................................... 48 
11.1 
Assessment of Response 
48 
11.2 
Primary Endpoint(s) 
48 
11.3 
Secondary Endpoint(s) 
48 
11.4 
Exploratory Endpoint(s) 
49 
12.0 
Statistical Considerations ..................................................................................................................................... 49 
12.1 
Study Design 
49 
12.2 
Evaluable Participants and Participant Replacement 
51 
12.3 
Sample Size and Accrual Rate 
51 
12.4 
Monitoring for Stem Cell Mobilization Failure and Non-relapse Mortality after ASCT 
51 
12.5 
Toxicity monitoring for post-HCT Pola 
52 
12.6 
Statistical Analysis Plan 
52 
12.7 
Analysis of the exploratory objectives 
53 
13.0 
Data Handling, Data Management, Record Keeping ............................................................................................ 53 
13.1 
Source Documents 
53 
13.2 
Data Capture Methods and Management 
53 
13.3 
Case Report Forms/Data Submission Schedule 
53 
13.4 
Regulatory Records 
54 
14.0 
Reporting of Adverse Events, Unanticipated Problems & Other Events of Interest .............................................. 54 
14.1 
Assessment of Adverse Events 
54 
14.2 
Adverse Events of Special Interest (AESI) 
55 
14.3 
Pregnancies 
56 
14.6 
Expedited Reporting 
57 
14.7 
Reporting to the FDA 
58 
14.8 
Reporting to Industry Partner 
59 
14.9 
Case Transmission Verification of Single Case Reports 
60 
14.10 
Queries 
60 
14.11 
Safety Crisis Management 
60 
14.12 
Compliance with Pharmacovigilance Agreement / Audit 
61 
15.0 
Adherence to the Protocol & Reporting of Protocol Deviations ........................................................................... 61 
16.0 
Study Oversight, Quality Assurance, & Data and Safety Monitoring .................................................................... 62 
16.1 
All Investigator Responsibilities 
62 
16.2 
Study Principal Investigator Responsibilities 
62 
16.3 
Protocol Management Team (PMT) 
62 
16.4 
Quality Assurance 
62 
16.5 
Risk Determination 
62 
16.6 
City of Hope Data and Safety Monitoring Committee 
62 
17.0 
Ethical and Regulatory Considerations ................................................................................................................. 63 
17.1 
Ethical Standard 
63 
17.2 
Regulatory Compliance 
63 
17.3 
Institutional Review Board 
63 
17.4 
Informed Consent 
64 
17.5 
Participant Withdrawal 
64 
17.6 
Special and Vulnerable Populations 
65 
17.7 
Participant Confidentiality 
65 
17.8 
Use of Unused (Leftover) Specimens Collected for this Trial 
66 
17.9 
Conflict of Interest 
66 
17.10 
Financial Obligations, Compensation, and Reimbursement of Participants 
66 
17.11 
Publication/ Data Sharing 
67 
18.0 
References ........................................................................................................................................................... 68 
Appendix A: Performance Status ....................................................................................................................................... 71 
Appendix B: Lymphoma Response Criteria [38] ................................................................................................................. 72 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 11  
Appendix C: NYHA Cardiac Grading Criteria ....................................................................................................................... 76 
Appendix D: Registration Coversheet ................................................................................................................................ 77 
Appendix E: Correlative Tissue Form (for all sites) ............................................................................................................. 78 
Appendix F: Tissue Shipping Guidelines to City of Hope Pathology Core ............................................................................ 79 
Appendix G: Correlative Blood Collection Form for Non-COH Sites Only ........................................................................... 80 
Appendix H: Blood Shipping Guidelines to City of Hope APCF............................................................................................ 81 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 12  
ABBREVIATIONS  
Abbreviation 
Meaning 
ADC 
AE 
ASCT 
CFR 
COH 
CR 
CRA 
CRF 
CTCAE 
DCC 
DLBCL 
DLT 
DSMC 
EOT 
FDA 
GCP 
HIV 
IB 
IDS 
IND 
IRB 
IV 
MMAE 
NCI 
OIDRA 
OS 
PD 
PET 
PI 
PMT 
Pola 
PR 
R-ICE 
SAE 
SD 
Antibody-drug conjugate 
Adverse Event 
Autologous Stem Cell Transplantation 
Code of Federal Regulations 
City of Hope 
Complete Response 
Clinical Research Coordinator 
Case Report Form 
Common Terminology Criteria for Adverse Events 
Data Coordinating Center 
Diffuse Large B-Cell Lymphoma 
Dose Limiting Toxicity 
Data & Safety Monitoring Committee 
End of Treatment 
Food and Drug Administration 
Good Clinical Practice 
Human Immunodeficiency Virus 
Investigator’s Brochure 
Investigational Drug Services 
Investigational New Drug 
Institutional Review Board 
Intravenous 
Monomethyl auristatin E 
National Cancer Institute 
Office of IND Development and Regulatory Affairs 
Overall Survival 
Progressive Disease 
Positron Emission Tomography 
Principal Investigator 
Protocol Management Team 
Polatuzumab Vedotin 
Partial Response 
Rituximab, ifosfamide, carboplatin, etoposide 
 
Serious Adverse Event 
Stable disease 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 13  
1.0 OBJECTIVES 
1.1 Primary Objectives 
Safety Lead-In 
o Evaluate the safety and tolerability of polatuzumab vedotin (Pola) added to rituximab, ifosfamide, 
carboplatin, and etoposide (PolaR-ICE) as first salvage therapy for relapsed or refractory (R/R) diffuse large 
B-cell lymphoma (DLBCL). 
Phase 2 
o Evaluate the anti-tumor activity of PolaR-ICE as first salvage therapy for R/R DLBCL as assessed by the 
complete response rate after 2 cycles. 
1.2 Secondary Objectives 
o Evaluate the overall response rate to PolaR-ICE as first salvage therapy for R/R DLBCL. 
o Evaluate the progression-free and overall survival of patients who received PolaR-ICE as first salvage 
therapy for R/R DLBCL followed by autologous stem cell transplantation (ASCT) and single-agent Pola 
consolidation after ASCT. 
o Evaluate the CR rate after Pola consolidation among those who were PR at ASCT. 
o Evaluate the toxicity of PolaR-ICE salvage therapy and that of Pola consolidation after ASCT. 
o Assess the rate of stem cell mobilization and collection failure in patients with R/R DLBCL who receive 
PolaR-ICE as first salvage therapy. 
1.3 Exploratory Objectives 
o Assess the kinetics of circulating tumor DNA after PolaR-ICE as first salvage therapy for R/R DLBCL followed 
by ASCT and single-agent Pola consolidation after ASCT. 
o Assess possible biomarkers of response to PolaR-ICE in patients with R/R DLBCL. 
o Examine the association between clinical outcomes (response, PFS) and pathological tumor characteristics. 
o Examine the association between clinical outcomes (response, PFS) and ctDNA characteristics (mutation 
profile, kinetics of clearance). 
2.0 BACKGROUND 
2.1 Introduction/Rationale for Development 
2.1.1 
Diffuse Large B-cell Lymphoma 
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and accounts for 30-40% of newly 
diagnosed patients with non-Hodgkin lymphoma (NHL), representing the most common lymphoid neoplasm in 
adults.[9] DLBCL is considered as one of the aggressive type of NHL, with median age 70 years at diagnosis. 
Although the majority of patients with newly diagnosed DLBCL achieve long-term remissions with rituximab and 
multi-agent chemotherapy, approximately 30% of patients will experience relapse or progression.  At the time of 
relapsed disease, the treatment approach is based on whether the patient is a candidate for autologous stem cell 
transplant (ASCT). In patients considered to be transplant eligible, the decision to proceed to ASCT is determined 
by the response to salvage treatment.[10, 11] The goals of salvage therapy are typically to minimize disease 
burden and induce remission, providing the best opportunity to benefit from consolidative ASCT. 
Various multi-agent salvage regimens incorporating rituximab have been explored in DLBCL patients. A large 
randomized comparison of the most commonly used salvage regimens demonstrated the equivalence of rituximab 
combined with either ICE (ifosfamide, carboplatin, etoposide) or DHAP (dexamethasone, cytarabine, cisplatin).[8] 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 14  
There were no significant differences overall between these regimens, and the combined results supported an 
overall response rate (ORR) of 63%, with 37% of patients achieving a complete remission (CR of 25%, unconfirmed 
CR of 12%). The median progression-free survival (PFS) was found to be approximately 1 year, with a 3-year event-
free survival of 31% and 3-year overall survival (OS) of 50%. Patients with chemo-sensitive disease who achieved 
a CR or partial remission (PR) and had adequate stem cell collection were candidates to proceed to ASCT; only 
50% of patients were able to undergo ASCT following salvage therapy. The most common reason to not proceed 
to ASCT was treatment failure to induce remission.   
In general, treatment guidelines support ASCT as the treatment of choice for patients with chemo-sensitive 
relapsed or refractory DLBCL.[10, 11] Patients who are candidates for ASCT should be treated with multi-agent 
chemotherapy regimens combined with rituximab, such as DHAP, ESHAP (etoposide, methylprednisolone, high-
dose cytarabine and cisplatin), GDP (gemcitabine, dexamethasone, and cisplatin), GCD (gemcitabine, carboplatin, 
dexamethasone), GemOx (gemcitabine and oxaliplatin), ICE or MINE (mesna, ifosfamide, mitoxantrone, 
etoposide); there is no clear advantage of one regimen over another. Patients achieving remission should then 
proceed to consolidative ASCT.[10, 11] 
Obtaining a positive emission tomography (PET)-negative CR following second-line salvage therapy has been 
associated with improvement in outcome in relapsed DLBCL patients who proceed to ASCT.[1-3] A meta-analysis, 
including 300 patients with DLBCL, demonstrated that a positive PET scan pre-ASCT was associated with a 
significantly shorter PFS interval (random effects hazard ratio 4.3; 95% CI 3.1, 6; p<0.0001).[3] A PET-positive 
status pre-ASCT resulted in a 4 to 5-fold higher risk for treatment failure versus a PET-negative status. A smaller 
study evaluating the prognostic value of pre-ASCT PET scanning in relapsed DLBCL patients found a striking 
difference in long term outcome, with a 3-year PFS of 81% for patients with a negative scan versus 35% for those 
with a positive scan. This translated into similar 3-year OS findings, with 81% of patients alive with a negative scan 
versus 39% with a positive scan.[1]  
Novel treatment strategies are needed to improve outcomes for relapsed, transplant-eligible DLBCL patients. The 
goal of treatment in this population is to achieve a high-quality remission that enables subsequent ASCT. The 
primary unmet need is the failure to achieve a high rate of CR. Achieving a CR with salvage therapy prior to ASCT 
has been associated with improved long-term outcomes. Chemo-immunotherapy regimens such as RICE or RDHAP 
result in less than half of patients achieving CR; adding a novel agent with demonstrated activity in relapsed DLBCL 
to these regimens has the potential to improve outcomes.  
2.1.2 
Polatuzumab vedotin 
Polatuzumab vedotin (Pola) is an ADC with a monomethyl auristatin E (MMAE) payload directed against CD79b, a 
part of the B-cell receptor complex that is ubiquitously expressed on B cells. Pola has been studied in B-cell NHL 
(B-NHL) and CLL as a single agent, and in multiple Pola-based combination studies in patients with B-NHL. The 
initial phase I dose-escalation study enrolled 95 patients with R/R NHL or CLL, with 86 receiving Pola as a single 
agent and 9 patients receiving Pola combined with rituximab. Pola was well-tolerated as a single agent and in 
combination with rituximab, with most treatment-emergent AEs being mild, and the most common grade 3-4 AEs 
being neutropenia (40%), anemia (11%), or peripheral neuropathy (9%) in heavily treated patients (80% with ≥ 3 
prior lines of therapy). At the recommended phase 2 dose of Pola, the ORR to monotherapy among patients with 
NHL (indolent B-NHL, n=16; DLBCL, n=27; MCL, n=2) was 55%, including an ORR of 56% and CR rate of 15% in 
patients with DLBCL.[12] In the randomized phase II ROMULUS study, patients with R/R FL or DLBCL were 
randomized to receive either Pola or the anti-CD22 ADC pinatuzumab vedotin (PiV) plus rituximab. Patients with 
R/R DLBCL who received Pola plus rituximab (n=39) had an ORR of 56% with a CR rate of 15% while patients with 
R/R FL had an ORR of 70% and a CR rate of 40% (n=20). Similarly, in a separate phase Ib/II study of Pola plus 
obinutuzumab, patients with R/R DLBCL had a best ORR of 52% and CR rate of 29% and patients with R/R FL had 
an ORR of 78% and CR rate of 30%. Pola has also been combined with 6 cycles of bendamustine and either 
rituximab or obinutuzumab in patients with R/R DLBCL or FL as part of a phase I/II study that had dose expansion 
and randomized cohorts (rituximab-bendamustine, BR vs Pola+rituximab-bendamustine, Pola-BR). In patients 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 15  
with R/R DLBCL, the best ORR and CR rate to Pola+BR in the randomized phase II portion of the study (n=40) were 
70% and 57.5% as compared to 32.5% and 20%, respectively, in patients who received BR alone (n=40). The best 
ORR and CR rate to Pola with bendamustine and obinutuzumab were 59% and 41%, respectively. PFS and OS were 
significantly longer in patients who received Pola-BR, with a median OS of 12.4 months compared to 4.7 months 
in patients who received BR (HR 0.42; 95% CI, 0.24 to 0.75). In patients with R/R FL, the CR rate at the end of 6 
cycles of Pola+BR (n=39, 69%) was similar to BR (n=41, 63%) and PFS was also similar (17 versus 17.3 months) with 
OS not reached in both arms.[13] Based on these findings, the FDA approved Pola plus BR for use in patients with 
relapsed/refractory DLBCL who have received at least two prior therapies. Pola has also been evaluated as part of 
initial therapy (cyclophosphamide, doxorubicin, and prednisone with either rituximab, R-CHP, or obinutuzumab, 
G-CHP) in a phase I study of patients with newly diagnosed DLBCL. The end of treatment ORR and CR rate after R-
CHP (n=45) were 91% and 78%, respectively, and the ORR and CR rate after G-CHP (n=21) were 91% and 81%, 
respectively. [14]  There is currently a randomized, double-blinded, placebo-controlled, phase III trial evaluating 
the addition of Pola to R-CHP compared to R-CHOP as initial therapy for DLBCL (POLARIX, clinicaltrials.gov: 
NCT03274492). 
2.1.3 
Rituximab with ifosfamide, carboplatin, and etoposide (R-ICE) 
RICE is a standard chemo-immunotherapy regimen consisting of rituximab, etoposide, ifosfamide, and 
carboplatin. Rituximab is a CD20-directed cytolytic antibody. Etoposide is a topoisomerase inhibitor. Ifosfamide is 
a nitrogen mustard alkylating agent. Carboplatin is a platinum-based antineoplastic agent that intercalates with 
DNA to interfere with DNA repair. RICE is a commonly used regimen for salvage therapy before ASCT in DLBCL 
patients. 
The dose of rituximab (375 mg/m2) is the standard approved dose for patients with previously untreated DLBCL 
when given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or other 
anthracycline-based chemotherapy regimens. There is no standard dose or schedule for rituximab in the relapsed 
or refractory setting; however, the dose (375 mg/m2) and schedule (every 3 weeks) selected in the current study 
have been safely and effectively employed in combination with various single- and multi-agent chemotherapy 
regimens for this patient population.[8, 11] The doses of ifosfamide (5000 mg/m2), carboplatin (area under the 
curve 5 mg/mL x min; maximum dose, 750 mg), and etoposide (100 mg/m2 per day for 3 days) are based on the 
original publication from Memorial Sloan Kettering Cancer Center and are the standard doses when given in a 
combination setting.[15]  
Ifosfamide is extensively metabolized (70-86% of the dose) by CYP3A4 and CYP2B6 (Ifosfamide Prescribing 
Information, APP Pharmaceuticals, January 2008). Carboplatin is mainly eliminated by renal glomerular filtration 
(Paraplatin Prescribing Information, Bristol-Myers Squibb, July 2010). Etoposide is eliminated by multiple 
mechanisms, including renal and biliary excretion and several metabolic pathways (sulfation, glucuronidation, and 
oxidation by CYP3A4) (Etoposide Prescribing Information, Bristol-Myers Squibb, March 2011). 
2.1.4 
Rationale for combination of PolaR-ICE followed by Pola consolidation after ASCT in R/R DLBCL 
As described above, novel treatment strategies are needed to improve outcomes for relapsed/refractory (R/R), 
transplant-eligible DLBCL patients, where the goal is to achieve a high-quality remission that enables subsequent 
ASCT. The primary unmet need is the failure to achieve a high rate of CR, as achievement of a PET-negative CR 
following second-line salvage therapy has been associated with improvement in outcome in relapsed DLBCL 
patients who proceed to ASCT.[1-3] Pola is a potent anti-CD79b ADC with demonstrated anti-tumor efficacy in R/R 
DLBCL and has been combined safely with chemotherapy resulting in higher response rates compared to 
chemotherapy alone.[16] Notably, Pola combined with BR in a population of heavily treated patients also resulted 
in improved PFS and OS compared to BR alone. Therefore, it has been demonstrated that Pola combined with 
chemotherapy can improve outcomes in patients with DLBCL. An important observation about the clinical use of 
Pola is that peripheral neuropathy has limited the therapeutic index of the drug, with the ultimate dose of the 
drug being 1.8 mg/kg as opposed to the 2.4 mg/kg dose initially chosen as the recommended phase 2 dose. In 
addition, the duration of Pola dosing has been limited to 6 doses, prior to the onset of dose-limiting neuropathy. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 16  
Therefore, the ideal dosing of Pola may be as a short course to improve upon the efficacy of combination 
chemotherapy, as demonstrated with bendamustine and CHOP in other studies. With the need for more effective 
bridging therapy prior to ASCT in R-R DLBCL, there is an ideal opportunity to utilize Pola as part of salvage therapy 
to increase the CR rate prior to ASCT. The CR rate prior to transplant is an important prognostic factor for ASCT 
outcome; therefore, our hypothesis is that improving salvage therapy with Pola may increase the durable response 
rate with a salvage/ASCT approach.  
In addition, it has been demonstrated in Hodgkin lymphoma that the use of an effective ADC (brentuximab 
vedotin) after ASCT can improve progression-free survival. The AETHERA trial demonstrated that brentuximab 
vedotin consolidation treatment following ASCT prolongs PFS in patients with high risk relapsed or refractory 
classical Hodgkin lymphoma compared to placebo.[5] Like brentuximab vedotin in R/R Hodgkin lymphoma, Pola 
is an ADC that has potent anti-tumor activity in patients with R/R DLBCL. Pola has already been associated with 
improved survival in patients with R/R DLBCL receiving chemotherapy as compared to chemotherapy alone. [17] 
Therefore, we propose to use Pola as consolidation therapy after ASCT with the goal of increasing the proportion 
of patients with durable remission after ASCT. 
2.2 Rationale for Correlative Studies 
The correlative analyses that will be performed as part of this clinical trial are exploratory and intended to 
generate hypotheses that can be validated in a larger study. The assays described are still under development and 
refinement, so the exact analyses may change during the course of this study. 
2.2.1 
Circulating tumor DNA 
The detection of circulating tumor DNA (ctDNA) has been studied in lymphoma. Next-generation sequencing 
(NGS)-based ctDNA detection performed by NGS of the immunoglobulin (Ig) or T-cell receptor genes can identify 
ctDNA in the peripheral blood mononuclear cells (PBMC) and plasma (cell-free DNA) at diagnosis in a range of 
lymphomas, including diffuse large B-cell lymphoma (DLBCL).[18-21] In addition, ctDNA levels correlate with 
treatment response in DLBCL, and the persistence or recurrence of ctDNA during and after upfront therapy is 
associated with subsequent DLBCL relapse.[20, 21] While the Ig-NGS method is powerful, the investigation of only 
Ig genes limits its sensitivity, resulting in a sizable minority of patients in whom the assay is not applicable. 
Meanwhile, ctDNA assessment using capture-based NGS for recurrent mutations and rearrangements has been 
explored in DLBCL, and the method appears feasible and highly sensitive.[22, 23] Like IgNGS, capture-based NGS 
MRD detection exploits the genetic features of a lymphoma to identify tumor-specific DNA in the peripheral blood 
of patients with lymphoma. Utilizing bioinformatics pipelines optimized for low input DNA, hybridization capture-
based NGS is performed on a patient sample (i.e. peripheral blood, tumor tissue) that evaluates a panel of single-
nucleotide variants (SNVs), insertions/deletions (indels), and chromosomal translocations known to be recurrently 
mutated in a specific lymphoma subtype (to date, primarily DLBCL). CtDNA can be quantitated by calculating the 
proportion of tumor-specific cfDNA molecules within a sample (the variant allele fraction). Thus far, studies have 
demonstrated that genetic alterations detected in ctDNA using capture-based NGS analysis of the peripheral 
blood are highly concordant with genetic alterations determined by NGS of a primary DLBCL tumor sample.[24-
26] Similar to IgNGS, capture-based NGS based MRD detection can identify ctDNA in patients with DLBCL prior to 
treatment, can quantify ctDNA levels that track with treatment response and resistance, and can detect relapse 
prior to and at the time of clinically apparent relapse.[23-25, 27] In a study examining DLBCL patients receiving 
frontline or salvage therapy at several independent centers, ctDNA was detectable in 98% of patients, and 
pretreatment ctDNA levels and molecular responses were independently prognostic of outcomes.[28]  
2.2.2 
Gene expression profiling 
Gene expression profiles define distinct subsets of DLBCL and are associated with outcome after standard therapy 
in patients with DLBCL.[29, 30] Both the cell of origin and a newer double-hit signature identify subsets of patients 
who have poorer outcomes with standard therapy.[31] We will study both COO and the double-hit signature in 
patients treated with PolaR-ICE and evaluate associations with response to therapy and PFS. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 17  
2.2.3 
Mutation profiling 
Recent work from multiple laboratories have studied the mutational landscape in DLBCL and identified biological 
clusters of mutation profiles that have prognostic significance. We will perform next-generation sequencing to 
evaluate the mutational landscape in patients treated with PolaR-ICE and associations with response to study 
treatment and PFS.[32-34] 
2.2.4 
Multispectral immunofluorescence 
We will use the Vectra spatial multispectral immunofluorescence (mIF) system to evaluate pre-treatment and on-
treatment changes in immune cell subset density and relative proximities in the tumor microenvironment.  
Proof of concept that mIF is a valuable tool in studying the tumor microenvironment in lymphomas was 
demonstrated in Hodgkin lymphoma by the Shipp lab, where unique microenvironmental features of the HL 
microenvironment were elucidated.[35] 
2.3 Overview and Rationale for Study Design 
This is a phase 2 study of PolaR-ICE followed by ASCT and Pola consolidation in patients with relapsed or refractory 
(R/R) DLBCL. Adult patients with pathologically documented relapsed or refractory DLBCL after induction therapy 
will be enrolled. Patients with subsets of DLBCL, including mediastinal large B-cell lymphoma, transformed DLBCL, 
and aggressive B-cell lymphoma unclassified will not be excluded. Patients must have received anthracycline- or 
anthracenedione-containing induction chemotherapy. The Safety Lead-In will use a design that is slightly modified 
from the IQ rolling 6 design.[7] Dose level 1 will use the standard doses of R-ICE (rituximab 375 mg/m2, ifosfamide 
5000 mg/m2 or 3 x 1670 mg/m2, carboplatin area under the curve 5 mg/mL x min; maximum dose, 750 mg, and 
etoposide 100 mg/m2 per day for 3 days) with the approved dose of Pola (1.8 mg/kg). There will be a dose de-
escalation dose level (dose level -1), only if necessary. Dose level -1 will use the standard doses of R-ICE with a 
reduced dose of Pola (1.4 mg/kg).  The maximum number of PolaR-ICE cycles is 3. ASCT will be performed 
according to institutional standards. Patients who proceed to ASCT directly after PolaR-ICE and have achieved an 
objective response to PolaR-ICE will receive single-agent Pola consolidation after ASCT at the standard dose of 
Pola (1.8 mg/kg) every 21 days. The maximum number of Pola-containing cycles of therapy is 6. 
After the tolerable dose is confirmed the study will progress to the phase 2 portion of the study, which will employ 
a two-stage design to evaluate the CR rate of PolaR-ICE after 2 cycles. Patients who were enrolled during the safety 
lead-in portion at the final dose level deemed tolerable for Phase 2 will also be included in the Phase 2 response 
evaluation if they are evaluable for response. At the first stage, 20 patients will be enrolled. If <8 complete 
responses are seen, the accrual will be terminated. If at least 8 patients achieve a complete response, the trial will 
continue to the second stage. At the second stage, 20 additional patients will be entered. At the end of stage 2, if 
21 or more patients out of the total 40 patients experience a complete response, the combination will be 
considered worthy of further study.  
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 18  
3.0 ELIGIBILITY CRITERIA 
Patient MRN (COH Only) 
Patient Initials (F, M, L): 
Institution:     
Participants must meet all of the following criteria on screening examination to be eligible to participate in the 
study:  
3.1 Inclusion Criteria 
Informed Consent and Willingness to Participate 
__1. Documented informed consent of the participant and/or legally authorized representative. 
 
Assent, when appropriate, will be obtained per institutional guidelines 
__2. Be willing to provide archival tissue of a biopsy that was performed after the frontline systemic therapy. 
 
If unavailable, exceptions may be granted with Study PI approval. 
Age Criteria, Performance status 
__3. Age: ≥ 18 years 
__4. ECOG ≤ 2 
Nature of Illness and Illness Related Criteria 
__5. Histologically confirmed diagnosis of diffuse large B-cell lymphoma according to the WHO classification, with 
hematopathology review at the participating institution. Subtypes of DLBCL including transformed indolent 
lymphomas (TIL), primary mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma not 
otherwise specified (HGBCL-NOS) are eligible. 
__6. Biopsy-proven relapsed or refractory disease after 1 line of frontline CD20-directed immunotherapy with 
anthracycline- or anthracenedione-based multi-agent chemotherapy. Monotherapy with rituximab or other CD20-
directed immunotherapy prior to frontline chemotherapy or as maintenance therapy, and radiation therapy in a 
limited field or as a part of the frontline treatment plan are permitted. 
__7. Prior lymphoma therapy should be completed at least 2 weeks before start of protocol therapy. 
__8. Measurable disease by CT or PET/CT scan with one or more sites of disease ≥ 1.5 cm in longest dimension. 
__9. Considered eligible for high-dose chemotherapy followed by ASCT. 
__10. Fully recovered from the acute toxic effects (except alopecia) to ≤ Grade 1 to prior anti-cancer therapy. 
Clinical Laboratory and Organ Function Criteria 
__11. Without bone marrow involvement: ANC ≥ 1,000/mm3  
With bone marrow involvement: ANC ≥ 750/mm3 
NOTE: Growth factor is not permitted within 7 days of ANC 
assessment unless cytopenia is secondary to disease involvement. 
ANC: 
Date: 
__12. Without bone marrow involvement: Platelets ≥ 100,000/mm3 
With bone marrow involvement: Platelets ≥ 75,000/mm3 
NOTE: Platelet transfusions are not permitted within 7 days of 
platelet assessment unless cytopenia is secondary to disease 
involvement. 
Plts: 
 
Date: 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 19  
Patient MRN (COH Only) 
Patient Initials (F, M, L): 
Institution:     
 
__13. Hemoglobin ≥ 8 g/dL (no erythropoietin and/or pRBC transfusion 
allowed within 7 days prior to screening) 
Exception: unless cytopenia is secondary to disease involvement. 
Hgb: 
Date: 
__14. Total bilirubin ≤ 1.5 X ULN 
If hepatic involvement by lymphoma, or Gilbert’s disease: ≤ 3X ULN 
ULN: 
Bil: 
Liver 
involvement: Y/N 
Gilbert’s disease: 
Y/N 
Date: 
__15. AST ≤ 2.5 x ULN 
 If hepatic involvement by lymphoma: AST ≤ 5 x ULN 
 
ULN: 
AST: 
Liver 
involvement: Y/N 
Date: 
__16. ALT ≤ 2.5 x ULN 
 If hepatic involvement by lymphoma: ALT ≤ 5 x ULN 
ULN: 
ALT: 
Liver 
involvement: Y/N 
Date: 
__17. Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the 
Cockcroft-Gault formula or  
 
Serum Cr: 
 
Cr Clearance: 
Date: 
__18. If not receiving anticoagulants: International Normalized Ratio 
(INR) OR Prothrombin (PT) ≤ 1.5 x ULN 
If on anticoagulant therapy: PT must be within therapeutic range 
of intended use of anticoagulants 
ULN: 
INR: 
PT: 
On anticoagulant 
therapy: Yes/No 
Date: 
__19. If not receiving anticoagulants: Activated Partial Thromboplastin 
Time (aPTT) ≤ 1.5 x ULN 
If on anticoagulant therapy: aPTT must be within therapeutic 
range of intended use of anticoagulants 
ULN: 
 
aPTT: 
On anticoagulant 
therapy: Yes/No 
Date: 
__20. Women of childbearing potential (WOCBP): negative urine or 
serum pregnancy test  
If the urine test is positive or cannot be confirmed as negative, a 
serum pregnancy test will be required 
Urine: 
Serum: 
Date: 
 
 
 
 
 
 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 20  
Patient MRN (COH Only) 
Patient Initials (F, M, L): 
Institution:     
Contraception 
Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain 
from heterosexual activity for the course of the study through at least 12 months after the last dose of 
polatuzumab vedotin or rituximab for women, at least 5 months following the last dose of polatuzumab vedotin 
or 3 months following the last dose of rituximab for men, and at least 6 months following the last dose of 
ifosfamide, carboplatin, or etoposide for both women and men.  
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been 
free from menses for > 1 year (women only).  
3.2 Exclusion Criteria 
Prior and concomitant therapies 
__1.  Patients who are not hematopoietic stem cell transplant candidates are excluded. 
__2.  Prior solid organ transplantation. 
__3.  Systemic steroid therapy or any other form of immunosuppressive therapy for lymphoma symptom control 
must be tapered down to ≤ 10 mg/day prednisone or equivalent. Exceptions are: 
- Inhaled or topical steroids 
- Adrenal replacement doses > 10 mg daily prednisone equivalents in the absence of active autoimmune 
disease. 
Other illnesses or conditions 
__4.  Peripheral neuropathy ≥ grade 2 or demyelinating form of Charcot-Marie-Tooth disease. 
__5.  Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal 
involvement. 
__6.  Active infection requiring systemic therapy. 
__7.  Other active malignancy requiring therapy. Exceptions include basal cell carcinoma of the skin or squamous 
cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 
__8.  History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to 
study agents. 
__9.  Recent major surgery (within 4 weeks) prior to start of protocol therapy, other than for diagnosis. 
__10.  Symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery 
disease, and symptomatic arrhythmias), cerebrovascular event/stroke or myocardial infarction within the past 6 
months. See Appendix C. 
__11.  Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with past HBV infection 
(defined as negative HBsAg and positive hepatitis B core antibody [HBcAb]) are eligible if HBV DNA is undetectable. 
Patients who are positive for HCV antibody are eligible if PCR is negative for HCV RNA. 
Testing to be done only in patients suspected of having infections or exposures. 
__12.  Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or 
unquantifiable HIV viral load with CD4 > 200 and are on HAART medication are allowed. Testing to be done only in 
patients suspected of having infections or exposures. 
__13.  History of or current progressive multifocal leukoencephalopathy (PML). 
__14.  Females only: Pregnant or breastfeeding. 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 21  
Patient MRN (COH Only) 
Patient Initials (F, M, L): 
Institution:     
 
__15.  Any other condition that would, in the Investigator’s judgment, contraindicate the patient’s participation 
in the clinical study due to safety concerns with clinical study procedures. 
Noncompliance 
__16.  Prospective participants who, in the opinion of the investigator, may not be able to comply with all study 
procedures (including compliance issues related to feasibility/logistics). 
Eligibility Confirmed* by 
(Choose as applicable): 
Print Name 
Signature 
Date 
 Site PI 
 
 
 
 Authorized study MD 
 
 
 
 Study Nurse 
 
 
 
 Study CRA/ CRC 
 
 
 
Other:______________ 
 
 
 
*Eligibility should be confirmed per institutional policies. 
4.0 PARTICIPANT ENROLLMENT 
NOTE: Sites must meet activation requirements prior to enrolling participants. 
4.1 Pre-Enrollment Informed Consent and Screening Procedures 
Diagnostic or laboratory studies performed exclusively to determine eligibility will be done only after obtaining 
written informed consent. Studies or procedures that are performed for clinical indications (not exclusively to 
determine study eligibility) may be used for baseline values and/or to determine pre-eligibility, even if the studies 
were done before informed consent was obtained. 
The informed consent process is to be fully documented (see Section 17.4), and the prospective participant must 
receive a copy of the signed informed consent document. Screening procedures are listed in Section 10.0 (Study 
Calendar). 
4.2 Participant Enrollment 
4.2.1 
COH DCC Availability and Contact Information 
Eligible participants will be registered on the study centrally by the Data Coordinating Center (DCC) at City of Hope.   
DCC staff are available between the hours of 8.00 am and 5.00 pm PST, Monday through Friday (except holidays).  
o E-mail: DCC@coh.org 
4.2.2 
Slot verification and reservation 
A designated study team member should email the DCC to verify current slot availability, and to reserve a slot for 
a specific prospective subject (provide DCC with subject initials), including a tentative treatment date. Slots can 
only be held for a limited time, at the discretion of the study PI. 
The DCC should be notified of cancellations of prospective participants holding slots as soon as possible.   
4.2.3 
Registration Process  
Allow up to 24 hours for the DCC to review. To register a participant the subsequent procedure is to be followed: 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 22  
1. The study team should contact the DCC via email to provide notification regarding the pending registration 
and communicate desired timeline of the registration, especially if it must be completed promptly to meet 
the registration window.  
2. The study team will email a Complete Registration Packet to the DCC, which consists of a copy of the 
following documents: 
o Registration Cover Sheet (Appendix D) 
o Completed eligibility checklist (printed from Section 3.0 of the protocol) with required 
signature(s) 
o Signed Informed Consent  
o Signed HIPAA authorization form (if separate from informed consent) 
o Signed subject’s bill of Rights (California only) 
3. In some cases, the DCC may request additional documentation prior to registration. Please refer to the 
Work Instruction – Reviewing Packets and Registering Subjects for more information. A copy of this work 
instruction can be provided by the DCC, upon request. 
4. When all documents are received, the DCC will review and work with the study team to resolve any 
missing elements. Any missing documents may delay registration.  A participant failing to meet all 
requirements will not be registered and the study team will be immediately notified. 
5. The DCC will send a Confirmation of Registration Form, including the Subject Study Number and cohort 
assignment to:  
o The study team: Site Lead Investigator, treating physician/ sub-investigator, protocol nurse, CRC 
and pharmacy (as needed). 
o The COH Study PI and COH study team designees (including but not limited to study monitor(s) 
and statistician(s)). 
6. Upon receipt of the Confirmation of Registration Form, COH study team will register the patient in OnCore. 
The DCC will register non-COH patients in OnCore. 
4.3 Screen Failures and Registered Participants Who Do Not begin Study Treatment 
Notify the DCC immediately if the participant screen fails after registration or if the participant does not start 
treatment. 
For non-COH sites, the reason for screen failure will be documented in the registration coversheet (Appendix D) 
and submitted to the DCC. 
Issues that would cause treatment delays should be discussed with the Study Principal Investigator. 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 23  
5.0 TREATMENT PROGRAM 
5.1 Treatment Program Overview 
This is a multicenter, open-label, phase 2 clinical trial of polatuzumab vedotin plus rituximab, ifosfamide, 
carboplatin, and etoposide (PolaR-ICE), followed by single agent polatuzumab vedotin (Pola) consolidation post-
ASCT, for patients with DLBCL who are refractory or relapsed after frontline therapy. 
The trial consists of a: 
o Safety Lead-in stage to evaluate safety/tolerability of PolaR-ICE (Section 5.4.) and  
o Phase 2 stage to evaluate anti-tumor activity of the regimen in the study population (Section 5.5).  
For both Salvage and Consolidation, each cycle will be 21 days. During Salvage, patients will receive 2-3 cycles of 
PolaR-ICE. Participants with objective response (CR or PR) following Salvage will be eligible to proceed to 
autologous stem cell transplantation (ASCT), prior to continuing with 3-4 cycles of single-agent Pola Consolidation. 
ASCT will be performed according to institutional standards. See Section 5.6 and Section 5.7 for details. 
Participants who end protocol therapy will undergo follow-up (Section 5.11).  Windows for all assessments and 
treatments are detailed in Section 10. 
5.2 Salvage and Consolidation: Treatment Cycle Definition 
In the absence of a delay due to toxicity, each treatment cycle lasts 21 days with a ± 3 day window during both 
Salvage and Consolidation. 
o Salvage PolaR-ICE (Section 5.6):  
 
Day 1 of each cycle will be defined as the first day of administration of Pola.  
 
If Pola is not administered, then Day 1 will be defined as the day of administration of rituximab.  
o Consolidation Pola (Section 5.7): 
 Day 1 of each treatment cycle is defined by the day of administration of Pola. 
5.3 Treatment Plan 
The treatment plan for the Safety Lead-in and Phase 2 cohorts is as follows (Table 5.3). 
Treatment may be given on an inpatient or outpatient basis. 
The maximum number of Pola-containing cycles of therapy is 6 (See Sections 5.6 and 5.7). 
Table 5.3 Treatment Regimen and Schedule 
Notes: 
- 
For rituximab and G-CSF, the use of biosimilars is allowed. 
- 
For the drugs that are given as standard of care (i.e. R-ICE), the schedule (e.g. day of drug administration), 
and order of drug administration may be modified for any component of R-ICE at the investigator’s 
discretion/ per institutional standards. In addition, dose modifications/ discontinuation of ifosfamide, 
carboplatin, and etoposide, whether or not they are due to toxicity are permitted at the investigator’s 
discretion/ per institutional standards. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 24  
 
SALVAGE - PolaR-ICE ‡ (Section 5.6) 
 
Agent 
Dose 
Route 
Schedule (Days within 
each 21-day cycle) 
Maximum # Cycles 
 
R-ICE 
(Inpatient 
Schedule)** 
Rituximab 
375 mg/m2 
IV 
Day 1  
2-3 
 
Etoposide 
100 mg/m2 
IV 
Days 1-3 
Carboplatin 
AUC 5 (750 mg max) 
IV 
Day 2 
Ifosfamide ** 
5000 mg/m2 
IV 
Day 2  
 
Polatuzumab Vedotin 
(Pola) 
Safety Lead-in:  
 
*Dose Level 1: 1.8 mg/kg  
 
  Dose Level -1: 1.4 mg/kg 
(Section 5.4) 
IV 
Day 1  
2-3 
 
Phase 2:  
Tolerable dose from Safety 
Lead-in 
(Section 5.5) 
CONSOLIDATION - Pola ‡‡ (Section 5.7) 
Agent 
Dose 
Route 
Schedule (Days within 
each 21-day cycle) 
Maximum # Cycles 
Polatuzumab Vedotin 
(Pola) 
1.8 mg/kg 
IV 
Day 1 
3-4 
 
* Starting dose is Dose Level 1. 
** Outpatient treatment is allowed and schedule is similar to Inpatient schedule, except for ifosfamide which will be 
given at a dose of 1670 mg/m2 on Days 1-3 (instead of 5000 mg/m2 on Day 2). Ifosfamide is always given with Mesna, 
according to institutional standards (Section 5.14). 
‡ G-CSF prophylaxis should be administered with each PolaR-ICE Salvage cycle. The schedule and G-CSF formulation 
are at the investigator’s discretion. 
‡‡ For participants with objective response (CR or PR).  
 
5.4 Safety Lead-In Cohort 
During the Safety Lead-in, up to 5-16 evaluable participants will be enrolled using a design that is slightly modified 
from the IQ rolling 6 design.[7] (see Section 12 for details). The starting dose for polatuzumab vedotin will be 1.8 
mg/kg in combination with R-ICE (Table 5.3). Unacceptable toxicities (defined in Section 11.2) will be evaluated 
during the first 2 cycles of PolaR-ICE Salvage therapy. 
In the event the initial starting polatuzumab vedotin dose is not tolerated (2+ patients with unacceptable toxicity 
out of ≤6, 3+/7, or 3+/8 evaluable participants), a polatuzumab vedotin dose of 1.4 mg/kg (Dose Level -1) will be 
explored in an additional up to 8 evaluable participants. If Dose Level -1 is not tolerated, the study will be stopped. 
5.5 Phase 2 Cohort 
The tolerable dose of polatuzumab vedotin established during the Safety Lead-in will be used for the Phase 2 
portion (Table 5.3). Participants treated at the final dose level deemed tolerable for Phase 2 during the Safety 
Lead-in will be included in the Phase 2 portion of the study if they are evaluable for response. Between 20-40 
patients will be enrolled using a two-stage design (see Section 12 for details). 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 25  
5.6 Salvage (PolaR-ICE) 
o See Section 5.14 regarding G-CSF administration as supportive care. 
o 2-3 cycles of PolaR-ICE: 
- All patients are planned to receive 2 cycles of PolaR-ICE. 
- Patients with PR after 2 cycles will receive an additional cycle of PolaR-ICE (3 cycles total). Patients with 
CR or SD after 2 cycles may receive an additional cycle of PolaR-ICE (3 cycles total) at the treating 
physician’s discretion. 
o If one agent is discontinued due to toxicity, then the participant may continue to receive the other 
protocol therapy agents. Note: if an agent is discontinued, administration of R-ICE should be prioritized 
since it is the standard of care and as the use of polatuzumab vedotin as part of salvage therapy remains 
investigational. 
Timing and windows for imaging are detailed in Section 10.0. 
5.7 Consolidation (Polatuzumab Vedotin Single-Agent) 
NOTE: Participants must meet criteria in Section 5.7.1 to initiate Consolidation.  
o See Section 5.14 regarding G-CSF administration as supportive care. 
o 3-4 cycles of Pola: 
- Patients who received 2 cycles of PolaR-ICE during Salvage will receive 4 cycles of Pola Consolidation. 
- Patients who received 3 cycles of PolaR-ICE during Salvage will receive 3 cycles of Pola Consolidation. 
The maximum number of Pola-containing cycles of therapy is 6. 
o Initiate after autologous stem cell transplantation (ASCT). Stem cell mobilization and collection and ASCT 
will be performed per institutional standards. 
o Initiate Consolidation between Day + 30 and Day + 60 post-ASCT. A delay of up to Day + 75 is permitted 
following consultation with the Study PI for certain criteria (see Section 5.7.1 below). Screening may 
initiate 21 days after ASCT. 
Timing and windows for imaging are detailed in Section 10.0. 
5.7.1 
Criteria to Receive Consolidation Polatuzumab Vedotin  
Participants must meet the below criteria to receive Consolidation therapy with single-agent Pola after completing 
PolaR-ICE Salvage. Criteria must be met within 28 days of starting Consolidation therapy, except where otherwise 
specified (labs). 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 26  
 
Criteria to be met in order to initiate 
Consolidation with polatuzumab vedotin 
Action if criterion to the left is NOT met 
1. Achieved objective response per 2014 Lugano 
Classification at end of Salvage  
Discontinue protocol therapy.   
2. No ≥ Grade 2 peripheral neuropathy  
For Grade 2 or 3: 
 Wait until toxicity improves to ≤ Grade 1. 
 Administer Pola consolidation at the 
permanently reduced dose of 1.4 mg/kg. If 
patient was already at 1.4 mg/kg during 
salvage, discontinue protocol therapy. 
Following consultation with Study PI delay 
initiation of Consolidation up to Day +75 post-
ASCT may be permitted. 
For Grade 4: 
Discontinue protocol therapy. 
3. Absence of unrelated toxicity not present at baseline 
that might adversely affect participation/ administration 
of polatuzumab vedotin  
Discontinue protocol therapy.   
4. Recovered from ASCT toxicities 
Including: outpatient status, able to drink and eat 
normally, and do not need intravenous hydration prior 
to Cycle 1 Day 1 of Consolidation therapy 
 
 
 
 
Following consultation with Study PI delay 
initiation of Consolidation up to Day +75 post-
ASCT may be permitted. 
 
 
5. Will initiate treatment between Day +30 and Day +60 
post-ASCT 
6. ECOG ≤ 2  within the screening period  
7. ANC ≥ 1,000/mm3 within 14 days prior to Day 1 of 
Consolidation 
8. Platelets ≥ 75,000/mm3 within 14 days prior to Day 1 of 
Consolidation 
9. Total serum bilirubin ≤ 1.5X upper limit of normal (ULN), 
OR if Gilbert’s disease: ≤ 3X ULN, within 14 days prior to 
Day 1 of Consolidation 
10. AST ≤ 2.5 x ULN, OR if hepatic involvement by 
lymphoma: AST  ≤  5 x ULN, within 14 days prior to Day 
1 of Consolidation 
11. ALT ≤ 2.5 x ULN, OR If hepatic involvement by lymphoma: 
ALT ≤ 5 x ULN, within 14 days prior to Day 1 of 
Consolidation 
12. Creatinine clearance of ≥ 40 mL/min within 14 days prior 
to Day 1 of Consolidation 
13. No active  ≥ Grade 3 infection within 14 days prior to Day 
1 of Consolidation 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 27  
Criteria to be met in order to initiate 
Consolidation with polatuzumab vedotin 
Action if criterion to the left is NOT met 
14. No other active malignancy requiring therapy. Exceptions 
include basal cell carcinoma of the skin or squamous cell 
carcinoma of the skin that has undergone potentially 
curative therapy, or in situ cervical cancer. 
Discontinue protocol therapy.   
15. No symptomatic cardiac disease (including symptomatic 
ventricular dysfunction, symptomatic coronary artery 
disease, and symptomatic arrhythmias), cerebrovascular 
event/stroke or myocardial infarction within the last 6 
months 
Discontinue protocol therapy.   
16. No central nervous system involvement by lymphoma, 
including leptomeningeal involvement  
Discontinue protocol therapy.   
17. No history of or current progressive multifocal 
leukoencephalopathy (PML)  
Discontinue protocol therapy.   
 
 
5.8 Agent Administration 
Refer to Section 5.14 for supportive care, including mandatory prophylaxis for infusion-related reactions and 
growth factor support. 
Note: For the drugs that are given as standard of care (i.e. R-ICE), the schedule (e.g. day of drug administration), 
and order of drug administration may be modified for any component of R-ICE at the investigator’s discretion/ per 
institutional standards. In addition, dose modifications/ discontinuation of ifosfamide, carboplatin, and etoposide, 
whether or not they are due to toxicity are permitted at the investigator’s discretion/ per institutional standards. 
5.8.1 
Order of drug administration on Days 1 during Salvage 
Rituximab will be administered first. Once the rituximab infusion is completed, patients are to be observed for 30 
min before the start of the next infusion. Pola will be administered next (follow guidelines in Section 5.8.2). ICE 
will be administered as per institutional standards. 
 
5.8.2 
Polatuzumab vedotin 
Administer the initial dose of polatuzumab vedotin over 90 min (+/- 10 min). Monitor patients for infusion-related 
reactions during the infusion and for a minimum of 90 min following completion of the initial dose. If the initial 
infusion was well tolerated, the subsequent doses may be administered over 30 min (+/- 10 min) and patients 
should be monitored during the infusion and for at least 30 min after completion of the infusion. 
Dosing should be based on the patient’s baseline weight (C1D1, pre-dose). Doses will be adjusted for patients who 
experience a ≥10% change in weight during the study. Rounding is permissible according to institutional standards. 
 
5.8.3 
Rituximab, Ifosfamide, Carboplatin, Etoposide (R-ICE) 
Administer R-ICE per institutional standards. Inpatient or outpatient administration is allowed. Dosing should be 
based on the patient’s baseline height and weight (C1D1, pre-dose) or per institutional standards. Doses will be 
adjusted for patients who experience a ≥10% change in weight during the study. Rounding is permissible according 
to institutional standards. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 28  
Mesna will be given with ifosfamide according to institutional standards.  
5.9 Assessments and Special Monitoring 
For a detailed list of all study procedures including timing and windows, see Section 10. 
Note: Initiate a new cycle after all procedures/safety assessments have been completed. 
5.9.1 
Infusion-related reactions 
o Infusion or hypersensitivity reactions may occur to polatuzumab vedotin or R-ICE.  
o If such a reaction were to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, 
arthralgias, hypotension, hypertension, bronchospasm, or other allergic-like reactions. 
o Refer to Section 5.14 for infusion-related reaction/hypersensitivity guidelines. 
5.9.2 
Peripheral neuropathy 
o Patients receiving polatuzumab vedotin may develop peripheral neuropathy (sensory and/or motor). 
o Patients receiving study treatment should be monitored for symptoms of neuropathy, including 
hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait 
disturbance, or neuropathic pain. 
o Refer to Section 7.1 for dose modification guidelines. 
5.10 Duration of Therapy and Criteria for Removal from Protocol Therapy 
Participants will receive protocol therapy (Salvage and Consolidation) until one of the below criteria are met: 
o Confirmed Disease progression per 2014 Lugano Classification 
o Participant unable to proceed with Consolidation 
o Completed protocol therapy (Salvage and Consolidation) 
o Participant is deemed intolerant to protocol therapy because of toxicity, despite dose modification/ 
delay  
 Note: If one agent is discontinued due to toxicity, then the participant may continue to receive 
the other study agents  
o General or specific changes in the patient's condition which render the patient unacceptable for 
further treatment in the judgment of the investigator 
o Withdrawal of consent for further protocol therapy (See Section 17.5) 
Once a participant meets criteria for removal from protocol therapy, the participant should then proceed to 
follow-up assessments (Section 5.11). 
Documentation of the reason for discontinuing protocol therapy and the date effective should be made in the 
Electronic Health Record/medical record and appropriate eCRF. 
The COH DCC and the Study PI should be promptly notified of the change in participant status. 
5.11 Follow-Up 
All participants who end protocol therapy will enter follow-up for 2 years. 
NOTE: Assessments may be combined if the windows for the two visits overlap. 
Follow-up is comprised of: 
o Safety Follow-up- 30 days post-last dose of protocol therapy. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 29  
 
Note the period for safety follow-up will be extended until stabilization or resolution for all 
reportable AEs (per the agreement of the Study PI) and accompanying follow-up safety report. 
o Response Follow-up- for those who have yet to have disease progression. 
o Survival Follow-up- for all participants who have progressed OR completed Active Response Follow-
Up OR initiated a new anti-lymphoma therapy. This follow-up will be performed typically via medical 
record review. It will entail (a) Disease status (for those who have yet to progress) (b) Vital status (all 
participants). 
Assessment time points and windows are detailed in Section 10. 
5.12 Duration of Study Participation 
Study participation may conclude when any of the following occur:  
o Completion of study activities (treatment and follow-up after protocol treatment) 
o Withdrawal of consent (See Section 17.5) 
o Participant is lost to follow-up. All attempts to contact the participant must be documented. 
o At the discretion of the investigator for safety, behavioral, study termination or administrative 
reasons 
Documentation of the reason for discontinuing study participation and the date effective should be made in the 
Electronic Health Record/medical record and appropriate eCRF. 
The COH DCC and the Study PI should be promptly notified of the change in participant status. 
5.13 Prohibited and Concomitant Therapies/Medications  
5.13.1 Allowed concomitant medications 
If concomitant therapy must be added or changed, including over-the-counter medications or alternative 
therapies, the reason and name of the agent/therapy should be recorded in the eCRF and documented in the 
Electronic Health Record/medical record. 
5.13.2 Prohibited medications/ therapies 
- Prohibited from Day 1 of protocol therapy until end of protocol therapy (last day of study agent or decision to 
end study agent(s) whichever occurs later). 
 Herbal and natural remedies 
 Other investigational therapy  
 Other concurrent systemic anti-cancer therapy: chemotherapy, biological response modifiers, hormone 
therapy, surgery, palliative radiation therapy, or immunotherapy. 
- Prohibited during Salvage: 
 
Strong CYP3A4 inducer or inhibitor. A washout period of 10 days is required before start of Salvage 
therapy.  
- Exception post- Salvage but prior to Consolidation with polatuzumab vedotin: 
 
Consolidation ASCT. 
5.14 Supportive care 
With the exception of prohibited therapies (Section 5.13), participants should receive prophylactic or supportive 
as clinically indicated per institutional policies. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 30  
Prophylaxis for infusion-related reactions  
 
Patients should be pre-medicated with at least an anti-histamine and antipyretic (e.g. 50-100 mg 
diphenhydramine, 500-1000 mg oral acetaminophen) prior to all rituximab and polatuzumab vedotin 
infusions, per institutional standards. 
 
If not already pre-medicated for rituximab administration, administer an antihistamine and antipyretic at 
least 30 to 60 minutes prior to Pola infusion for potential infusion-related reactions. 
Blood products and growth factors 
 
Platelet and/or red blood cell supportive growth factors or transfusions 
− 
Permitted when applicable. For growth factors, the use of biosimilars is allowed. 
 
Colony stimulating factors (CSFs) (The use of biosimilars is allowed). 
− 
Salvage:  All patients should receive G-CSF with each PolaR-ICE cycle. The schedule and G-CSF formulation 
are per investigator discretion. 
− 
Consolidation: Per investigator’s discretion and institutional practice. 
Anti-emetic prophylaxis 
 
Routine anti-emetic prophylaxis regimen should be administered per institutional standards. 
Prophylaxis for hemorrhagic cystitis 
 
Mesna is to be administered with ifosfamide according to institutional standards (e.g. 5000 mg/m2 on 
Day 2 (inpatient schedule) or 1670 mg/m2 on Days 1-3 (outpatient schedule)). 
Corticosteroids 
 
Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic 
absorption) 
− 
Permitted 
 
Systemic corticosteroids 
− 
Physiologic replacement doses permitted even if > 10 mg/day prednisone or equivalent. 
 
Brief course of corticosteroids (< 3 weeks)  
− 
Permitted for prophylaxis (e.g. contrast dye allergy)  
− 
Permitted for treatment of non-autoimmune conditions (e.g, delayed-type hypersensitivity reaction 
caused by contact allergen)  
Management of infusion related reactions 
 
 
Grade 1-2: 
− 
Slow or hold infusion 
− 
Give supportive treatment* 
− 
Upon symptom resolution, may resume infusion (rate escalation at the investigator’s discretion**) 
Note: for Grade 2 wheezing or urticaria, patient must be premedicated for any subsequent doses. If 
symptoms recur, the infusion must be stopped immediately and study drug permanently discontinued. 
 
Grade 3:  
− 
Discontinue infusion 
− 
Give supportive treatment* 
− 
Upon symptom resolution, may resume infusion (rate escalation at the investigator’s discretion**) 
Note: if the same adverse event recurs with same severity, treatment must be permanently discontinued. 
Note: for Grade 3 hypotension or fever, patient must be premedicated before re-treatment. If symptoms 
recur, then study drug must be permanently discontinued. 
Note: if patient has Grade 3 wheezing, bronchospasm, or generalized urticaria at first occurrence, study 
drug must be permanently discontinued. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 31  
 
Grade 4:  
− 
Discontinue infusion immediately, treat symptoms aggressively, and permanently discontinue study drug. 
 
* Supportive treatment: patients should be treated with acetaminophen/paracetamol and an antihistamine 
such as diphenhydramine if they have not been received in the previous 4 hours. IV saline may be indicated. 
For bronchospasm, urticaria, or dyspnea, patients may require antihistamines, oxygen, corticosteroids (e.g. 
100 mg IV prednisolone or equivalent), and/or bronchodilators. Patients with hypotension who require 
vasopressor support must be permanently discontinued from study drug. 
** Infusion rate escalation after re-initiation: upon complete resolution of symptoms, the 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 50mg/hour every 30 minutes. 
P-gp inhibitors 
 
Closely monitor for AEs when administered concomitantly with polatuzumab vedotin. 
Anti-viral and anti-pneumocystis prophylaxis  
 
Routine anti-viral (coverage for HSV and VZV) and anti-pneumocystis prophylaxis is required beginning at 
the initiation of study treatment and continuing for at least 6 months after completion of study treatment, 
per institutional standards. If clinically indicated, anti-infective prophylaxis for other infectious agents is 
permitted. For patients who proceed to AHCT, continue prophylaxis for at least 9 months after AHCT. If 
prophylaxis is held, the reasoning (e.g. renal dysfunction) must be documented. 
Intrathecal prophylactic treatment for cerebral/meningeal disease  
 
Permitted at the discretion of the investigator 
Tumor lysis syndrome (TLS) prophylaxis and management 
 
Permitted at the discretion of the investigator, per institutional standards 
For patients that are considered at risk for TLS [e.g. bulky disease, or high LDH (≥ 1000 IU/L) at baseline, 
or high uric acid (≥ 7 mg/dL) at baseline], allopurinol (300 mg po daily, dose adjusted per renal function) 
may be given. If a diagnosis of TLS is established, monitoring and multi-disciplinary management will be 
per institutional practice. 
6.0 ANTICIPATED ADVERSE EVENTS 
6.1 Polatuzumab vedotin 
The Investigator’s Brochure (IB) is the primary source for safety information. Refer to the most recent IB, which is 
updated periodically, for current information on polatuzumab vedotin. 
The most common adverse reactions (≥20%) include neutropenia, thrombocytopenia, anemia, peripheral 
neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. 
Table 6.1 (polatuzumab vedotin IB V11, October 2019) lists all expected serious adverse drug reactions (SADRs) 
for polatuzumab vedotin. These SADRs were selected based on individual and aggregate assessment, medical 
review, and prior reports of the adverse reactions in clinical trials. Frequencies are based on pooled clinical trial 
data and/or single clinical trial data using only related serious adverse events as noted. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 32  
Table 6.1 Serious adverse drug reactions (SADRs) to polatuzumab vedotin in B-cell lymphomas including 
indolent non-Hodgkin lymphoma and diffuse large B-cell lymphoma considered expected for safety reporting 
purposes 
System Organ Class 
SADRs 
 (Cumulative clinical trial exposure (N=635) 
All SADRs 
N* (%) 
Fatal SADRs 
N* (%) 
Life-threatening 
SADRs 
N* (%) 
Blood and lymphatic disorders 
Leukopenia 
Febrile neutropenia 
Neutropenia 
2 (0.3) 
43 (6.7) 
11 (1.7) 
n/a 
n/a 
n/a 
n/a 
n/a 
n/a 
Nervous system disorders 
Peripheral motor neuropathy 
Peripheral sensory neuropathy 
3 (0.5) 
3 (0.5) 
n/a  
n/a 
n/a 
n/a 
Infections and infestations 
Pneumonia 
10 (1.57) 
n/a 
n/a 
Gastro-intestinal disorders 
Abdominal pain 
Diarrhea 
Vomiting 
2 (0.3) 
9 (1.4) 
2 (0.3) 
n/a  
n/a 
n/a 
n/a 
n/a 
n/a 
General disorders and 
administration 
Pyrexia 
8 (1.3) 
n/a 
n/a 
n/a = fatal or life-threatening SADRs are not considered expected. 
All fatal or life-threatening SADRs are considered unexpected for regulatory purposes. 
N* = number of patients who experienced the SADR. 
 
Table 6.2 summarizes commonly reported reactions in study GO29365 (NCT02257567) where Pola was combined 
with chemotherapy. 
Table 6.2 Adverse reactions occurring in >10% of patients with relapsed or refractory DLBCL and ≥5% more in 
the polatuzumab vedotin (Pola) plus bendamustine and rituximab (BR) product group. 
Adverse Reactions by Body System 
Pola + BR 
(n=45) 
All Grades (%) 
BR 
(n=39) 
All Grades (%) 
Blood and Lymphatic System Disorders 
 
Neutropenia 
49 
44 
Thrombocytopenia 
49 
33 
Anemia 
47 
28 
Lymphopenia 
13 
  8 
Nervous System Disorders 
 
Peripheral neuropathy 
40 
  8 
Dizziness 
13 
  8 
Gastrointestinal Disorders 
 
Diarrhea 
38 
28 
Vomiting 
18 
13 
General Disorders 
 
Infusion-related reaction 
18 
  8 
Pyrexia 
33 
23 
Decreased appetite 
27 
21 
Infections 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 33  
Adverse Reactions by Body System 
Pola + BR 
(n=45) 
All Grades (%) 
BR 
(n=39) 
All Grades (%) 
Pneumonia 
22 
15 
Upper respiratory tract infection 
13 
  8 
Investigations 
 
Weight decreased 
16 
  8 
Metabolism and nutrition disorders 
 
Hypokalemia 
16 
10 
Hypoalbuminemia 
13 
  8 
Hypocalcemia 
11 
  5 
 
 
 
Other clinically relevant adverse reactions (<10% or with a <5% difference) in recipients of polatuzumab vedotin 
plus BR included: 
▪ 
Blood and lymphatic system disorders: pancytopenia (7%) 
▪ 
Musculoskeletal disorders: arthralgia (7%) 
▪ 
Investigations: hypophosphatemia (9%), transaminase elevation (7%), lipase increase (7%) 
▪ 
Respiratory disorders: pneumonitis (4.4%) 
6.2 Rituximab 
The most common (≥25%) adverse reactions in clinical trials for NHL and CLL were infusion reactions, fever, 
lymphopenia, chills, infection, asthenia, and neutropenia. 
According to the package insert for rituximab, rituximab can cause: 
 Infusion reactions: Rituximab can cause severe, including fatal, infusion reactions. Severe reactions typically 
occurred during the first infusion with time to onset of 30-120 minutes. 
 Severe mucocutaneous reactions: These reactions include paraneoplastic pemphigus, Stevens-Johnson 
syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of 
these reactions has been variable and includes reports with onset on the first day of rituximab exposure. 
 Hepatitis B virus reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant 
hepatitis, hepatic failure and death, can occur in patients treated with drugs classified as CD20-directed 
cytolytic antibodies, including rituximab. 
 Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur 
in rituximab-treated patients with hematologic malignancies. 
 Tumor 
lysis 
syndrome: 
Acute 
renal 
failure, 
hyperkalemia, 
hypocalcemia, 
hyperuricemia, or 
hyperphosphatemia from tumor lysis, some fatal, can occur within 12-24 hours after the first infusion of 
rituximab in patients with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor 
burden, confers a greater risk of TLS. 
 Infections: Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during 
and following the completion of rituximab-based therapy.  
 Cardiac arrhythmias and angina 
 Renal toxicity 
 Bowel obstruction and perforation 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 34  
 Cytopenias 
6.3 Ifosfamide 
In clinical trials of ifosfamide monotherapy, the most common (≥10%) adverse reactions were alopecia, 
nausea/vomiting, leukopenia, anemia, CNS toxicity, hematuria, and infection. 
According to the package insert for ifosfamide, ifosfamide can cause: 
 
Myelosuppression: Can be severe and lead to fatal infections. 
 
Neurotoxicity: Severe and fatal neurotoxicity can occur. Carefully monitor the patient for CNS toxicity and 
other neurotoxic effects.   
 
Urotoxicity: Severe nephrotoxicity with renal failure and death can occur. Monitor for nephrotoxicity with 
serum and urine chemistries. Mesna should be used to reduce hemorrhagic cystitis. 
 
Cardiotoxicity: Arrhythmias, other ECG changes, and cardiomyopathy can occur and result in death. Use with 
caution in patients with cardiac risk factors and in patients with preexisting cardiac disease. The risk of 
cardiotoxicity is dose dependent. 
 
Pulmonary toxicity: Interstitial pneumonitis, pulmonary fibrosis, and other forms of pulmonary toxicity with 
fatal outcomes can occur. Monitor for signs and symptoms of pulmonary toxicity and treat as clinically 
indicated.   
 
Secondary malignancies as late sequelae have occurred. 
 
Veno-occlusive Liver Disease. 
 
Pregnancy: Can cause fetal harm. Women should not become pregnant and men should not father a child 
during therapy. 
 
Effects on Fertility. Sterility may be irreversible in some patients. 
 
Anaphylactic/anaphylactoid reactions have been reported. 
 
Impairment of wound healing. 
 
Nursing: Ifosfamide is excreted in breast milk. 
6.4 Carboplatin 
According to the package insert for carboplatin, carboplatin can cause: 
 
Hematologic Toxicity: Bone marrow suppression is the dose-limiting toxicity of carboplatin. 
Thrombocytopenia with platelet counts below 50,000/mm3 occurs in 25% of the patients; neutropenia with 
granulocyte counts below 1000/mm3 occurs in 16% of the patients; leukopenia with WBC counts below 
2000/mm3 occurs in 15% of the patients. The nadir usually occurs about day 21 in patients receiving single-
agent therapy. By day 28, 90% of patients have platelet counts above 100,000/mm3; 74% have neutrophil 
counts above 2000/mm3; 67% have leukocyte counts above 4000/mm3. 
Anemia with hemoglobin less than 11 g/dL has been observed in 71% of the patients who started therapy 
with a baseline above that value. The incidence of anemia increases with increasing exposure to carboplatin. 
Transfusions have been administered to 26% of the patients treated with carboplatin. 
Bone marrow depression may be more severe when carboplatin is combined with other bone marrow 
suppressing drugs or with radiotherapy. 
 
Gastrointestinal Toxicity: Vomiting occurs in 65% of the patients and in about one-third of these patients it 
is severe. Nausea alone occurs in an additional 10 to 15% of patients. Both nausea and vomiting usually cease 
within 24 hours of treatment and are often responsive to antiemetic measures. Emesis was increased when 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 35  
carboplatin was used in combination with other emetogenic compounds. Other gastrointestinal effects 
observed frequently were pain, in 17% of the patients; diarrhea, in 6%; and constipation, also in 6%. 
 
Neurologic Toxicity: Peripheral neuropathies have been observed in 4% of the patients receiving carboplatin 
with mild paresthesias occurring most frequently.  
Clinical ototoxicity and other sensory abnormalities such as visual disturbances and change in taste have 
been reported in only 1% of the patients. Central nervous system symptoms have been reported in 5% of the 
patients and appear to be most often related to the use of antiemetics. 
 
Nephrotoxicity: Development of abnormal renal function test results is uncommon, despite the fact that 
carboplatin, unlike cisplatin, has usually been administered without high-volume fluid hydration and/or 
forced diuresis. The incidences of abnormal renal function tests reported are 6% for serum creatinine and 
14% for blood urea nitrogen (10% and 22%, respectively, in pretreated ovarian cancer patients). Most of 
these reported abnormalities have been mild and about one-half of them were reversible. 
 
Hepatic Toxicity: The incidences of abnormal liver function tests in patients with normal baseline values were 
reported as follows: total bilirubin, 5%; SGOT, 15%; and alkaline phosphatase, 24%; (5%, 19%, and 37%, 
respectively, in pretreated ovarian cancer patients). These abnormalities have generally been mild and 
reversible in about one-half of the cases, although the role of metastatic tumor in the liver may complicate 
the assessment in many patients. 
 
Electrolyte Changes: The incidences of abnormally decreased serum electrolyte values reported were as 
follows: sodium, 29%; potassium, 20%; calcium, 22%; and magnesium, 29%. 
 
Allergic Reactions: Hypersensitivity to carboplatin has been reported in 2% of the patients. These allergic 
reactions have been similar in nature and severity to those reported with other platinum- containing 
compounds, ie, rash, urticaria, erythema, pruritus, and rarely bronchospasm and hypotension. Anaphylactic 
reactions have been reported as part of postmarketing surveillance. These reactions have been successfully 
managed with standard epinephrine, corticosteroid, and antihistamine therapy. 
 
Injection Site Reactions: Injection site reactions, including redness, swelling, and pain, have been reported 
during postmarketing surveillance. Necrosis associated with extravasation has also been reported. 
 
Other Events: Pain and asthenia were the most frequently reported miscellaneous adverse effects; their 
relationship to the tumor and to anemia was likely. Alopecia was reported (3%). Cardiovascular, respiratory, 
genitourinary, and mucosal side effects have occurred in 6% or less of the patients. Cardiovascular events 
(cardiac failure, embolism, cerebrovascular accidents) were fatal in less than 1% of the patients and did not 
appear to be related to chemotherapy. Cancer-associated hemolytic uremic syndrome has been reported 
rarely. 
Malaise, anorexia and hypertension have been reported as part of postmarketing surveillance. 
 
Pregnancy: Carboplatin may cause fetal harm when administered to a pregnant woman. Carboplatin has 
been shown to be embryotoxic and teratogenic in rats. There are no adequate and well-controlled studies in 
pregnant women. 
6.5 Etoposide 
The most common adverse reaction is neutropenia. 
According to the package insert for etoposide, etoposide can cause: 
 
Myelosuppression: Etoposide causes myelosuppression that results in thrombocytopenia and neutropenia. 
Fatal infections and bleeding have occurred. 
 
Secondary Leukemias: Secondary leukemias have occurred with long term use of etoposide.  

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 36  
 
Hypersensitivity Reactions: Etoposide can cause hypersensitivity reactions, including rash, urticaria, pruritus, 
and anaphylaxis.  
 
Embryo-Fetal Toxicity: Based on animal studies and its mechanism of action, etoposide can cause fetal harm 
when administered to a pregnant woman. 
 
Lactation: There is no information regarding the presence of etoposide in human milk or its effects on 
breastfed infant milk production. There is a potential for serious adverse reactions in nursing infants from 
etoposide. 
 
Infertility: Etoposide may result in permanent loss of fertility. 
 
Gastrointestinal Toxicity: Nausea and vomiting are the major gastrointestinal toxicities. The severity of 
nausea and vomiting is generally mild to moderate, with treatment discontinuation required in 1% of 
patients. 
Other clinically important adverse reactions in clinical trials were:  
 
Gastrointestinal: abdominal pain, constipation, dysphagia.  
 
General: fever.  
 
Ocular: transient cortical blindness, optic neuritis.  
 
Respiratory: interstitial pneumonitis/pulmonary fibrosis.  
 
Skin: pigmentation, radiation recall dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.  
 
Neurologic: seizure, aftertaste.  
 
Hepatobiliary disorder: hepatotoxicity.  
7.0 DOSE DELAY / MODIFICATION GUIDELINES 
7.1 Dose Delay / Modification 
o Toxicities will be graded using the NCI CTCAE v 5.0. 
o Baseline values are from the last values obtained prior to treatment. 
o When attribution of a toxicity is unclear due to overlapping toxicity profiles of the drugs included in 
protocol therapy (e.g. hematologic, infections, febrile neutropenia), administration of R-ICE should be 
prioritized since it is the standard of care and as the use of polatuzumab vedotin as part of salvage 
therapy remains investigational. Therefore, dose reduction/delay of polatuzumab vedotin should be 
attempted before dose reduction/delay of agents included in R-ICE. 
o If one agent is held due to toxicity for a given cycle, administration of the delayed agent should resume 
once the toxicity is resolved on the same schedule with the next cycle of combination therapy.   
o If one agent is permanently discontinued, then the participant may continue with other agent(s). Refer 
to Section 5.6. 
o If all agents are held together due to toxicity and the delay lasts > 6 weeks, then protocol therapy will be 
discontinued.  
o Polatuzumab vedotin  
 Dose delay/modification guidelines for polatuzumab vedotin-related toxicity are described in Table 
7.1.  
 If a delay due to toxicity lasts > 6 weeks, permanently discontinue polatuzumab vedotin. 
 Doses reduced for polatuzumab vedotin-related toxicity should not be re-escalated without 
discussion with the Study PI.  

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 37  
 Dose reductions below 1.4 mg/kg are not permitted, and toxicities should be managed with dose 
delays or polatuzumab vedotin should be permanently discontinued. 
o R-ICE 
 Dose modifications for rituximab are not permitted. 
 Dose modifications/ discontinuation of ifosfamide, carboplatin, and etoposide, whether or not they 
are due to toxicity are permitted at the investigator’s discretion/ institutional standards. 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 38  
Table 7.1 Dose Modifications for Polatuzumab Vedotin   
Toxicity 
Polatuzumab Vedotin Dose Management Guidelines 
Peripheral Neuropathy 
Grade 1 
Asymptomatic; clinical or diagnostic observations 
only; intervention not indicated 
Continue at same dose level 
Grade 2/3 
G2:Moderate symptoms; limiting instrumental 
ADL 
G3: Severe symptoms; limiting self care ADL; 
assistive device indicated 
 
Withhold until toxicity resolves to ≤ Grade 1, then resume 
treatment at 1.4 mg/kg  
See above for guidance if the participant dose is already 1.4 
mg/kg. 
Grade 4 
Life-threatening consequences; urgent 
intervention indicated 
 
Discontinue polatuzumab vedotin 
Infusion Related Reaction 
Grade 1/2 
G1: Mild transient reaction; infusion interruption 
not indicated; intervention not indicated 
G2: Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment 
(e.g., antihistamines, NSAIDS, narcotics, IV fluids); 
prophylactic medications indicated for <=24 hrs 
 
Refer to Section 5.14 for supportive care 
 
Maintain same dose level during subsequent cycles 
 
Grade 3 
Prolonged (e.g., not rapidly responsive to 
symptomatic medication and/or brief interruption 
of infusion); recurrence of symptoms following 
initial improvement; hospitalization indicated for 
clinical sequelae 
 
Refer to Section 5.14 for supportive care 
 
Polatuzumab vedotin may be restarted at the same dose level 
per Investigator’s discretion with prophylaxis premedication 
(Section 5.14). Otherwise, permanently discontinue 
polatuzumab vedotin. 
Grade 4 
Life-threatening consequences; urgent 
intervention indicated 
 
Refer to Section 5.14 for supportive care 
 
Discontinue polatuzumab vedotin 
Other unspecified non-hematologic  
Grade 1/2 
Continue at same dose level 
Grade 3  
Withhold dose until toxicity is ≤ Grade 2, then resume treatment 
at the same dose level.  
− 
Note: Patients who develop Grade 3 electrolyte 
laboratory abnormalities may continue study treatment 
without interruption. 
Grade 4 
Discontinue polatuzumab vedotin 
− 
Note: Patients who develop Grade 4 electrolyte 
laboratory abnormalities should have correction to Grade 
3 prior to treatment resumption at the same dose. 
  
Hematologic 
Grades 1-2 
Continue at same dose level 
Grade 3-4 
 Withhold until toxicity resolves to ≤ Grade 2  

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 39  
Toxicity 
Polatuzumab Vedotin Dose Management Guidelines 
− 
 NOTE: Patients who develop Grade 3 or 4 lymphopenia 
may continue study treatment without interruption 
 Growth factor support (G-CSF or GMCSF) for neutropenia 
should be considered for subsequent cycles, if not already 
given. 
 First occurrence: resume at same dose level 
 Second occurrence: 
- 
For any toxicity (including neutropenia despite the use of 
G-CSF), dose reduction to 1.4 mg/kg should be considered  
- 
If the participant is already receiving 1.4 mg/kg, dose 
discontinuation should be considered. 
 
 
8.0 AGENT INFORMATION 
8.1 Polatuzumab vedotin 
Polatuzumab vedotin is FDA-approved for the treatment of adult patients with relapsed or refractory DLBCL, not 
otherwise specified, in combination with bendamustine and a rituximab product, after at least two prior therapies. 
8.1.1 
Other names 
Polivy, DCDS4501A. 
8.1.2 
Description 
Polatuzumab vedotin is an ADC that contains a humanized IgG1 anti-CD79b monoclonal antibody (MCDS4409A) 
and a potent antimitotic agent (MMAE) linked through a protease-cleavable linker. An average of 3.5 molecules 
of MMAE are attached to each antibody molecule. 
Polatuzumab vedotin is approved by the FDA for the treatment of diffuse large B-cell lymphoma, relapsed or 
refractory, in combination with bendamustine and a rituximab product, after at least 2 prior therapies. 
Please refer to the investigator brochure for a detailed description. 
8.1.3 
Mechanism of action 
Polatuzumab vedotin targets the cell surface antigen CD79b which is expressed on mature B cells, with the 
exception of plasma cells. Following internalization, the ADC is cleaved by lysosomal enzymes to release MMAE 
and other potentially active catabolites. Free MMAE binds to the microtubule network and subsequently leads to 
cell cycle arrest and apoptosis. 
8.1.4 
Pharmacokinetics and Metabolism 
ADC Vd: 
3.15 L 
MMAE protein binding: 
71-77% 
MMAE Metabolism: 
Substrate of CYP3A4 and P-gp 
ADC Total body excretion: 
0.9 L/day 
ADC Elimination half-life: 
12 days 
MMAE Elimination half-life 
4 days 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 40  
8.1.5 
Toxicology 
8.1.5.1 Expected human toxicities  
See Section 6.1 for a detailed list of anticipated AEs. 
8.1.5.2 Potential effects on fertility, pregnancy and lactation 
Adverse effects on human reproduction and fertility are anticipated with the administration of polatuzumab 
vedotin based on the mechanism of action of the cytotoxic component of polatuzumab vedotin as a microtubule 
inhibitor. Given that MMAE, the cytotoxic component of polatuzumab vedotin, is a microtubule inhibitor targeting 
rapidly dividing cells and is a known teratogen, polatuzumab vedotin is expected to be teratogenic and 
embryotoxic. 
 
It is not known whether polatuzumab vedotin can be found in sperm. Based on findings from animal studies, 
polatuzumab vedotin may impair male fertility. Individual patients seeking to preserve fertility should discuss the 
options available to them with their physicians prior to treatment initiation. 
 
No clinical studies assessing the reproductive and developmental toxicity of polatuzumab vedotin have been 
conducted to date. It is not known whether polatuzumab vedotin can cross the placenta or cause harm to the 
fetus when administered to pregnant women or whether it affects reproductive capacity. Therefore, polatuzumab 
vedotin should not be administered to pregnant women.  
 
It is not known whether polatuzumab vedotin is excreted in human breast milk. Because many drugs are excreted 
in human milk and because of the potential for harm to nursing infants, polatuzumab vedotin should not be 
administered to nursing mothers. 
8.1.6 
Formulation 
Polatuzumab vedotin is provided in 140 mg, white to grayish-white lyophilized powder for reconstitution, in single-
use vials.  
8.1.7 
Handling, storage, dispensing and disposal 
Store refrigerated at 2°C to 8°C in original carton to protect from light. Do not use beyond the expiration date. Do 
not freeze. Do not shake. 
For polatuzumab vedotin reconstitution, dilution, and storage of diluted solutions, please refer to the USPI. 
Polatuzumab vedotin is a cytotoxic drug. Follow applicable special handling and disposal procedures. 
8.1.8 
Administration 
Administer polatuzumab vedotin as an intravenous infusion only. 
Polatuzumab vedotin 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 a catheter. 
 
Compatibility between polatuzumab vedotin and closed system transfer devices (CSTDs) or needle free transfer 
devices has not been assessed. If CSTDs or needle free transfer devices must be used to comply with site 
regulations, the site should be aware that their use may lead to the introduction of particles and may not allow 
the withdrawal of the labeled quantity of drug from the vial. Sites should perform a thorough visual inspection of 
the IV bag for particulates. In addition, sites must use a 0.2 or 0.22 μm polyethersulfone (PES) filter during infusion. 
The preparation should be discarded if particulates are observed in the IV bag. 
  
Do not mix polatuzumab vedotin with, or administer as an infusion with, other medicinal products.  

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 41  
See Section 5.8.2 for administration guidelines. 
8.1.9 
Supplier 
Polatuzumab vedotin will be supplied free of charge by Genentech. 
8.1.10 Ordering 
Sites will place orders for polatuzumab vedotin via the Genentech investigator initiated study drug supply request 
form.  
Sites should place orders at least 2 weeks in advance. 
8.1.11 Accountability 
The investigator, or a responsible party designated by the investigator, must maintain a careful record of the 
inventory and disposition of the agent using a drug accountability log. 
8.1.12 Destruction and Return 
The investigator is responsible for keeping accurate records of the clinical supplies received from Genentech or 
designee, the amount dispensed to participants, and the amount remaining at the conclusion of the trial.  
Any unused agent at the end of the study, expired agent, and damaged agent will be destroyed according to 
applicable federal, state, local and institutional guidelines and procedures.  
Destruction will be documented in a drug accountability log. 
8.2 Rituximab, Etoposide, Ifosfamide, and Carboplatin (R-ICE) 
Agents contained in the R-ICE regimen are approved by the FDA for use in treating patients with multiple types 
of cancer. Please refer to the package insert for a detailed description. 
8.2.1 
Other names 
Rituximab: Rituxan 
Etoposide: VePesid, Etopophos, Toposar (VP-16) 
Ifosfamide: Ifex 
Carboplatin: Paraplatin 
8.2.2 
Description and mechanism of action 
R-ICE is a standard chemo-immunotherapy regimen consisting of rituximab, etoposide, ifosfamide, and 
carboplatin. Rituximab is a CD20-directed cytolytic antibody. Etoposide is a topoisomerase inhibitor. Ifosfamide is 
a nitrogen mustard alkylating agent. Carboplatin is a platinum-based antineoplastic agent with a mechanism of 
action that interacts with DNA to inferfere with DNA repair. 
8.2.3 
Pharmacokinetics and Metabolism 
Refer to respective package inserts for additional information. 
Ifosfamide: 
Half-life: 
Mean terminal t½ between 7-15 hours with single doses 
Distribution: 
0.64-0.72 L/kg 
Protein binding: 
low 
Metabolism: 
Hepatic 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 42  
Elimination: 
Urine (70-86%) 
Ifosfamide is a substrate for both CYP3A4 and CYP2B6. 
 
Carboplatin: 
Half-life: 
Initial t½ is 1.1-2 hours. Post-distribution t½ is 2.6-5.9 hours 
Distribution: 
16 L 
Protein binding: 
None 
Elimination: 
Urine (65-71%) 
 
Etoposide: 
Half-life: 
Initial t½ is 1.5 hours. Mean terminal t½ is 4 to 11 hours 
Distribution: 
7-17 L/m2 
Protein binding: 
94-98% 
Metabolism: 
Hepatic via CYP3A4 
Elimination: 
Urine (56%) within 120 hours; feces (44%) within 120 hours 
8.2.4 
Human Toxicity 
See Sections 6.2 to 6.5. 
8.2.5 
Formulation 
Refer to respective package inserts. 
8.2.6 
Storage 
Rituximab, etoposide, ifosfamide, and carboplatin should be stored per their respective package insert. 
8.2.7 
Preparation and Handling 
Rituximab, etoposide, ifosfamide, and carboplatin should be prepared and handled per their respective package 
insert and institutional standard. 
8.2.8 
Administration 
See Section 5.8.3. 
8.2.9 
Supplier 
Agents contained in the R-ICE regimen are commercially available and will be billed to patients and/or their third-
party payer. 
9.0 CORRELATIVE/ SPECIAL STUDIES 
9.1 Research Sample Collection and Dispensation 
9.1.1 
Correlative tumor tissue 
9.1.1.1 Time points of Collection 
Baseline tissue: Archival tissue from diagnostic tumor biopsies will be retrieved and submitted post-enrollment. 
NOTE: If unavailable, exceptions may be granted with the lead study PI approval. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 43  
If safe and feasible, submission of left-over tissue from a standard of care tumor biopsy (fresh core or excisional 
biopsy) for participants who progress/relapse during study is encouraged. 
9.1.1.2 Guidelines for archival specimens 
Using the formalin-fixed paraffin embedded (FFPE) tissue block, the following samples will be processed for 
correlative studies:  
o If tissue block is available submit: 
     6 paraffin scrolls measuring 10 µm thick placed into a tube and frozen at -80° C  
AND 
     10 x 5 µm thick unstained slides 
o If tissue block is unavailable submit:  
                   20 x 5 µm thick unstained slides  
9.1.1.3 Labeling of samples 
Samples will be labeled with the COH protocol #, subject ID (issued by DCC), institution, date, time point of 
collection, and if applicable patient initials. 
9.1.1.4 Sample shipment and receiving lab 
Samples will either be taken to (COH only) or batch-shipped (non-COH sites) to COH Pathology Core. For all sites, 
please include the Correlative Tissue form (Appendix E) with your shipment. 
Please note that samples should be batch-shipped from non-COH sites on Monday to Wednesday in time for 
receipt Tuesday to Friday. Refer to Appendix F for tissue shipping details. 
 
9.1.2 
Correlative blood 
9.1.2.1 Overview and Time points 
Peripheral blood will be collected prior to study treatment/procedures at the time points indicated in Table 9.1.2.1 
Table 9.1.2.1 Overview of correlative blood studies 
Time points of collection 
Total 
volume 
collected 
Tube type 
Receiving 
laboratory 
Type of 
analysis 
 
C1D1 
 
C2D1 
 
End of Salvage 
 
C1D1 of Consolidation 
 
End of Consolidation* 
 
At Progression/Relapse 
20 ml 
Cell-free DNA BCT® 
(Streck) 
 
APCF 
ctDNA/MRD 
APCF = COH Analytical Pharmacology Core Facility. 
Cell-Free DNA BCT® (glass, 10 mL volume) tubes from Streck. Cat. No, as of April 2020, for a box of 100 tubes is: 
218962. 
* For this time point, correlative blood will be collected at the safety visit (30 days post-). 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 44  
9.1.2.2 Labeling of blood samples 
Label tubes with COH protocol #, subject ID (issued by DCC), institution, date and actual time point of collection 
(e.g. C1D1 for Day 1 of Cycle 1), and if applicable patient initials. 
 
9.1.2.3 Collection and post-collection guidelines 
Refer to Table 9.1.2.3 for collection and post-collection instructions. 
Refer to Appendix G and Appendix H for blood collection form and blood shipping guidelines, respectively. 
 
Table 9.1.2.3 Blood sample collection and post-collection instructions. 
Tube Type 
Collection details 
Site of 
collection 
Post-collection instructions 
Cell-free DNA 
BCT® (Streck)* 
1- Blood samples will be collected 
from an indwelling venous catheter or 
by venipuncture. 
Prevention of backflow: 
(Because cell-free DNA BCT® contain 
chemical additives)  
a. Keep patient’s arm in the downward 
position during the collection procedure. 
b. Hold the tube with the stopper in the 
uppermost position so that the tube 
contents do not touch the stopper or the 
end of the needle during sample 
collection.  
c. Release tourniquet once blood starts to 
flow in the tube, or within 2 minutes of 
application. 
2- Fill tube completely. 
3- Remove tube from adapter and 
immediately mix by gentle inversion 8 
to 10 times. 
4- Do not freeze samples. Store 
samples at 18-25oC until shipment. 
COH 
Only 
 
Promptly deliver the blood samples to the 
APCF, Shapiro room 1042. 
 
Non-COH 
Sites Only 
Ship to APCF laboratory. See Appendix H. 
Include with shipment: 
 Blood sample collection form (Appendix G). 
Copy of latest CBC results (with differential) 
and date of test. 
* Tubes are stable when stored at 2-300C through expiration date.  
  
9.2 Laboratory Studies Performed 
Please refer to Section 2.2. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 45 of 81 
10.0 STUDY CALENDAR 
All assessments may increase in frequency as clinically indicated. 
 
 
Protocol therapy b 
Follow-up (~2 years) 
Protocol Activity 
Screening a 
Salvage PolaR-ICE c 
End of 
Salvage h 
Consolidation Pola d 
C1 
C2 
(C3)  
C1 
C2 
C3 
(C4) 
Safety 
30-days post 
i 
Active 
12 months & 
24 months j 
Survival 
k 
D1e 
D1e 
D15g 
D1e 
D15g 
D1e  
D1e,f 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
Registration 
X 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam l 
&  Vital signs m 
X 
X 
X 
 
X 
 
X 
X 
X  
X 
 
 
ECOG Status (Appx. 
A) 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
 
Con-med review 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
 
AE Assessment 
X 
X 
X 
 
X 
 
X 
X 
X  
X 
 
 
Pregnancy n 
X  
X 
X 
 
X 
 
 
X 
X 
 
 
 
CBC w/diff, plt  
& Serum chemistry p 
X o 
X 
X 
 
X 
 
X 
X 
X  
X 
 
 
PT/INR and aPTT 
X 
 
 
 
 
 
 
 
 
 
 
 
Correlative blood q 
 
X 
X 
 
 
 
X 
X 
 
(X) 
 
 
Correlative tumor 
tissue  
X r 
------------------------------------------------------------------------------------------ X s------------------------------------------------------------------------------- 
Bone marrow 
biopsy/ aspirate  
(X) u 
-------------------------------------------------------------------------------------------X t ------------------------------------------------------------------------------ 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 46 of 81 
 
 
Protocol therapy b 
Follow-up (~2 years) 
Protocol Activity 
Screening a 
Salvage PolaR-ICE c 
End of 
Salvage h 
Consolidation Pola d 
C1 
C2 
(C3)  
C1 
C2 
C3 
(C4) 
Safety 
30-days post 
i 
Active 
12 months & 
24 months j 
Survival 
k 
D1e 
D1e 
D15g 
D1e 
D15g 
D1e  
D1e,f 
PET-CT  
X 
 
 
X 
 
X 
 
 
 
X v 
X v 
 
Polatuzumab vedotin 
for Salvage 
 
D1 of each cycle 
 
 
 
 
 
 
Rituximab 
 
D1 of each cycle 
 
 
 
 
 
 
Etoposide 
 
D1-3 of each cycle 
 
 
 
 
 
 
Carboplatin 
 
D2 of each cycle 
 
 
 
 
 
 
Ifosfamide (+Mesna) 
 
D2 (Inpatient) or D1-3 (Outpatient) of 
each cycle 
 
 
 
 
 
 
Criteria to initiate 
Consolidation 
 
 
 
 
 
 
 
X 
 
 
 
 
Polatuzumab vedotin 
for Consolidation 
 
 
 
 
 
 
 
X 
X 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
 
 
 
X 
a. Screening activities to occur within 28 days prior to start of protocol therapy except for laboratory assessments and bone marrow biopsy. 
b. In the absence of treatment delay, each treatment cycle lasts 21 ± 3 days. 
c. 
All patients will receive 2 cycles of PolaR-ICE. Patients with PR after 2 cycles will receive an additional cycle of PolaR-ICE (3 cycles total). Patients with CR 
or SD after 2 cycles may receive an additional cycle of PolaR-ICE (3 cycles total) at the treating physician’s discretion. 
d. Patients must meet the criteria to receive Consolidation Pola within timelines specified in Section 5.7.1. Patients who received 2 cycles of PolaR-ICE 
during Salvage will receive 4 cycles of Pola Consolidation. Patients who received 3 cycles of PolaR-ICE during Salvage will receive 3 cycles of Pola 
Consolidation. The maximum number of Pola-containing cycles of therapy is 6. 
e. Activities to be performed within 72 hours prior to initiation of the cycle. 
f. 
Evaluations performed within 14 days prior to start of Consolidation Day 1 may serve as Day 1 evaluations. 
g. 
Day 15 assessments have a ± 7 day window.  

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 47 of 81 
h. End of salvage visit to occur within 30 days from last dose. Patients eligible for AHCT will then proceed to AHCT. 
i. 
The Safety 30 days post-last dose assessments to occur 30 (±7) days post-last dose or, if > 30 days elapsed since last dose, within 7 days after decision 
to end treatment. Expedited reporting will occur during this period. Safety follow-up may be extended until resolution/ stabilization of reportable AEs. 
j. 
For participants yet to progress, Active Follow-up will occur at 12 months (± 30 days) and 24 months (± 30 days) from the start of treatment until 
progression or the initiation of a new anti-lymphoma therapy. 
k. 
Participants who end Active Follow-up will enter Survival Follow-up. Survival assessment to occur bi-annually or as requested by the Study PI via medical 
record review, review of social security registry, or telephone call. 
l. 
Standard physical exam includes weight. 
m. Vital signs: heart rate, blood pressure, respiration rate, and temperature. 
n. Women of child bearing potential: Pregnancy serum or urine test. For the screening time point, pregnancy test must be performed within 7 days prior 
to start of protocol therapy. 
o. Screening laboratory assessments to be performed within 14 days prior to start of protocol therapy. 
p. Serum chemistry panel to include: glucose, Blood Urea Nitrogen (BUN), creatinine, uric acid, total protein, albumin, magnesium, bicarbonate, calcium, 
inorganic phosphorous, sodium, potassium, chloride, total bilirubin, alkaline phosphatase, ALT, AST, and LDH. 
q. Refer to Section 9.1.2. 
r. 
Archival tumor tissue to be submitted post-enrollment. Note: If unavailable, exceptions may be granted by the Study PI. Refer to Section 9.1.1. 
s. 
If safe and feasible, submission of left-over tissue from a standard of care tumor biopsy (fresh core or excisional biopsy) for participants who 
progress/relapse during study is encouraged. Refer to Section 9.1.1. 
t. 
Bone marrow biopsies will be performed only as clinically indicated, and to confirm CR. 
u. Bone marrow biopsy will be performed only as clinically indicated.  
v. 
CT in lieu of PET-CT is allowed if patient is in CR and CR was already confirmed by PET-CT. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
CONFIDENTIAL 
Page 48 of 81 
11.0 ENDPOINT DEFINITIONS/MEASUREMENT OF EFFECT 
11.1 Assessment of Response 
Lymphoma response/progression will be evaluated using 2014 Lugano Classification (see Appendix B). 
[38] 
Disease assessment will be performed by PET-CT. For patients in CR, diagnostic quality CT is acceptable at 
the end of consolidation and during active Follow-up. Assessment with PET-CT is required to confirm CR. 
Patients with bone marrow involvement at baseline must have a bone marrow biopsy performed to 
confirm CR (if applicable). After CR, additional bone marrow biopsy is only required if clinically indicated. 
Additional necessary restaging studies including dedicated CT scans or MRI, are permitted at the 
investigator’s discretion. PET-CT and CT results will be read by a radiologist at each study site and 
investigator response assessment will be performed. 
For patients with progression of disease on imaging, it is strongly recommended that a confirmatory 
biopsy be obtained whenever possible.  
11.2 Primary Endpoint(s) 
Unacceptable Toxicity: defined as any of the following events occurring during the first 2 cycles of 
treatment that is at least possibly related to study treatment: 
− 
Any Grade 3 or higher non-hematologic toxicity that does not resolve to Grade 1 or better within 7 
days with the exception of: 
o Grade 3 asymptomatic laboratory abnormalities, including lipase or amylase, that are 
not clinically relevant, not requiring hospitalization or delay of treatment 
o Grade 4 isolated electrolyte abnormalities that are not clinically significant including, but 
not limited to, hypo-or hyperglycemia, hypo-or hypernatremia,  hypo-or hyperkalemia, 
hypo-or hypermagnesemia, or hypo-or hypophosphatemia, that resolve, with or without 
intervention, to Grade 2 in less than 72 hours 
o Grade 3 nausea, vomiting, or fatigue controlled with supportive measures (and does not 
require hospitalization, TPN, or tube feeding) 
o Grade 3 infusion reaction that resolves with appropriate management to Grade 1 or 
better within 24 hours 
o Alopecia of any grade 
− 
Any Grade 3 or 4 thrombocytopenia associated with clinically significant bleeding. 
− 
Any Grade 4 neutropenia (despite the use of growth factor) or grade 4 thrombocytopenia (without 
clinically significant bleeding) that lasts > 21 days. 
− 
Any Grade 4 anemia unexplained by underlying disease. 
− 
Any treatment-related toxicity that delays cycle 2 treatment for >2 weeks. 
− 
Any Grade 5 toxicity. 
Complete response (CR) rate: defined as the proportion of response-evaluable participants (see Section 
12.2) that achieve a CR after 2 cycles of PolaR-ICE therapy. 
11.3 Secondary Endpoint(s) 
Overall response rate (ORR): defined as the proportion of response-evaluable participants (see Section 
12.2) that achieve a best response of either CR or PR at the end of PolaR-ICE therapy. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 49 of 81 
Progression-Free Survival (PFS): defined as the duration of time from start of protocol treatment to time 
of disease relapse/progression or death due to any cause, whichever occurs earlier. For patients who are 
alive and have not had disease relapse/progression at the last follow-up, it is censored at the time of last 
follow-up. If a patient starts non-protocol anti-lymphoma therapy without disease relapse/progression, it 
will be censored at the start of the non-protocol anti-lymphoma therapy.   
Overall Survival (OS): defined as the duration of time from start of protocol treatment to time of death 
due to any cause. For patients who are alive at last follow-up, it will be censored at the time of last follow-
up. 
CR rate among patients who were PR at ASCT: defined as the proportion of patients that achieve CR after 
Pola consolidation among those who were PR at ASCT. 
Stem cell mobilization failure rate:  defined as the portion of patients who failed to collect adequate CD34 
stem cells (within 2 attempts) among those who attempt stem cell collection. 
11.4 Exploratory Endpoint(s) 
Exploratory endpoints include ctDNA measures and other biomarkers. 
12.0 STATISTICAL CONSIDERATIONS 
12.1 Study Design 
This is a multicenter, single-arm Phase 2 study evaluating PolaR-ICE as initial salvage therapy before ASCT 
for relapsed and refractory DLBCL. PolaR-ICE salvage therapy will be given in 21-day cycles. Patients will 
first receive 2 cycles of PolaR-ICE; patients in CR after 2 cycles may proceed to ASCT or may receive a 3rd 
salvage cycle of PolaR-ICE at the treating physician’s discretion. Patients in PR after 2 cycles will receive a 
3rd salvage cycle of PolaR-ICE. Patients in SD after 2 cycles may receive a 3rd salvage cycle of PolaR-ICE at 
the treating physician’s discretion. A patient may proceed to ASCT if patient is CR/PR after 3 cycles, 
otherwise the patient will go off protocol. After ASCT, patients who received 2 salvage cycles of PolaR-ICE 
will receive 4 cycles of single-agent Pola (21-day cycles) as consolidation therapy, while patients who 
received 3 salvage cycles of PolaR-ICE will receive 3 consolidation cycles of single-agent Pola.  
The primary endpoint is complete response (CR) rate after 2 cycles of PolaR-ICE salvage therapy. 
Secondary endpoints include toxicities of PolaR-ICE salvage therapy, toxicities of single-agent Pola 
consolidation therapy, overall response rate to PolaR-ICE, the rate of stem cell mobilization and collection 
failure in patients who attempt stem cell collection, progression free survival, overall survival, and CR rate 
after Pola consolidation among patients who were PR at ASCT.  
The first 5-16 patients will be monitored as part of the Safety Lead-in portion as described below in Section 
12.1.1 to confirm the tolerable dose of PolaR-ICE. Once the tolerable dose level of PolaR-ICE is confirmed, 
the study will go into the Phase 2 portion with a 2-stage design and a total sample size of 40 patients for 
the Phase 2 response evaluation.  
12.1.1 Safety Lead-in 
Prior to formally initiating the Phase 2 response assessment, a patient safety lead-in portion will be 
conducted to ensure there are no unexpected toxicities with PolaR-ICE salvage therapy. The decision to 
open to Phase 2 will primarily be based on the number of safety lead-in patients experiencing 
unacceptable toxicities  during the first 2 cycles of PolaR-ICE salvage, but will also take into consideration 
other data available at the time of decision making, including toxicities observed in cycle 3, the ability to 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 50 of 81 
proceed to transplant after PolaR-ICE and delays due to study treatment-related toxicity between PolaR-
ICE and transplant. The unacceptability toxicities are defined in Section 11.2. Patients evaluable for 
unacceptable toxicities during the Safety Lead-in are defined in Section 12.2.  
During the safety lead-in portion of the study, a design that is slightly modified from the IQ rolling 6 design 
will be used.[7] In this design, up to 8 evaluable patients may be treated at each dose level, and the highest 
dose level with <33% evaluable patients having unacceptable toxicities will be considered tolerable with 
respect to unacceptable toxicities. Given the expected safety profile of PolaR-ICE, we adopt this design 
which may allow up to 6 patients at risk at any time instead of some other designs which allow up to 3 at 
risk. The rules of the proposed design are outlined below. 
1) When there is no patient with unacceptable toxicities, accrual can continue for up to 8 patients 
with up to 6 patients at risk (i.e., under unacceptable toxicity observation) at the same time.  
2) If there is no DLT in 5+ evaluable patients with no others at risk, (i.e., 0/5, 0/6, 0/7, or 0/8), the 
current dose level will be considered tolerable.  
3) After 1 patient with unacceptable toxicity is reported, accrual can continue to up to 6 patients (i.e. 
<6 at risk); to accrue the 7th or the 8th patient, there must be ≤3 patients at-risk.  
4) If there is 1 patient with unacceptable toxicity in 6-8 evaluable patients with no others at risk (i.e., 
1/6, 1/7, or 1/8), the current dose level will be considered tolerable.  
5) If there are 2 patients with unacceptable toxicities when ≤6 patients are treated, the current dose 
level will be considered intolerable (and dose de-escalated if at dose level 1). 
6) If there are 2 patients with unacceptable toxicities when 7 or 8 patients are treated, accrual to 
this dose level will be on hold if there are still any patients at risk. If the rate of unacceptable 
toxicity is ≥33% (i.e., 2 out of ≤6, 3/7, or 3/8 evaluable), the current dose level will be considered 
intolerable (and the dose de-escalated if at dose level 1); if the rate of unacceptable toxicity is 
<33% (i.e., 2/7 or 2/8 evaluable), the dose level will be considered tolerable.  
7) Any time 3+ patients with unacceptable toxicities occur, the current dose level will be considered 
intolerable (and dose de-escalated if at dose level 1). 
12.1.2 Phase 2 design 
The Phase 2 portion of the study adopts a two-stage design. Patients who were enrolled during the safety 
lead-in portion at the final dose level deemed tolerable for Phase 2 will also be included in the Phase 2 
response evaluation if they are evaluable for response.  
At the first stage, 20 patients will be enrolled. If <8 complete responses are seen, the accrual will be 
terminated. If at least 8 patients achieve a complete response, the trial will continue to the second stage. 
At the second stage, 20 additional patients will be entered. At the end of stage 2, if 21 or more patients 
out of the total 40 patients experience a complete response, the combination will be considered worthy 
of further study. If <21 patients experience a complete response then no further investigation of the 
combination is warranted. 
The 2-stage design aims to differentiate between the null hypothesis (disappointing rate) of 40% CR rate 
and an alternative hypothesis (promising rate) of 60% CR rate. The null hypothesis of 40% CR rate is based 
on a large randomized study comparing R-ICE with R-DHAP (rituximab, dexamethasone, cytarabine, 
cisplatin) as salvage regimen followed by ASCT for relapsed/refractory DLBCL.[8] Similar complete 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 51 of 81 
response rates were observed after 3 cycles of R-ICE (37%, n=197) vs. 3 cycles R-DHAP (40%, n=191). 
Therefore, we would consider a 40% CR rate a discouraging rate and 60% a promising CR rate for this 
regimen to merit further study. The design has a 1-sided type I error of 7.3% and a power of 87%. The 
expected sample size under the null hypothesis is 31.7, and the design has a 42% chance of early 
termination after Stage I if the true CR rate is 40%.  
12.2 Evaluable Participants and Participant Replacement 
o Evaluable for toxicity: Patients who receive at least one dose of protocol therapy are evaluable 
for toxicity. 
o Evaluable for unacceptable toxicity during Safety Lead-in: Patients evaluable for unacceptable 
toxicity (defined in Section 11.2) are: 
1) Those who receive the full dose of Pola, the full doses of rituximab and carboplatin,  and 
at least 67% of the doses of etoposide and ifosfamide during the first 2 cycles of Salvage, 
OR  
2) Those who experience any unacceptable toxicity during the first 2 cycles of Salvage 
regardless of actual dose of protocol therapy received.  
    During safety lead-in, patients who are not evaluable for unacceptable toxicities will be replaced. 
o Evaluable for response during Phase 2:  
Evaluable patients are defined as eligible participants who have received at least one cycle of 
PolaR-ICE salvage therapy and have at least one disease evaluation post-baseline.  
Patients will be evaluable and be considered non-CR in the primary response evaluation if they 
discontinued study therapy prior to having a response assessment after 2 cycles of PolaR-ICE 
because of progressive disease or unacceptable toxicity (rather than due to withdrawal of consent 
or investigator decision). If a patient discontinues study treatment prior to the first response 
assessment after 2 cycles of PolaR-ICE due to progressive disease, the treating physician is 
encouraged to obtain imaging to confirm progression.   
During Phase 2 enrollment, participants who are not evaluable for response will be replaced and 
excluded from Phase 2 efficacy analyses, but will be included in the general toxicity analyses if 
they receive any protocol treatment. 
12.3 Sample Size and Accrual Rate  
The minimum study accrual will be 4 patients, when both dose levels are found to be not tolerable during 
the safety lead-in portion. The expected total sample size for the study is 40 evaluable patients, assuming 
that dose level 1 (starting dose level) is safe and passes the first stage response evaluation in Phase 2, and 
safety lead-in patients are also evaluable for response. However if dose level 1 is not tolerable and dose 
level -1 is tolerable, the study will need to accrue up to 48 evaluable patients for the safety lead-in and 
phase 2 evaluations. Accounting for up to 10% inevaluable patients for unacceptable toxicity evaluation 
during Safety lead-in or inevaluable for response during Phase 2, the maximum accrual for the study is 
estimated to be 53 patients. Given that this is a multicenter study including high-volume DLBCL centers, 
we anticipate completing study accrual within 24 months.  
12.4 Monitoring for Stem Cell Mobilization Failure and Non-relapse Mortality after ASCT 
The rate for failure to collect adequate CD34 stem cells (after 2 attempts) for autologous transplantation 
will be monitored in patients who proceed to stem cell collection (regardless of the dose level of PolaR-

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 52 of 81 
ICE they were enrolled on). Routine collection failure rate for RICE would be around 15%. A Bayesian rule 
will be used for this monitoring. The prior distribution of the failure rate is assumed to be Beta (0.15, 0.85) 
with a mean of 15%. If based on the observed collection failure data, the posterior probability of the 
failure rate being greater than 15% is 90% or higher, the stopping rule will be triggered. Operationally, the 
rule will be triggered if at least 3/5, 4/10, 6/20, 8/30, or 10/40 patients fail to mobilize adequate CD34 
cells within 2 attempts.  
The incidence of non-relapse mortality in the first 100 days after ASCT will also be monitored among 
patients who went to ASCT, regardless of the dose level of PolaR-ICE they were enrolled on. A second case 
of such death within 100 days following ASCT will trigger a stopping rule.  
If either monitoring rule is triggered, the study accrual will be halted. A full review of the study data will 
be undertaken by the study team, and the results will be submitted to the DSMC. The study team may 
propose to modify the study if deemed necessary. The DSMC will also perform their independent 
assessment of these events. The study accrual will not be resumed without approval from the DSMC.  
12.5 Toxicity monitoring for post-HCT Pola 
To assess the safety of Pola consolidation in the post-HCT setting, we will monitor the number of patients 
experiencing severe toxicities during post-HCT Pola consolidation, defined as any of the following AEs that 
is at least possibly attributed to Pola or to PolaR-ICE: 
 Grade 3 peripheral neuropathy that does not resolve to grade 2 or better within 7 days 
 Any Grade 4 AE with the exception of: 
− Grade 4 neutropenia (despite the use of growth factor) or grade 4 thrombocytopenia 
that lasts ≤ 21 days 
− Grade 4 laboratory abnormalities that resolve to Grade ≤ 2 within 10 days 
− 
Grade 4 metabolic laboratory abnormalities that are not clinically significant  
 Any Grade 5 AE 
The City of Hope Data Safety Monitoring Committee (DSMC) will review the toxicity data on this study 
every 6 months. The stopping rule for “severe” toxicities will start when there are at least 6 patients on 
the study who received post-HCT Pola (regardless of the dose level of PolaR-ICE they received or whether 
they were enrolled in the safety lead-in or Phase 2 portion of the study). If during such review, the 
proportion of patients having any of the severe toxicities is 33% or higher, the study accrual will be halted. 
A full review of the study data will be undertaken by the study team, and the results will be submitted to 
the DSMC. The study team may propose to modify the study if deemed necessary. The DSMC will also 
perform their independent assessment of these events. The study accrual will not be resumed without 
approval from the DSMC.     
12.6 Statistical Analysis Plan  
Patient demographics, baseline disease characteristics and prior treatment therapy will be summarized 
using descriptive statistics. For continuous variables, descriptive statistics such as number, mean, standard 
deviation, standard error, median (range) etc. will be provided. For categorical variables, patient counts 
and percentages will be provided. 
CR rate after PolaR-ICE salvage therapy will be estimated by the proportion of response-evaluable patients 
achieving CR after 2 cycles of salvage therapy, along with the 95% exact binomial confidence interval. ORR 
after PolaR-ICE salvage therapy will be similarly estimated. PFS and OS will be estimated using the product-
limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence 
interval will be constructed based on log-log transformation. Median PFS/OS will be estimated when 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 53 of 81 
available. Observed toxicities of PolaR-ICE salvage therapy and Pola single-agent consolidation therapy 
will be summarized by type (organ affected or laboratory determination such as absolute neutrophil 
count), severity, and attribution.  
12.7 Analysis of the exploratory objectives 
For the exploratory objectives, descriptive statistics will be used to summarize the correlative study 
measures such as ctDNA measures or other biomarkers. For continuous variables, number, mean, 
standard deviation, standard error, median (range) etc., will be provided. For categorical variables, patient 
counts and percentages will be provided. Changes in these measures before, during, and after treatment 
(when measured) will also be summarized by descriptive statistics and tables/plots.  
Various statistical analyses will be used to explore the association between these correlative measures (at 
different time points and the changes over time, when measured) with clinical outcomes. For the 
exploratory correlation of these endpoints with response, analyses comparing groups of participants 
defined by response may be conducted by various two sample tests such as two-sample t-test or Wilcoxon 
rank sum test for the continuous correlative endpoints, or Chi-square test/Fisher’s exact test for the 
categorical correlative endpoints. For the exploratory correlation of these endpoints with survival 
outcomes, survival analysis techniques such as Log rank test will be considered. Appropriate regression 
models will also be considered which examine the association of these correlative measures with disease 
outcome adjusting for other disease risk factors, such as logistic regression for response and Cox 
proportional hazards models for survival outcomes.  All these analyses are exploratory in nature and are 
intended to generate hypotheses that may be validated in larger studies; no multiple comparison 
adjustments will be made in these exploratory analyses.  
13.0 DATA HANDLING, DATA MANAGEMENT, RECORD KEEPING 
13.1 Source Documents 
Source documents are original documents, data, and records (e.g., medical records, pharmacy dispensing 
records, recorded data from automated instruments, laboratory data) that are relevant to the clinical trial. 
The Investigator or their designee will prepare and maintain adequate and accurate source documents. 
These documents are designed to record all observations and other pertinent data for each patient 
enrolled in this clinical trial. Source documents must be adequate to reconstruct all data transcribed onto 
the case report forms. 
13.2 Data Capture Methods and Management 
Data for this trial will be collected using City of Hope’s electronic capture system (EDC) that is compliant 
with 21 CFR Part 11.  
Study personnel will enter data from source documents corresponding to a subject’s visit into the 
protocol-specific electronic Case Report Form (eCRF).   
13.3 Case Report Forms/Data Submission Schedule 
The Investigator is responsible for all information collected on subjects enrolled in this study. All data 
collected during the course of this study must be reviewed and verified for completeness and accuracy by 
the Investigator. All case report forms must be completed by designated study personnel. The completed 
case report forms must be reviewed, signed and dated by the Investigator or designee in a timely fashion. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 54 of 81 
All data will be collected using electronic data collection, stored as indicated in Section 13.2, and will be 
submitted according to the timelines indicated in Table 13.3. 
Table 13.3 Data Submission Schedule 
Form 
Submission Timeline 
Eligibility Checklist 
Complete prior to registration  
On Study Forms 
Within 14 calendar days of registration 
Baseline Assessment Forms 
Within 14 calendar days of registration 
Treatment Forms 
Within 10 calendar days of treatment administration 
Adverse Event Report Forms 
Safety Lead-in Salvage Cycles 1 & 2: Within 7 calendar days of 
AE assessment/notification 
Safety Lead-in remaining cycles and Phase 2: Within 10 
calendar days of AE assessment/notification  
Response Assessment Forms 
Within 10 calendar days of the response assessment 
Other Assessment Forms (concomitant 
medications) 
Within 10 calendar days of the assessment 
Off Treatment/Off Study Forms 
Within 10 calendar days of end of treatment/study 
Follow up/Survival Forms 
Within 14 calendar days of the follow up activity 
13.4 Regulatory Records 
The Investigator will maintain regulatory records, including updating records in accordance with Good 
Clinical Practice guidelines and FDA regulations. 
 
14.0 REPORTING OF ADVERSE EVENTS, UNANTICIPATED PROBLEMS & OTHER EVENTS OF INTEREST 
The research team is responsible for classifying adverse events (AEs) and unanticipated problems (UPs) as 
defined in the relevant regulations and reporting to all applicable parties, including but not limited to the 
COH IRB, DSMC, Food and Drug Administration (FDA), National Institutes of Health (NIH) and other 
collaborators, e.g., pharmaceutical companies. The research team is responsible for the continued 
monitoring and tracking of all AEs in order to ensure non-reportable events are reviewed and monitored 
and do not rise to a reporting level. 
14.1 Assessment of Adverse Events 
The site Investigator will be responsible for determining the event name, and assessing the severity (i.e., 
grade), expectedness, and attribution of all adverse events as applicable per the City of Hope Clinical 
Research Adverse Event and Unanticipated Problem policy (available from the DCC). Adverse events will 
be characterized using the descriptions and grading scales found in NCI CTCAE v5.0. A copy of the scale 
can be found at: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. 
The following definitions will be used to determine the causality (attribution) of the event to the study 
agent or study procedure. 
• 
Unrelated – The event is clearly NOT related to study treatment, and is clearly related to other 
factors such as the participant’s clinical state, other therapeutic interventions, or concomitant 
medications administered to the participant. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 55 of 81 
• 
Unlikely – The event is unlikely related to the study treatment, and is most likely related to other 
factors such as the participant’s clinical state, other therapeutic interventions, or concomitant 
drugs. 
• 
Possible – The event may be related to study treatment, as it follows a reasonable temporal 
sequence from the time of drug administration, but could have been produced by other factors 
such as the participant’s clinical state, other therapeutic interventions, or concomitant drugs.  
• 
Probable – The event is most likely related to the study treatment, as it follows a reasonable 
temporal sequence from the time of drug administration and a known response pattern to the 
study drug, and is unlikely related to the participant’s clinical state, other therapeutic 
interventions, or concomitant drugs. 
Definite – The event is clearly related to the study treatment, as it follows a reasonable temporal 
sequence from the time of drug administration and a known response pattern to the study drug, 
and is not reasonably explained by other factors such as the participant’s condition, therapeutic 
interventions, or concomitant drugs.  
14.2 Adverse Events of Special Interest (AESI) 
AESIs are a subset of events to monitor of scientific and medical concern specific to the study, for which 
ongoing monitoring and rapid communication by the Investigator to the Sponsor and industry partner 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. 
14.2.1 Potential Drug-induced Liver Injury (DILI) 
A potential DILI includes an elevated ALT or AST in combination with either an elevated bilirubin or clinical 
jaundice, as defined by Hy’s Law: 
 
Treatment-emergent ALT or AST > 3 × ULN in combination with total bilirubin > 2 × ULN 
 
Treatment-emergent ALT or AST > 3 × ULN in combination with clinical jaundice 
14.2.2 Suspected transmission of an infectious agent by the study drug 
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 patient exposed to medicinal product. This term applies only when a contamination of the study drug 
is suspected. 
14.2.3 Tumor lysis syndrome (TLS) 
TLS of any grade (irrespective of causality). 
14.2.4 Secondary Malignancy 
A secondary malignancy is a cancer caused by treatment for a previous malignancy (e.g., treatment with 
investigational agent/intervention, radiation or chemotherapy). A secondary malignancy is not considered 
a metastasis of the initial neoplasm. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 56 of 81 
14.3 Pregnancies 
14.3.1 Female participants: 
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or disease 
state) of a female participant occurring after the participant receives the first dose of protocol therapy up 
to 90 days post-last dose of polatuzumab vedotin are considered immediately reportable events. Protocol 
therapy is to be discontinued immediately. The pregnancy, suspected pregnancy, or positive pregnancy 
test must be reported to the Study PI and the DCC immediately within 24 hours of awareness (Section 
14.6). The female subject may be referred to an obstetrician-gynecologist (preferably one with 
reproductive toxicity experience) or another appropriate healthcare professional for further evaluation. 
The Investigator should make every effort to follow the female participant until completion of the 
pregnancy per institutional policies, and should notify the Study PI.  
Abnormal pregnancy outcomes, neonatal deaths that occur within 28 days of birth, and any congenital 
anomaly/birth defect should be reported as an SAE per expedited reporting guidelines. 
Any infant death after 28 days that the Investigator suspects is related to the in utero exposure to protocol 
therapy should also be reported as an SAE per expedited reporting guidelines. 
Follow guidelines in Section 14.8 for reporting to Genentech. 
14.3.2 Male participants: 
If a female partner of a male participant becomes pregnant, the male participant should notify the 
Investigator, and the pregnant female partner should be advised to call their healthcare provider 
immediately. 
Pregnancy of a male participant’s partner occurring after the participant receives the first dose of protocol 
therapy up to 90 days post-last dose of polatuzumab vedotin are considered immediately reportable 
events. 
The Investigator should make every effort to follow the outcome of the pregnancy per institutional 
policies, and should notify the Study PI. 
Follow guidelines in Section 14.8 for reporting to Genentech. 
14.4 Post-Study Adverse Events 
Any SAE occurring after a subject has completed or discontinued study participation if attributed to prior 
polatuzumab vedotin should be expeditiously reported to Genentech (see Section 14.8). If the investigator 
should become aware of the 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 subject, this should 
be adequately reported as an SAE to Genentech. 
14.5 Routine AE Collection and Reporting Guidelines 
Routine recording of adverse events will occur via data entry into the study eCRF. Adverse events will be 
collected from the signing of informed consent until ending study participation, except those occurring 
between the end of salvage visit and the start of consolidation for subjects proceeding to HCT. Adverse 
events will be monitored by the Protocol Management Team (PMT). AEs reported through expedited 
processes (e.g., reported to the IRB, DSMC, FDA, etc.) must also be reported in routine study data 
submissions. 
AEs recorded in the eCRF include: 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 57 of 81 
o The highest grade of any toxicity for each cycle during protocol treatment and for the period 
of safety follow-up after end of treatment 
o For Cycles 1 and 2 only, all Grade ≥2 AEs (highest grade or not) will also be collected 
o All SAEs 
14.6 Expedited Reporting  
Table 14.6 indicates what events must be reported expeditiously. 
Table 14.6 Criteria for Expedited Reporting 
Time point 
What to report  
From signing of the consent to study completion 
 All UPs 
For the time period beginning at treatment 
through 90 days following cessation of treatment, 
or 30 days following cessation of treatment if the 
subject initiates new anticancer therapy, 
whichever is earlier 
 
 All SAEs regardless of relationship to protocol therapy  
 All UPs and AEs that meet the definition of a UP 
 AESIs* 
 Secondary malignancy 
 Pregnancies and lactation 
From Day 1 of protocol therapy up to 90 days 
post-last polatuzumab vedotin dose 
 Pregnancies and lactation  
Post Safety Follow-Up to removal from study  
 All SAEs that are considered possibly, probably or 
definitely related to protocol therapy.  
* AESIs (except secondary malignancy) do not require an expedited report unless the event results in 
unplanned hospitalization or prolongation of hospitalization. However, they must still be reported through 
the routine mechanism in the eCRFs, and to Genentech within the timelines indicated in Section 14.8. 
NOTE: All events reported expeditiously require follow-up reporting until the event is resolved, stabilized, or 
determined to be irreversible by the investigator.  
The DCC should be consulted prior to ending the follow-up of events that have stabilized. 
14.6.1 Expedited reporting guidelines (COH only) 
14.6.1.1 
To the COH DSMC/IRB 
Serious Adverse Events that require expedited reporting and unanticipated problems will be reported 
according to the approved City of Hope Clinical Research Adverse Event and Unanticipated Problem policy. 
This includes all SAEs and UPs that meet COH DSMC/IRB expedited reporting criteria that occurred at COH 
and non-COH sites. For non-COH sites, the DCC will be responsible for reporting (see Section 14.6.2). 
 
14.6.1.2 
To Participating Investigators 
▪ Report all expedited reportable AEs to participating investigators as an IND Safety Report occurring 
within 30 calendar days of receipt of sponsor (lead site) notification, and indicate whether or not a 
protocol and/or consent form change is required. A cover letter will indicate the protocol title, the 
IND#, whether the FDA was informed (if applicable), and, for non-COH sites, a statement that the 
report should be submitted to their local IRB for review if applicable per local IRB policy. 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 58 of 81 
▪ Forward to participating sites all IND safety reports received from Genentech, indicating whether a 
consent form or protocol change is required within 30 days of notification to Study PI. 
14.6.2 Expedited reporting guidelines (non-COH sites only) 
14.6.2.1 
To the DCC/Study PI 
All events that meet the criteria specified in Table 14.6 will be reported to the DCC and Study PI within 
24 hours of notification that the event met the expedited reporting criteria. 
1. Sites are to report to their local IRB per their site’s specific institutional and IRB guidelines. As soon 
as possible, non-COH sites will provide to the COH DCC copies of the IRB submission and 
corresponding IRB response. 
2. Document/describe the AE/UP on each of the following: 
a. MedWatch 3500A or local IRB submission document* 
MedWatch 3500A is downloadable form at http://www.fda.gov/medwatch/getforms.htm 
*The local IRB submission document may be used if the document template is approved 
by the DCC 
b. Expedited Reporting Coversheet. A modifiable Microsoft Word document is available from 
the DCC. An electronic signature on the document will be accepted. 
3. Scan and email above documents to the Study PI (aherrera@coh.org) and DCC@coh.org with the 
subject title as “[PolaR-ICE as initial salvage for R/R DLBCL] SAE COH IRB #20148”.  
a. If available, sites may include the local IRB submission for this event in the submission.  
4. If an email receipt from DCC personnel is not received within one working day, please email 
DCC@coh.org. 
14.7 Reporting to the FDA 
The study PI (or designee) will be responsible for contacting the Office of IND Development and Regulatory 
Affairs (OIDRA) at COH to ensure prompt reporting of safety reports to the FDA. OIDRA will assist the PI 
with the preparation of the report and submit the report to the FDA in accordance with the approved City 
of Hope Clinical Research Adverse Event and Unanticipated Problem policy. 
Serious Adverse Events meeting the requirements for expedited reporting to the Food and Drug 
Administration (FDA), as defined in 21 CFR 312.32, regardless of the site of occurrence, will be reported 
as an IND safety report using the MedWatch Form FDA 3500A for Mandatory Reporting. 
The criteria that require reporting using the MedWatch 3500A are: 
o Any unexpected fatal or life threatening adverse experience associated with use of the drug must 
be reported to the FDA no later than 7 calendar days after initial receipt of the information [21 
CFR 312.32(c)(2)] 
o Any adverse experience associated with use of the drug that is both serious and unexpected must 
be submitted no later than 15 calendar days after initial receipt of the information [21 CFR 
312.32(c)(1)] 
o Any follow-up information to a study report shall be reported as soon as the relevant information 
becomes available. [21 CFR 312.32(d)(3)] 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 59 of 81 
The final IND report will be distributed to the Study PI and DCC. If it is determined that the IND safety 
report requires a change to the protocol or the consent form, the DCC will include instructions to 
participating sites for local IRB reporting. 
In addition, on behalf of the study PI, OIDRA will submit annually within 60 days of the anniversary of the 
date the IND went into effect, an annual report to the FDA which is to include a narrative summary and 
analysis of the information of all FDA reports within the reporting interval, a summary report of adverse 
drug experiences, and history of actions taken since the last report because of adverse drug experiences. 
14.8 Reporting to Industry Partner 
The Study PI (or designee) will: 
o Report to Genentech per the guidelines provided in Table 14.8.  
Email: usds_aereporting-d@gene.com; Fax: 650-238-6067 
Table 14.8 Timeframes for Reporting to Genentech 
Type of Report 
Reporting Timeframes to Genentech 
Pregnancy 
Within 30 calendar days of being aware of the event using the 
Genentech Pregnancy Reporting Form. 
 
All expedited SAE reports 
Post-study SAE reports 
 
Within 15 calendar days of being aware of the event via a 
MedWatch 3500A form. 
 
AESIs 
Within 15 calendar days of the awareness event. 
Aggregate safety reports  
Forward to Genentech every 6 months (e.g. at time of COH PMT 
report). 
Special Situation Reports* 
Within 30 calendar days of the awareness event. 
Product complaints** 
Within 15 calendar days of the awareness event. 
Product complaints without an AE should be reported by calling: 
PC Hotline Number : (800)-334-0290 (M-F : 5am to 5pm PST) 
o Assist Genentech in investigating any SAE and will provide any follow-up information reasonably 
requested by Genentech. 
o *Special Situations Reports: In addition to all SAEs, pregnancy reports and AESIs, the following 
Special Situations Reports should be collected even in the absence of an Adverse Event and 
transmitted to Genentech: 
•  Data related to polatuzumab vedotin 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 patient, in order to be able to identify potential safety signals specific to a 
particular population 
o **Product Complaints: 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. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 60 of 81 
o Fax to Genentech/Roche Safety copies of all written IND safety reports submitted to the FDA: 
Fax: (650) 225-4682 or (650) 225-4630 
o Email to Genentech Drug Safety CTV all IND annual reports and the final study report submitted 
to the FDA: 
Email: ctvist_drugsafety@gene.com 
 
14.9 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 the investigator emailing Genentech a Quarterly line-
listing documenting single case reports sent by the investigator to Genentech in the preceding time 
period.  
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 the investigator 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 
14.10 Queries 
Queries related to the Study will be answered by the investigator. 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 polatuzumab vedotin. The investigator agrees that it shall not answer such queries from regulatory 
authorities and other sources relating to polatuzumab vedotin independently but shall redirect such 
queries to Genentech. 
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. 
14.11 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 polatuzumab vedotin 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 polatuzumab vedotin. The investigator agrees that it shall not answer such queries from media 
and other sources relating to polatuzumab vedotin but shall redirect such queries to Genentech. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 61 of 81 
14.12 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. 
 
15.0 ADHERENCE TO THE PROTOCOL & REPORTING OF PROTOCOL DEVIATIONS 
Deviations from the protocol should be avoided, except when necessary to eliminate immediate hazard(s) 
for the protection, safety, and well-being of a research participant. As a result of deviations, corrective 
actions are to be developed by the study staff and implemented promptly. All protocol deviations and 
planned protocol deviations will be reported in accordance with the City of Hope Clinical Research 
Protocol Deviation policy. 
Non-COH Sites: 
Deviations meeting the criteria specified in the City of Hope Clinical Research Protocol Deviation policy 
(available from the DCC) will be reported to the DCC and Study PI within 24 hours of notification that the 
event occurred.  
Procedure for reporting deviations to the COH DCC: 
1. Document the deviation on the Deviation Reporting Coversheet or submit your site-specific 
protocol deviation log if the log format has been approved for use by the DCC. This modifiable 
Microsoft Word document is available from the DCC. An electronic signature on this 
document will be accepted.  
2. Scan and email the Deviation Reporting Coversheet or protocol deviation log to the Study PI 
(aherrera@coh.org) and DCC@coh.org within 24 hours of notification of the deviation with 
the email subject title of “[PolaR-ICE as initial salvage for R/R DLBCL] Deviation COH IRB 
#20148”. If an email receipt from the DCC is not received within one working day, please email 
DCC@coh.org.  
Sites are to report to their local IRB and DSMC per their site’s specific institutional and IRB guidelines. As 
soon as possible, non-COH sites will provide to the COH DCC copies of the IRB and/or DSMC submission 
and corresponding response(s). 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 62 of 81 
16.0 STUDY OVERSIGHT, QUALITY ASSURANCE, & DATA AND SAFETY MONITORING 
16.1 All Investigator Responsibilities 
An investigator is responsible for ensuring that an investigation is conducted according to the signed 
investigator statement, the investigational plan, and applicable regulations; for protecting the rights, 
safety, and welfare of subjects under the investigator's care; and for the control of drugs under 
investigation.  
16.2 Study Principal Investigator Responsibilities 
The Study Principal Investigator is responsible for the conduct of the clinical trial, including overseeing 
that sponsor responsibilities are executed in accordance with federal regulations.  
16.3 Protocol Management Team (PMT) 
The Protocol Management Team (PMT), minimally consisting of the study PI, collaborating investigators, 
site investigators, research nurse, clinical research associate/coordinator, and the study biostatistician, is 
responsible for ongoing monitoring of the data and safety of this study, including implementation of the 
stopping rules for safety/toxicity. 
The PMT is recommended to meet (in person or via teleconference) to review study status. The meeting 
is a forum to discuss study related issues including accrual, SAE/AE/UPs experienced, study response, 
deviations/violations, and study management issues. The appropriateness of further subject enrollment 
and the specific intervention for subsequent subject enrollment are addressed. 
16.4 Quality Assurance 
Clinical site monitoring is conducted to ensure that the rights of human subjects are protected, that the 
study is implemented in accordance with the protocol and regulatory requirements, and that the quality 
and integrity of study data and data collection methods are maintained.  Monitoring for this study will be 
performed by the City of Hope Office of Clinical Trials Monitoring (OCTM), within City of Hope’s Office for 
Safety and Data Quality.  
Details of clinical site monitoring are documented in the OCTM SOP and the Risk Based Monitoring (RBM) 
plan. These documents specify the frequency of monitoring, monitoring procedures, the amount of 
subject data to be reviewed, and the distribution of monitoring reports to the study team and the COH 
DSMC.  
16.5 Risk Determination  
This is a high risk study, as defined in the City of Hope Institutional DSMP.  This determination was made 
because this study involves a COH IND. 
16.6 City of Hope Data and Safety Monitoring Committee 
The COH Data and Safety Monitoring Committee (DSMC) will review and monitor study progress, 
compliance, toxicity, safety, and accrual data from this trial via the PMT Progress Report (submitted by 
the Study Principal Investigator according to the frequency outlined in the City of Hope Institutional 
DSMP). The DSMC is composed of clinical specialists who have no direct relationship with the study. 
Information that raises any questions about participant safety will be addressed with the Protocol 
Management Team.  

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 63 of 81 
17.0 ETHICAL AND REGULATORY CONSIDERATIONS 
17.1 Ethical Standard 
This study will be conducted in conformance with the principles set forth in The Belmont Report: Ethical 
Principles and Guidelines for the Protection of Human Subjects of Research (US National Commission for 
the Protection of Human Subjects of Biomedical and Behavioral Research, April 18, 1979) and the 
Declaration of Helsinki. 
17.2 Regulatory Compliance 
This study is to be conducted in compliance with the IRB approved protocol and according to the following 
considerations: 
o US Code of Federal Regulations (CFR) governing clinical study conduct 
 
Title 21 Part 11 – Electronic Records; Electronic Signatures  
 
Title 21 Part 50 – Protection of Human Subjects  
 
Title 21 Part 54 – Financial Disclosure by Clinical Investigators  
 
Title 21 Part 56 – Institutional Review Boards  
 
Title 21 Part 58 – Good Laboratory Practice for Nonclinical Laboratory Studies  
 
Title 21 Part 312 – Investigational New Drug Application 
 
Title 45 Part 46 – Protection of Human Subjects  
o US Federal legislation, including but not limited to 
 
Health Insurance Portability and Accountability Act of 1996  
 
Section 801 of the Food and Drug Administration Amendments Act   
o Applicable state and local laws. For research occurring in California, this includes but is not 
limited to State of California Health and Safety Code, Title 17 
o Applicable institutional research policies and procedures 
17.3 Institutional Review Board 
An Institutional Review Board (IRB) that complies with the federal regulations at 45 CFR 46 and 21 CFR 50, 
56 and State of California Health and Safety code, Title 17, must review and approve this protocol, 
informed consent form and any additional documents that the IRB may need to fulfill its responsibilities 
(Investigator’s Brochure, information concerning patient recruitment, payment or compensation 
procedures, or other pertinent information) prior to initiation of the study. Revisions to approved 
documents will require review and approval by the IRB before the changes are implemented in the study. 
All institutional, NCI, Federal, and State of California regulations must be fulfilled. 
Each participating non-COH institution must provide for the review and approval of this protocol and the 
associated informed consent documents by an appropriate IRB holding a current US Federal wide 
Assurance issued by and registered with the Office for Human Research Protections (OHRP). The protocol 
and consent will be reviewed and approved by the COH IRB before submission to a participating site IRB. 
The IRB’s written unconditional approval of the study protocol and the informed consent document must 
be in the possession of the investigator, and, for external sites, the possession of the DCC, before the 
study is initiated. 
The IRB will be informed of serious unexpected, unanticipated adverse experiences, and unanticipated 
problems occurring during the study, and any additional adverse experiences in accordance with the 
standard operating procedures and policies of the IRB; new information that may affect adversely the 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 64 of 81 
safety of the patients of the conduct of the study; an annual update and/or request for re-approval; and 
when the study has been completed. 
All participating sites must follow the lead institution’s IRB-approved protocol. 
17.4 Informed Consent 
Each participating non-COH institution will be provided with a model informed consent form. Each 
institution may revise or add information to comply with local and/or institutional requirements, but may 
not remove procedural or risk content from the model consent form. Furthermore, prior to submission to 
the site’s IRB (initial submission and amendments), the consent and accompanying HIPAA form, if 
separate to the consent, must be reviewed and approved by the DCC. 
The Principal Investigator or IRB approved named designee will explain the nature, duration, purpose of 
the study, potential risks, alternatives and potential benefits, and all other information contained in the 
informed consent document. In addition, they will review the experimental subject’s bill of rights if 
applicable, and the HIPAA research authorization form. Prospective participants will be informed that they 
may withdraw from the study at any time and for any reason without prejudice, including as applicable, 
their current or future care or employment at City of Hope or participating institution or any relationship 
they have with City of Hope or participating institution. Prospective participants will be afforded sufficient 
time to consider whether or not to participate in the research. 
After the study has been fully explained, written informed consent will be obtained from either the 
prospective participant or his/her guardian or legal representative before study participation. The method 
of obtaining and documenting the informed consent and the contents of the consent must comply with 
the ICH-GCP and all applicable regulatory requirements. 
A copy of the signed informed consent will be given to the participant or his/her legally authorized 
representative. The original signed consent must be maintained by the site investigator and available for 
inspection by sponsor designated representatives, or regulatory authority at any time. 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the study 
and continues throughout study participation. 
17.5 Participant Withdrawal 
Participants may withdraw from the study at any time and for any reason without prejudice. The 
withdrawal must be documented per institutional policies. The COH DCC should be promptly notified of 
the change in participant status.   
Participant withdrawal may consist of any of the following with regard to study procedures and data 
collection: 
o Withdrawal from study treatment, but agreement to continue with active study procedures 
and chart review and survival follow-up. 
o Withdrawal from study treatment and all active procedures, but agreement for chart review 
and survival follow-up. 
o Withdrawal from study treatment, all active procedures, and any future data collection. 
Participants who agreed to the collection of research blood samples may withdraw consent to use their 
specimens, if they are not yet processed as detailed in the consent form. Once the PI and site PI is notified 
of this withdrawal of informed consent, the research specimens will not be used in any research. At that 
time, any of the existing specimens will be destroyed. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 65 of 81 
17.6 Special and Vulnerable Populations 
17.6.1 Women and Minorities 
The study is open to anyone regardless of gender, race or ethnicity. Efforts will be made to extend the 
accrual to a representative population. If differences in outcome that correlate to gender, racial, or ethnic 
identity are noted, accrual may be expanded or additional studies may be performed to investigate those 
differences more fully.   
Pregnant women are excluded because the study drugs have been determined to be embryotoxic and 
teratogenic in animal testing. 
17.6.2 Pediatric Population 
Pediatric participants (< 18 years of age) are excluded from this study because safety and effectiveness of 
protocol therapy has not yet been defined for the study population. Additional studies may be performed 
in the pediatric population once safety and effectiveness of protocol therapy is defined in the adult study 
population. 
17.6.3 HIV Positive Individuals 
Participants with HIV are included based on specifications outlined in inclusion criteria. 
17.6.4 Vulnerable Populations 
Per 45 CFR §46.111 (a)(3) and 45 CFR §46, Subparts B-D identifies children, prisoners, pregnant women, 
mentally incapacitated persons, and economically or educationally disadvantaged persons as vulnerable 
populations.  
Adults lacking capacity to consent are not excluded from participation. This study does not pose additional 
risks for adults lacking capacity than for the general population. In such instances, informed consent will 
be sought and documented from the prospective participant’s legally authorized representative in 
agreement with institutional policies and local IRB approval. 
Economically/educationally disadvantaged persons are not actively targeted for participation, nor are 
they excluded from participation. This study does not pose additional risks for economically/educationally 
disadvantaged persons than for the general population. 
17.7 Participant Confidentiality 
Participant confidentiality is strictly held in trust by the investigators, study staff, and the sponsor(s) and 
their agents. This confidentiality is extended to cover testing of biological samples in addition to any study 
information relating to participants.  
This research will be conducted in compliance with federal and state requirements relating to protected 
health information (PHI), including the requirements of the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA). HIPAA regulations require a signed subject authorization informing 
the subject of the nature of the PHI to be collected, who will have access to that information and why, 
who will use or disclose that information, and the rights of a research participant to revoke their 
authorization for use of their PHI. In the event that a subject revokes authorization to collect or use PHI, 
the investigator, by regulation, retains the ability to use all information collected prior to the revocation 
of subject authorization. For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the end 
of their scheduled study period. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 66 of 81 
Release of research results should preserve the privacy of medical information and must be carried out in 
accordance with Department of Health and Human Services Standards for Privacy of Individually 
Identifiable Health Information, 45 CFR 164.508. When results of this study are reported in medical 
journals or at meetings, identification of those taking part will not be disclosed and no identifiers will be 
used.  
Medical records of subjects will be securely maintained in the strictest confidence, according to current 
legal requirements. Data will be entered, analyzed and stored in encrypted, password protected, secure 
computers that meet all HIPAA requirements. All data capture records, drug accountability records, study 
reports and communications will identify the patient by initials and the assigned patient number.  
Source documents provided to the DCC for the purpose of auditing or monitoring will be de-identified and 
labeled with the study number, subject ID, and if applicable patient initials. 
The Investigator/Institution will permit direct access to source data and documents by sponsor 
representatives, the FDA, and other applicable regulatory authorities. The access may consist of trial-
related monitoring, including remote monitoring, audits, IRB/IEC reviews, and FDA/regulatory authority 
inspections. The patient’s confidentiality will be maintained and will not be made publicly available to the 
extent permitted by the applicable laws and regulations. 
Participant specimens will be de-identified (coded) prior to submission to research laboratories. The 
specimens will be labeled with the study number, subject (accession) ID, date and time point of collection. 
The key to the code will be maintained in the COH clinical trials management system which is a secure 
environment.  
17.8 Use of Unused (Leftover) Specimens Collected for this Trial  
Unused samples in existence at study completion (i.e. completion of all research activities under this 
study) will either be: (a) placed in a COH IRB approved biorepository with some clinical information and 
potentially PHI attached or (b) discarded. 
With regard to which option will apply, each site IRB may choose to either: (a) leave the determination to 
the participant via a question in the informed consent document, which would be communicated to the 
study registrar (DCC) at the time of participant registration, OR b) may choose to make a single 
determination on behalf of their respective participants, and communicate that determination to their 
respective participants via the informed consent. 
17.9 Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial 
gain greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by a 
properly constituted Conflict of Interest Committee with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study Sponsor (City of Hope) prior to participation in 
this study. All City of Hope investigators will follow the City of Hope conflict of interest policy. 
17.10 Financial Obligations, Compensation, and Reimbursement of Participants 
Polatuzumab vedotin will be provided free of charge to participants.  
Neither the research participant nor the insurance carrier will be responsible for the research procedures 
related to this study. 
Standard of care drugs or procedures provided during the course of study participation will be the 
responsibility of the research participant and/or the insurance carrier. The participant will be responsible 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 67 of 81 
for all copayments, deductibles, and other costs of treatment and diagnostic procedures as set forth by 
the insurance carrier. The participant and/or the insurance carrier will be billed for the costs of treatment 
and diagnostic procedures in the same way as if the participant were not in a research study.   
In the event of physical injury to a participant resulting from research procedures, appropriate medical 
treatment will be available at City of Hope or at the non-COH site to the injured participant. There are no 
plans for City of Hope to provide financial compensation in the event of physical injury to a participant.  
The research participant will not receive reimbursement or payment for taking part in this study. 
17.11 Publication/ Data Sharing 
Neither the complete nor any part of the results of the study carried out under this protocol, nor any of 
the information provided by City of Hope for the purposes of performing the study, will be published or 
passed on to any third party without the written approval of the Study PI. Any investigator involved with 
this study is obligated to provide City of Hope with complete test results and all data derived from the 
study. 
The preparation and submittal for publication of manuscripts containing the study results shall be in 
accordance with a process determined by mutual written agreement between City of Hope and 
Genentech, and participating non-COH institutions. City of Hope will forward a copy of the publication to 
Genentech/Roche upon completion of the study. The publication or presentation of any study results shall 
comply with all applicable privacy laws, including, but not limited to, the Health Insurance Portability and 
Accountability Act of 1996.  
In accordance with the U.S. Public Law 110-85 (Food and Drug Administration Amendments Act of 2007 
or FDAAA), Title VIII, Section 801, this trial will be registered onto ClinicalTrials.gov. Results will be 
reported on ClinicalTrials.gov generally within 12 months after the completion date unless criteria to delay 
submission are met per the final rule. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 68 of 81 
18.0 REFERENCES 
1. 
Dickinson, M., et al., Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative 
pre-transplant FDG-PET scan following salvage chemotherapy. Br J Haematol, 2010. 150(1): p. 39-45. 
2. 
Johnston, P.B., G.A. Wiseman, and I.N. Micallef, Positron emission tomography using F-18 
fluorodeoxyglucose pre- and post-autologous stem cell transplant in non-Hodgkin's lymphoma. Bone 
Marrow Transplant, 2008. 41(11): p. 919-25. 
3. 
Terasawa, T., I.J. Dahabreh, and T. Nihashi, Fluorine-18-fluorodeoxyglucose positron emission tomography 
in response assessment before high-dose chemotherapy for lymphoma: a systematic review and meta-
analysis. Oncologist, 2010. 15(7): p. 750-9. 
4. 
Sehn LH, Herrera AF, Matasar MJ, 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. Poster presented at: 59th 
Annual Meeting & Exposition for the American Society of Hematology; December 10, 2017; Atlanta, GA. 
5. 
Moskowitz, C.H., et al., Brentuximab vedotin as consolidation therapy after autologous stem-cell 
transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a 
randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2015. 
6. 
Sehn LH, Herrera AF, Matasar MJ, 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. Poster presented at: 59th 
Annual Meeting & Exposition for the American Society of Hematology; December 10, 2017; Atlanta, GA. 
7. 
Frankel, P.H., et al., Model of a Queuing Approach for Patient Accrual in Phase 1 Oncology Studies. JAMA 
Network Open, 2020. 3(5): p. e204787-e204787. 
8. 
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. 
9. 
Swerdlow, S.H., et al., Chapter 10: Mature B-cell Neoplasms. WHO classification of tumours of 
haematopoietic and lymphoid tissues, ed. F. Lyon, International Agency for Research on Cancer. 2008. 
10. 
Ghielmini, M., et al., ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse 
large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann Oncol, 
2013. 24(3): p. 561-76. 
11. 
Network, N.C.C., NCCN Guidelines Version I.2015: Non-Hodgkin's Lymphomas. http://www.nccn.org/ 
Accessed: 1/9/2015. 2015. 
12. 
Morschhauser, F., et al., Updated Results of a Phase II Randomized Study (ROMULUS) of Polatuzumab 
Vedotin or Pinatuzumab Vedotin Plus Rituximab in Patients with Relapsed/Refractory Non-Hodgkin 
Lymphoma. Blood, 2014. 124(21): p. 4457-4457. 
13. 
Sehn LH, Herrera AF, Matasar MJ, 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. Poster presented at: 59th 
Annual Meeting & Exposition for the American Society of Hematology; December 10, 2017; Atlanta, GA. 
14. 
Tilly, H., et al., POLA-R-CHP: POLATUZUMAB VEDOTIN COMBINED WITH RITUXIMAB, CYCLOPHOSPHAMIDE, 
DOXORUBICIN, PREDNISONE FOR PATIENTS WITH PREVIOUSLY UNTREATED DIFFUSE LARGE B-CELL 
LYMPHOMA. Hematological Oncology, 2017. 35: p. 90-91. 
15. 
Moskowitz, C.H., et al., Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and 
peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's 
lymphoma. J Clin Oncol, 1999. 17(12): p. 3776-85. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 69 of 81 
16. 
Sehn LH, Herrera AF, Matasar MJ, 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. Poster presented at: 59th 
Annual Meeting & Exposition for the American Society of Hematology; December 10, 2017; Atlanta, GA. 
17. 
Sehn LH, Herrera AF, Matasar MJ, 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. Poster presented at: 59th 
Annual Meeting & Exposition for the American Society of Hematology; December 10, 2017; Atlanta, GA. 
18. 
Armand, P., et al., Detection of circulating tumour DNA in patients with aggressive B-cell non-Hodgkin 
lymphoma. Br J Haematol, 2013. 163(1): p. 123-6. 
19. 
Oki, Y., et al., Detection of classical Hodgkin lymphoma specific sequence in peripheral blood using a next-
generation sequencing approach. Br J Haematol, 2015. 169(5): p. 689-93. 
20. 
Roschewski, M., et al., Circulating tumour DNA and CT monitoring in patients with untreated diffuse large 
B-cell lymphoma: a correlative biomarker study. Lancet Oncol, 2015. 16(5): p. 541-9. 
21. 
Kurtz, D.M., et al., Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-
throughput sequencing. Blood, 2015. 125(24): p. 3679-87. 
22. 
Scherer F, K.D., Newman AM, et al. Noninvasive Genotyping And Assessment of Treatment Response in 
Diffuse Large B-Cell Lymphoma. in ASH 2015, abstract #126. 
23. 
Kurtz DM, S.F., Newman AM, et al. Dynamic Noninvasive Genome Monitoring for Outcome Prediction in 
Diffuse Large B-Cell Lymphoma. in ASH 2015, abstract #130. 
24. 
Scherer, F., et al., Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by 
circulating tumor DNA. Sci Transl Med, 2016. 8(364): p. 364ra155. 
25. 
Rossi, D., et al., Diffuse large B-cell lymphoma genotyping on the liquid biopsy. Blood, 2017. 
26. 
Bohers, E., et al., Somatic mutations of cell-free circulating DNA detected by next-generation sequencing 
reflect the genetic changes in both germinal center B-cell-like and activated B-cell-like diffuse large B-cell 
lymphomas at the time of diagnosis. Haematologica, 2015. 100(7): p. e280-4. 
27. 
Assouline, S.E., et al., Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-
cell lymphoma. Blood, 2016. 128(2): p. 185-94. 
28. 
Kurtz, D.M., et al., Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-
Cell Lymphoma. J Clin Oncol, 2018. 36(28): p. 2845-2853. 
29. 
Alizadeh, A.A., et al., Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. 
Nature, 2000. 403(6769): p. 503-11. 
30. 
Rosenwald, A., et al., The use of molecular profiling to predict survival after chemotherapy for diffuse large-
B-cell lymphoma. N Engl J Med, 2002. 346(25): p. 1937-47. 
31. 
Ennishi, D., et al., Double-Hit Gene Expression Signature Defines a Distinct Subgroup of Germinal Center B-
Cell-Like Diffuse Large B-Cell Lymphoma. J Clin Oncol, 2019. 37(3): p. 190-201. 
32. 
Chapuy, B., et al., Molecular subtypes of diffuse large B cell lymphoma are associated with distinct 
pathogenic mechanisms and outcomes. Nat Med, 2018. 24(5): p. 679-690. 
33. 
Reddy, A., et al., Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell, 2017. 171(2): p. 481-
494 e15. 
34. 
Schmitz, R., et al., Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Engl J Med, 2018. 
378(15): p. 1396-1407. 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 70 of 81 
35. 
Carey, C.D., et al., Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-
Sternberg cells in Hodgkin lymphoma. Blood, 2017. 130(22): p. 2420-2430. 
36. 
Jung, S.H., et al., Admissible two-stage designs for phase II cancer clinical trials. Stat Med, 2004. 23(4): p. 
561-9. 
37. 
Skolnik, J.M., et al., Shortening the timeline of pediatric phase I trials: the rolling six design. J Clin Oncol, 
2008. 26(2): p. 190-5. 
38. 
Cheson, B.D., et al., Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin 
and Non-Hodgkin Lymphoma: The Lugano Classification. Journal of Clinical Oncology, 2014. 32(27): p. 3059-
3067. 
39. 
Oken, M.M., et al., Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin 
Oncol, 1982. 5(6): p. 649-55. 
40. 
Dolgin, M., et al., Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9 edn 
(Boston, Little, Brown and Company). 1994. 
 
 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 71 of 81 
APPENDIX A: PERFORMANCE STATUS 
ECOG Performance Scale [39] 
Grade 
Descriptions 
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. Ambulatory and capable of all self-
care, but unable to carry out any work activities. Up and 
about 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. 
 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 72 of 81 
APPENDIX B: LYMPHOMA RESPONSE CRITERIA [38] 
Response 
Site 
CT-Based Response 
PET-CT Based Response 
Complete 
Response 
 
Complete radiologic response 
(all of the following) 
Complete metabolic response (even 
with a persistent mass) 
Lymph nodes and 
extralymphatic 
sites 
Target nodes/nodal masses 
must regress to ≤1.5 cm in 
longest diameter (LDi).  
No extralymphatic sites of 
disease. 
Score ≤ 3* with or without a residual 
mass on 5-point scale†. 
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 inferred if uptake at sites 
of initial involvement is no 
greater than surrounding normal 
tissue even if the tissue has high 
physiologic uptake. 
Nonmeasured 
lesion 
Absent 
Not applicable 
Organ enlargement 
Regress to normal 
Not applicable 
New lesions 
None 
None 
Bone marrow 
Normal by morphology; if 
indeterminate, IHC negative 
No evidence of FDG-avid disease in 
marrow 
 
Partial 
Response 
 
 
 
 
 
 
 
 
 
Partial remission (all of the 
following) 
Partial metabolic response 
Lymph nodes and 
extralymphatic 
sites 
≥ 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 
Score 4 or 5† with reduced uptake 
compared with baseline and 
residual mass(es) of any size 
At interim, these findings suggest 
responding disease 
At end of treatment, these findings 
indicate residual disease 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 73 of 81 
Response 
Site 
CT-Based Response 
PET-CT Based Response 
Nonmeasured 
lesion 
Absent/normal, regressed, but 
no increase 
Not applicable 
Organ enlargement 
Spleen must have regressed by 
> 50% in length beyond 
normal 
Not applicable 
New lesions 
None 
None 
Bone marrow 
Not applicable 
Residual uptake higher than uptake 
in normal marrow but reduced 
compared with baseline (diffuse 
uptake compatible with 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 with MRI or 
biopsy or an interval scan 
No response 
or stable 
disease 
 
Stable disease 
No metabolic response 
Target nodes/nodal 
masses, 
extranodal 
lesions 
< 50% decrease from baseline 
in SPD of up to 6 dominant, 
measurable nodes and 
extranodal sites; no criteria 
for progressive disease are 
met 
Score 4 or 5† with no significant 
change in FDG uptake from 
baseline at interim or end of 
treatment 
Nonmeasured 
lesion 
No increase consistent with 
progression 
Not applicable 
Organ enlargement 
No increase consistent with 
progression 
Not applicable 
New lesions 
None 
None 
Bone marrow 
Not applicable 
No change from baseline 
Progressive 
disease 
 
Progressive disease requires at 
least 1 of the following 
Progressive metabolic disease 
Individual target 
nodes/nodal 
masses 
PPD progression: 
Score 4 or 5† with an increase in 
intensity of uptake from baseline 
and/or 
Extranodal lesions 
An individual node/lesion must 
be abnormal with: 
Longest diameter (LDi) > 1.5 cm 
and 
Increase by ≥ 50% from PPD 
nadir and 
An increase in LDi or shortest 
diameter (SDi) from nadir 
New FDG-avid foci consistent with 
lymphoma at interim OR 
End-of-treatment assessment 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 74 of 81 
Response 
Site 
CT-Based Response 
PET-CT Based Response 
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 
Nonmeasured 
lesion 
New or clear progression of 
preexisting nonmeasured 
lesions 
None 
New lesions 
Regrowth of previously 
resolved lesions 
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 FDG-avid foci consistent with 
lymphoma rather than another 
etiology (eg, infection, 
inflammation).  
If uncertain regarding etiology of 
new lesions, biopsy or interval 
scan may be considered. 
Bone marrow 
New or recurrent involvement 
New or recurrent FDG-avid foci 
Measured dominant lesions:  
Up to six 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 in solid organs (e.g., liver, spleen, kidneys, lungs), GI involvement, cutaneous lesions, 
or those noted on palpation.  
Nonmeasured lesions:  
Any disease not selected as measured, 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 (eg, with marrow activation as a result of 
chemotherapy or myeloid growth factors). 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 75 of 81 
*A score of 3 in many patients 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). 
†PET 5-point scale:  
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. 
Abbreviations:   
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. 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 76 of 81 
APPENDIX C: NYHA CARDIAC GRADING CRITERIA 
 
Modified from Dolgin et al., 1994 [40] 
 
New York Heart Association Classification of Heart Failure 
Class I 
No symptoms. Ordinary physical activity such as walking and climbing stairs does not cause fatigue 
or dyspnea. 
Class II 
Symptoms with ordinary physical activity. Walking or climbing stairs rapidly, walking uphill, walking 
or stair climbing after meals, in cold weather, in wind or when under emotional stress causes undue 
fatigue or dyspnea. 
Class III 
Symptoms with less than ordinary physical activity. Walking one to two blocks on the level and 
climbing more than one flight of stairs in normal conditions causes undue fatigue or dyspnea. 
Class IV 
Symptoms at rest. Inability to carry on any physical activity without fatigue or dyspnea. 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 77 of 81 
APPENDIX D: REGISTRATION COVERSHEET  
COH IRB# 20148: A Phase 2 Study of Polatuzumab Vedotin with Rituximab, Ifosfamide, Carboplatin, and Etoposide 
(PolaR-ICE) as Initial Salvage Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma 
Data Coordinating Center:   
City of Hope 
1500 Duarte Road 
Duarte, CA 91010  
Tel:  (626)-218-7904 
Email:  DCC@coh.org (use #secure# in subject line) 
Site Principal Investigator  
Name: 
 
CRA/Study Coordinator:     
Contact Number:   
Patient’s Initials: (F M L): 
Institution: 
PI/ Sub-Investigator: 
Patient’s DOB: 
IRB approval valid until (date): 
Sex: 
______Male 
______Female 
Date Informed Consent Signed: 
Projected start date of treatment: 
Race 
Ethnicity 
Method of 
Payment:_______________________ 
 
Black 
 Hispanic 
Codes: 
 
Caucasian 
 Non-Hispanic 
01 Private 
06 Military or Veterans 
Adm. sponsored 
 
Asian 
 Other_________________ 
02 Medicare 
07 Self-pay (no 
insurance) 
 
American Indian 
 
03 Medicare & 
private ins. 
08 No means of 
payment  (no insurance) 
 
Native Hawaiian/Pacific 
Islander 
04 Medicaid 
09 Unknown 
 
Other_______________
____________________ 
05 Medicaid & Medicare 
Reason for Screen Failure:  
 
Reason for Failing to Initiate Protocol Therapy: 
 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 78 of 81 
APPENDIX E: CORRELATIVE TISSUE FORM (FOR ALL SITES) 
 
A copy of this form should accompany the sample shipments to COH Pathology Core. 
Non-COH sites: refer to Appendix F for shipping instructions to COH Pathology Core. 
 
COH IRB number: 20148 
Shipping date (MM-DD-YYYY):   ________/________/________ 
Subject ID (issued by DCC):   
Participant Initials (F, M, L) (if applicable): 
Institution: 
Date of collection/ biopsy (MM-DD-YYYY):    ________/________/________ 
Time point:     
  Baseline       
  Progression 
Diagnosis: 
Tissue type (FFPE scrolls, slides, biopsies): 
Number of scrolls: 
Number of slides: 
 
 
 
 
 
 
CRA/Study Coordinator/Nurse Printed Name:   
CRA/Study Coordinator/Nurse Signature:   
Contact Number: 
 
 
 
 
 
 
 
 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 79 of 81 
APPENDIX F: TISSUE SHIPPING GUIDELINES TO CITY OF HOPE PATHOLOGY CORE 
 
These guidelines apply to non-COH sites only. 
All biological material must be shipped according to applicable government and International Air 
Transport Association (IATA) regulations.  
Shipping guidelines can also be found on the FedEx website. 
 
1. Aim to ship samples on a Monday through Wednesday. If this is not feasible, advance 
arrangements should be made with City of Hope Pathology Core (DL-PATHCORE-
BiospecimenSupport@COH.org).   
2. Notify City of Hope Pathology Core (DL-PATHCORE-BiospecimenSupport@COH.org) of impending 
shipment. Sites must create their own FedEx shipping labels. 
3. Slides/ Blocks: Batch ship at room temperature via FedEx. During extreme heat, include 
refrigerated (not frozen) gel packs or gel insulators. 
It is recommended to ship samples via FedEx overnight (for a delivery by 3 pm or earlier the next 
day) or FedEx 2-day (with a morning delivery). During extreme heat, ship via FedEx overnight (for 
a delivery ideally by 10.30 am, or 3 pm the next day). 
4. Frozen samples should be batch shipped on dry ice via FedEx overnight (for a delivery by 10.30 
am the next day). The shipment should contain enough dry ice to last at least 72 hours. 
5. On the day of shipment, email the sample shipment information to City of Hope Pathology Core 
(DL-PATHCORE-BiospecimenSupport@COH.org). 
6. Ship samples with a copy of the correlative tissue form (Appendix E) and a copy of the pathology 
report to: 
 
Karen Miller 
COH Pathology Core 
City of Hope National Medical Center 
1500 E. Duarte Road 
Familian Science (Building 084), Room 1207 
Duarte, CA 91010 
Telephone: 626-218-8408 
Email: DL-PATHCORE-BiospecimenSupport@COH.org 
 
 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 80 of 81 
APPENDIX G: CORRELATIVE BLOOD COLLECTION FORM FOR NON-COH SITES ONLY 
Subject ID (issued by DCC):   
Participant Initials (F, M, L) (if applicable): 
Institution: 
 
To be used by non-COH sites for the following blood samples being sent to COH APCF: 
 
Sample # 
Time point of 
Collection 
Expected 
Volume 
Tube Type Used 
Collected 
Volume 
Time of Collection 
Date of 
Collection 
Indicate 
which sample 
was collected 
1. 
 
Salvage 
Cycle 1, Day 1 
20 mL 
Cell-free DNA BCT 
_____ mL 
____:____ AM/ PM 
____/____/____ 
 
2. 
 
Salvage 
Cycle 2, Day 1 
20 mL 
Cell-free DNA BCT 
_____ mL 
____:____ AM/ PM 
____/____/____ 
 
3. 
 
End of Salvage 
20 mL 
Cell-free DNA BCT 
_____ mL 
____:____ AM/ PM 
____/____/____ 
 
4. 
 
Consolidation 
Cycle 1, Day 1 
20 mL 
Cell-free DNA BCT 
_____ mL 
____:____ AM/ PM 
____/____/____ 
 
5. 
 
End of Consolidation 
(30 days post-last dose) 
20 mL 
Cell-free DNA BCT 
_____ mL 
____:____ AM/ PM 
____/____/____ 
 
6. 
 
At Progression/Relapse 
20 mL 
Cell-free DNA BCT 
_____ mL 
____:____ AM/ PM 
____/____/____ 
 
 
 
A copy of this form should accompany the sample shipments to COH APCF. Refer to the blood shipping guidelines 
for shipping instructions to COH APCF (Appendix H). 
 
CRA/Study Coordinator/ Nurse:   
Contact Number: 
CRA/Study Coordinator/ Nurse Signature:   
Date: 
 
 

PolaR-ICE as initial salvage for R/R DLBCL 
City of Hope #:20148 
Version 02 - 12/20/2021 
 
CONFIDENTIAL 
Page 81 of 81 
APPENDIX H: BLOOD SHIPPING GUIDELINES TO CITY OF HOPE APCF 
These guidelines apply to non-COH sites only. 
All biological material must be shipped according to applicable government and International Air 
Transport Association (IATA) regulations.  
Shipping guidelines can also be found on the FedEx website. 
 
1. Aim to ship samples on a Monday through Wednesday. If this is not feasible, advance 
arrangements should be made with APCF (DL-APCF@coh.org). Sites must create their own FedEx 
shipping labels. 
1. Cell-free BCT tubes should be shipped as soon as possible but no more than 3 days after being 
drawn via overnight courier at ambient temperature. 
2. On the day of shipment, email APCF (DL-APCF@coh.org) the FedEx shipment #. 
3. Ship samples with a copy of the correlative blood collection form (Appendix G) and a copy of the 
latest CBC results (with differential) and the date of the test to: 
 
Dr. Tim Synold 
Analytical Pharmacology Core Facility  
Shapiro 1042 
City of Hope National Medical Center 
1500 E. Duarte Road 
Duarte, CA 91010