A Multi-Center, Open-Label, Compassionate Use Extension Study of Ublituximab (TG-1101) in Combination With Umbralisib (TGR-1202) for Patients Previously Enrolled in Protocol UTX-TGR-304
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Sponsor: TG Therapeutics, Inc.

Official Title: 
A Multi-Center, Open-Label, Study to Evaluate the Safety and Efficacy of 
Ublituximab (TG-1101) in Combination With TGR-1202 for Patients 
Previously Enrolled in Protocol UTX-TGR-304
NCT Number: 
NCT02656303 
Document Date: 
Protocol Version 6.0: 23 February 2019 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 3 of 74 
PROTOCOL ACCEPTANCE FORM 
Protocol Title: 
A Multi-Center, Open-Label, Compassionate Use Extension 
Study of Ublituximab (TG-1101) in Combination with 
Umbralisib (TGR-1202) for Patients Previously Enrolled in 
Protocol UTX-TGR-304 
 
Protocol Number: 
UTX-TGR-204 
Trial Drug: 
Ublituximab (TG-1101) + Umbralisib (TGR-1202) 
IND Numbers: 
Ublituximab 
TGR-1202 
114,779 
116,762 
Date FINAL: 
22 January 2019 
I have read the attached protocol and agree that it contains all the necessary details for performing 
UTX-TGR-204. 
I will provide copies of the protocol and of the ublituximab and umbralisib Investigators’ 
Brochures, which were furnished to me by TG Therapeutics (Sponsor), to all members of the study 
team for whom I am responsible and who participate in the study.  I will discuss this material with 
them to ensure that they are fully informed regarding ublituximab and umbralisib and the conduct 
of the study. 
Once the protocol has been approved by the IRB/IEC, I will not modify this protocol without 
obtaining the prior approval of TG Therapeutics and of the IRB/IEC.  I will submit the protocol 
modifications and/or any informed consent modifications to TG Therapeutics and the IRB, and 
approval will be obtained before any modifications are implemented. 
I understand the protocol and will work according to it, the principles of Good Clinical Practice 
(current ICH guidelines), and the Declaration of Helsinki (1964) including all amendments up to 
and including the Washington Clarification (2002). 
 
 
 
 
 
 
 
Print Name 
 
Signature 
 
Date 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 4 of 74 
TABLE OF CONTENTS 
Table of Contents ................................................................................................................................... 4 
STUDY SYNOPSIS ................................................................................................................................. 11 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ......................................................... 16 
1 INTRODUCTION ................................................................................................................................ 18 
1.1 Chronic Lymphocytic Leukemia .......................................................................................................................... 18 
1.2 Background .................................................................................................................................................................. 18 
1.3 Ublituximab ................................................................................................................................................................. 18 
1.4 TGR-1202 (Umbralisib) .......................................................................................................................................... 19 
1.5 Ublituximab in Combination with TGR-1202 ................................................................................................ 19 
2 OBJECTIVES ........................................................................................................................................ 21 
2.1 Study Objectives ........................................................................................................................................................ 21 
2.2 Efficacy Endpoints .................................................................................................................................................... 21 
3 ELIGIBILITY CRITERIA ................................................................................................................... 22 
3.1 Inclusion Criteria ....................................................................................................................................................... 22 
3.2 Exclusion Criteria ...................................................................................................................................................... 22 
4 STUDY DESIGN .................................................................................................................................. 23 
4.1 Overview of Study Design .......................................................................................................................... 23 
4.2 Registration ................................................................................................................................................................. 23 
4.3 Study Sites .................................................................................................................................................................... 23 
4.4 Discontinuation from Study Treatment ........................................................................................................... 23 
5 STUDY ASSESSMENTS AND TREATMENT SCHEDULE .......................................................... 25 
5.1 Laboratory Evaluations - Overview ................................................................................................................... 27 
5.1.1 Laboratory Evaluations (Local Lab)........................................................................................................................................................... 27 
6 TREATMENT PLAN .......................................................................................................................... 28 
6.1 Treatment Summary ................................................................................................................................................ 28 
6.2 Agent Administration .............................................................................................................................................. 28 
6.2.1 Guidelines for Administration of Ublituximab ...................................................................................................................................... 29 
6.2.2 Guidelines for Administration of Umbralisib (TGR-1202).............................................................................................................. 31 
6.3 Criteria for Ongoing Treatment ........................................................................................................................... 32 
6.4 DOSING DELAYS/DOSE MODIFICATION ......................................................................................................... 33 
6.4.1 Dose Delay: Ublituximab ................................................................................................................................................................................. 33 
6.4.2 Dose Delay/Modifications: Umbralisib (TGR-1202) .......................................................................................................................... 34 
6.4.3 Ordering Ublituximab and Umbralisib (TGR-1202)........................................................................................................................... 36 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 5 of 74 
6.4.4 Duration of Therapy .......................................................................................................................................................................................... 36 
7 STUDY MEDICATION OVERVIEW AND SAFETY ...................................................................... 37 
7.1 Ublituximab ................................................................................................................................................................. 37 
7.2 Umbralisib (TGR-1202) .......................................................................................................................................... 38 
7.3 Comprehensive Adverse Events and Possible Risks - Ublituximab + Umbralisib Combination
 .................................................................................................................................................................................................. 38 
7.3.1 Very Common (≥ 10%): ................................................................................................................................................................................... 38 
7.3.2 Common (≥ 1% - < 10%): ................................................................................................................................................................................ 38 
8 MEASUREMENT OF EFFECT .......................................................................................................... 40 
8.1 Method of Assessment ............................................................................................................................................ 40 
8.2 Identification and Measurement of Tumor Lesions and Organomegaly ............................................ 40 
8.2.1 Target Lesions ...................................................................................................................................................................................................... 40 
8.2.2 Spleen and Liver .................................................................................................................................................................................................. 41 
8.2.3 Non-Target Lesions ............................................................................................................................................................................................ 42 
8.3 Definitions of Tumor Response and Progression ........................................................................................ 42 
8.4 Complete Response .................................................................................................................................................. 42 
8.5 Partial Response ........................................................................................................................................................ 43 
8.6 Stable Disease ............................................................................................................................................................. 43 
8.7 Definitive Disease Progression ............................................................................................................................ 44 
8.8 Non-Evaluable ............................................................................................................................................................ 44 
8.9 Lymphocytosis During Therapy .......................................................................................................................... 45 
9 STATISTICAL CONSIDERATIONS ................................................................................................. 46 
9.1 Sample Size .................................................................................................................................................................. 46 
9.2 General Analysis Convention ................................................................................................................................ 46 
9.3 Analysis Populations ................................................................................................................................................ 46 
9.4 Subject Disposition ................................................................................................................................................... 47 
9.5 Subject Demographics and Baseline Characteristics .................................................................................. 47 
9.6 Medical History .......................................................................................................................................................... 47 
9.7 Extent of Exposure .................................................................................................................................................... 47 
9.8 EFFICACY ANALYSES ........................................................................................................................................ 47 
9.8.1 PRIMARY EFFICACY VARIABLE ................................................................................................................................................................... 47 
9.8.2 SECONDARY EFFICACY VARIABLES .......................................................................................................................................................... 48 
10 SAFETY REPORTING AND ANALYSIS ....................................................................................... 49 
10.1 Safety Analyses ........................................................................................................................................................ 49 
10.2 Adverse Event Characteristics .......................................................................................................................... 49 
10.3 Definitions of Adverse Events ........................................................................................................................... 49 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 6 of 74 
10.4 Adverse Events (AE’s) and Treatment Emergent Adverse Events (TEAE’s) ................................. 50 
10.5 Adverse Events / Serious Adverse Event Causality Assessment ........................................................ 50 
10.5.1 Recording of Adverse Events ...................................................................................................................................................................... 50 
10.5.2 Abnormal Laboratory Values and Vital Signs ..................................................................................................................................... 51 
10.5.3 Handling of Adverse Events ........................................................................................................................................................................ 51 
10.6 Serious Adverse Events ........................................................................................................................................ 52 
10.6.1 Definitions of Serious Adverse Events ................................................................................................................................................... 52 
10.6.2 Serious Adverse Event Reporting by Investigators ......................................................................................................................... 53 
10.7 Sponsor SAE Reporting Requirements .......................................................................................................... 53 
10.8 Recording of Adverse Events and Serious Adverse Events ................................................................... 54 
10.9 Diagnosis vs. Signs and Symptoms .................................................................................................................. 54 
10.9.1 Persistent or Recurrent Adverse Events ............................................................................................................................................... 54 
10.9.2 Abnormal Laboratory Values ..................................................................................................................................................................... 54 
10.9.3 Deaths .................................................................................................................................................................................................................... 55 
10.9.4 Hospitalization, Prolonged Hospitalization, or Surgery ................................................................................................................ 55 
10.9.5 Pre-Existing Medical Conditions ............................................................................................................................................................... 55 
10.9.6 Protocol-Defined Events of Special Interest ........................................................................................................................................ 55 
11 CLINICAL DATA COLLECTION AND MONITORING .............................................................. 57 
11.1 Site Monitoring Plan .............................................................................................................................................. 57 
12 ETHICAL, FINANCIAL, AND REGULATORY CONSIDERATIONS ....................................... 58 
12.1 IRB/IEC Approval ................................................................................................................................................... 58 
12.2 Regulatory Approval ............................................................................................................................................. 58 
12.3 Insurance and Indemnity .................................................................................................................................... 58 
12.4 Informed Consent ................................................................................................................................................... 58 
12.5 Confidentiality.......................................................................................................................................................... 59 
12.6 Investigator and Staff Information .................................................................................................................. 60 
12.7 Financial Information ........................................................................................................................................... 60 
13 RECORD RETENTION AND DOCUMENTATION OF THE TRIAL ....................................... 61 
13.1 Amendments to the Protocol ............................................................................................................................. 61 
13.2 Documentation Required to Initiate Trial .................................................................................................... 61 
13.3 Trial Documentation and Storage .................................................................................................................... 62 
13.4 Data Collection ......................................................................................................................................................... 63 
13.5 Trial Monitoring, Auditing, and Inspecting .................................................................................................. 64 
13.6 Quality Assurance and Quality Control ......................................................................................................... 64 
13.7 Disclosure and Publication Policy.................................................................................................................... 64 
14 REFERENCES ................................................................................................................................... 66 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 7 of 74 
15 Appendix A – IWCLL Response Criteria ................................................................................. 68 
16 Appendix B - Contraceptive Guidelines and Pregnancy .................................................. 71 
17 Appendix C – New York Heart Association (NYHA) Classifications ............................. 73 
18 Appendix D – Interpretation of Hepatitis B Results .......................................................... 74 
 
 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 8 of 74 
Version 2.0 (Dated 24 August 2016) of this Protocol is the first amendment to this clinical trial and 
contains the following modifications: 
• 
All subjects are now required to start prophylaxis treatment with pneumocystis jiroveci 
pneumonia (PCP) and antiviral therapy, whereas this was previously at investigator 
discretion (See Section 6.2.2); 
• 
The phrasing of response assessment intervals has been revised for clarity from “at Weeks 
12, 24, 36, 48, and every 12 weeks thereafter,” to “following the completions of cycles 3, 6, 9 
12, 15, 18 and every 3 cycles thereafter”;  
• 
Schedule of assessments and treatment schedule (Section 5) was updated, including 
o Revised wording for Tumor Evaluation (as listed above) and  
o Updated Urine Pregnancy Test schedule, 
• 
The shelf life of ublituximab has been increased to 36 months from 24 months when stored 
between +2 ͦC / +8 ͦC to reflect newly available stability data on ublituximab drug product; 
and 
• 
Sections 7.1.1, and 7.2.1 were updated to include the most recent adverse event information 
related to ublituximab and TGR-1202 corresponding to the latest Investigator Brochures. 
Version 3.0 (Dated 7 March 2017) of this Protocol is the second amendment to this clinical trial and 
contains the following modifications:  
• 
Inclusion criteria #1a has been updated to provide a minimum time on a study arm of 2 cycles 
• 
Inclusion criteria #2 has been updated to include units (per microliter) in regard to absolute 
neutrophil count and platelet count; 
• 
Exclusion criteria #4 has been updated to clarify prophylaxis as “anti-pneumocystis 
pneumonia prophylaxis”; 
• 
Exclusion criteria #6 has been added to exclude subjects with prior live virus vaccines; 
• 
Appendix B – Contraceptive Guidelines and Pregnancy has been revised to delete the word 
“highly” effective as well as to include follow up recommendations for subjects entering the 
study from treatment arm B in study UTX-TGR-304 (obinutuzumab arm). 
• 
CT scan evaluation has been revised to allow for every 3 or 6 cycle CT Scans after Cycle 9 at 
the discretion of the investigator, to limit exposure to radiation. 
• 
The 21-day timeframe for signing informed consent has been removed.  
Version 4.0 (Dated 29 March 2017) of this Protocol is the third amendment to this clinical trial and 
contains the following modifications: 
• 
Definition of Serious Adverse Event has been updated.  
 
Version 5.0 (Dated 20 October 2017) of this Protocol is the fourth amendment to this clinical trial 
and contains the following modifications: 
• 
Inclusion Criteria 1a was updated to include the statement: There is no required timeframe 
to begin treatment on the 204 protocol, however, if other therapies to treat the disease are 
implemented in the interim, the subject will not be eligible to enroll in the study.   
• 
Exclusion Criteria 4 was updated to clarify the use of anti-pneumocystis pneumonia 
prophylaxis 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 9 of 74 
• 
Treatment schedule in section 5 was updated to: 
o increase the screening period from 21 to 28 days. 
o include MRD testing for subjects who have a PR 
o increase the window for scans from +/- 7 days to +/- 14 days  
• 
Section 6.1 was updated to specify the treatment schema for subjects crossing over from each 
of the 4 arms in the 304 protocol 
• 
Section 6.2.1.3.1 and Section 7.1 were both updated to include information regarding a new 
vial size for ublituximab; 
• 
Sections in 6.4 were updated with the latest dose delay/modification guidance for 
ublituximab and TGR-1202. This section also includes guidance for diarrhea and colitis 
events.  
• 
Section 6.4.3 was updated to include process of transferring drug from the 304 protocol, if 
applicable 
• 
Sections 7.1.1, and 7.2.1 were updated to include the most recent adverse event information 
related to ublituximab and TGR-1202 corresponding to the latest Investigator Brochures;  
• 
The following statement was removed from section 8.2.1: “At follow-up time points, the LDs 
for individual lesions and the SPD of all nodal target lesions will be considered. Because nodal 
target lesions that have one or both diameters >0 cm and < 1.0 cm cannot be reliably 
measured, a default value of 1.0 cm will be assigned for each diameter that meets these 
criteria and the resulting PPD will be used in SPD calculations. Based on this convention, a CR 
may be achieved even if an SPD value is >0 cm2 (i.e., if all lymph nodes measure < 1.0 cm2)” 
to allow for more accurate measurements of nodal target lesions.  
• 
Minor administrative updates and typographical errors were corrected throughout.   
• 
Updated throughout to include the generic name of TGR-1202: umbralisib 
Version 6.0 (Dated 22 January 2019) of this Protocol is the fifth amendment to this clinical trial and 
contains the following modifications: 
• 
Protocol updated throughout with minor editorial and administrative changes.   
• 
Section 3 Eligibility Criteria updated as follows:  
 
o Inclusion Criteria 2a clarified to account for subjects with cytopenias due to bone 
marrow involvement.   
o Inclusion Criteria 2b clarified to allow subjects with Gilbert’s Disease and 
Autoimmune Hemolytic Anemia.  
o Inclusion Criteria 2d updated to utilize the modified Cockcroft Gault utilizing ideal 
body mass. 
o Exclusion Criteria 4 added as follows - Evidence of chronic active Hepatitis B (HBV, 
not including subjects with prior hepatitis B vaccination; or positive serum Hepatitis 
B antibody) or chronic active Hepatitis C infection (HCV), cytomegalovirus (CMV), or 
known history of HIV. If HBc antibody, HCV antibody or CMV IgM is positive the 
subject must be evaluated for the presence of HBV, HCV, or CMV by PCR 
• 
Section 5 Study Assessments and Treatment Schedule updated as follows: 
o Tumor Evaluations updated within the table with the following language - 
Evaluations are to be obtained during cycles 3, 6 & 12. Following cycle 12, 
evaluations should occur at least every 12 cycles.  

UTX-TGR-204 
 
Dated:22 January 2019  (Ver 6.0) 
Page 10 of 74 
o
Serum Virology added to include HBsAG, HBc antibody, HCV antibody, and CMV IgG
and IgM at screening and CMV surveillance added while subjects are receiving
umbralisib.
•
Section 5 -   Table 2: Follow Up Assessments Schedule added to clarify follow up 
assessments if a subject comes off study drug.
•
Section 6 Treatment Plan: Updated to clarify PJP and anti-viral prophylaxis language and 
modified to provide more clear guidelines for timing of pre-medications for ublituximab.
•
Section 6.4 Dosing Delays/Dose Modification: Removed requirement for subjects to 
discontinue study drugs if held for more than 28 days.
•
Section 7.3 Comprehensive Adverse Events and Potential Risks (CAEPRS) – Ublituximab + 
TGR-1202 Combination updated based on Investigator Brochures Version 6.0, dated 
20JUL2018. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 18 of 74 
1 INTRODUCTION 
1.1 CHRONIC LYMPHOCYTIC LEUKEMIA 
In the US, an estimated 15,720 new cases of Chronic Lymphocytic Leukemia (CLL) will be reported 
in 2014 with deaths totaling 4,600 due to the disease according to American Cancer Society estimates 
(American Cancer Society, 2014). CLL affects mainly older adults, accounts for one third of all 
diagnosed cases of leukemia and is characterized by the accumulation of clonal mature B 
lymphocytes in the blood, bone marrow, and secondary lymphoid tissues (Lin K, 2002).  CLL is a 
heterogeneous disease, with several higher risk cytogenetic abnormalities which are generally more 
difficult to treat, including 17p deletion, P53 gene mutation, and 11q deletion (Hallek M, 2008) (Lin 
K, 2002).  Subjects with 17p deletion show higher resistance to conventional chemotherapies as well 
as shorter duration of survival than non 17p deletion subjects.   Subjects with 11q deletion have been 
associated with marked lymphadenopathy (Hallek M, 2008).  Subjects with P53 gene mutations are 
associated with an adverse clinical outcome (Lin 2002).  
Chemotherapy regimens in combination with monoclonal antibody therapy comprise the current 
standard of care for subjects with CLL, with novel targeted agents now entering the market.  Frontline 
therapy for subjects with CLL generally consists of the anti-CD20 monoclonal antibody rituximab, in 
combination with either fludarabine and cyclophosphamide, or bendamustine.  Depending on the age 
and comorbidities of the subject, chlorambucil is also considered, though its use within the US has 
been limited.  Other anti-CD20 antibodies have also been approved for the treatment of CLL, 
including ofatumumab and obinutuzumab.  Recently the BTK inhibitor, ibrutinib was approved by 
the FDA for the treatment of subjects with CLL in the relapsed or refractory setting after 
demonstrating superiority to ofatumumab as measured by progression free survival (Byrd et al, 
2014).  Despite these advancements in available therapies, CLL remains an incurable disease, and 
many subjects will progress and eventually die from their disease.  Furthermore, subjects with higher 
risk cytogenetic abnormalities still present with a less than optimal response to approved therapies 
and shorter duration of response and progression free survival.  As such, there is a pressing need for 
new, innovative, targeted therapies for the treatment of subjects with relapsed/refractory CLL, 
especially those with cytogenetic abnormalities. 
1.2 BACKGROUND 
A Phase 3 randomized study (UTX-TGR-304) to assess the efficacy and safety of ublituximab in 
combination with TGR-1202 compared to obinutuzumab in combination with chlorambucil in 
subjects with chronic lymphocytic leukemia (CLL) was launched in September 2015.  As part of the 
study design, subjects from Treatment Arms B, C, and D with disease progression confirmed by the 
independent review committee (IRC), may be enrolled into this companion study.  In addition, at the 
end of the UTX-TGR-304 study, non-progressed subjects from all treatment arms may also be 
enrolled to this companion study.  
1.3 UBLITUXIMAB 
Ublituximab is a novel third generation chimeric anti-CD20 monoclonal antibody bioengineered for 
potent activity, exhibiting a unique glycosylation profile with a low fucose content, designed to 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 20 of 74 
was removed from study without progressive disease due to an event of itching which was deemed 
possibly related to TGR-1202.   
Subjects were heavily pretreated, and amongst subjects with DLBCL and CLL, contained numerous 
high-risk subjects (67% of CLL subjects had 17p del and/or 11q del, and 5/7 evaluable DLBCL 
subjects were of Germinal Center-B-Cell subtype).   
Responses are as follows: 
• 
All 9 CLL/SLL subjects showed significant nodal reductions with 6 (67%) achieving a PR per 
iwCLL criteria (Hallek 2008).  Additionally, all CLL subjects achieved a greater than 50% 
reduction in ALC by the end of Cycle 3.   
• 
All 9 evaluable FL subjects displayed a nodal reduction on the combination, with 2 subjects 
achieving a response per Cheson 2007 criteria, including one subject with a PET negative 
complete response. 
• 
Of the 7 evaluable DLBCL subjects, 3 (43%) achieved a response, including 2 complete 
responses which were confirmed by independent radiologic review.   
• 
The 1 subject with Richter’s Transformation exhibited a 49% nodal reduction and remains 
on study (duration as of data cutoff of 7+ months) 
Overall, the preliminary data suggests the combination of ublituximab and TGR-1202 is well 
tolerated and active in subjects with relapsed or refractory hematologic malignancies, including 
those with CLL (both high and low risk). 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 21 of 74 
2 OBJECTIVES 
2.1 STUDY OBJECTIVES 
Primary Objectives 
• 
To observe the overall response rate (ORR) defined as the sum of complete responses (CR) and 
partial responses (PR) 
Secondary Objective 
• 
To observe progression-free survival (PFS) and duration of response (DOR) 
• 
To observe the % of subjects that achieve MRD negativity 
• 
To observe the safety of ublituximab in combination with TGR-1202 
2.2 EFFICACY ENDPOINTS 
Overall response rate (ORR) 
ORR is defined as sum of CR and PR rates. 
 
Complete Response (CR) Rate 
CR rate is defined as the proportion of subjects who achieve a CR. 
 
Progression-free survival (PFS) 
PFS is defined as the interval from randomization to the earlier of the first documentation of 
definitive disease progression or death from any cause. 
Definitive disease progression based on standard criteria (Hallek et al. 2008) and occurring for any 
reason (i.e., increasing lymphadenopathy, organomegaly or bone marrow involvement; decreasing 
platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other 
than lymphocytosis. 
 
Minimal Residual Disease (MRD) Negativity Rate 
MRD negativity rate is defined as the proportion of subjects who are MRD negative. 
 
Duration of response (DOR) 
DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first 
documentation of definitive disease progression or death from any cause 
 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 22 of 74 
3 ELIGIBILITY CRITERIA 
3.1 INCLUSION CRITERIA 
1. Prior treatment in clinical trial UTX-TGR-304 
a. Confirmed progression by IRC on Arms B, C, or D after at least two cycles of treatment in trial 
UTX-TGR-304. There is no required timeframe to begin treatment on the UTX-TGR-204 
protocol; however, if other therapies to treat the disease are implemented in the interim, the 
subject will not be eligible to enroll in the study.   
b. Non-progressing subjects on Arm A may be eligible for enrollment when protocol UTX-TGR-
304 is completed.  
2. Adequate organ system function, defined as follows: 
a. Absolute neutrophil count (ANC) > 750 x 103/mm3 (0.75 K/μL) / platelet count > 40 x 
103/mm3 (40 K/μL) unless cytopenias are related to bone marrow involvement.  
b. Total bilirubin ≤1.5 times the upper limit of normal (ULN) with the exception of Gilbert’s 
Disease and Autoimmune Hemolytic Anemia.  
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if no liver 
involvement or ≤5 x the ULN if known liver involvement 
d. Calculated creatinine clearance >30 mL/min (as calculated by the modified Cockcroft-Gault    
             formula).  
3. ECOG performance status ≤ 2 
4. Ability to swallow and retain oral medication 
5. Willingness and ability to comply with trial and follow-up procedures, give written informed 
consent 
3.2 EXCLUSION CRITERIA 
1. 
Prior treatment with obinutuzumab + chlorambucil (Arm B subjects) or ublituximab (Arm C 
subjects) within 7 days of Cycle 1/Day 1 
2. 
Subjects refractory to (progressing on) UTX-TGR-304 Treatment Arm A (ublituximab + TGR-
1202) 
3. Known histological transformation from CLL to an aggressive lymphoma (i.e. Richter’s    
transformation) 
4.  Evidence of chronic active Hepatitis B defined as Hepatitis B surface antigen positive or Hepatitis 
B DNA positive by PCR (HBV, NOT including subjects with prior hepatitis B vaccination who are 
Hepatitis B surface antibody positive only;) or chronic active Hepatitis C infection (HCV) defined 
as Hepatitis C RNA positive by PCR, cytomegalovirus (CMV) DNA positive by PCR, or known 
history of HIV. If HBc antibody, HCV antibody or CMV IgG and/or IgM antibody is positive the 
subject must be evaluated for the presence of HBV, HCV, or CMV by PCR - See Appendix D.   
 5.   Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections 
of skin or nails.  NOTE:  Subjects may be receiving prophylactic antiviral or antibacterial 
therapies at investigator discretion.  Use of anti-pneumocystis pneumonia prophylaxis is 
required prior to Cycle 1/Day 1 and for the first 2 cycles. After Cycle 2, is per investigator 
discretion.  
6.     Woman who are pregnant or lactating. 
7.     Live virus vaccines four (4) weeks prior to or during ublituximab therapy. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 23 of 74 
4 STUDY DESIGN 
4.1 OVERVIEW OF STUDY DESIGN 
This Companion Study is intended for subjects who previously enrolled to the parent trial UTX-TGR-
304.  Subjects from Treatment Arms B, C, and D with disease progression confirmed by the 
independent review committee (IRC), may be enrolled into this Companion Study.  At the end of the 
UTX-TGR-304 study, non-progressed subjects from Treatment Arm A may also be enrolled to this 
Companion Study.  Subjects from Treatment Arms B, C, and D may start treatment with ublituximab 
+ TGR-1202, while subjects entering the Companion Study from Treatment Arm A may continue their 
treatment as specified by this protocol.  All subjects enrolled to the Companion Study should receive 
ublituximab in combination with TGR-1202 (at the same dose and schedule as the Treatment Arm A 
in UTX-TGR-304) until they show disease progression, are unable to continue treatment for any 
reason such as lack of tolerability, or until the treatment is commercially available. 
During the study period, all subjects will be evaluated for response by CT and/or MRI. Evaluations 
are to be obtained at approximately cycles 3, 6 and 12.  Following cycle 12, evaluations should occur 
at least every  12 cycles unless clinically indicated more frequently. Subjects should remain on study 
treatment until the occurrence of definitive disease progression, unacceptable toxicity, or 
withdrawal from the study due to investigator decision or other reasons.  Subjects who discontinue 
from study treatment (either for toxicity or physician choice) and have not progressed should 
continue to be followed for progression per institutional standard of care and reported in eCRF. Date 
of progression, beginning of new treatment, and/or death should be entered in the eCRF. 
4.2 REGISTRATION 
Subjects who are eligible and who have signed an informed consent will be enrolled.  Please see Study 
Manual for enrollment procedures. 
4.3 STUDY SITES 
 
Only sites participating in UTX-TGR-304 will be included in this study. 
4.4 DISCONTINUATION FROM STUDY TREATMENT 
Subjects will be discontinued from study treatment for any of the following reasons: 
• 
Disease progression 
• 
Intolerable toxicity related to study drug 
• 
Subject requests to withdraw consent or discontinue treatment 
• 
Pregnancy 
• 
Inability of the subject to comply with study requirements 
• 
Conditions requiring therapeutic intervention not permitted by the protocol 
• 
Non-compliance/lost to follow-up 
• 
Investigator discretion 
• 
Discontinuation of the study by the Sponsor 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 24 of 74 
Subjects who discontinue from study treatment (for reasons other than progressive disease) should 
continue to be followed for progression. 
Subjects who discontinue all study treatment but remain on study for disease progression 
assessment will have an End of Treatment (EOT) visit and will continue to be followed for  adverse 
events (treatment-related AEs and disease-related AEs), disease progression and other protocol 
required procedures (see Section 5, Table 2 for EOT and follow up assessment schedule).  All new 
treatment-related AEs occurring within 30 calendar days from treatment discontinuation must be 
reported and followed until resolution, unless, in the opinion of the investigator, these events are not 
likely to improve because of the underlying disease.  In this case the investigators must record the 
reason for not conducting the 30-day safety evaluation in the subject’s medical records and as a 
comment on the electronic Case Report Form (eCRF). 
All subjects who have CTCAE Grade 3 or 4 laboratory abnormalities at the time of withdrawal should 
be followed until the laboratory values have returned to Grade 1 or 2, unless in the opinion of the 
investigator, it is not likely that these values are to improve because of the underlying disease.  In this 
case, the investigator must record his or her reasoning for making this decision in the subject’s 
medical records and as a comment on the eCRF. 
Subjects who discontinue from the study will have an End of Study visit (EOS - see Section 5, Table 2) 
No formal futility analysis of efficacy or safety will be conducted in this study, however if Study 304 
is closed for futility for either safety or efficacy reasons, then this Study UTX-TGR-204 will also be 
terminated.     
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 29 of 74 
6.2.1 GUIDELINES FOR ADMINISTRATION OF UBLITUXIMAB 
• 
Method of Administration: Ublituximab will be administered as an intravenous infusion 
through a dedicated line. 
• 
Potential Drug Interactions:  No Drug Interactions have been reported to date. 
• 
Pre-medications: Ublituximab should be started approximately 30 minutes after the 
conclusion of the last pre-medication infusion and should include an antihistamine 
(diphenhydramine 50 mg or equivalent), and a corticosteroid (dexamethasone 10-20 mg or 
equivalent). If pre-medication is given orally, they should be given approximately 45-60 
minutes prior to the beginning of the ublituximab infusion. After C1 adjustments can be made 
to the antihistamine and/or corticosteroid dosing should subject exhibit adverse effects from 
the agents or have a medical condition the pre-medications adversely impacts after 
discussion with TG Therapeutics contact.  
o Use of oral acetaminophen 650 mg (or equivalent) should be restricted to subjects who 
experience fever or pyrexia after week 1 dose, or as clinically warranted. 
• 
Hypersensitivity and Infusion Reaction Precautions: Medication and resuscitation equipment 
must be available per institutional guidelines prior to ublituximab administration for the 
emergency management of potential anaphylactic reactions.   
• 
Subject Care Implications:   
o Ublituximab should not be administered as an IV push or bolus. 
o Diluted ublituximab should be checked before administration for cloudiness, color, or 
deposits.  Ublituximab should not be administered if does not conform to the 
specifications. Immediately inform the Monitor/Sponsor with any product quality 
concerns or questions. 
o It is recommended that ublituximab be administered immediately after dilution. 
o No other treatment may be co-administered with ublituximab (other than for 
immediate intervention for adverse event). 
o Concurrent glucocorticoid therapy as long as started for at least 7 days prior to study 
entry (< 10 mg per day of prednisone or equivalent) is allowed as clinically warranted.  
o Since infusion-related hypotension may occur, consider holding antihypertensive 
medications 12-24 hours prior to and throughout infusion of ublituximab. 
o For subjects at risk for tumor lysis syndrome in the opinion of the treating investigator, 
prophylaxis with allopurinol or per recommended institutional standards should be 
considered. 
 
6.2.1.1 INFUSION RELATED REACTIONS AND INFUSION RATE GUIDANCE - UBLITUXIMAB 
Infusion related reactions including severe reactions have been reported with ublituximab 
administration in subjects with CLL.  Guidelines are provided below for subjects who experience such 
reactions.  Symptomatic infusion reactions, despite premedication, may be treated at the discretion 
of the treating physician, including but not limited to: oral acetaminophen 650 mg (or equivalent), 
corticosteroids, antihistamines, oxygen, and bronchodilators.   

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 32 of 74 
• 
Pre-medications: Subjects are required to start prophylaxis treatment with pneumocystis 
jiroveci pneumonia (PJP) and antiviral therapy prior to Cycle 1, Day 1, and must continue 
through Cycle 2, and per investigator discretion afterward.  Choice of PJP and anti-viral 
prophylaxis therapy is per investigator discretion, with the below recommendations: 
o Anti-viral Prophylaxis:  Valtrex 500 mg daily or Acyclovir 400 mg BID or equivalent  
o PJP Prophylaxis: Dapsone 100 mg daily or equivalent. 
If anti-viral or anti-bacterial prophylaxis is not tolerated, we recommend alternating to a 
different prophylactic agent, reducing the dose or modifying the schedule for the prophylactic 
agent, or discontinuing prophylaxis at investigator discretion.  Final choice of PJP and anti-
viral prophylaxis therapy is per investigator discretion. 
TGR-1202 will be dispensed at the sites by the research coordinator or designee under the direction 
of the PI or by a pharmacist at the site.  Subjects must be provided drug in its original container.  
Subjects should be instructed to return any unused tablets when they return the bottle to the site. 
Study drug compliance should be reviewed with the subject at the beginning of each new treatment 
cycle and as needed.  Missed doses will be documented in the subjects’ medical record. 
Umbralisib will be self-administered (by the subject).  Tablets should be taken at approximately the 
same time each day with food (within 30 minutes of a meal).   Subjects should be instructed to 
swallow the tablets whole and should not chew or crush them. 
If a dose of umbralisib is missed, it should be taken as soon as possible on the same day.  If it is missed 
for a period greater than 12 hours, it should not be replaced.  If vomiting occurs, no attempt should 
be made to replace the vomited dose. 
6.2.2.1 DISPENSING OF UMBRALISIB 
Before dispensing, the site pharmacist or his/her representative must check that the umbralisib is in 
accordance with the product specifications and the validity is within the re-test date. 
The exact dose and the date of administration of umbralisib must be recorded within the eCRF, 
subject’s medical records, and/or in the drug accountability records.  For the purpose of drug 
accountability and dosing, subjects should record any missed doses of umbralisib on a drug diary.  
Any error in drug administration should be recorded (e.g., missed dose) in the eCRF 
The Pharmacist or his/her representative should record the date dispensed and subject’s number 
and initials, as well as complete the accountability record in the electronic drug accountability system 
with information concerning the dispensation of umbralisib.  
6.3 CRITERIA FOR ONGOING TREATMENT 
Continue treatment as per protocol provided that subject has: 
• 
No intolerable toxicities related to study drug. 
o If treatment is delayed greater than 2 cycles, notify TG Therapeutics prior to re-
initiation.  
• 
No clinical or radiographic evidence of disease progression.  
• 
Not withdrawn from the study for other reasons. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 36 of 74 
If a subject requires a dose reduction of umbralisib due to study drug related toxicity, the dose may 
not be re-escalated.  If further evaluation of the toxicity reveals the event was not related to 
umbralisib, this must be recorded in the medical record and dose re-escalation to the next higher 
dose level may be considered at the discretion of the investigator.     
 
6.4.3 ORDERING UBLITUXIMAB AND UMBRALISIB (TGR-1202) 
Once a subject is identified, a shipment of pre-determined quantity of ublituximab and umbralisib 
will be shipped to the clinical study site. 
Upon receipt of treatment supplies, the Pharmacist or the appropriate person of the site should 
update the accountability forms for both ublituximab and umbralisib.  If any abnormality on the 
supplied boxes (ublituximab) or bottles (umbralisib) is observed, the Pharmacist or the appropriate 
person must document that on the acknowledgement of receipt and contact that Sponsor and/or 
Sponsor designee. 
6.4.4 DURATION OF THERAPY 
In the absence of treatment delays due to adverse event(s), treatment should continue through Cycle 
1 and beyond unless one of the following criteria applies: 
• 
Disease progression or inter-current illness that prevents further treatment, 
• 
Subject decides to withdraw from the study, or changes in the subject's condition render the 
subject unacceptable for further treatment in the judgment of the investigator. 
During the study period, all subjects will be evaluated for response by CT and/or MRI. Evaluations 
are to be obtained at approximately cycles 3, 6 and 12.  Following cycle 12, evaluations should occur 
at least every 12 cycles unless clinically indicated more frequently. Subjects will remain on study 
treatment until the occurrence of definitive disease progression, unacceptable toxicity, or 
withdrawal from the study due to investigator decision or other reasons. Subjects who discontinue 
from study treatment (either for toxicity or physician choice) and have not progressed should 
continue to be followed for progression per institutional standard of care. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 37 of 74 
7 STUDY MEDICATION OVERVIEW AND SAFETY 
7.1 UBLITUXIMAB 
Chemical Name: 
ublituximab 
 
Other Names:    
TG-1101 
Classification:    
Recombinant chimeric anti-CD20 monoclonal antibody    
Mode of Action: 
Targets CD20 antigen on B-cells 
 
Description: 
Ublituximab is a genetically engineered chimeric murine/human mAb 
directed against the CD20 antigen found on the surface of B lymphocytes.  
Ublituximab displays the typical structure of immunoglobulins, consisting of 
two gamma (γ) heavy chains and two kappa (κ) light chains linked by disulfide 
bridges. It is composed of a murine variable region (37.2% of total amino 
acids) fused onto human constant regions. 
How Supplied: 
Concentration of 10 mg/mL in 15 mL (150 mg) or 25 mg/mL in 6 mL (150 mg) 
single-use glass vials.  
Storage: 
Ublituximab must be stored in a secured limited-access refrigerated area at a 
temperature ranging from +2°C / + 8°C.  Ublituximab must not be frozen. 
Stability: 
Once a vial of ublituximab has been opened and/or diluted it must be used 
immediately.  After dilution, ublituximab is stable in static conditions for 24 
hours at 25°C, and in dynamic conditions it is stable for 8 hours at 25°C.   
Ublituximab has a shelf-life of 36 months if stored between +2°C / + 8°C, 
based on stability data. 
Route of  
Administration: 
Intravenous 
Packaging: 
 
Ublituximab is packed in kits. Each kit contains:  
• 
Six vials containing 150 mg solution of ublituximab each 
or 
• 
One vial containing 150 mg solution of ublituximab (used as 
replacement, if needed) 
The container closure system for the vials containing 6mL is a type I glass vial 
closed by a siliconized chlorobutyl rubber stopper sealed with an aqua plastic 
and aluminum cap. 
 The container closure system for the vials containing 15 mL is a Type I plus 
borosilicate vial closed by a siliconized bromobutyl rubber stopper sealed 
with a white plastic and aluminum cap. 
Availability: 
 
Ublituximab is available from TG Therapeutics. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 38 of 74 
7.2 UMBRALISIB (TGR-1202) 
Classification:    
Phosphatidylinositol-3-Kinase (PI3K) Delta Inhibitor  
Formulation: 
 
See Investigator Brochure 
 
Mode of Action: 
Irreversibly inhibits activity of the Class I Delta isoform of PI3K 
 
How Supplied:  
Umbralisib: 200 mg tablets 
Storage: 
Store at 25°C.  Excursions permitted 15°C to 30°C. 
Stability: 
Retest dates will be provided periodically by Sponsor. 
Route of  
Administration: 
Oral 
Packaging: 
Umbralisib is provided in HDPE bottles each containing 30 tablets and a silica 
gel canister as a desiccant.  
Availability: 
 
Umbralisib is available from TG Therapeutics. 
7.3 COMPREHENSIVE ADVERSE EVENTS AND POSSIBLE RISKS - UBLITUXIMAB + 
UMBRALISIB COMBINATION 
The following adverse events were observed in subjects treated with the combination of ublituximab 
+ umbralisib and were considered at least possibly related to one or both of the study medications. 
The preliminary safety data as of May 1, 2018 is provided for a total of 75 subjects exposed to 
ublituximab + umbralisib with a maximum follow up of 3+ years. See the latest ublituximab and 
umbralisib Investigator’s Brochures for updated safety information a complete list of all adverse 
events reported regardless of causality. 
7.3.1 VERY COMMON (≥ 10%): 
Blood and Lymphatic System Disorders: anemia, neutropenia 
Gastrointestinal Disorders: diarrhea, nausea, vomiting 
General Disorders and Administration Site Conditions: fatigue 
Injury, Poisoning and Procedural Complications: infusion related reaction 
Metabolism and Nutrition Disorders: decreased appetite 
7.3.2 COMMON (≥ 1% - < 10%): 
Blood and Lymphatic System Disorders: thrombocytopenia 
Cardiac Disorders: cardiac failure congestive 
Ear and Labyrinth Disorders: ear congestion, ear discomfort 
Eye Disorders: conjunctival pallor, conjunctivitis, corneal oedema, vision blurred 
Gastrointestinal Disorders: abdominal discomfort, abdominal distension, abdominal pain, 
constipation, dyspepsia, flatulence, gastrooesophageal reflux disease, haematochezia, salivary 
hypersecretion, stomatitis 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 39 of 74 
General Disorders and Administration Site Conditions: asthenia, chills, face oedema, infusion site 
pain, local swelling, odedema peripheral, pyrexia, systemic inflammatory response syndrome 
Hepatobiliary Disorders: hyperbilirubinaemia 
Immune System Disorders: hypogammaglobulinaemia 
Infections and Infestations: bronchitis, cellulitis, clostridium difficile colitis, enterocolitis 
infectious, oral candidiasis, oral herpes, otitis media, pneumonia, pneumonia streptococcal, 
rhinovirus infection, sepsis, sepsis syndrome, sinusitis, skin infection, upper respiratory tract 
infection, urinary tract infection 
Injury, Poisoning and Procedural Complications: wound 
Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, blood 
alkaline phosphatase increased, blood creatinine increased, computerised tomogram thorax 
abnormal, immunoglobulins decreased, weight decreased 
Metabolism and Nutrition Disorders: dehydration, failure to thrive, hyperglycaemia, 
hyperuricaemia, hypokalaemia, hypophosphataemia 
Musculoskeletal and Connective Tissue Disorders: joint swelling, muscle spasms, muscular 
weakness, myalgia, pain in extremity 
Nervous System Disorders: dizziness, dysgeusia, headache, lethargy, sinus headache, somnolence 
Psychiatric Disorders: agitation, anxiety 
Renal and Urinary Disorders: micturition urgency, renal failure, renal failure acute 
Reproductive System and Breast Disorders: scrotal cyst, semen discolouration 
Respiratory, Thoracic and Mediastinal Disorders: choking, cough, dysphonia, dyspnea, epistaxis, 
hypoxia, oropharyngeal pain, pneumonitis, productive cough, sinus congestion 
Skin and Subcutaneous Tissue Disorders: alopecia, cold sweat, dermatitis acneiform, dermatitis 
bullous, dry skin, ecchymosis, pruritus, rash maculo-papular, rosacea, urticaria 
Vascular Disorders: hypertension 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 40 of 74 
8 MEASUREMENT OF EFFECT 
During the study period, all subjects will be evaluated for response by CT and/or MRI. Evaluations 
are to be obtained at approximately cycles 3, 6 and 12.  Following cycle 12, evaluations should occur 
at least every 12 cycles unless clinically indicated more frequently.  The determination of response 
and progression will be based on IWCLL criteria (Hallek M, 2008) by the treating investigator.   
 
CT scan is the preferred method of tumor assessment, but MRI may be used at the investigator’s 
discretion.  The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and throughout the study.  All baseline assessments 
to characterize disease will be performed within approximately 45 days of Cycle 1 Day 1, prior to 
initiation of therapy. 
  
Subjects should remain on study treatment until the occurrence of definitive disease progression, 
unacceptable toxicity, or withdrawal from the study due to investigator decision or other reasons. 
Subjects who discontinue from study treatment (either for toxicity or physician choice) and have not 
progressed will continue to be followed for progression as per the protocol. 
8.1 METHOD OF ASSESSMENT 
In addition to clinical examination, radiographic evaluation will be used in all subjects enrolled. CT 
scan is the preferred method for radiographic tumor assessment. MRI scanning may be used at the 
investigator’s discretion in subjects for whom this may be a preferred alternative to CT scanning; 
however, if MRI is performed, a non-contrast CT of the chest should be performed.  Contrast-
enhanced scanning is preferred, but iodine-containing or gadolinium contrast material may be 
omitted in subjects for whom use of a contrast agent would be medically contraindicated. Chest x-
ray, ultrasound, endoscopy, laparoscopy, PET, radionuclide scans, or tumor markers will not be 
considered for response assessment. 
 
For radiographic evaluations, the same method of assessment and the same technique (e.g., scan type, 
subject position, dose of contrast, injection/scan interval) should be used to characterize each 
identified and reported lesion at baseline and during study treatment and follow-up. However, if a 
subject is imaged without contrast at baseline, subsequent assessments should be performed with 
contrast, unless medically contraindicated. 
 
Relevant clinical and radiographic information required to make each tumor status assessment must 
be requested for source verification. 
8.2 IDENTIFICATION 
AND 
MEASUREMENT 
OF 
TUMOR 
LESIONS 
AND 
ORGANOMEGALY 
8.2.1 TARGET LESIONS 
At baseline, up to 6 lymph nodes should be selected as target lesions that will be used to quantitate 
the status of the disease during study treatment. Ideally, the target lesions should be located in 
disparate regions of the body. Only peripheral nodes need be selected as target lesions. However, it 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 41 of 74 
is optimal if mediastinal and retroperitoneal areas of disease are assessed whenever these sites are 
involved. 
 
Target lesions will be measured and recorded at baseline and as per the study assessment schedule.  
The cross-sectional dimensions (the largest cross-sectional diameter, i.e., the LD × LPD) will be 
recorded (in cm) for each target lesion. The product of the perpendicular diameters (PPD) (in cm2) 
for each target lesion and the sum of the products (SPD) (in cm2) for all target lesions will be 
calculated and recorded. The baseline SPD will be used as references by which objective tumor 
response will be characterized during treatment. The nadir LD of individual lesions and the nadir 
SPD will be used as references by which CLL progression will be characterized. All LD and LPD 
diameters will be reported in centimeters and all PPDs and SPDs will be reported in centimeters 
squared. 
 
A nodal mass may be selected as a nodal target lesion if it is both abnormal and measurable at 
baseline. A lymph node lesion is considered abnormal if it has a single diameter that is > 1.5 cm and 
is considered measurable if it has 2 perpendicular diameters that can be accurately measured in cross 
section with the LD being ≥ 1.0 cm and the LPD also being ≥ 1.0 cm. 
 
A new node that measures >1.5 cm in the LD and >1.0 cm in the LPD will be considered progressive 
disease. 
 
In cases in which a large lymph node mass has split into multiple components, all subcomponents 
regardless of size will be used in calculating the SPD. Progression of the lesion will be based on the 
SPD of sub-components. Lesion sub-components will have the true PPDs calculated. Similarly, lesion 
sub-components that are visible but neither abnormal nor measurable will have the default PPD of 
1.0 cm2 (1.0 cm × 1.0 cm) used in calculating the SPD. 
 
If lesions merge, a boundary between the lesions will be established so the LD of each individual 
lesion can continue to be measured. If the lesions have merged in a way that they can no longer be 
separated by this boundary, the newly merged lesion will be measured bi-dimensionally. 
 
8.2.2 SPLEEN AND LIVER 
Both the spleen and liver will be assessed by CT/MRI scan and/or by physical examination at baseline 
and as per the study assessment schedule. The baseline and nadir values for the longest vertical 
dimension (LVD) of each organ will be used as reference to further characterize the objective tumor 
response of the measurable dimensions of the CLL during treatment. All spleen and liver LVD 
measurements should be recorded in centimeters. 
 
By imaging, the spleen will be considered enlarged if it is >12 cm in LVD, with the LVD being obtained 
by multiplying the number of sections on which the spleen is visualized by the thickness of the 
sections (e.g., if the spleen is seen in 14 contiguous cross-sectional images with 0.5-cm thickness, the 
LVD is recorded as 7 cm). 
 
For subjects with splenomegaly at baseline or at the splenic LVD nadir, respective response and 
progression evaluations of the spleen will consider only changes relative to the enlargement of the 
spleen at baseline or nadir, not changes relative to the total splenic LVD. 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 42 of 74 
A 50% decrease (minimum 2 cm decrease) from baseline in the enlargement of the spleen in its LVD 
or decrease to ≤ 12 cm by imaging is required for declaration of a splenomegaly response. Conversely, 
an increase in splenic enlargement by ≥ 50% from nadir (minimum increase of 2 cm) is required for 
declaration of splenic progression.  By imaging, the liver will be considered enlarged if it is >18 cm in 
LVD. 
 
A 50% decrease (minimum 2 cm decrease) from baseline in the enlargement of the liver in its LVD 
or decrease to ≤ 18 cm is required for declaration of a hepatomegaly response.  Conversely, an 
increase in liver enlargement by ≥ 50% from nadir (minimum increase of 2 cm) is required for 
declaration of hepatic progression. 
8.2.3 NON-TARGET LESIONS 
Any other measurable and abnormal nodal lesions not selected for quantitation as target lesions may 
be considered non-target lesions. In addition, non-measurable evidence of CLL such as nodal lesions 
with both diameters <1.0 cm, extra-nodal lesions, bone lesions, leptomeningeal disease, ascites, 
pleural or pericardial effusions, lymphangitis of the skin or lung, abdominal masses that are not 
confirmed and followed by imaging techniques, cystic lesions, previously irradiated lesions, and 
lesions with artifacts may be considered as non-target disease. 
 
The presence or absence of non-target disease should be recorded at baseline and as per the study 
assessment schedule. If present at baseline, up to 6 non-target lesions should be recorded. The non-
target disease at baseline will be used as a general reference to further characterize regression or 
progression of CLL during assessments of the objective tumor response during treatment. 
Measurements are not required and these lesions should be followed as “present” or “absent”. 
8.3 DEFINITIONS OF TUMOR RESPONSE AND PROGRESSION 
Responses will be categorized as CR, PR, SD, or PD. In addition, a response category of not evaluable 
(NE) is provided for situations in which there is inadequate information to otherwise categorize 
response status. 
 
The best overall response will be determined. The best overall response is the best response 
recorded from the start of treatment until disease/recurrence progression (taking as a reference for 
disease progression the smallest measurements recorded since treatment started). Where imaging 
data are available, these data will supersede physical examination data in determining tumor status. 
8.4 COMPLETE RESPONSE 
 
To satisfy criteria for a CR, all of the following criteria must be met: 
 
• 
No evidence of new disease 
• 
ALC in peripheral blood of <4 x 109/L 
• 
Regression of all target nodal masses to normal size ≤1.5 cm in the LD 
• 
Normal spleen and liver size 
• 
Regression to normal of all nodal non-target disease and disappearance of all detectable non-
nodal, non-target disease 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 43 of 74 
• 
Morphologically negative bone marrow defined as <30% of nucleated cells being lymphoid 
cells and no lymphoid nodules in a bone marrow sample that is normocellular for age 
• 
Peripheral blood counts meeting all of the following criteria: 
o ANC >1.5 x 109/L without need for exogenous growth factors (e.g., G-CSF) 
o Platelet count ≥100 x 109/L without need for exogenous growth factors 
o Hemoglobin ≥110 g/L (11.0 g/dL) without red blood cell transfusions or need for 
exogenous growth factors (e.g., erythropoietin) 
 
Subjects who fulfill all the criteria for a CR (including bone marrow criteria) but who have a persistent 
anemia, thrombocytopenia, or neutropenia or a hypocellular bone marrow that is related to prior or 
ongoing drug toxicity (and not to CLL) will be considered as a CR with incomplete marrow recovery 
(CRi). 
8.5 PARTIAL RESPONSE 
 
To satisfy criteria for a PR, all of the following criteria must be met: 
• 
No evidence of new disease 
• 
A change in disease status meeting ≥2 of the following criteria, with 2 exceptions in which 
only 1 criterion is needed: 1) only lymphadenopathy is present at baseline; 2) only 
lymphadenopathy and lymphocytosis are present at baseline. In these 2 cases, only 
lymphadenopathy must improve to the extent specified below:   
o In a subject with baseline lymphocytosis (ALC ≥4 x 109/L), a decrease in peripheral 
blood ALC by ≥50% from baseline or a decrease to <4 x 109/L 
o A decrease by ≥50% from the baseline in the SPD of the target nodal lesions 
o In a subject with enlargement of the spleen at baseline, a splenomegaly response as 
defined in Section 8.2.2 
o In a subject with enlargement of the liver at baseline, a hepatomegaly response as 
defined in Section 8.2.2 
o A decrease by ≥50% from baseline in the CLL marrow infiltrate or in B-lymphoid 
nodules 
• 
No target, splenic, liver, or non-target disease with worsening that meets the criteria for 
definitive PD 
• 
Peripheral blood counts meeting 1 of the following criteria: 
o ANC >1.5 x 109/L or >50% increase over baseline without need for exogenous growth 
factors (e.g., G-CSF) 
o Platelet count ≥100 x 109/L or ≥50% increase over baseline without need for 
exogenous growth factors 
o Hemoglobin ≥110 g/L (11.0 g/dL) or ≥50% increase over baseline without red blood 
cell transfusions or need for exogenous growth factors (e.g., erythropoietin) 
8.6 STABLE DISEASE 
 
To satisfy criteria for SD, the following criteria must be met: 
• 
No evidence of new disease 
• 
There is neither sufficient evidence of tumor shrinkage to qualify for PR nor sufficient 
evidence of tumor growth to qualify for definitive PD 
 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 44 of 74 
8.7 DEFINITIVE DISEASE PROGRESSION 
 
The occurrence of any of the following events indicates definitive PD: 
• 
Evidence of any new disease: 
o A new node that measures >1.5 cm in the LD and >1.0 cm in the LPD 
o New or recurrent splenomegaly, with a minimum LVD of 14 cm 
o New or recurrent hepatomegaly, with a minimum LVD of 20 cm 
o Unequivocal reappearance of an extra-nodal lesion that had resolved 
o A new unequivocal extra-nodal lesion of any size  
o *New non-target disease (e.g., effusions, ascites, or other organ abnormalities related to 
CLL). 
 
*Isolated new effusions, ascites, or other organ abnormalities are not sufficient evidence alone of PD 
unless histologically confirmed. Thus, a declaration of PD should not be made if this is the only 
manifestation of apparently new disease. 
• 
Evidence of worsening of target lesions, spleen or liver, or non-target disease: 
o Increase from the nadir by ≥50% from the nadir in the SPD of target lesions 
o Increase from the nadir by ≥50% in the LD of an individual node or extra-nodal mass that 
now has an LD of >1.5 cm and an LPD of > 1.0 cm 
o Splenic progression, defined as an increase in splenic enlargement by ≥50% from nadir 
(with a minimum 2 cm increase and a minimum LVD of 14 cm) 
o Hepatic progression, defined as an increase in hepatic enlargement by ≥50% from nadir 
(with a minimum 2 cm increase and minimum LVD of 20 cm) 
o Unequivocal increase in the size of non-target disease (e.g., effusions, ascites, or other 
organ abnormalities related to CLL) 
o Transformation to a more aggressive histology (e.g., Richter’s syndrome) as established 
by biopsy (with the date of the biopsy being considered the date of CLL progression if the 
subject has no earlier objective documentation of CLL progression). 
 
• 
Decrease in platelet count or hemoglobin that is attributable to CLL, is not attributable to an 
autoimmune phenomenon, and is confirmed by bone marrow biopsy showing an infiltrate of 
clonal CLL cells 
o The current platelet count is <100 x 109/L and there has been a decrease by >50% from 
the highest on-study platelet count 
o The current hemoglobin is <110 g/L (11.0 g/dL) and there has been a decrease by >20 
g/L (2 g/dL) from the highest on-study hemoglobin 
 
Worsening of disease during temporary interruption of study treatment (e.g., for intercurrent illness) 
is not necessarily indicative of resistance to study treatment. In these instances, CT/MRI or other 
relevant evaluations should be considered in order to document whether definitive disease 
progression has occurred. If subsequent evaluations suggest that the subject has experienced 
persistent definitive CLL progression, then the date of progression should be the timepoint at which 
progression was first objectively documented. 
8.8 NON-EVALUABLE 
 
In a subject who does not have evidence of PD, the occurrence of any of the following conditions 
indicates a response status of NE: 
• 
There are no images or inadequate or missing images 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 45 of 74 
• 
Images of the liver and spleen are missing at that time point (with the exception that absence 
of splenic images will not result in an NE designation in a subject known to have undergone 
splenectomy). 
 
A time-point will be considered to have a response of NE if any target lesion is missing. PD may be 
assigned at any time point regardless of the extent of missing target or non-target lesions. Missing 
non-target lesions will not impact the ability to assess for response or disease progression. 
8.9 LYMPHOCYTOSIS DURING THERAPY 
 
Upon initiation of umbralisib, a temporary increase in lymphocyte counts (i.e., ≥ 50% increase from 
baseline and above absolute lymphocyte count of 5,000/mcL) may occur. The onset of isolated 
lymphocytosis usually occurs during the first few weeks of umbralisib therapy and usually resolves 
within three to four months.  Subjects with lymphocytosis should be continued on study drug until 
the occurrence of definitive disease progression (i.e., disease progression that is manifest by 
worsening CLL-related signs other than lymphocytosis alone), or the occurrence of another reason 
to discontinue study therapy. 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 46 of 74 
9 STATISTICAL CONSIDERATIONS 
This section describes the statistical methods to be used to analyze the efficacy and safety endpoints.   
9.1 SAMPLE SIZE 
As no formal hypothesis testing is being conducted in this study, the sample size is not based on 
powering for any study objectives.  Subjects from Treatment Arms B, C and D in Study 304 may enter 
this study upon documented progression of disease as confirmed by the independent central 
radiology review group.  At the end of the study, non-progressed subjects from Treatment Arm A may 
also be enrolled to this Phase 2 Companion Study.  It is undetermined the number of subjects that 
may enter this Companion Study, however it may not exceed the total number of subjects that have 
enrolled in Study 304, which may be up to approximately 700 subjects. 
9.2 GENERAL ANALYSIS CONVENTION 
The primary objective of this compassionate use study is to allow subjects progressing in Arms B, C, 
and D of study UTX-TGR-304 to receive, and for subjects previously in Arm A to continue to receive, 
combination therapy with ublituximab plus umbralisib.  As the study is primarily observational, no 
formal hypothesis testing will be conducted.  Continuous data will be described using the following 
descriptive statistics: n, mean, median, minimum and maximum. Data will be displayed in all listings 
sorted by treatment group (based on the treatment arm the subject was on in Study 304) and subject 
number.   
When count data are presented, the percentage will be suppressed when the count is zero in order 
to draw attention to the non-zero counts.  A row denoted “Missing” will be included in count 
tabulations where necessary to account for dropouts and missing values.  Unless otherwise specified, 
the denominator for percentages will be the number of subjects with a non-missing assessment in a 
given treatment group within the analysis population of interest. 
9.3 ANALYSIS POPULATIONS 
The Intent-to-Treat (ITT) population will consist of all subjects who were enrolled and have at least 
one post-treatment efficacy measurement. Primary efficacy analyses will be performed based on the 
ITT population. 
The Safety Population will include all subjects who were enrolled and received at least one dose of 
study drug.  All safety assessments including toxicity will be performed on the Safety Population. 
The Per-Protocol Population (PP) will consist of all ITT subjects without a major protocol deviation. 
The criteria for a major protocol deviation will be determined and documented prior to data base 
lock.  Subject exclusion from the PP population will also be determined and documented prior to 
database lock.  Supportive analyses may be performed based on the PP population. 
Furthermore, in the analyses/summaries, subjects will be assigned a treatment group based on the 
treatment they received on study UTX-TGR-304 prior to their entering of this Companion Study as 
appropriate.   

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 47 of 74 
9.4 SUBJECT DISPOSITION 
The disposition of subjects includes the number and percentage of subjects for the following 
categories: subjects enrolled, subjects treated (safety population), subjects in the ITT population, 
subjects completed, and subjects discontinued from the study.  The reasons for study discontinuation 
will also be summarized in this table.  Only one primary reason for study discontinuation will be 
reported in the summary.  However, all reasons will be presented in the listing.  The disposition will 
be summarized by treatment group and overall. 
A listing will present data concerning subject disposition. 
9.5 SUBJECT DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
Baseline demographic and clinical characteristics will be summarized as percentages for categorical 
variables and as mean, standard deviation, median, minimum and maximum for continuous 
measures. The analyses of baseline characteristics will be performed for the ITT Population by 
treatment group and overall. 
9.6 MEDICAL HISTORY 
Medical history will be captured at the Screening visit.  Medical history will be coded using MedDRA 
and will be summarized by MedDRA system organ class and preferred term for the Safety population. 
9.7 EXTENT OF EXPOSURE 
The dose (mg) of study drugs administered, the total number of doses of study drugs, and the 
duration of treatment (number of study cycles) will be summarized with descriptive statistics.  The 
number and percentage of subjects whose dose is modified at any time will be summarized by each 
type of modification by cycle and overall.  The proportion of subjects completing each cycle of 
treatment will be summarized. 
9.8 EFFICACY ANALYSES   
All subjects included in the study must have a baseline tumor assessment within 30 days of Cycle 
1/Day 1 and at least one post-treatment efficacy evaluation in order to be included in the efficacy 
analyses.  Each subject will be assigned one of the following categories:  1) complete response, 2) 
partial response, 3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) 
early death from toxicity, 7) early death because of other cause, or 9) unknown (not assessable, 
insufficient data). 
9.8.1 PRIMARY EFFICACY VARIABLE 
Overall response rate (ORR), where ORR = complete responses (CR) + partial response (PR), will be 
the primary efficacy variable.  The overall response rate (ORR) and the 90% one-sided confidence 
interval of the rate will be estimated by treatment group, if appropriate (i.e., if sample sizes are 
sufficient) and overall.   

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 48 of 74 
CR and PR will be similarly analyzed as ORR. 
9.8.2 SECONDARY EFFICACY VARIABLES 
Progression free survival (PFS) is defined as the time from study entry to the first documentation of 
tumor progression or death due to any cause whichever comes first.  For subjects previously on Arm 
A of Study UTX-TGR-304, PFS will be calculated from the date of randomization on Study UTX-TGR-
304 to the first documentation of tumor progression or death due to any cause whichever comes first.  
This variable will be analyzed via Kaplan-Meier methodology.  The median PFS will be estimated by 
treatment group, if appropriate (i.e., if sample sizes are sufficient) and overall. 
MRD negativity rate is defined as the proportion of subjects who are MRD negative.  This variable 
will be analyzed by the total number and percentage of subjects who are confirmed to achieve MRD 
negativity as per laboratory confirmation by treatment group and overall. 
Duration of response is defined as the time from documentation of a response to treatment to the 
first documentation of tumor progression or death due to any cause whichever comes first. For 
subjects previously on Arm A of Study UTX-TGR-304, unless the subject’s best overall response 
during study UTX-TGR-304 was stable disease, the duration of response will be determined from the 
first documented response on Study UTX-TGR-304.  Duration of the response will be summarized 
using n (sample size), mean, standard deviation, median, minimum and maximum for the responders 
by treatment group and overall. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 49 of 74 
10 SAFETY REPORTING AND ANALYSIS 
10.1 SAFETY ANALYSES 
Safety evaluations will be based on the incidence, intensity, and type of adverse events, as well as on 
clinically significant changes in the subject’s physical examination, vital signs, and clinical laboratory 
results.  Safety analyses will be performed using the safety population.  Safety variables will be 
tabulated and presented by the dose of the combination of ublituximab + umbralisib study drug 
actually received.  Exposure to study treatment and reasons for discontinuation of study treatment 
will also be tabulated by treatment group and overall. 
10.2 ADVERSE EVENT CHARACTERISTICS 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in the revised 
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.  A 
copy 
of 
the 
CTCAE 
version 
4.0 
can 
be 
downloaded 
from 
the 
CTEP 
web 
site 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.     
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ for expedited reporting purposes only. 
Expected AEs are defined as those described in the ublituximab Investigator Brochure and the 
umbralisib Investigator Brochure. 
10.3 DEFINITIONS OF ADVERSE EVENTS 
An adverse event (AE) is any untoward medical occurrence in a subject or clinical investigation 
subject administered a pharmaceutical product. An AE does not necessarily have to have a causal 
relationship with this treatment.   An adverse event (AE) can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding, for example), symptom, or disease 
temporarily associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. This includes any occurrence that is new in onset or aggravated in severity or 
frequency from the baseline condition. 
In clinical studies, an AE can include an undesirable medical condition occurring at any time, 
including run-in or washout periods, even if no study treatment has been administered.  The NCI 
Common Terminology Criteria for Adverse Events (CTCAE) v4.0 is to be used for the grading of 
severity of symptoms and abnormal findings.  For adverse events not covered by the NCI-CTCAE 
Version 4.0 grading system, the following definitions will be used: 
• 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• 
Grade 2: Moderate; minimal, local or non-invasive intervention indicated. 
• 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated. 
• 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
• 
Grade 5: Death related to AE. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 50 of 74 
10.4 ADVERSE EVENTS (AE’S) AND TREATMENT EMERGENT ADVERSE EVENTS 
(TEAE’S) 
All AEs and SAEs occurring on study will be listed by subject.  The frequency and percentages of 
subjects with treatment-emergent adverse events (TEAEs) will be tabulated by system organ class 
(SOC) and preferred term (PT), where treatment-emergent is defined as any AE that: 
• 
Occurs after first dosing of study medication and through the end of the study or up through 
30 days after the last dose of study treatment, or 
• 
Is considered treatment-related regardless of the start date of the event, or  
• 
Is present before first dosing of study medication but worsens in intensity or the investigator 
subsequently considers treatment-related.  
 
TEAEs that are considered at least possibly related to study treatment will be tabulated as well as 
deaths, SAEs, and events resulting in treatment discontinuation. 
AEs that occur after informed consent but before first dosing of study medication will not be 
summarized but will be listed.   
At each level of summarization, a subject will be counted only once for each AE, SOC, or PT 
experienced within that level.  In the summation for AE severity, within each level of AE, SOC, or PT 
experienced, the one with the highest severity will be included.  In the summation for AE’s 
relationship to the study drug, within each level of AE, SOC, or PT experienced, the one with the 
closest relationship to the study drug will be included. 
10.5 ADVERSE EVENTS / SERIOUS ADVERSE EVENT CAUSALITY ASSESSMENT 
The Investigator must also assess the relationship of any adverse event to the use of study drugs 
(whether none, one, or both), based on available information, using the following guidelines: 
• 
Not Related: Clear-cut temporal and/or mechanistic relation to a cause other than the study 
drug(s). 
• 
Doubtful: There is no reasonable possibility that the event is related to the study drug(s) but 
a definite cause cannot be ascertained. 
• 
Possible: There is still a reasonable possibility that the cause of the event was the study 
drug(s) but there exists a more likely cause of the event such as complications of progressive 
disease. 
• 
Probable: The most likely cause of the event is the study drug(s) but other causes cannot be 
completely excluded. 
• 
Definite: Clear cut temporal and/or mechanistic relation to the study drug(s).  All other 
causes have been eliminated.  Events classified as definite will often be confirmed by 
documenting resolution on discontinuation of the study drug and recurrence upon 
resumption. 
10.5.1 RECORDING OF ADVERSE EVENTS 
All adverse events of any subject during the course of the study will be reported on the case report 
form, and the investigator will give his or her opinion as to the relationship of the adverse event to 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 51 of 74 
study drug treatment (i.e., whether the event is related or unrelated to study drug administration –
ublituximab + umbralisib).  If the adverse event is serious, it should be reported as soon as possible 
and no greater than 24 hours to the sponsor or designee.  Other untoward events occurring in the 
framework of a clinical study are also to be recorded as AEs (i.e., AEs that occur prior to assignment 
of study treatment that are related to a protocol-mandated intervention, including invasive 
procedures such as biopsies, medication washout, or no treatment run-in). 
All AEs regardless of seriousness or relationship to ublituximab + umbralisib treatment spanning 
from Cycle 1/Day 1 until 30 calendar days after discontinuation or completion of either protocol-
specific treatment as defined by the protocol for that subject, are to be recorded on the eCRF. 
10.5.2 ABNORMAL LABORATORY VALUES AND VITAL SIGNS 
The reporting of abnormalities of vital signs as adverse events should be avoided.  Abnormalities of 
vital signs should not be reported unless any criterion for an SAE is fulfilled, the vital signs 
abnormalities cause the subject to discontinue study treatment, or the investigator insists that the 
abnormality should be reported as an AE.  Abnormal laboratory results should be noted in the eCRF 
as an adverse event if they are associated with an overdose, require or prolong inpatient 
hospitalization, or are otherwise considered clinically significant by the investigator. If an abnormal 
laboratory value or vital sign is associated with clinical signs and/or symptoms, the sign or symptom 
should be reported as an AE, and the associated laboratory value or vital sign should be considered 
additional information that must be collected in the relevant eCRF.  If the laboratory abnormality is 
a sign of a disease or syndrome, only the diagnosis needs to be recorded on the SAE Report Form or 
AE eCRF. 
Clinical Laboratory Results will be summarized.  Summary statistics for actual values and for changes 
from baseline will be tabulated for laboratory results by scheduled visit.  Subjects with laboratory 
values outside of the normal reference range at any post-baseline assessment will be summarized 
and graded per NCI CTCAE Version 4.0 when applicable.  Subject incidence of abnormal laboratory 
results will be summarized by treatment group and maximum grade for each abnormal laboratory 
finding. 
10.5.3 HANDLING OF ADVERSE EVENTS 
All adverse events resulting in discontinuation from the study should be followed until resolution or 
stabilization.  Subjects should be followed for AEs for 30 calendar days after discontinuation or 
completion of protocol-specific treatment (either ublituximab and/or umbralisib).  All new AEs 
occurring during this period must be reported and followed until resolution unless, in the opinion of 
the investigator, these values are not likely to improve because of the underlying disease.  In this case, 
the investigators must record his or her reasoning for this decision in the subject’s medical record 
and as a comment on the eCRF.  After 30 days, only AEs, SAEs, or deaths assessed by the investigator 
as treatment related are to be reported. 
 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 52 of 74 
10.6 SERIOUS ADVERSE EVENTS 
10.6.1 DEFINITIONS OF SERIOUS ADVERSE EVENTS 
The definitions of serious adverse events (SAEs) are given below.  The investigator is responsible for 
ensuring that all staff involved in the study are familiar with the content of this section. 
An SAE or reaction is defined as any untoward medical occurrence that:  
• 
results in death, is immediately life-threatening,  
• 
in-patient hospitalization or prolongation of existing hospitalization,  
• 
results in persistent or significant disability/incapacity, and/or 
• 
causes a congenital anomaly/birth defect. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the previous definition.  These should also 
usually be considered serious.  Examples of such events are intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse. 
Progression of malignancy (including fatal outcomes), if documented by use of appropriate method 
(for example, as per IWCLL Hallek et al. 2008, should not be reported as a serious adverse event.   
A suspected unexpected serious adverse reaction (SUSAR) is defined as an SAE that is suspected to 
be at least possibly related to study medication(s) and is an unexpected event. SUSAR reporting is 
encompassed within SAE reporting guidelines as defined in this section. 
Treatment within or admission to the following facilities is not considered to meet the criteria of “in-
patient hospitalization” (although if any other SAE criteria are met, the event must still be treated as 
an SAE and immediately reported): 
• 
Emergency Department or Emergency Room 
• 
Outpatient or same-day surgery units 
• 
Observation or short-stay unit 
• 
Rehabilitation facility 
• 
Hospice or skilled nursing facility 
• 
Nursing homes, Custodial care or Respite care facility 
• 
Admissions to receive protocol defined therapy 
Hospitalization during the study for a pre-planned surgical or medical procedure (one which was 
planned prior to entry in the study), does not require reporting as a serious adverse event to the 
Sponsor. 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 53 of 74 
10.6.2 SERIOUS ADVERSE EVENT REPORTING BY INVESTIGATORS 
It is important to distinguish between “serious” and “severe” adverse events, as the terms are not 
synonymous.  Severity is a measure of intensity; however, an AE of severe intensity need not 
necessarily be considered serious.  For example, nausea which persists for several hours may be 
considered severe nausea but may not be considered an SAE.  On the other hand, a stroke which 
results in only a limited degree of disability may be considered only a mild stroke but would be 
considered an SAE.  Severity and seriousness should be independently assessed when recording AEs 
and SAEs on the eCRF. 
Adverse events classified by the treating investigator as serious require expeditious handling and 
reporting to the Sponsor in order to comply with regulatory requirements.  Serious adverse events 
may occur at any time from the signing of the informed consent form through the 30-day follow-up 
period after the last study treatment.  Sponsor or designee should be notified of all SAEs, regardless 
of causality, within 24 hours of the first knowledge of the event by the treating physician or research 
personnel.   
To report an SAE, see the appropriate form. 
All SAEs (regardless of causality assessment) occurring on study or within 30 days of last study 
treatment should be immediately reported to the sponsor as SAEs within the CRF and followed until 
resolution (with autopsy report if applicable). 
CLL progression or death due to CLL progression should be reported by the investigator as a serious 
adverse event only if it is assessed that the study drugs caused or contributed to the CLL progression 
(i.e. by a means other than lack of effect).  Unrelated events of CLL progression should be captured 
on the appropriate eCRF. 
The investigator must review and sign off on the SAE data on the SAE report.  The SAE should be 
reported to the Sponsor (or Sponsor designee) as outlined in the Safety Monitoring Plan.   
When an SAE is reported to the sponsor or designee, the same information should be entered on the 
eCRF within 24 hours (1 business day).  Transmission of the SAE report should be confirmed by the 
site personnel submitting the report. 
Follow-up information for SAEs and information on non-serious AEs that become serious should also 
be reported to the sponsor or designee as soon as it is available; these reports should be submitted 
using the appropriate SAE form.  The detailed SAE reporting process will be provided to the sites in 
the Safety Monitoring Plan. 
Investigators must report SAEs and follow-up information to their responsible Institutional Review 
Board (IRBs)/Independent Ethics Committee according to the policies of the responsible IRB 
(Research Ethics Committee). 
10.7  SPONSOR SAE REPORTING REQUIREMENTS 
Sponsor is responsible for reporting relevant SAEs to the competent authority, other applicable 
regulatory authorities, and participating investigators, in accordance with ICH guidelines, FDA 
regulations, and/or local regulatory requirements. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 54 of 74 
Sponsor is responsible for reporting unexpected fatal or life-threatening events associated with the 
use of the study drugs to the regulatory agencies and competent authorities within 7 calendar days 
after being notified of the event.  The Sponsor will report all related but unexpected SAEs including 
non-death/non-life-threatening related but unexpected SAEs (SUSAR) associated with the use of the 
study medications to the regulatory agencies and competent authorities by a written safety report 
within 15 calendar days of notification.  Following the submission to the regulatory agencies and 
competent authorities, Investigators and trial sites will be notified of the SUSAR.  Investigators must 
report SUSARs and follow-up information to their responsible Institutional Review Board 
(IRBs)/Independent Ethics Committee according to the policies of the responsible IRB (Research 
Ethics Committee). 
10.8 RECORDING OF ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
Investigators should use correct medical terminology/concepts when recording AEs or SAEs on the 
SAE Report Forms and AE eCRF.  Avoid colloquialisms and abbreviations. 
All AEs, including those that meet SAE reporting criteria, should be recorded on the AE eCRF; AEs 
that meet the definition of an SAE should additionally be reported. 
10.9 DIAGNOSIS VS. SIGNS AND SYMPTOMS 
All AEs should be recorded individually in the subject’s own words (verbatim) unless, in the opinion 
of the Principal Investigator or designated physician, the AEs constitute components of a recognized 
condition, disease, or syndrome.  In the latter case, the condition, disease, or syndrome should be 
named rather than each individual sign or symptom.  If a constellation of signs and/or symptoms 
cannot be medically characterized as a single diagnosis or syndrome at the time of reporting, each 
individual event should be recorded as an AE or SAE as appropriate on the relevant form(s) (SAE 
Report Form and/or AE eCRF).  If a diagnosis is subsequently established, it should be reported as 
follow-up information is available.  If a diagnosis is determined subsequent to the reporting of the 
constellation of symptoms, the signs/symptoms should be updated to reflect the diagnosis. 
10.9.1 PERSISTENT OR RECURRENT ADVERSE EVENTS 
A persistent AE is one that extends continuously, without resolution, between subject evaluation time 
points.  Such events should only be recorded once on the SAE Report Form and/or the AE eCRF.    If 
a persistent AE becomes more severe (changes from a Grade 1 or 2 AE to a Grade 3 or 4 AE) or lessens 
in severity (changes from a Grade 3 or 4 AE to a Grade 1 or 2 AE), it should be recorded on a separate 
SAE Report Form and/or AE eCRF.   
A recurrent AE is one that occurs and resolves between subject evaluation time points, and 
subsequently recurs.  All recurrent AEs should be recorded on an SAE Report Form and/or AE eCRF 
for each recurrence. 
10.9.2 ABNORMAL LABORATORY VALUES 
Abnormal laboratory results should be noted in the eCRF as an adverse event if they are associated 
with an overdose, require or prolong inpatient hospitalization, or are otherwise considered clinically 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 55 of 74 
significant by the investigator. If an abnormal laboratory value or vital sign is associated with clinical 
signs and/or symptoms, the sign or symptom should be reported as an AE, and the associated 
laboratory value or vital sign should be considered additional information that must be collected in 
the relevant eCRF.  If the laboratory abnormality is a sign of a disease or syndrome, only the diagnosis 
needs to be recorded on the SAE Report Form or AE eCRF. 
10.9.3 DEATHS 
Deaths that occur during the protocol-specified AE reporting period that are attributed by the 
investigator solely to progression of the subject’s CLL for up to 30 days post the last dose of study 
drug will be recorded on the appropriate study eCRF and reported on the Adverse Event page of the 
eCRF, i.e. are exempted from expedited reporting. All other on-study deaths, regardless of attribution, 
will be recorded on an SAE Report Form and expeditiously reported to the Sponsor. 
When recording a serious adverse event with an outcome of death, the event or condition that caused 
or contributed to the fatal outcome should be recorded as the single medical concept on the Adverse 
Event page of the eCRF.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, record “Death NOS” on the eCRF Adverse Event page. 
10.9.4 HOSPITALIZATION, PROLONGED HOSPITALIZATION, OR SURGERY 
Any AE that results in hospital admission of >24 hours or prolongs hospitalization should be 
documented and reported as an SAE unless specifically instructed otherwise in this protocol.  There 
are some hospitalization scenarios that do not require reporting as an SAE when there is no 
occurrence of an AE.  See section 10.6.1.   
10.9.5 PRE-EXISTING MEDICAL CONDITIONS 
A pre-existing relevant medical condition is one that is present at the start of the study.  Such 
conditions should be recorded on the study’s appropriate medical history eCRF.  A pre-existing 
medical condition should be recorded as an AE or SAE only if the frequency, severity, or character of 
the condition worsens during the study.  When recording such events on the appropriate SAE Report 
Form and/or AE eCRF, it is important to convey the concept that the pre-existing condition has 
changed by including applicable descriptors. 
10.9.6 PROTOCOL-DEFINED EVENTS OF SPECIAL INTEREST 
The following are events of special interest, and will need to be reported expeditiously: 
Pregnancy, Abortion, Birth Defects/Congenital Anomalies 
During the course of the study, all female subjects of childbearing potential must contact the treating 
investigator immediately if they suspect that they may be pregnant (a missed or late menstrual 
period should be reported to the treating investigator).   
If an investigator suspects that a subject may be pregnant prior to administration of study drug(s), 
the study drug(s) must be withheld until the result of the pregnancy test is confirmed.  If a pregnancy 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 56 of 74 
is confirmed, the subject must not receive any study drug(s), and must be discontinued from the 
study.   
If an investigator suspects that a subject may be pregnant after the subject has been receiving study 
drug(s), the study drug(s) must immediately be withheld until the result of the pregnancy test is 
confirmed.  If a pregnancy is confirmed, the study drug(s) must be immediately and permanently 
stopped, the subject must be discontinued from the study, and the investigator must notify the Study 
Chair or Medical Monitor as soon as possible.   
If a subject becomes pregnant while enrolled in the study, an SAE form should be completed and 
submitted to the Sponsor.  Abortions (spontaneous, accidental, or therapeutic) must also be reported 
to the Sponsor. 
Congenital anomalies/birth defects always meet SAE criteria, and should therefore be expeditiously 
reported as an SAE, using the previously described process for SAE reporting. 
Study Drug Overdose 
Symptomatic and non-symptomatic overdose must be reported in the eCRF.  Any accidental or 
intentional overdose with the study treatment (ublituximab and/or umbralisib) that is symptomatic, 
even if not fulfilling a seriousness criterion, is to be reported to the Sponsor immediately (within 24 
hours) using the corresponding SAE form, and following the same process described for SAEs.  If a 
study drug overdose occurs, subjects should stop study drug dosing and be clinically monitored as 
appropriate, managing symptoms/side effects that may occur. 
Secondary/Second Primary Malignancy 
Any secondary/second primary malignancy event must be reported via the SAE form (in addition to 
the routine AE reporting mechanisms).  Any malignancy possibly related to cancer treatment should 
also be reported via the routine reporting mechanisms outlined in the protocol. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 57 of 74 
11 CLINICAL DATA COLLECTION AND MONITORING 
11.1 SITE MONITORING PLAN 
A Sponsor representative or designee will have made a site visit to each institution within 6 months 
prior to initiating the protocol to inspect the drug storage area, and fully inform the Investigator of 
his/her responsibilities for studies and the procedures for assuring adequate and correct 
documentation.  A study initiation site visit or a teleconference will be performed to review 
investigator responsibilities, the protocol, and its requirements with the Investigator(s).  During the 
initiation, the case report forms (CRFs)/ eCRF’s and other pertinent study materials will be reviewed 
with the investigator’s research staff.  During the course of the study, the Sponsor will make visits to 
the sites as necessary in order to review protocol compliance, examine CRFs, and individual subject 
medical records, and ensure that the study is being conducted according to the protocol and pertinent 
regulatory requirements.  Selected CRF entries will be verified with source documentation.  The 
review of medical records will be done in a manner to assure that subject confidentiality is 
maintained. 
Site monitoring shall be conducted to ensure the human subject protection, trial procedures, 
laboratory, trial intervention administration, and data collection processes are of high quality and 
meet the Sponsor, GCP/ICH and, when appropriate, regulatory guidelines.  The Site Monitoring Plan 
shall define aspects of the monitoring process. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 58 of 74 
12 ETHICAL, FINANCIAL, AND REGULATORY CONSIDERATIONS 
This trial will be conducted according to the standards of Good Clinical Practice outlined in the ICH 
E6 Tripartite Guideline and CFR Title 21 part 312, applicable government regulations, institutional 
research policies and procedures and any other local applicable regulatory requirement(s).  
12.1 IRB/IEC APPROVAL 
The trial protocol, ICF, IB, available safety information, subject documents (e.g., trial diary), subject 
recruitment procedures (e.g., advertisements), information about payments (i.e., PI payments) and 
compensation available to the subjects and documentation evidencing the PI’s qualifications must be 
submitted to the IRB/IEC for ethical review and approval prior to the trial start.   
The PI/Sponsor and/or designee will follow all necessary regulations to ensure initial and ongoing, 
IRB/IEC trial review. The PI/Sponsor (as appropriate) must submit and, where necessary, obtain 
approval from the IRB/IEC for all subsequent protocol amendments and changes to the informed 
consent document.  Investigators will be advised by the sponsor or designee whether an amendment 
is considered substantial or non-substantial and whether it requires submission for approval or 
notification only to an IRB/IEC. 
If applicable, the PI will notify the IRB/IEC within 90 days of the end of the trial, or if the trial 
terminates early, the PI must notify the IRB within 15 days of the termination.  A reason for the early 
termination must be provided (as defined in Directive 2001/20/EC). The Sponsor will either prepare 
or review all submission documents prior to submission to the IRB. 
12.2 REGULATORY APPROVAL 
As required by local regulations, the Sponsor will ensure all legal aspects are covered, and approval 
of the appropriate regulatory bodies obtained, prior to trial initiation. If required, the Sponsor will 
also ensure that the implementation of substantial amendment to the protocol and other relevant 
trial documents happen only after approval by the relevant regulatory authorities. 
Safety updates for ublituximab and umbralisib will be prepared by the Sponsor (or its 
representative), as required, for submission to the relevant regulatory authority.   
12.3 INSURANCE AND INDEMNITY 
Details of insurance and/or indemnity will be contained within the written agreement between the 
PI or site and the Sponsor. 
12.4 INFORMED CONSENT 
Informed consent is a process by which a subject voluntarily confirms his or her willingness to 
participate in a particular trial, after having been informed of all aspects of the trial that are relevant 
to the subject's decision to participate.  Informed consent is documented by means of a written, 
signed and dated informed consent form. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 59 of 74 
The ICF will be submitted for approval to the IRB/IEC that is responsible for review and approval of 
the trial.  Each consent form must include all of the relevant elements currently required by the 
responsible regulatory authority, as well as local county authority or state regulations and national 
requirements. 
Before recruitment and enrollment into the trial, each prospective candidate will be given a full 
explanation of the trial.  Once the essential information has been provided to the prospective 
candidate, and the investigator is sure that the individual candidate understands the implications of 
participating in this trial, the candidate will be asked to give consent to participate in the trial by 
signing an informed consent form.  A notation that written informed consent has been obtained will 
be made in the subject’s medical record.  A copy of the informed consent form, including the subject’s 
signature, will be provided by the investigator to the subject.   
If an amendment to the protocol substantially alters the trial design or the potential risks to the 
subjects, the subject’s consent to continue participation in the trial must be obtained. 
12.5 CONFIDENTIALITY 
Subject Confidentiality 
Confidentiality of subject’s personal data will be protected in accordance with the Health Insurance 
Portability and Accountability Act of 1996 (HIPAA), and national data protection laws. HIPAA 
regulations require that, in order to participate in the trial, a subject must sign an authorization from 
the trial that he or she has been informed of following: 
• 
What protected health information (PHI) will be collected from subjects in this trial; 
• 
Who will have access to that information and why; 
• 
Who will use or disclose that information;  
• 
That health information may be further disclosed by the recipients of the information, and 
that if the information is disclosed the information may no longer be protected by federal or 
state privacy laws;  
• 
The information collected about the research trial will be kept separate from the subject’s 
medical records, but the subject will be able to obtain the research records after the 
conclusion of the trial; 
• 
Whether the authorization contains an expiration date; and 
• 
The rights of a research subject to revoke his or her authorization.  
In the event that a subject revokes authorization to collect or use his or her 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 trial period. 
In compliance with ICH GCP guidelines and applicable parts of 21 CFR it is a requirement that the 
investigator and institution permit authorized representatives of the Sponsor, the regulatory 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 60 of 74 
authorities and the IRB direct access to review the subject’s original medical records at the site for 
verification of trial-related procedures and data.  
Measures to protect confidentiality include: only a unique trial number and initials will identify 
subjects on the CRF or other documents submitted to the Sponsor. This information, together with 
the subject’s date of birth, will be used in the database for subject identification. Subject names or 
addresses will not be entered in the CRF or database. No material bearing a subject’s name will be 
kept on file by the Sponsor. Subjects will be informed of their rights within the ICF. 
12.6 INVESTIGATOR AND STAFF INFORMATION 
Personal data of the investigators and sub-investigators may be included in the Sponsor database, 
and shall be treated in compliance with all applicable laws and regulations.  When archiving or 
processing personal data pertaining to the investigator or sub-investigator, the Sponsor shall take all 
appropriate measures to safeguard and prevent access to this data by any unauthorized party. 
12.7 FINANCIAL INFORMATION  
The finances for this trial will be subject to a separate written agreement between the Sponsor and 
applicable parties.  Any Investigator financial disclosures as applicable to 21CFR Part 54 shall be 
appropriately provided. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 61 of 74 
13 RECORD RETENTION AND DOCUMENTATION OF THE TRIAL 
13.1 AMENDMENTS TO THE PROTOCOL 
Amendments to the protocol shall be planned, documented and signature authorized prior to 
implementation.   
If an amendment to the protocol is required, the amendment will be originated and documented by 
the Sponsor.  All amendments require review and approval of the Sponsor and the Principal 
Investigator supporting the trial.  The written amendment must be reviewed and approved by the 
Sponsor, and submitted to the IRB/IEC at the investigator’s facility for the board’s approval. 
Amendments specifically involving change to trial design, risk to subject, increase to dosing or 
exposure, subject number increase, addition or removal of new tests or procedures, shall be reviewed 
and approved by the IRB/IEC at the Investigator’s facility. 
The amendment will be submitted formally to the FDA or other regulatory authorities by the Sponsor 
as applicable, and specifically when an increase to dosing or subject exposure and/or subject number 
has been proposed; or, when the addition or removal of an Investigator is necessitated. 
Items requiring a protocol amendment with IRB and REC and/or FDA and Competent Authority 
approval include, but are not limited to, the following: 
• 
Change to trial design  
• 
Risk to subject 
• 
Increase to dose or subject exposure to drug  
• 
Subject number increase of more than 20% 
• 
Addition or removal of tests and / or procedures  
• 
Addition/removal of a new Investigator  
It should be further noted that, if an amendment to the protocol substantially alters the trial design 
or the potential risks to the subjects, their consent to continue participation in the trial should be 
obtained. 
13.2 DOCUMENTATION REQUIRED TO INITIATE TRIAL 
Before the trial may begin, documentation required by FDA regulations must be provided by the 
Investigator.  The required documentation should be submitted to the Sponsor. 
Documents at a minimum required to begin the trial include, but are not limited to, the following: 
• 
A signature-authorized protocol and contract; 
• 
A copy of the official IRB/IEC approval of the trial and the IRB/IEC members list; 
• 
Current Curricula Vita for the principal investigator and any associate investigator(s) who 
will be involved in the trial; 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 62 of 74 
• 
Indication of appropriate accreditation for any laboratories to be used in the trial and a copy 
of the normal ranges for tests to be performed by that laboratory; 
• 
Original Form FDA 1572 (Statement of Investigator), appropriately completed and signed; 
• 
A copy of the IRB/IEC-approved consent form containing permission for audit by 
representatives of the Sponsor, the IRB, and the FDA;  
• 
Financial disclosure forms for all investigators listed on Form FDA 1572; 
• 
GCP Certificate for trial training; 
• 
Site qualification reports, where applicable; 
• 
Verification of Principal Investigator acceptability from local and/or national debarment 
list(s). 
The Sponsor/Sponsor designee will ensure that all documentation that is required to be in place 
before the trial may start, in accordance with ICH E6 and Sponsor SOPs, will be available before any 
trial sites are initiated. 
13.3 TRIAL DOCUMENTATION AND STORAGE 
The PI must maintain a list of appropriately qualified persons to whom he/she has delegated trial 
duties and should ensure that all persons assisting in the conduct of the trial are informed of their 
obligations. All persons authorized to make entries and/or corrections on the CRFs are to be included 
on this document. All entries in the subject’s CRF are to be supported by source documentation where 
appropriate. 
Source documents are the original documents, data, records and certified copies of original records 
of clinical findings, observations and activities from which the subject’s CRF data are obtained. These 
can include, but are not limited to, hospital records, clinical and office charts, laboratory, medico-
technical department and pharmacy records, diaries, microfiches, EKG traces, copies or 
transcriptions certified after verification as being accurate and complete, photographic negatives, 
microfilm or magnetic media, X-rays, and correspondence. 
The PI and trial staff are responsible for maintaining a comprehensive and centralized filing system 
(Site Trial File/SSF or ISF) of all trial-related (essential) documentation, suitable for inspection at any 
time by representatives from the Sponsor and/or applicable regulatory authorities.  The ISF/SSF 
must consist of those documents that individually or collectively permit evaluation of the conduct of 
the trial and the quality of the data produced.  The ISF/SSF should contain as a minimum all relevant 
documents and correspondence as outlined in ICH GCP Section 13 and 21 CFR Part 312.57, including 
key documents such as the IB and any amendments, protocol and any amendments, signed ICFs, 
copies of completed CRFs, IRB/IEC approval documents, Financial Disclosure forms, subject 
identification lists, enrollment logs, delegation of authority log, staff qualification documents, 
laboratory normal ranges, records relating to the trial drug including accountability records.  Drug 
accountability records should, at a minimum, contain information regarding receipt, shipment, and 
disposition.  Each form of drug accountability record, at a minimum, should contain PI name, date 
drug shipped/received, date, quantity and batch/code, or lot number for identity of each shipment.  
In addition, all original source documents supporting entries in the CRF must be maintained and be 
readily available. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 63 of 74 
The Sponsor shall maintain adequate investigational product records and financial interest records 
as per 21CFR Part 54.6 and Part 312.57 for no less than 2 years after the last marketing application 
has been approved by FDA; or, in the event that the marketing application has not been approved by 
FDA, for no less than 2 years after the last shipment / delivery of the drug for investigational use is 
discontinued and FDA has been notified of the discontinuation. 
The IRB/IEC shall maintain adequate documentation / records of IRB activities as per 21CFR 
Part 56.115 for at least 3 years after completion of the research. 
The Investigator shall maintain adequate records of drug disposition, case histories and any other 
trial-related records as per 21 CFR Part 312.62 for no less than 2 years after the last marketing 
application has been approved by FDA; or, in the event that the marketing application has not been 
approved by FDA, for no less than 2 years after the last shipment / delivery of the drug for 
investigational use is discontinued and FDA has been notified of the discontinuation. 
To enable evaluations and/or audits from regulatory authorities or from the Sponsor or its 
representative, the investigator additionally agrees to keep records, including the identity of all 
participating subjects (sufficient information to link records e.g., medical records), all original, signed 
informed consent forms, and copies of all CRFs, SAE Reporting forms, source documents, detailed 
records of treatment disposition, and related essential regulatory documents.  The documents listed 
above must be retained by the investigator for as long as needed to comply with national and 
international regulations (generally 2 years after discontinuing clinical development or after the last 
marketing approval).  The Sponsor or its representative will notify the investigator(s)/institutions(s) 
when the trial-related records are no longer required.   
If the investigator relocates, retires, or for any reason withdraws from the trial, the sponsor and/or 
its representative should be prospectively notified.  The trial records must be transferred to an 
acceptable designee, such as another investigator, another institution, or to sponsor.  The 
investigator must obtain the sponsor written permission before disposing of any records, even if 
retention requirements have been met.  All trial files will be maintained by the Sponsor or its 
representative throughout the trial and will be transferred to the Sponsor at the conclusion of the 
trial. 
13.4 DATA COLLECTION 
The trial CRF is the primary data collection instrument for the trial. A case report form (CRF/eCRF) 
will be utilized for the collection of all data and all data will be entered using the English language 
and should be kept current to enable the monitor to review the subjects’ status throughout the course 
of the trial. 
In order to maintain confidentiality, only trial number, subject number, initials and date of birth will 
identify the subject in the CRF.  If the subject’s name appears on any other document (e.g. laboratory 
report), it must be obliterated on the copy of the document to be supplied to the investigator site and 
replaced instead with the subject number and subject’s initials.  The investigator will maintain a 
personal subject identification list (subject numbers with corresponding subject identifiers) to 
enable records to be identified and verified as authentic. Subject data/information will be kept 
confidential, and will be managed according to applicable local, state, and federal regulations. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 64 of 74 
13.5 TRIAL MONITORING, AUDITING, AND INSPECTING 
The investigator will permit trial-related monitoring, quality audits, and inspections by the sponsor, 
government regulatory authorities, the Sponsor or its representative(s) of all trial-related documents 
(e.g., source documents, regulatory documents, data collection instruments, case report forms).  The 
investigator will ensure the capability for inspections of applicable trial-related facilities.  The 
investigator will ensure that the trial monitor or any other compliance or QA reviewer is given access 
to all trial-related documents and trial-related facilities.   
Participation as an investigator in this trial implies the acceptance of potential inspection by 
government regulatory authorities, the sponsor or its representative(s).  
At the Sponsor’s discretion Source Document Verification (SDV) may be performed on all data items 
or a percentage thereof. 
13.6 QUALITY ASSURANCE AND QUALITY CONTROL 
In addition to the Clinical Monitoring component of this protocol, the Sponsor’s Quality Assurance 
(QA) department shall establish an Auditing Plan document separate from the protocol to establish 
the criteria by which independent auditing shall be conducted during the conduct of the trial to assess 
compliance with GCP and applicable regulatory requirements.  Data or documentation audited shall 
be assessed for compliance to the protocol, accuracy in relation to source documents and compliance 
to applicable regulations. 
Each trial site shall be required to have Standard Operating Procedures (SOP’s) to define and ensure 
quality assurance/control processes for trial conduct, data generation & collection, recording of 
data/documentation and reporting according to the protocol, GCP and any applicable local, national 
or international regulations. 
13.7 DISCLOSURE AND PUBLICATION POLICY 
All information provided regarding the trial, as well as all information collected/documented during 
the course of the trial, will be regarded as confidential.  The Sponsor reserves the right to release 
literature publications based on the results of the trial. 
A clinical trial report will be prepared upon completion of the study.  The Sponsor will disclose the 
trial results, in the form of a clinical trial report synopsis, to the IEC and the applicable regulatory 
authorities within one year of the end of the trial.  The format of this synopsis and that of the clinical 
trial report and its addendum will comply with ICH E3 guidelines for structure and content of a 
clinical trial report. 
The financial disclosure information will be provided to the Sponsor prior to trial participation from 
all PIs and Sub-Investigators who are involved in the trial and named on the FDA 1572 form. 
By conducting this study, the Investigator affirms to the Sponsor that he or she will maintain, in strict 
confidence, information furnished by the Sponsor including data generated from this study and 
preliminary laboratory results, except as exempted for regulatory purposes.  

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 65 of 74 
All data generated during the conduct of this study is owned by the Sponsor and may not be used by 
the Investigator or affiliates without the expressed written consent of the Sponsor. 
All manuscripts, abstracts, or other presentation materials generated by site investigators must be 
reviewed and approved by the Sponsor prior to submission. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 66 of 74 
14 REFERENCES 
1. 
Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, 
Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, 
Edwards BK (eds). SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, 
MD, http://seer.cancer.gov/csr/1975 2007/, based on November 2009 SEER data submission, 
posted to the SEER web site, 2010. 
2.  
Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM,… Clow MF. Ibrutinib versus 
ofatumumab in previously treated chronic lymphoid leukemia. NEJM. 2014;371(3), 213-223 
3. 
de Romeuf C, Dutertre CA, Le Garff-Tavernier M, Fournier N, Gaucher C, Glacet A, et al. Chronic 
lymphocytic leukaemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for 
improved engagement of FcgammaRIIIA/CD16. British journal of haematology. 2008;140(6):635-43. 
4. 
Baritaki S, Militello L, Malaponte G, Spandidos DA, Salcedo M, Bonavida B. The anti-CD20 mAb 
ublituximab interrupts the dysregulated NF-kappaB/Snail/RKIP/PTEN resistance loop in B-NHL 
cells: role in sensitization to TRAIL apoptosis. Int J Oncol. 2011;38(6):1683-94. 
5. 
Esteves I, Dumontet C, Herveau S et al.  ublituximab a Third Generation Monoclonal Anti-
CD20 Antibody Displays an Additive Antitumor Activity with Antileukemic Chemotherapeutic Agents 
in Mouse Xenograft Models.  American Society of Clinical Oncology 2011 Poster Presentation. 
6. 
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines 
for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International 
Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 
1996 guidelines. Blood. 2008;111(12):5446-56. PMCID: 2972576. 
7. 
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response 
criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579-86. 
8.  
Fowler NH, Nastoupil LJ, Lunning MA, Vose J, Siddiqi T, Flowers C,… O'Brien, SM. Safety and 
activity of the chemotherapy-free triplet of ublituximab, TGR-1202, and ibrutinib in relapsed B-cell 
malignancies. American Society of Clinical Oncology Annual Meeting. 2015; abstract 8501 
9.  
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Cronin KA et al. SEER Cancer 
Statistics Review, 1975-2009 (Vingage 2009 populations), National Cancer Institute. Bethesda, MD. 
http://seer.cancer.gov/csr/1975 2009 pops09, based on November 2011 SEER data submission, 
posted to the SEER website, 2012. 
10. 
Lin K, Sherrington PD, Dennis M, Matrai Z, Cawley JC, Pettitt AR. Relationship between p53 
dysfunction, CD38 exp and IgVH mutatio in chronic lymphocytic leukemia. Blood. 2002;100(4) 
11.  
Lunning M, Vose J, Fowler N, Nastoupil L, Burger JA, Wierda WG,… O'Brien S. Ublituximab + 
TGR-1202 Demonstrates Activity and Favorable Safety Profile in Relapsed/Refractory B-Cell NHL 
and High-Risk CLL. American Society of Clinical Oncology Annual Meeting. 2015; abstract 8548 
12. 
 PI3Kα enzyme assay. Shameerpet, India: Incozen Therapeuticis 
PVT Ltd; 2011 May Protocol IVT-5264-EAA-17 Sponsored by Rhizen Pharmaceutical S.A Switzerland  

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 67 of 74 
13. 
 PI3Kβ enzyme assay. Shameerpet, India: Incozen Therapeuticis 
PVT Ltd; 2011 May Study Report IVT-5264-EAB-18 Sponsored by Rhizen Pharmaceutical S.A 
Switzerland  
14. 
 PI3Kδ enzyme assay. Shameerpet, India: Incozen Therapeuticis 
PVT   2011 March Study Report IVT-5264-EAD-20 Sponsored by Rhizen Pharmaceutical S.A 
Switzerland  
15. 
 PI3Kγ enzyme assay. Shameerpet, India: Incozen Therapeuticis 
PVT Ltd; 2011 April Protocol IVT-5264-EAG-19 Sponsored by Rhizen Pharmaceutical S.A Switzerland  
16. 
 AKT phosphorylation in THP-1 cells. Shameerpet, India: Incozen 
Therapeuticis PVT Ltd; 2011 July Study Report IVT-5264-ATP-08 Sponsored by Rhizen 
Pharmaceutical S.A Switzerland  
17. 
 AKT phosphorylation in MOLT-4 cells. Shameerpet, India: Incozen 
Therapeuticis PVT Ltd; 2011 June Study Report IVT-5264-APM-10 Sponsored by Rhizen 
Pharmaceutical S.A Switzerland 
18. 
 AKT phosphorylation in DB cells. Shameerpet, India: Incozen 
Therapeuticis PVT Ltd; 2011 June Study Report IVT-5264-APD-11 Sponsored by Rhizen 
Pharmaceutical S.A Switzerland 
19. 
 AKT phosphorylation in JURKAT cells. Shameerpet, India: Incozen 
Therapeuticis PVT Ltd; 2011 August Study Report IVT-5264-APG-12 Sponsored by Rhizen 
Pharmaceutical S.A Switzerland 
20. 
 AKT phosphorylation in HL-60 cells. Shameerpet, India: Incozen 
Therapeuticis PVT Ltd; 2011 August Study Report IVT-5264-APH-09 Sponsored by Rhizen 
Pharmaceutical S.A Switzerland  
21. 
 Leukemic cell proliferation assay. Shameerpet, India: Incozen 
Therapeuticis PVT Ltd; 2012 April Protocol IVT-5264-LCA-01Sponsored by Rhizen Pharmaceutical 
S.A Switzerland 
 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 68 of 74 
15 APPENDIX A – IWCLL RESPONSE CRITERIA 
Chronic Lymphocytic Leukemia Response Definition (Hallek et al. 2008) 
Assessment of response should include a careful physical examination and evaluation of the blood and 
marrow. 
Complete 
Response: 
(CR) 
CR requires all of the following criteria as assessed at least 2 months after completion of therapy: 
1. Peripheral blood lymphocytes (evaluated by blood and differential count) below 4 x 109/L 
(4000/µL). 
2. Absence of significant lymphadenopathy (e.g., lymph nodes >1.5 cm in diameter) by physical 
examination. 
3. No hepatomegaly or splenomegaly by physical examination and CT. 
4. Absence of constitutional symptoms. 
5. Blood counts above the following values: 
• 
Neutrophils >1.5 x 109/L (1500/µL) without need for exogenous growth factors. 
• 
Platelets >100 x 109/L (100 000/µL) without need for exogenous growth factors. 
• 
Hemoglobin >110 g/L (11.0 g/dL) without red blood cell transfusion or need for 
exogenous erythropoietin. 
 
For patients in clinical trials, a marrow aspirate and biopsy should be performed at least 2 months 
after the last treatment and if clinical and laboratory results listed above a-e demonstrate that a CR 
has been achieved.  To define a CR, the marrow sample must be at least normocellular for age, with less 
than 30% of nucleated cells being lymphocytes.  Lymphoid nodules should be absent.  In some cases, 
lymphoid nodules can be found, which often reflect residual disease.  These nodules should be recorded as 
"nodular PR."  Moreover, immunohistochemistry should be performed to define whether these nodules are 
composed primarily of T cells or lymphocytes other than CLL cells or of CLL cells.  If the marrow is 
hypocellular, a repeat determination should be performed after 4 weeks, or until peripheral blood counts 
have recovered.  However, this time interval should not exceed 6 months after the last treatment.  A 
marrow biopsy should be compared with that of pretreatment marrow. In general practice, the use of a 
marrow biopsy for evaluating a CR is at the discretion of the physician.  
In clinical trials aiming at maximizing the CR rate, the quality of the CR should be assessed for MRD by 
flow cytometry or by immunohistochemistry. 
A controversial issue is how best to categorize the response of patients who fulfill all the criteria for 
a CR (including the marrow examinations described above) but who have a persistent anemia or 
thrombocytopenia or neutropenia apparently unrelated to CLL but related to drug toxicity.  We 
recommend that these patients be considered as a different category of remission:  CR with incomplete 
marrow recovery (CRi).  For the definition of this category, CRi, the marrow evaluation (described above) 
should be performed with scrutiny and not show any clonal infiltrate.  In clinical trials, CRi patients 
should be monitored prospectively to determine whether their outcome differs from that of patients with 
detectable residual or with noncytopenic CR. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 69 of 74 
Chronic Lymphocytic Leukemia Response Definition (Hallek et al. 2008) (continued) 
Partial 
Response: 
(PR) 
To define a PR (partial remission): at least two of the criteria of Group A plus one of the criteria 
of Group B have to be met. The parameters below should be documented for no less than 
2 months.  Constitutional symptoms persisting for >1 month should be recorded. 
Group A 
a. 
Decrease in the number of blood lymphocytes by 50% or more from the value before 
therapy. 
b. Reduction in lymphadenopathy (by PE and CT scans) as defined by the following: 
• 
A decrease in lymph node size by 50% or more either in the sum products of up to 
6 lymph nodes, or in the largest diameter of the enlarged lymph node(s) detected 
prior to therapy. 
• 
No increase in any lymph node, and no new enlarged lymph node. In small lymph 
nodes (<2 cm), an increase of less than 25% is not considered to be significant. 
c. 
Reduction in the noted pretreatment enlargement of the spleen or liver by 50% or more, as 
detected by CT scan. 
Group B 
d. Blood count should show one of the following: 
• 
Neutrophils >1.5 x 109/L (1500/µL) without need for exogenous growth factors. 
• 
Platelet count >100 x 109/L (100 000/µL) or 50% improvement over baseline 
without need for exogenous growth factors. 
• 
Hemoglobin >110 g/L (11.0 g/dL), or 50% improvement over baseline without 
requiring red blood cell transfusions or exogenous erythropoietin. 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 70 of 74 
 Chronic Lymphocytic Leukemia Response Definition (Hallek et al. 2008) (continued) 
Progressive 
Disease: 
(PD) 
Progressive disease during or after therapy is characterized by at least one of the following: 
a. 
Lymphadenopathy:  Progression of lymphadenopathy is often discovered by 
physical examination and should be recorded. In CLL, the use of CT scans 
usually does not add much information for the detection of progression or 
relapse.  Therefore, the use of imaging methods to follow CLL progression is at 
the discretion of the treating physician. Disease progression occurs if one of the 
following events is observed: 
• 
Appearance of any new lesion, such as enlarged lymph nodes (>1.5 
cm), splenomegaly, hepatomegaly, or other organ infiltrates. 
• 
An increase by 50% or more in greatest determined diameter of any 
previous site. 
b. An increase in the previously noted enlargement of the liver or spleen by 50% or 
more, or the de novo appearance of hepatomegaly or splenomegaly. 
c. 
An increase in the number of blood lymphocytes by 50% or more, with at least 
5000 B-lymphocytes per µL. 
d. Transformation to a more aggressive histology (e.g., Richter syndrome).  
Whenever possible, this diagnosis should be established by lymph node biopsy. 
e. 
Occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable 
to CLL  
• 
During therapy:  Cytopenias may occur as a side effect of many 
therapies.  During therapy, cytopenias cannot be used to define disease 
progression. 
• 
After treatment:  The progression of any cytopenia (unrelated to 
autoimmune cytopenia), as documented by a decrease of Hb levels by 
>20 g/L (2 g/dL) or to <100 g/L (10 g/dL), or by a decrease of platelet 
counts by >50% or to <100 x 109/L (100,000/µL), which occurs at least 
3 months after treatment, defines disease progression, if the marrow 
biopsy demonstrates an infiltrate of clonal CLL cells. 
 
Stable 
Disease:  
(SD) 
Patients who have not achieved a CR or a PR, and who have not exhibited progressive disease, will 
be considered to have stable disease (which is equivalent to a non-response). 
Source:  Hallek M, Cheson BD, Catovsky D, et al.  Guidelines for the diagnosis and treatment of chronic 
lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the 
National Cancer Institute–Working Group 1996 guidelines. Blood. 2008;111:5446-56. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 71 of 74 
16 APPENDIX B - CONTRACEPTIVE GUIDELINES AND PREGNANCY 
Women Not of Childbearing Potential are Defined as Follows: 
Women are considered post-menopausal and not of child bearing potential if they have had 12 
months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age 
appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum 
FSH levels > 40 mIU/mL [for US only: and estradiol < 20 pg/mL] or have had surgical bilateral 
oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy 
alone, only when the reproductive status of the woman has been confirmed by follow up hormone 
level assessment is she considered not of child bearing potential. 
Contraceptive Guidelines for Women of Child-Bearing Potential: 
Women of child-bearing potential, defined as all women physiologically capable of becoming 
pregnant, must use effective contraception during the study and for 4 months after stopping 
treatment. If a women of child-bearing potential was on treatment arm B (obinutuzumab arm) from 
trial UTX-TGR-304, effective contraception should continue to be used for 18 months after the last 
treatment dose of obinutuzumab.  Effective contraception is defined as: 
1. True abstinence: When this is in line with the preferred and usual lifestyle of the subject. 
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and 
withdrawal are not acceptable methods of contraception. 
2. Sterilization:  have had surgical bilateral oophorectomy (with or without hysterectomy) or 
tubal ligation at least six weeks ago.  In case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow up hormone level 
assessment. 
3. Male partner sterilization (with the appropriate post-vasectomy documentation of the 
absence of sperm in the ejaculate). For female subjects on the study, the vasectomised male 
partner should be the sole partner for that subject. 
4. Oral contraception, injected or implanted hormonal methods. 
5. Use of a combination of any two of the following (a+b): 
a. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 
b. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. 
The following are unacceptable forms of contraception for women of childbearing potential:  
• 
Female condom  
• 
Natural family planning (rhythm method) or breastfeeding  
• 
Fertility awareness  
• 
Withdrawal  
• 
Cervical shield 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 72 of 74 
Women of child-bearing potential must have a negative serum pregnancy test ≤ 72 hours prior to 
initiating treatment. 
Fertile Males: 
Fertile males, defined as all males physiologically capable of conceiving offspring must use condom 
during treatment, and for an additional 4 months after study drug discontinuation, and should not 
father a child in this period.   
Pregnancies 
To ensure subject safety, each pregnancy in a subject on study treatment must be reported to TG 
Therapeutics Inc. within 24 hours of learning of its occurrence. The pregnancy should be followed up 
for 3 months after the termination of the pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications. 
Pregnancy should be recorded on a Clinical Study Pregnancy Form and reported by the investigator 
to TG Therapeutics Inc.  Pregnancy follow-up should be recorded on the same form and should 
include an assessment of the possible relationship to the study drug and reported by the investigator 
to TG Therapeutics Inc.  Any SAE experienced during pregnancy must be reported on the SAE Report 
Form. 
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study.  Consent to report information regarding these pregnancy outcomes should 
be obtained from the mother. 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 73 of 74 
17 APPENDIX C – NEW YORK HEART ASSOCIATION (NYHA) 
CLASSIFICATIONS 
 
Class 
Functional Capacity 
Objective Assessment 
I 
Patients with cardiac disease but without resulting 
limitations of physical activity.  Ordinary physical 
activity does not cause undue fatigue, palpitation, 
dyspnea, or anginal pain. 
No objective evidence of 
cardiovascular disease. 
II 
Patients with cardiac disease resulting in slight 
limitation of physical activity.  They are comfortable at 
rest.  Ordinary physical activity results in fatigue, 
palpitation, dyspnea, or anginal pain. 
Objective evidence of 
minimal cardiovascular 
disease. 
III 
Patients with cardiac disease resulting in marked 
limitation of physical activity.  They are comfortable at 
rest.  Less than ordinary activity causes fatigue, 
palpitation, dyspnea, or anginal pain. 
Objective evidence of 
moderately severe 
cardiovascular disease. 
IV 
Patients with cardiac disease resulting in inability to 
carry on any physical activity without discomfort.  
Symptoms of heart failure or the anginal syndrome 
may be present even at rest.  If any physical activity is 
undertaken, discomfort is increased. 
Objective evidence of 
severe cardiovascular 
disease. 
Source:  The Criteria Committee of New York Heart Association.  Nomenclature and Criteria for 
Diagnosis of Diseases of the Heart and Great Vessels.  9th Ed. Boston, MA:  Little, Brown & Co; 
1994:253-256. 
 
 
 

UTX-TGR-204 
 
 
Dated:22 January 2019  (Ver 6.0) 
 
Page 74 of 74 
18 APPENDIX D – INTERPRETATION OF HEPATITIS B RESULTS