Clinical trial NCT05108805
Conditions: Large B-cell Lymphoma Diffuse Large B-cell Lymphoma
Sponsor: Vanderbilt-Ingram Cancer Center
Start date: 2021-12-02; Completion date: 2023-12-08
Enrollment: 25 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
We hope to demonstrate that YESCARTA can be safely administered in the outpatient setting if we closely monitor subjects with physical exams, wearable devices, and telemedicine visits and only admit those who meet specified criteria

Detailed description:
Primary Objectives

* To explore the feasibility of treating subjects with YESCARTA in the outpatient setting and guide the development of a subsequent, larger study that will determine the tolerability and safety profile of YESCARTA in the outpatient setting.
* To determine the time to specific interventions post infusion and the number of subjects who remain outpatient through 72 hours, 7, 14, and 30 days.

Secondary Objectives:

* Identify risk factors that preclude outpatient administration, and to obtain clinical data that will guide the development of guidelines by which YESCARTA treatment in the outpatient setting can be done safely.
* Assess the impact of close monitoring with telemedicine and twice-daily physical exam on specific outcomes including CRS and ICANS in subjects treated with YESCARTA in the outpatient setting.
* Cumulative steroid exposure within 28 days post YESCARTA infusion.
* To calculate the estimated cost of YESCARTA administered in the outpatient setting.

Exploratory Objectives:

* Time from YESCARTA infusion to the following: fever, fever with neutropenia, fever without neutropenia.
* Time from fever to Tocilizumab, fever to ICU admission, fever to low BP, fever to IV Fluid, fever to vasopressor, fever to onset to arrhythmias and fever to hospitalization.
* Calculate modified Neutropenic Fever Symptom Burden (NFSB) score for days 1-3 for each subject. Appendix D
* Obtain subject reported outcomes measured by Subject-Reported Outcomes Measurement Information System (PROMIS; Appendix F) \[16, 17\]
* Feasibility of using wearable devices to monitor vital signs in the outpatient setting. Data collected are for research only

Arms: arm 1: Patients receive cyclophosphamide IV and fludarabine IV on days -5 to -3. Patients then receive YESCARTA IV for over 30 minutes on day 0 in the absence of disease progression of unacceptable toxicity.
Interventions: intervention 1: Telemedicine Visit intervention 2: Vital sign measurements intervention 3: Out-Patient Clinic Visit intervention 4: Blood pressure and pulse oximeter intervention 5: Axicabtagene Ciloleucel intervention 6: Cyclophosphamide intervention 7: Fludarabine
Intervention descriptions: intervention 1: A remote telemedicine visit with audio and video, using the internet with a nurse practitioner (NP) located elsewhere. The participant and NP will activate the telemedicine App in their electronic device. Family will obtain vital signs (BP, heart rate (HR), respiration rate (RR), SPO2) and provide NP with the information. NP will also review the previous vital signs. Review of system questions are asked, and the answers given by subject recorded. Neurological assessment done, and ICE score calculated. intervention 2: Participant and their family will record and measure vital signs using a wearable device and will place a call to the covering nurse practitioner to report the vital signs prior to reporting to the out patient visit. intervention 3: Physical exam and review of all available data intervention 4: Participant and their family take their blood pressure and pulse oximeter intervention 5: Axicabtagene Ciloleuce given by IV intervention 6: Given IV intervention 7: Given IV

Protocol documents:
Prot_SAP_001.pdf: 
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CLINICAL STUDY PROTOCOL 
 
 
Safety and Feasibility Study of Chimeric Antigen Receptor 
(CAR) T Cell Therapy with YESCARTA in the Outpatient 
Setting 
Concept Summary Safely transitioning YESCARTA® (axicabtagene ciloleucel) 
treatment to the outpatient setting 
Investigational Site Vanderbilt-Ingram Cancer Center 
Support Kite Pharma, Inc. 
Clinicaltrials.gov number NCT05108805 
Sponsor-Investigator Olalekan O. Oluwole, MD, MPH 
Original Protocol Date 17 June 2021 
Protocol v2.0 21 December 2021 
Protocol v2.1 03 February 2022 
Protocol v3.0 13 April 2022 
Protocol v4.0 16 August 2022 
Protocol v4.1 11 November 2022 
Protocol v4.2 06 January 2023 
Protocol v4.3 05 September 2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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PROTOCOL SYNOPSIS 
 
Title Safely transitioning YESCARTA® (axicabtagene ciloleucel) treatment to the 
outpatient setting. 
Indication Exploring the feasibility of outpatient treatment with YESCARTA. 
Stucdy Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This study is an open label non-randomized treatment with YESCARTA in 
the outpatient setting. The purpose is to demonstrate that YESCARTA can 
be safely administered in the outpatient setting if we closely monitor 
subjects with physical exams, wearable devices, and telemedicine visits 
and only admit those who meet specified criteria 
 
Enrollment and apheresis: Eligible subjects are enrolled and apheresed per 
YESCARTA protocol 
 
Day -5 to -3: Pre-lymphodepleting Period. Subjects and family are trained 
to do vital signs, use wearable devices, and operate equipment suitable 
for telemedicine. Patients who remain eligible for outpatient therapy will 
proceed to receive lymphodepleting chemotherapy day -5 to -3 
 
Day 0:  
Subjects report to the clinic in the morning of day 0 for physical exam and 
laboratory tests. The Immune Effector Cell-Associated Encephalopathy 
(ICE) score will be calculated. 
 
YESCARTA is infused in the outpatient clinic and subject monitored for 2 
hours post-infusion before they are discharged to the apartment. A 
telemedicine evaluation is done at 16:30 PM and 22:00 ± 1 hour which 
includes a review of systems, physical exam including neurological 
assessment (ICE score), and vital signs. Subject will awake in AM, family 
will obtain vital signs at 06:30 ± 1 hour, and place a call to the covering NP 
to report the vital signs prior to presenting to the outpatient clinic at 08:00 
AM. 
 
Day 1 – Day 14:  
1. 08:00 AM: Subject reports to the outpatient clinic at 8am daily 
including weekends. Vital signs log reviewed by NP and equipment 
checked. Laboratory tests are ordered per protocol. Physical exam 
by NP and attending physician both of whom review all available 
data including the ICE score. Subject discharged back to the 
apartment by 10:00 AM or shortly after if no criteria for 
hospitalization are met. 
2. 12:00: Subject and family take their blood pressure and pulse 
oximeter using the device provided. They will call NP line if they 


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become aware of abnormal vital signs or a change in patient’s 
status. 
3. 16:30 and 22:00 ± 1 hour: Telemedicine visit with night NP. 
 
Telemedicine details: Subject and NP will activate the telemedicine App in 
their electronic device. Family will obtain vital signs (BP, HR, RR, SPO2) and 
provide NP with the information. NP will also review the previous vital 
signs at 12:00 and/or 16:30. Review of system questions are asked, and 
the answers given by subject recorded. Neurological assessment done, 
and ICE score calculated.  
 
Criteria for admission to the hospital: 
1. Fever ≥102̊ F or higher, or fever 100.4 to < 102 with a change in 
status (e.g. hypotension, altered mental status or other sign of end 
organ dysfunction). Fever < 102 alone without other symptom can 
be closely monitored in the outpatient setting per written 
institution guidelines.  
2. Hemodynamic instability: (any of the following) Hypotension that 
requires IV fluids, MAP < 20% of baseline or SBP < 90 mmHg or HR 
> 130/min 
3. Sustained hypoxia with SPO2 < 90% 
4. Abnormal neurological function (grade 1 or higher ICANS) based on 
the ICE score 
5. Other criteria at the discretion of the covering physician. 
 
For study requirements, refer to Section 7 and the schedule of 
assessments (SOAs) in Section 8 for details.  
 
A study schema is provided in Figure 1 (Section 6.3.4.2).  
Study 
Objectives The primary objective is to explore the feasibility of treating subjects with 
YESCARTA in the outpatient setting and determine the number of subjects 
who remain outpatient through 72 hours, 7, 14, and 30 days.  
Secondary Objectives are to identify risk factors that preclude outpatient 
administration, obtain clinical data that will inform the development of 
guidelines by which YESCARTA treatment can be done in safely in the 
outpatient setting, and assess the impact of telemedicine and close 
monitoring on specific outcomes including CRS and ICANS in subjects 


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treated with YESCARTA in the outpatient setting. Data from wearable 
device are collected for research only. 
Study 
Hypothesis  
No formal statistical hypothesis will be tested. All analyses will be 
descriptive. 
Study Endpoints 
1. Number of subjects that remain an outpatient at 3, 7 and 30 days 
after YESCARTA infusion.  
2. Time to requirement for inpatient hospitalization after YESCARTA 
infusion. 
3. Incidence/grade of adverse events, CRS and ICANS 
4. Incidence of steroid and/or tocilizumab administration 
5. YESCARTA treatment response rate. 
Sample Size Twenty subjects will receive YESCARTA treatment  
Study Eligibility Refer to Section 5 for a complete and detailed list of inclusion and 
exclusion criteria.  
Treatment 
1. Conditioning chemotherapy regimen consisting of 
cyclophosphamide 500 mg/m2/day and fludarabine 30 mg/m2/day 
will be administered for 3 days prior to YESCARTA infusion. Refer 
to Section 6 for chemotherapy treatment details.  
2. YESCARTA treatment consists of a single infusion of chimeric 
antigen receptor (CAR) transduced autologous T cells administered 
intravenously at a target dose of 2 x 106 anti-CD19 CAR T cells/kg. 
Refer to Section 6 and Section 7 for treatment details.  
Adjunct to treatment: oral dexamethasone 10 mg once daily for 3 days, 
starting prior to YESCARTA infusion on Day 0 
 
Safety Review 
and Data 
Monitoring 
A safety review team (SRT) will be established that consists of PI, sub-I and 
study sponsor representative. The SRT will review safety data after 10 
subjects are treated and make recommendations regarding further study 
conduct based on the overall safety profile of YESCARTA.  
Statistical 
Considerations 
The statistical reporting of the safety and efficacy endpoints will be 
entirely descriptive; no formal statistical testing will be performed.  
The subject incidence rates of AEs and clinically significant changes in 
safety lab values will be summarized. See Appendix E for detailed 
statistical considerations. 
 
 
 
STUDY GLOSSARY 
 
AE 
ALL 
ALT   
ANC   
Adverse event 
Acute lymphoblastic leukemia 
Alanine aminotransferase 
Absolute neutrophil count 


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ASCT   
AST   
AUC   
BBB   
BP   
BUN   
CAR   
CBC   
CLL   
CMP   
CMV   
CNS   
CPF 
CR   
CRF   
CRP   
CRS   
CSF   
CTCAE   
DLBCL   
DLT   
DOR   
DSMB   
eACTTM   
EBV   
ECG   
ECHO   
ECOG   
EQ-5D   
FAS   
FL 
GCP   
GOT   
GPT 
HCT   
HGBCL   
HIV   
HR   
HLH  
HSCT  
IB  
ICE   
ICANS   
IC  
ICF  
ICH  
ICU  
ID  
Autologous stem cell transplant 
Aspartate aminotransferase 
Area under the curve 
Blood brain barrier 
Blood Pressure                                                                                            
Blood urea nitrogen 
Chimeric antigen receptor 
Complete blood count 
Chronic lymphocytic leukemia 
Complete Metabolic panel                                                                                             
Cytomegalovirus 
Central nervous system 
Cell processing facility 
Complete response 
Case report form 
C-reactive protein 
Cytokine release syndrome 
Cerebrospinal fluid 
Common Terminology Criteria for Adverse Events                                               
Diffuse large B-cell lymphoma 
Dose-limiting toxicity 
Duration of response 
Data Safety Monitoring Board 
Engineered autologous cell therapy 
Epstein-Barr virus 
Electrocardiogram 
Echocardiogram 
Eastern Cooperative Oncology Group 
European Quality of Life-5 Dimensions 
Full analysis set 
Follicular lymphoma 
Good Clinical Practice 
Glutamic-oxaloacetic transaminase                                                                          
Glutamic-pyruvic transaminase 
Hematopoietic stem cell transplant                                                            
High grade B-cell lymphoma 
Human immunodeficiency virus                                                                                       
Heart Rate                                                                                                                          
Hemophagocytic lymphohistiocytosis  
Hematopoietic stem cell transplantation  
Investigator’s Brochure  
Immune Effector Cell-Associated Encephalopathy                                                  
Immune effector cell-associated neurotoxicity syndrome           
Investigator’s choice  
Informed consent form  
International Conference on Harmonization  
Intensive care unit  
Identification  


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IDSA  
IEC  
IFN  
IHC  
IL  
ImiD  
IP  
IPM  
IRB  
IRT  
IUD  
IV  
LDH 
LTFU  
LVEF  
mAb  
MASCC 
MDS  
mITT  
MRI  
NCI  
NHL  
NK  
NPT  
ORR  
OS  
PBMC  
PCR  
PD  
PET-CT  
PFS  
PK 
PO  
PR  
qd  
qPCR  
RCR  
REMS  
SAE  
scFv  
SCT  
SD  
SmPC  
SOA  
SRT  
SSAP  
TEAE  
TLS  
Infectious Diseases Society of America  
Independent Ethics Committee  
Interferon  
Immunohistochemistry  
Interleukin  
Immunomodulatory drug  
Investigational product  
Investigational Product Manual  
Institutional Review Board  
Interactive response technology  
Intrauterine device  
Intravenous  
Long-term follow-up  
Left ventricular ejection fraction  
Lactate Dehydrogenase                                                                                                
Monoclonal antibody                                                                    
Multinational Association of Supportive Care of Cancer                                                    
Myelodysplastic syndrome  
Modified intent-to-treat  
Magnetic resonance imaging  
National Cancer Institute  
Non-Hodgkin lymphoma  
Natural killer  
Nasopharyngeal-throat  
Objective response rate  
Overall survival  
Peripheral blood mononuclear cell  
Polymerase chain reaction  
Progressive disease  
Positron emission tomography-computed tomography  
Progression-free survival  
Pharmacokinetics 
Taken orally  
Partial response  
Every day  
Quantitative polymerase chain reaction  
Replication-competent retrovirus  
Risk Evaluation and Mitigation Strategy  
Serious adverse event  
Single-chain variable fragment  
Stem cell transplant  
Stable disease  
Summary of product characteristics  
Schedule of assessment  
Safety review team  
Supplementary statistical analysis plan  
Treatment-emergent adverse event  
Tumor lysis syndrome  


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TNF  
UA  
ULN  
USPI  
UTI  
WBC 
Tumor necrosis factor  
Urinalysis  
Upper limit of normal  
United States Prescribing Information  
Urinary tract infection  
White blood cell 
 
 
 
 
 


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1. OBJECTIVES 
 
1.1. 
Primary Objectives 
 
• 
To explore the feasibility of treating subjects with YESCARTA in the 
outpatient setting and guide the development of a subsequent, larger study 
that will determine the tolerability and safety profile of YESCARTA in the 
outpatient setting.  
 
• 
To determine the time to specific interventions post infusion and the 
number of subjects who remain outpatient through 72 hours, 7, 14, and 30 
days.  
 
 
1.2. 
Secondary Objectives 
 
• 
Identify risk factors that preclude outpatient administration, and to obtain 
clinical data that will guide the development of guidelines by which 
YESCARTA treatment in the outpatient setting can be done safely. 
 
• 
Assess the impact of close monitoring with telemedicine and close 
monitoring on specific outcomes including CRS and ICANS in subjects 
treated with YESCARTA in the outpatient setting. 
 
 
• 
Cumulative steroid exposure within 28 days post YESCARTA infusion. 
 
 
• 
To calculate the estimated cost of YESCARTA administered in the outpatient 
setting. 
 
 
1.3. 
Exploratory Objectives 
 
• 
Time from YESCARTA infusion to the following: fever, fever with 
neutropenia, fever without neutropenia. 
 
• 
Time from fever to Tocilizumab, fever to ICU admission, fever to low BP, 
fever to IV Fluid, fever to vasopressor, fever to onset to arrhythmias and 
fever to hospitalization. 
 
 
• 
Calculate modified Neutropenic Fever Symptom Burden (NFSB) score for 
days 1-3 for each subject. Appendix D 
 
 
• 
Obtain subject reported outcomes measured by Subject-Reported 
Outcomes Measurement Information System (PROMIS; Appendix F) [16, 17] 


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• 
Feasibility of using wearable devices to monitor vital signs in the outpatient 
setting. Data collected are for research only. 
 
 
2. DISEASE BACKGROUND AND RATIONALE 
 
2.1. 
Background 
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of large B-cell 
lymphoma with approximately 22,000 new diagnoses each year in the United States. 
Cytotoxic chemotherapy is curative in 40 to 60% of the subjects. However, subjects with 
relapsed or chemotherapy refractory DLBCL have a particularly dire prognosis.[1]  
2.2. 
Yescarta 
Axicabtagene ciloleucel (YESCARTA®) is approved by the US Food and Drug Administration 
(FDA) based on ZUMA-1 data with objective response rate was 82%, the complete response 
rate was 54% and the overall rate of survival at 18 months was 52%.[2] The current 
standard practice is to only administer YESCARTA as inpatient and monitor for at least 7 to 
10 days for side effects including cytokine release syndrome (CRS) and Immune effector 
cell-associated neurotoxicity syndrome (ICANS). 
To date, YESCARTA is the best product in its class with the highest objective response rate 
and longest duration of response of any CAR T therapy. However, the prolonged hospital 
stays, and high cost have limited its use[3]. Furthermore, outpatient therapies in general are 
viewed more favorably due to less resource utilization and it is conceivable that many 
centers may opt for a competing product like tisagenlecleucel or lisocabtagene maraleucel 
because of the perceived notion that they might be more amenable to being used in the 
outpatient setting.[4, 5] 
 
2.3. 
Rationale for Outpatient Therapy 
Whereas YESCARTA treatment in the inpatient setting is feasible and the ZUMA-1 trial 
reported grade 3 or higher CRS and ICANS in 13% and 28% of subjects respectively, the 
impact of such a therapy in the outpatient setting and the safety profile of outpatient 
therapy remains largely unexplored.[6, 7] 
Zuma-1 data and our institution data suggest that fever is the earliest sign of CRS in the 
recipients of YESCARTA. In our database search of 20 subjects treated with YESCARTA at 
Vanderbilt, nine (45%) did not develop fever until after 72 hours from the time of YESCARTA 
infusion suggesting that there is the possibility that subjects could have been managed at 
least in part in the outpatient setting which will lead to a reduction in the total number of 
days spent in the hospital. A similar system was used to determine who could undergo HCT 
in the outpatient setting. That study showed a reduction in hospital length of stay and 
significant cost savings.[8]  


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At Vanderbilt, 70% of all allogeneic HCT are done in the out-patient setting. Most matched 
related and unrelated transplants are done in the outpatient setting with brief period of 
hospitalization to administer thymoglobulin, while we electively admit haploidentical 
transplant subjects till completion of high dose Cytoxan. In our single institution quality 
review for 2018, we performed 18 matched related transplants in the outpatient setting. 
Eight of the 18 subjects ended up being admitted and incurred a total of 42 hospital days at 
an average of 2.3 days per subject for the whole cohort. In that same year, we performed 4 
haploidentical transplants in the inpatient setting and incurred a total of 24 days of 
hospitalization which is an average of 6 days per subject (unpublished data). While cost 
comparisons are not as easy to do, we can postulate that the reduction in hospital length of 
stay translates into fewer interruptions in subject’s life, reduced exposure to hospital 
acquired infections, improved quality of life and healthcare savings. Currently, no risk model 
has been developed with the ability to carefully identify those who can safely be treated in 
the outpatient setting with any CAR T product and the benefit of using specific clinical 
parameters to determine who will benefit from early escalation of care to the inpatient 
setting is also unknown. 
 
2.4. 
Rationale for Selecting Vanderbilt Transplant and Cellular Therapy Program 
In 2005, Vanderbilt invested in the design of our outpatient transplant unit (OTU) where our 
HCT program is nested and with which we transitioned all hematopoietic cell transplants 
(autologous and allogeneic) to the outpatient setting. These subjects are only admitted if a 
clinical need arises which cannot be managed in the outpatient setting. Our internal quality 
data suggests that this transition has been cost-effective through reduction in number of 
hospital days per subject without negatively impacting transplant outcomes. The outpatient 
transplant unit is complete with a series of dedicated infusion bay areas where subjects can 
receive immediate attention from nurses, mid-level providers and attending physicians. 
Subjects are seen daily and as needed. The unit is open 8:00 AM – 5:00 PM, seven days a 
week. We also have a dedicated telemedicine service for cellular therapy subjects which can 
be utilized for any urgent issues or routine clinical monitoring when subject is not in the 
clinic.  Our quality metrics, subject outcomes, and subject satisfaction compare favorably to 
the other transplant centers which primarily manage the complex subjects in the inpatient 
units during early peri-transplant period. We transplant between 300 and 400 subjects 
annually and many of the subjects remain in the outpatient setting throughout the 
transplant process. Subjects are housed within 30 miles from the hospital in specified 
lodging facilities, and we have a tested system of stat bed(s) with which we can initiate 
specific therapy within 30 – 60 minutes at any time day or night. For the proposed pilot 
study, subjects will be housed in select apartments that allow for them to reach the hospital 
within 15 minutes. Our telemedicine service line has outcomes comparable to face to face 
clinic visits and has been successfully integrated into our HCT workflow (unpublished data).  
 
3. STUDY DESIGN 
 
3.1. 
General Study Design 


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This is an open label non-randomized feasibility study primarily designed to evaluate the 
safety and effectiveness of close monitoring and telemedicine in the treatment of subjects 
with YESCARTA in the outpatient setting.  
Study candidates are adults with recurrent large B-cell lymphoma who are refractory to 
prior chemotherapy or have had ASCT. They must have at least 1 measurable lesion and 
meet multiple organ function criteria.  
 
3.2. 
Rationale for Close Monitoring in the Outpatient Setting 
Subjects who are hospitalized get to have vital signs up to six times each day and physical 
exams and/or close monitoring by physician and 1 or more nurses which allows ample 
opportunities to pick up on and act on changes to the subject’s status. This is in stark 
contrast to the outpatient with whom there may be long gaps when there is no contact with 
any health personnel. The desire to bridge this gap and ensure safety in the outpatient 
setting is the rationale behind asking that outpatients be seen and examined twice each 
day.  
 
3.3. 
Participating Site and Number of Subjects 
Vanderbilt University Medical Center.  
 
3.4. 
Number of Subjects 
Participants in this study will be referred to as “subjects.” It is anticipated that 20 will be 
enrolled into this study.  
 
3.5. 
Study Duration 
 
3.5.1. Study Duration for Individual Subjects 
The duration of the study for individual subjects will vary. For a subject who completes the 
entire protocol from the date of informed consent through the completion of the long-term 
follow-up (LTFU) period, the duration of the study is 12 months. However, an individual 
subject’s study duration will vary depending on the subject’s screening requirements, 
response to treatment, and survival.  
 
3.5.2. Completion of Study 
Completion of the study is defined as the time at which the last subject completes the LTFU 
period visit, is considered lost to follow-up, withdraws consent, or dies. 
 
4. ENROLLMENT PROCEDURES 
 
 


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All patients MUST be registered prior to the start of study procedures such as tissue 
acquisition. Registration can only be conducted during the business hours of 8AM – 5PM 
Central Time, Monday through Friday. 
 
 
1) If a subject ID number is required prior to patient enrollment (i.e. at screening due 
to sample collection requirement), the site must submit the following documents 
with their email notification to the Study Coordinator: 
 
• Copy of the patient’s signed and dated Informed Consent including 
documentation of the consent process. 
 
• HIPAA authorization form (if separate from the main consent form). 
 
• VICC Patient Enrollment Form. 
 
 
The Study Coordinator will then provide a subject ID number via email. 
 
2) Email the following documents to the VICC CTO Registrar Office for eligibility review 
and (viccctsrregistraroffice@vumc.org): 
 
• Copy of the patient’s signed and dated Informed Consent, including 
documentation of the consent process. 
 
• HIPAA authorization form (if separate from the main consent form). 
 
 
• VICC Patient Enrollment Form. 
 
 
• Eligibility supporting documents such as pathology reports, laboratory 
tests, etc. or EMR access.  Note: all source documents should be de-
identified and screening/subject ID number added prior to sending. 
 
 
• Signed and completed Eligibility Checklist.  To be eligible for registration 
to the study, the participant must meet each inclusion and exclusion 
criterion listed in the eligibility checklist. 
 
 
 


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Note:  The VICC CTO Registrar Office requires 3 business days to review all documents and 
confirm eligibility. Registrations will only be accepted with prior notice and discussion with 
the Lead Institution.  Please email the clinical tr
 
vumc.org. 
 
Upon satisfactory review of eligibility documents submitted, the Study Coordinator will 
approve enrollment and issue a subject ID number if one was not issued at screening.  Once 
registration/enrollment confirmation from the Study Coordinator is received, proceed with 
protocol procedures. 
 
Please contact the assigned Study Contact with any questions regarding this process.  You 
can also reach out to your assigned CRA once the study is activated. 
 
The Study Coordinator will assign Subject ID numbers to all patients whose eligibility has 
been confirmed.  Only patients deemed eligible will be registered to the study.  
Sequence/study ID numbers will not be re-used if a patient screen fails. Following 
registration, eligible participants should begin the study consistent with the protocol no 
later than 28 days after registration/enrollment by the VICC Coordinating Center.   
 
Subjects who are unable to complete or meet the eligibility criteria will be permitted to 
rescreen one time.  If rescreening occurs within 28 days of the signing of the original 
informed consent, only the procedure(s)/assessment(s) that did not originally meet the 
eligibility criteria needs to be repeated; all other initial screening procedures/assessments 
do not need to be repeated.  If rescreening occurs, or leukapheresis is delayed, more than 
28 days from the signing of the original informed consent, subjects must be reconsented 
and repeat all screening procedures/assessments. 
 
If a participant does not begin the study following registration within the allowed time 
period, the participant’s registration on the study will be canceled.  The Study Contact will 
be notified of cancellations as soon as possible.  Patients being re-screened will need to 
consent to repeated procedures.  As such, the Coordinating Center will require a new, 
signed Informed Consent document. 
 
Issues that would cause treatment delays should be discussed with the sponsor-
investigator. 
As is generally accepted, standard of care procedures performed prior to consent, but 
within the protocol defined screening window for each assessment, can be used for study 
purposes.  All research-only procedures must be performed after patient consent. 
 
 


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5. SUBJECT ELIGIBILITY 
 
5.1. 
Inclusion Criteria (before leukapheresis) 
 
1. 
Age 18 years and above. 
 
2. 
Histologically proven large B cell lymphoma or transformed follicular lymphoma 
to DLBCL in relapse/refractory after two lines of therapies which included an 
anthracycline and CD20-targeted therapy. 
 
 
Or 
 
3. 
Chemotherapy refractory disease evidenced by lack of adequate response to first 
line therapy. This consists of either progressive disease as best response to first 
line therapy or stable disease as best response after 4 cycles of appropriate 
chemotherapy  
 
Or  
 
4. Refractory after ASCT at any time point 
 
And 
 
5. ECOG performance status 0-2. 
 
6. Adequate hematologic, hepatic, renal and cardiac function evidenced by:  
 
 
a. ANC ≥1000/µL 
 
b. Platelet ≥ 75,000/ µL  
 
 
c. T-bilirubin ≤ 1.5 mg/dL 
 
 
d. Normal serum creatinine or creatinine clearance ≥ 60 mL/min/1.73 m2  
 
 
e. Cardiac ejection fraction ≥ 50%  
 
 
f. Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 
5 times upper limit of normal (ULN). 
 
 
7. At least 1 measurable lesion 
 


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8. Baseline oxygen saturation ≥92% on room air. 
 
 
9. Ability to stay at a distance which allows for subjects to come in and for 
specific interventions like antibiotics and tocilizumab to be started in 1 hour or 
less. This is approximately 30 miles of Vanderbilt.  
 
 
10. A caregiver who can be educated to operate equipment for vital signs 
monitoring. 
 
 
11. Caregiver Eligibility 
 
i. Willingness to serve as a caregiver 
ii. Ability to read, write and operate a phone 
iii. Willingness to be taught to operate electronic device 
iv. Willingness and ability to assist subject to wear electronic device such 
including patch, blood pressure machine, thermometer 
v. Pass caregiver assessment test 
 
 
12. Subject and caregiver willing to be taught to operate an iPad or other 
electronic media for telemedicine, use wearable devices, and pass the 
caregiver competence test. 
 
 
5.2. 
 Exclusion Criteria 
 
1. History of malignancy other than nonmelanoma skin cancer or carcinoma in 
situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for 
at least 3 years.  
 
2. Known CD19 negative tumor. 
 
 
3. History of Richter’s transformation of CLL. 
 
 
4. Autologous stem cell transplant with therapeutic intent within 6 weeks of 
planned YESCARTA infusion. 
 
 
5. History of allogeneic stem cell transplantation.  
 
 


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6. Prior CAR therapy or other genetically modified T-cell therapy. 
 
 
7. History of severe, immediate hypersensitivity reaction attributed to 
aminoglycosides. 
 
 
8. Presence or suspicion of fungal, bacterial, viral, or other infection that is 
uncontrolled or requiring IV antimicrobials for management. Simple urinary 
tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if 
responding to active treatment and after consultation with the sponsor’s 
medical monitor. 
 
 
9. History of human immunodeficiency virus (HIV) infection or acute or chronic 
hepatitis B or hepatitis C infection. Subjects with history of hepatitis infection 
must have cleared their infection as determined by standard serological and 
genetic testing per current Infectious Diseases Society of America (IDSA) 
guidelines or applicable country guidelines. 
 
 
10. Presence of any in-dwelling line or drain (e.g., percutaneous nephrostomy 
tube, in-dwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial 
catheter). Dedicated central venous access catheters, such as a Port-a-Cath or 
Hickman catheter, are permitted. 
 
 
11. Subjects with detectable cerebrospinal fluid malignant cells, or brain 
metastases, or with a history of CNS lymphoma or primary CNS lymphoma, 
cerebrospinal fluid malignant cells or brain metastases. Patients with treated 
secondary CNS involvement of lymphoma are allowed. 
 
 
12. History or presence of CNS disorder, such as seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, progressive multifocal 
leukoencephalopathy, or any autoimmune disease with CNS involvement if it 
impairs ability to complete an effective and reliable neurological assessment. 
 
 
13. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement. 
 
 
14. History of myocardial infarction, cardiac angioplasty or stenting, unstable 
angina, or other clinically significant cardiac disease within 12 months of 
enrolment. 
 


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15. Requirement for urgent therapy due to tumor mass effects (e.g., blood vessel 
compression, bowel obstruction, or transmural gastric involvement). 
 
 
16. Primary immunodeficiency.  
 
 
 
17. Any medical condition likely to interfere with assessment of safety or efficacy 
of study treatment. 
 
18. Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen.  
 
 
19. History of severe immediate hypersensitivity reaction to any of the agents 
used in this study.  
 
 
20. Women of child-bearing potential who are pregnant or breastfeeding because 
of the potentially dangerous effects of the preparative chemotherapy on the 
fetus or infant. Females who have undergone surgical sterilization or who 
have been postmenopausal for at least 2 years are not considered to be of 
childbearing potential.  
 
 
21. Subjects of both genders who are not willing to practice birth control from the 
time of consent through 6 months after the completion of conditioning 
chemotherapy.  
 
 
22. In the investigator’s judgment, the subject is unlikely to complete all protocol-
required study visits or procedures, including follow-up visits, or comply with 
the study requirements for participation.  
 
 
23. History of autoimmune disease (e.g. Crohn’s, rheumatoid arthritis, systemic 
lupus) resulting in end organ injury or requiring systemic 
immunosuppression/systemic disease modifying agents within the last 2 
years. 
 
 
24. Must not have received immunomodulating agents including checkpoint 
inhibitors, BTK inhibitors, and Revlimid within 2 months or 5 half-lives 
whichever is shorter.  
 
 
 


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6. PROTOCOL TREATMENT 
 
6.1. 
Treatment Terminology 
Bridging therapy refers to treatment used to control a subject’s disease prior to 
lymphodepleting chemotherapy. 
 
Telemedicine refers to the use of specified video and audio software with the purpose to 
evaluate the status of the subject. 
 
6.2. 
Study Treatment 
 
6.2.1. Pre-lymphodepleting period  
 
6.2.1.1. 
Leukapheresis  
Leukapheresis refers to the procedure for collecting peripheral blood 
mononuclear cells (PBMCs) that are used to manufacture the subject-specific 
YESCARTA treatment. Subjects will undergo leukapheresis to obtain T cells for 
the manufacturing of YESCARTA. Leukapheresed cells obtained will be shipped to 
the supporter’s manufacturing facility as described in the Investigational Product 
Manual (IPM).  
 
6.2.1.2. 
Bridging Therapy 
Bridging therapy will be obtained by the investigative site unless otherwise 
noted.  
 
Table 1. Bridging Therapy 
Type 
Therapy Regimen 
Timing and washout 
Corticosteroid 
Dexamethasone at a dose of 20 mg to 
40 mg or equivalent, either PO or IV 
daily for 1 to 4 days. 
May be administered after 
apheresis/enrollment and must be 
completed at least 5 days prior to the start 
of lymphodepleting chemotherapy. 
HDMP + Rituximab 
 
1 gram/m2 of high dose 
methylprednisolone (HDMP) for 3 days 
in combination with rituximab at 375 
mg/m2 weekly for 3 weeks. 
May be administered after enrollment and 
completed at least 7 days prior to the start 
of lymphodepleting chemotherapy. 
 
6.2.1.3. 
Subject and caregiver training 
Subject and caregiver education procedure included a series of training sessions 
designed to equip them with necessary skills to take reliable and reproducible 
vital signs. It also includes training to operate a tablet, laptop or smartphone 
application that will be used for the telemedicine encounter. This process ends 
with a caregiver certification process during which the nurse formally tests and 
verifies that family can measure vital signs reliably. A dry run of the telemedicine 


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on a set date will also be done and be repeated as needed till all aspects are 
completed without error. Upon successful completion of caregiver education 
and dry run, the subject will proceed to get lymphodepletion chemotherapy as 
from Day -5. 
 
6.2.1.4. 
Verification of Eligibility to proceed to Lymphodepletion Therapy 
Preparation for lymphodepleting chemotherapy is done between  
Day -9 and Day -6 to ensure that only those who remain eligible per criteria 
below will continue the treatment pathway for outpatient YESCARTA. Ineligible 
patients will receive YESCARTA per standard of care. This second screening does 
not require another consent.  
1. ANC ≥1k/µL, 
 
2. Platelet ≥ 75k/ µL, 
 
 
3. T-bili ≤ 1.5 mg/dL,  
 
 
4. Creatinine clearance ≥ 60 mL/min/1.73 m2, and  
 
 
5. Oxygen saturation ≥92% on room air. 
 
 
6.2.2. Lymphodepletion Chemotherapy 
Lymphodepleting chemotherapy refers to fludarabine and cyclophosphamide used for 
lymphodepletion before administration of YESCARTA. Lymphodepleting chemotherapy will 
be supplied by the investigative site unless otherwise noted. Refer to the current product 
label for guidance on packaging, storage, preparation, administration, and toxicity 
management associated with the administration of chemotherapy agents. 
 
6.2.2.1. 
Fludarabine  
Fludarabine phosphate is a synthetic purine nucleoside that differs from 
physiologic nucleosides in that the sugar moiety is arabinose instead of ribose or 
deoxyribose. Fludarabine is a purine antagonist antimetabolite. Refer to the 
most recent version of the package insert for specific details surrounding the 
administration of fludarabine.  
 
6.2.2.2. 
Cyclophosphamide  
Cyclophosphamide is a nitrogen mustard-derivative that acts as an alkylating 
agent following conversion to active metabolites in the liver and has potent 
immunosuppressive activity. The serum half-life after IV administration ranges 
from 3 to 12 hours; the drug and/or its metabolites can be detected in the serum 
for up to 72 hours after administration. Refer to the current version of the 


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package insert for specific details associated with the administration of 
cyclophosphamide.  
 
6.2.2.3. 
Mesna  
Mesna is a detoxifying agent used to inhibit the hemorrhagic cystitis induced by 
chemotherapy. The active ingredient in mesna is a synthetic sulfhydryl 
compound designated as sodium-2- mercaptoethane sulfonate with a molecular 
formula of C2H5NaO3S2. Mesna should be administered per institutional 
guidelines. Refer to the current version of the package insert for specific details 
surrounding the administration of mesna.  
 
6.2.3. YESCARTA 
YESCARTA is supplied cryopreserved in cryostorage bags. The product in the bag is slightly 
cloudy and cream to yellow color. The cryostorage bag containing YESCARTA arrives frozen 
in a liquid nitrogen dry shipper. The bag must be stored in a vapor phase of liquid nitrogen 
and remain frozen until the subject is ready for treatment to assure that viable live 
autologous cells are administered to the subject. Several inactive ingredients are added to 
the product to assure viability and stability of the live cells through the freezing, thawing, 
and infusion process.  
YESCARTA is a subject-specific product. The product is labelled per sponsor protocol. Upon 
receipt, verification that the product and subject-specific labels match the subject’s 
information is essential. Do not infuse the product if the information on the subject specific 
label does not match the intended subject. The volume of YESCARTA infused, the thaw 
start/stop time, and YESCARTA administration start/stop time will all be noted in the subject 
medical record. The product must not be thawed until the subject is ready for the infusion. 
Refer to the IPM for details and instructions on storage, thawing, and administration of 
YESCARTA. There have been no instances of accidental overdose of subjects in this program 
to date. In case of accidental overdose, treatment should be supportive. Corticosteroid 
therapy may be considered if any dose is associated with severe toxicity. Toxicity 
management guidelines are found in the current product IB version 10.0 (e.g. Section 6.5) 
and should be consulted. If any problems related to the use of YESCARTA or any products 
that support the management of YESCARTA (e.g., cryostorage bags, subject ID labels) are 
identified, research staff should report the problem per the instructions in the IPM.  
 
6.2.4. Concomitant Therapy  
Concomitant therapy refers to treatment that subjects receive during the conduct of the 
study. During the course of the study, investigators may prescribe any concomitant 
therapies deemed necessary to provide adequate supportive care except those medications 
listed in Section 6.2.5. All concomitant therapies, including medications, intubation, dialysis, 
oxygen, and blood products, will be recorded.  
All concurrent therapies, including medications, intubation, dialysis, oxygen, and blood 
products, will be recorded from the date of the informed consent through day 30 after 
completing treatment with YESCARTA or until disease progression, whichever occurs first.  


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For subjects who are enrolled but not dosed with YESCARTA, concurrent therapies will only 
be recorded from the date of the informed consent through 30 days after the last study 
specific procedure (e.g., leukapheresis, lymphodepleting chemotherapy). For subjects who 
are not enrolled (e.g., screen failure or not leukapheresed), only concurrent therapies 
related to any serious adverse event(s) will be recorded.  
 
6.2.5. Excluded Medications  
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 7 
days prior to leukapheresis, and 5 days prior to YESCARTA administration. Corticosteroids 
and other immunosuppressive drugs should also be avoided for 3 months after YESCARTA 
administration, unless used to manage YESCARTA related toxicities (refer to the investigator 
brochure version 10.0 and YESCARTA package insert). Other medications that might 
interfere with the evaluation of the investigational product, such as non-steroidal anti-
inflammatory agents should also be avoided for the same time period unless medically 
necessary.  
Treatment for lymphoma such as chemotherapy, immunotherapy, targeted agents, 
radiation, and high dose corticosteroid, other than defined/allowed in this protocol, and 
other investigational agents are prohibited, except as needed for treatment of disease 
progression after the YESCARTA infusion.  
 
6.3. 
Study Treatment Schedule  
 
6.3.1. Leukapheresis (Within Approximately 5 Days of Eligibility Confirmation)  
Subjects will undergo leukapheresis (12-15 liter apheresis with a goal to target 
approximately 5-10 x 10^9 mononuclear cells) for the manufacturing of YESCARTA. 
Leukapheresed cells are shipped to the cell processing facility (CPF) overnight as described 
in the Investigational Product Manual. Once a subject commences leukapheresis, the 
subject is considered enrolled in the study.  
 
6.3.2. Chemotherapy General Instructions  
Subjects will initiate lymphodepleting chemotherapy with cyclophosphamide and 
fludarabine beginning on Day -5.  
 
6.3.3. YESCARTA General Instructions 
The following medications should be administered approximately 1 hour prior to YESCARTA 
infusion.  
• Acetaminophen 500 to 1000 mg PO  
• Diphenhydramine (12.5 to 25 mg IV or 25 mg PO)  
• Dexamethasone 10mg PO, 1 hour before Yescarta infusion and on days 1 and 2 
Central venous access, such as a port or a peripherally inserted central catheter, is required 
for the administration of YESCARTA. Catheter care, per institutional guidelines, should be 


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followed. Materials and instructions for the thawing, timing, and administering of YESCARTA 
are outlined in the Investigational Product Manual which must be reviewed prior to 
administration of YESCARTA.  
 


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 .02222 
6.3.4. Post Infusion Monitoring 
Figure 1: Subject’s daily monitoring workflow during first 14 days after YESCARTA infusion. 
 
6.3.4.1. 
Day Zero 
Subject will report to the clinic in the morning for evaluation including physical 
exam and laboratory tests. Baseline BP, HR, RR, SPO2, laboratory tests (CBC, 
CMP, LDH, CRP, ferritin, magnesium, uric acid, phosphorus, and fibrinogen) will 
be obtained. Baseline neurological exam details are verified. The Immune 
Effector Cell-Associated Encephalopathy (ICE) score will be calculated. [9] 
YESCARTA will be infused in the outpatient clinic and subject monitored for 2 
hours post-infusion before they are discharged to the apartment. Telemedicine 
visit by NP is done at 16:30 PM and 22:00 ± 1 hour. This includes a review of 
systems, physical exam including neurological assessment (ICE score), and vital 
signs Subject will awake in am, obtain vital signs at 06:30 ± 1 hourand call in with 
the vital signs prior to presenting to the outpatient clinic at 8am.  
 
6.3.4.2. 
Day 1 – Day 14: (Figure 1)  
 
  
1. 
6:00 AM:  
Subject and family take their vital signs (BP, HR, RR, SPO2) and record in the 
logbook. Call NP line if pre-specified criteria for hospital admission are met. 
2. 
8:00 AM:  
Subject will report to the outpatient clinic at 8am daily including weekends. Vital 
signs log reviewed by nurse practitioner (NP) and equipment checked for 
functionality. Laboratory tests including correlatives are ordered per protocol. 
Physical exam by NP and attending physician both of whom will review all 
available data including the ICE score. Subject discharged back to the apartment 
by 10:00 AM or shortly after if no criteria for hospitalization are met. 
 
3. 
12:00 noon:  
Subject and family take their vital signs (BP, HR, RR, SPO2) and record in the 
logbook. Call NP line if pre-specified criteria for hospital admission are met. 
 
 
4. 
16:30 and 22:00 ± 1 hour:  
Telemedicine visit. Vitals log reviewed. Vitals checked (BP, HR, RR, SPO2), and ICE 
score calculated. Subject will remain in apartment if no criteria for admission are 
met.  
 
 
5. 
 
 


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Wearable device details:  Subjects are trained to apply the devices which comprises of a 
patch that is applied on the left anterior chest, a blood pressure cuff that they will apply 
intermittently on the forearm, and a pulse oximeter that they will apply intermittently to 
the digits. They will wear the patch continuously but only apply the BP cuff and pulse 
oximeter at specific times as stated in the chart above. If patient fails to apply the BP cuff 
and pulse oximeter at the time stipulated, a vendor systems generated reminder will go to 
them. Any alerts issued by vendor can be viewed by the PI and all authorized users of the 
program. Data are recorded in the device database and are for research only but are 
accessible by specific clinical trial staff. Please see appendix G for more details 
Telemedicine details: Subject and NP will activate the telemedicine App in their electronic 
device. Family will obtain vital signs (BP, HR, RR, SPO2) and provide NP with the figures. NP 
will also review the previous vital signs. Review of system questions are asked, and the 
answers given by subject recorded. Neurological assessment will be done, and ICE score 
calculated.  
 
6.3.5. Criteria for Hospital Admission 
 
1. 
Fever ≥102̊ F or higher, or fever 100.4 to < 102 with a change in status (e.g. 
hypotension, altered mental status or other end organ dysfunction). Fever < 102 
alone without other symptom can be closely monitored in the outpatient setting 
per written institution guidelines. [10, 11] 
 
2. 
Hemodynamic instability: (any of the following) Hypotension that requires IV 
fluids, MAP < 20% baseline or SBP < 90 mmHg or HR > 130/min 
 
 
3. 
Hypoxia with SPO2 < 90% 
 
 
4. 
Abnormal neurological function (grade 1 or higher ICANS) based on the ICE score 
as stated on Table 3 
 
 
5. 
Other criteria at the discretion of the covering physician (discussed with PI). 
  
Subjects that meet the criteria specified above will be admitted either as observation or 
inpatient depending on the severity of symptoms. 
 
The following will trigger admission to observation status: Grade 2 CRS responding to fluids 
and hypoxia responding to supplemental oxygen by nasal cannula. Such subjects will be 
reviewed by treating physician who may recommend that they may be discharged to 
continue outpatient monitoring if there is resolution of symptoms. If the same symptom 




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corticosteroids, fever is no longer required to grade subsequent CRS severity. In this case, 
CRS grading is driven by hypotension and/or hypoxia. 
 
b. CRS grade is determined by the more severe event: hypotension or hypoxia not attributable 
to any other cause. For example, a patient with temperature of 39.5° C, hypotension 
requiring 1 vasopressor, and hypoxia requiring low-flow nasal cannula is classified as Grade 
3 CRS. 
  
c. Low-flow nasal cannula is defined as oxygen delivered at ≤ 6 L/minute. Low flow also 
includes blow-by oxygen delivery, sometimes used in pediatrics. High-flow nasal cannula is 
defined as oxygen delivered at > 6 L/minute. 
 
 
 






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3. Vital signs, including blood pressure, heart rate, and temperature. 
 
 
4. ECOG performance status. 
 
 
5. Baseline PET-CT of the neck, chest, abdomen, and pelvis: 
  
a. PET-CT performed after the subject’s last line of therapy and prior to signing the 
informed consent may be used. 
 
b. If a subject receives bridging therapy, a repeat PET-CT is recommended to 
establish a new baseline. 
 
 
6. Bone marrow aspirate/biopsy as needed (if not done within 12 months of screening). 
 
7. Laboratory tests (may be drawn anytime between signing of informed consent and prior 
to the start of lymphodepleting chemotherapy): 
 
a. Chemistry panel 
b. Complete blood count (CBC) with differential 
c. β-HCG pregnancy test (serum or urine) on all women of childbearing potential 
d. C-reactive protein (CRP) 
e. Blood draws for cytokines and PBMC. 
 
8. AE and SAE reporting (see below Section 10). 
 
9. Concomitant medications documentation and previous cancer treatment history. 
 
 
7.4. 
Physical Exam, Vital Signs, Performance Status, and ICANS Score 
A full neurological assessment including ICE score will be completed during screening to 
establish a baseline. Subsequent post-baseline assessments will be performed before as 
specified in the SOA. 
 
7.5. 
Cardiac Function 
Cardiac function, as measured by left ventricular ejection fraction (LVEF), and 
electrocardiogram (ECG) will be assessed during the screening period to confirm study 
eligibility. 
 
7.6. 
Bone Marrow Biopsy if not previously done 
A bone marrow aspirate/biopsy will be performed at screening, if not previously performed 
within 12 months of signing consent, to assess bone marrow involvement. 
 


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7.7. 
Lumbar Puncture 
Subjects with symptoms of central nervous system malignancy, such as new onset severe 
headaches, neck stiffness, or any focal neurologic findings on physical exam, will have 
lumbar puncture performed at the screening visit for examination of CSF. 
 
7.8. 
Disease response Assessment 
PET with non-contrast CT scan will be done as SOC as from day + 30. Response assessment 
per Cheson 2014.[12] 
 
 


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7.9. 
Laboratory 
The below samples will be collected at the time points indicated in the SOA. Additional 
samples (e.g., blood, urine, CSF, tissue, etc.) may be collected as needed for further safety 
testing: 
 
1. Sodium (Na), potassium (K), chloride (Cl), total CO2 (bicarbonate), creatinine, 
glucose, blood urea nitrogen (BUN) or urea (if BUN test cannot be analyzed by the 
local lab), albumin, calcium total, magnesium total (Mg), inorganic phosphorus, 
alkaline phosphatase, ALT/glutamic-pyruvic transaminase (GPT), AST/glutamic-
oxaloacetic transaminase (GOT), total bilirubin, direct bilirubin, lactate 
dehydrogenase (LDH), phosphorus and uric acid.  
 
2. C-reactive protein (CRP) ferritin. 
  
3. Complete blood count (CBC) with differential and platelet count. 
  
4. A urine or serum sample will be collected and assessed locally for females of 
childbearing potential. If the screening pregnancy test is positive, the subjects 
should not be enrolled. 
 
 
7.10. Correlative sample storage for potential future biomarker analysis 
Biomarker analysis will be performed on blood and tumor samples to evaluate 
pharmacodynamic markers for Yescarta. 
 
Correlative laboratory tests include: 
1. Cytokine panel (including IL-1, IL-2, IL-6, IL-10, IL-15, granzyme B, TNF, IFN gamma, 
MCP1, GMCSF), CAR T cell quantification at day -5, 0, 1, 2, 3, 4, 7, 14, 30 (day 30 +/- 3 
days) 
2. CBC with differentials, ALC, monocyte count, LDH, chemistry (CMP including calcium, 
LDH, uric acid, phosphorus, magnesium), fibrinogen, CRP, ferritin 
3. Product attributes, transduction rate, viability, IFN gamma in culture, pre-infusion 
doubling time 
4. Optional paired CSF samples at day -5 and day +1. Optional paired tissue biopsy at 
day -5 and 2. We will make every effort to collect relapse biopsy specimen to better 
understand the mechanisms of tumor escape. 
5. T cell elispot analysis for CART cell immunogenicity by peripheral blood at apheresis, 
day 30 (+/- 3 days), month 3, 6 and 12 
6. Lymphocyte subsets to interrogate the pattern of recovery of B and T cells including 
the pattern of CD4 lymphopenia. Collect at apheresis, day zero, day 30 (+/- 3 days), 
months 3, 6 and 12 
7. Collect CSF specimens in subjects with grade ≥2 ICANS when feasible. Correlative 
testing will be done at the end of the study based on a mutually agreed upon plan 
between Vanderbilt and Kite translational research  


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PBMC, serum and plasma are collected at specific time points as stated above. PBMCs are 
cryopreserved per lab manual and will be sent to Kite in batches. Samples will be analyzed 
at the end of the study for clues as to what series of parameters may be predictive of need 
for more care including hospitalization. 
 
The samples will be collected per SOA and batch run at the end of the study. We will 
retrospectively check to see if any specific lab parameter may be predictive of need for 
more care including hospitalization. 
 
7.11. Description of Study Periods 
Investigative sites will maintain a log of all screened subjects who were reviewed and 
evaluated for study participation. Information collected on the screening log should include 
limited information such as the date of screening, date the subject was enrolled or the 
reason for why the subject failed screening. 
 
7.11.1.  Screening 
The screening period begins on the date the subject signs the IRB/IEC approved ICF and 
continues through confirmation of enrollment. Informed consent must be obtained before 
completion of any non-standard of care study specific procedures. After written informed 
consent has been obtained, subjects will be screened to confirm study eligibility and 
participation. Only subjects who meet the eligibility criteria listed above in protocol Section 
5 and who commence leukapheresis will be enrolled in the study.  
 
The following assessments/procedures are to be completed during the screening period at 
the time points outlined in the SOA: 
 
1. Medical history and disease assessment. 
 
2. Physical examination including height and weight. 
 
3. Subjects with symptoms of central nervous system malignancy such as new onset 
severe headaches, neck stiffness, or any focal neurologic findings on physical exam 
will have lumbar puncture for examination of cerebral spinal fluid. 
 
4. Vital signs, including blood pressure, heart rate, oxygen saturation, and 
temperature. 
 
5. ECOG performance status. 
 
6. ECG. 
 
 
7. ECHO for confirmation of normal cardiac function (e.g., LVEF) and pericardial 
effusion assessment 
 
 


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8. Imaging Studies with PET with non-contrast CT scan to confirm measurable disease. 
CT chest, abdomen and pelvis is acceptable as clinically indicated. 
 
 
9. Brain MRI. 
 
 
 


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10. Baseline PET with non-contrast CT scan of the neck, chest, abdomen and pelvis: 
 
a. PET with non-contrast CT scan performed following the subjects last line of 
therapy and prior to signing the consent may be used for confirmation of 
measurable disease. CT chest, abdomen and pelvis is acceptable as clinically 
indicated 
 
b. If PET with non-contrast CT scan is performed > 28 days prior to the initiation 
of lymphodepleting chemotherapy and if subject receives any anti-cancer 
therapy between screening and lymphodepleting chemotherapy, the scans 
must be repeated to establish a new baseline. CT chest, abdomen and pelvis 
is acceptable as clinically indicated 
 
 
11. Bone marrow aspirate/biopsy as needed (if not done at initial diagnosis or between 
diagnosis and screening). 
 
12. Laboratory tests: 
 
 
a. Chemistry panel 
 
b. CBC with differential. 
 
 
13. β-HCG pregnancy test (serum or urine) on all women of child-bearing potential 
 
7.11.2. Enrollment/Leukapheresis 
Before leukapheresis commences, the following criteria must be met. If leukapheresis is 
delayed beyond 5 days, baseline CBC with differential and chemistry panel must be 
repeated to verify eligibility. 
 
1. No evidence or suspicion of an infection. 
 
2. Corticosteroid therapy at a pharmacologic dose (≥5 mg/day of prednisone or 
equivalent doses of other corticosteroids) and other immunosuppressive drugs must 
be avoided for 7 days prior to leukapheresis. 
 
 
3. Once a subject commences leukapheresis, the subject will be considered enrolled 
into the study. 
 
 
The following procedures/requirements will occur on the leukapheresis collection day and 
as outlined in the SOA: 
 
1. Vital signs, including blood pressure, heart rate, oxygen saturation, and 
temperature. 
 
2. Weight. 


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3. Laboratory tests (to be drawn prior to leukapheresis, on the day of or day before 
leukapheresis): 
 
 
a. Chemistry panel 
 
b. CBC with differential, CRP, ferritin, LDH 
 
 
c. Anti-CD19 CAR T cells 
 
 
d. Lymphocyte subsets 
 
 
e. Cytokine levels 
 
 
f. Anti-YESCARTA antibodies. 
 
 
4. Adverse/Serious Adverse Event reporting. 
 
5. Concomitant medications documentation. 
 
 
7.12.3. Requirements for Initiating Lymphodepleting Chemotherapy 
Lymphodepleting chemotherapy and YESCARTA infusion should only be initiated after it is 
reasonably assured that cell infusion can safely proceed. Subject will have a mini screen to 
ensure that they are able to be treated outpatient before proceeding. 
 
If temperature rises above 38°Celsius or CRP above 100 mg/L within 72 hours of 
lymphodepleting chemotherapy, additional testing must be performed with satisfactory 
results before proceeding.  
 
The subject must not have received systemic antimicrobials for the treatment of known or 
suspected infection within 48 hours before lymphodepleting chemotherapy (prophylactic 
use of antimicrobials is allowed). 
 
Treatment course of any antimicrobials given for known or suspected antecedent infection 
should be completed as appropriate before stopping or switching to prophylactic 
antimicrobials. 
 
If the subject is confirmed to have an infectious process for which antimicrobials are not 
available (e.g., viral pneumonia), the infection must be clinically resolved as determined by 
the investigator and in consultation with infectious disease service (if applicable). 


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The most recently collected blood, urine, or other body fluid cultures must show no growth 
for at least 48 hours, and any other infectious workup performed (e.g., bacterial, viral 
serologies, PCR, stood studies, imaging studies) must be negative. If clinical suspicion is for 
an infection for which cultures are unlikely to be positive within 48 hours (e.g., fungal 
infection), adequate time must be allowed for cultures to become positive. 
 
Once the above criteria are met, then the subject can proceed with lymphodepleting 
chemotherapy. 
 
7.12.4. Lymphodepleting Chemotherapy Administration 
The following procedures will be completed during Day –5 to Day –3 as listed in the SOA: 
 
• Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature 
• Laboratory tests (to be drawn prior to chemotherapy) 
• Chemistry Panel 
• CBC with differential 
• Fludarabine and cyclophosphamide administration 
• Adverse/Serious Adverse Event reporting 
• Concomitant medications documentation. 
 
7.12.5. Requirements for Initiating YESCARTA Infusion 
These are the same as for lymphodepleting chemotherapy (i.e. above Section 7.12.3). 
 
If the YESCARTA infusion is delayed > 2 weeks (14 days) from the planned infusion date, 
established institutional standards should be followed regarding the need for repeat 
lymphodepleting chemotherapy. 
 
7.12.6. Monitoring After YESCARTA Infusion 
All subjects will receive YESCARTA infusion at a healthcare facility followed by close 
monitoring for signs and symptoms of CRS and neurologic toxicities. Subjects may be 
hospitalized at any time post infusion and be observed for CRS and neurologic toxicities in 
the hospital setting, if deemed appropriate by the investigator. 
 
If subjects are hospitalized, subjects should not be discharged from the hospital until all 
YESCARTA related non-hematological toxicities return to ≤ Grade 1 or return to Baseline as 
determined by the treatment team. Subjects may be discharged with non-critical and 
clinically stable or improving toxicities (e.g., renal insufficiency) even if > Grade 1, if deemed 
appropriate by the investigator. 
 
Subjects should be instructed to remain within proximity of the clinical study site for at least 
4 weeks following YESCARTA infusion. Subjects and their family members/caregivers should 
be educated on potential CRS and neurologic symptoms, such as fever, dyspnea, confusion, 
aphasia, dysphagia, somnolence, encephalopathy, ataxia, or tremor. 


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Subjects or their family members/caregivers should be instructed to immediately contact 
the treating investigator or seek immediate medical attention if any of these symptoms 
develop. 
 
During this period, the following procedures will be completed at the time points outlined in 
the SOA. 
 
7.12.7. Post-treatment Assessment Period 
After completing YESCARTA infusion, all subjects will be followed in the post-treatment 
assessment period. Counting from Day 0 (YESCARTA infusion), subjects will return to the 
clinic at the Intervals stated in the SOA. 
 
7.12.8. Long-term Follow-up Period 
All enrolled subjects will be followed in the long-term follow-up period for survival and 
disease status. Subjects will begin long-term follow-up after completion of the Day 30 visit.  






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2.  Targeted review of non-serious and serious Adverse Events of Special Interest (AESI, as defined in protocol Section 10.6) and concomitant medications 
used to prevent or treat such events will be conducted as indicated and until at least 30 days after initiation of YESCARTA infusion. 
3. 
Hematopathology review of archival tissue slides to confirm diagnosis. 
4.  Lumbar puncture (LP) at screening if clinically indicated. LP also to be done for new onset neurological symptom(s). 
5.  Optional paired samples of tumor on Day -5 (before lymphodepleting chemo) and Day 2 (48 hours post CAR T infusion). 
6.  PET scan can be replaced with a CT scan in cases where a PET scan is out of window and a second PET scan cannot be obtained or as clinically 
indicated. Preparation for lymphodepleting chemotherapy requires new PET with non-contrast CT scan if debulking therapy given and if the first screening 
images are > 28 days. CT chest, abdomen and pelvis can be substituted for PET as clinically indicated 
7.  Blood for cytokine levels, PBMC and quantification of CAR T cells at screening, Days – 5, 0, 1, 2, 3, 4, 7, 14, 30 (±3 days). 
8.  Bridging therapy is optional as determined by the treating physician and will be given after apheresis. See Section 6. 
9.  Tocilizumab may be given between Day 0-14 in the event of cytokine release syndrome (CRS). 
10.  Keppra may be given from Day 0-28 and then taper to off.  
11.  Plasma sample for MRD assessment by clonoseq and capseq. 
12.  12-Month post-treatment visit is for additional blood collection tests only as noted in the schedule of assessments. 
13.  QoL survey (Subject-Reported Outcomes Measurement Information System (PROMIS)) 14 days prior to lymphodepletion +/- 5 days 
14.  QoL survey 3, 6. 9 and 12 months post-treatment follow up +/- 14 days 
15.  Dexamethasone 10mg should be given PO before axicabtagene ciloleucel infusion on Day 0. Dexamethasone can be given at any time on Days 1 and 2. 
16. Brain imaging by MRI or CT if clinically indicated. CT acceptable if MRI is not able to be obtained 
 
  


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9. 
SUBJECT WITHDRAWAL 
 
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution. 
 
Subjects can decline to continue to receive study required treatment and/or other protocol 
required procedures at any time during the study but continue to participate in the study. 
This is referred to as partial withdrawal of consent. 
 
If partial withdrawal of consent occurs, the investigator must discuss with the subject the 
appropriate process for discontinuation from investigational product, study treatment or other 
protocol required therapies and must discuss options for continued participation, completion 
of procedures and the associated data collection as outlined in the SOA. The level of follow up 
and method of communication should also be discussed between the research staff and the 
subject and documented in the source documents. 
 
Withdrawal of full consent from a study means that the subject does not wish to receive 
further protocol required therapy or undergo procedures and the subject does not wish to 
continue further study follow-up. Subject data collected up to withdrawal of consent will be 
retained and included in the analysis of the study, and where permitted by local regulations, 
publicly available data (death records) can be included after withdrawal of consent. The 
investigator is to discuss with the subject appropriate procedures for withdrawal from the 
study. 
 
Public records, such as those establishing survival status, if available, may be searched to obtain 
survival data for any subject for whom the survival status is not known. Autopsy reports may 
also be retrieved to confirm status of disease at the time of death. 
 
The investigator and/or sponsor can also decide to withdraw a subject from the 
investigational product and/or other protocol-required therapies, protocol procedures, or the 
study as a whole or at any time prior to study completion. 
 
9.1. 
 Reasons for Removal from Treatment 
Reasons for removal from protocol required investigational products or procedures include 
any of the following: 
1. Adverse Event 
2. Subject request 
3. Product not available 
4. Lost to Follow-up 
5. Death 
6. Decision by sponsor. 
 
 


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9.2. 
Reasons for Removal from Study 
1. Reasons for removal of a subject from the study are as follows: 
2. Subject withdrawal of consent from further follow-up 
3. Investigator decision 
4. Lost to follow-up 
5. Death. 
 
10.1 
General Considerations 
Information on adverse events, whether serious or not, whether reported by the participant, 
directly observed, or detected by physical examination, laboratory test or other means, will be 
collected, recorded, followed and reported as described in the following sections. 
 
The therapy administered in this trial – YESCARTA (axicabtagene ciloleucel) – is an approved 
treatment for the patient population eligible to participate in this study.  Therefore, collection 
of data regarding adverse events and serious adverse events will be limited in this study: 
 
• After informed consent but prior to initiation of YESCARTA infusion, serious and non-
serious adverse events should be reported only if possibly, probably or definitely 
attributed by the patient’s study physician to a protocol-mandated research procedure 
or intervention. 
 
• Any serious adverse event that occurs ≤ 30 days after initiation of YESCARTA, regardless 
of causality to participation in the study, must be reported to the Study Coordinator 
fashion as directed below (Reporting Procedures). 
 
 
• For purposes of this study, cytokine release syndrome, neurological events, 
hematological severe infections greater than or equal to Grade 3, autoimmune events, 
and secondary malignancy events are considered Adverse Events of Special Interest 
(AESI).   
  
• From the time of initiating YESCARTA infusion and until at least 30 days after initiation 
of the YESCARTA infusion, all adverse events of special interest (AESI) experienced by a 
participant must be collected in the study data, regardless of attribution to participation 
in the study. 
  
Additionally (as addressed below in Section 10.6), if an event of special interest (AESI) is 
also a non-serious adverse event (AE) greater than or equal to Grade 3, or a serious 
adverse event (SAE) of any grade, the AESI must also be reported in an expedited 
manner by the site to the Study Coordinator, within 24 hours of the investigator 
becoming aware of the event (i.e. a ‘substantial’ AESI must not only be conventionally 
recorded in the general study data/electronic case report form, but also reported via 
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• During the 30-day follow-up period (i.e. the 30 days following initiation of the YESCARTA 
infusion), non-serious adverse events which are not adverse events of special interest 
(AESI) are required to be recorded in the study data only if, in the opinion of the 
investigator, there is a reasonable possibility the event is attributable to a protocol-
mandated research procedure or intervention.  For example, provided they are not 
adverse events of special interest (AESI), non-serious adverse events related to disease, 
standard-of-care YESCARTA or the next phase of the patient’s disease treatment or 
management are not required to be recorded in the study data.  All serious adverse 
events (SAEs) and adverse events of special interest (AESI) occurring within the 30-day 
follow-up period must be reported, regardless of suspected causality. 
 
• Participants who experience an ongoing serious adverse event (SAE) or an adverse event 
of special interest (AESI) > 30 days after initiation of YESCARTA deemed possibly, 
probably or definitely related to YESCARTA, will continue to be contacted by a member 
of the study team until the event is resolved, stabilized, or determined to be irreversible 
or not clinically significant by the participating investigator. 
 
 
Participants should be instructed to report any serious post-study event(s) that might 
reasonably be related to participation in this study.  The investigator should notify the IRB and 
the Study Coordinator of any unanticipated death or adverse event occurring after a participant 
has discontinued or terminated study participation that may reasonably be related to the study. 
 
10.3 
Grading of Adverse Events 
Adverse events will be graded according to the NCI’s Common Terminology Criteria for Adverse 
Events (NCI CTCAE), Version 5.0, dated November 27, 2017, currently locatable via the 
following URL: 
<https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick
_Reference_8.5x11.pdf>. 
 
If events are not listed in the CTCAE, severity may be designated as mild, moderate, severe, life-
threatening, or fatal which respectively correspond to Grades 1, 2, 3, 4, and 5 on the NCI 
CTCAE, with the following definitions: 
 
• Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated; 
 
• Moderate: Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL) such as preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc; 
  
• Severe: Medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL such as 
bathing, dressing and undressing, feeding self, using the toilet, taking medications; 
 


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• Life-threatening: Urgent intervention indicated to prevent risk of death present at 
the time of the event; 
  
• Fatal: An event that results in the death of the patient. 
10.4.1. 
Adverse Event (AE) 
An adverse event is any undesirable sign, symptom or medical condition or 
experience that develops or worsens in severity after starting the first dose of study 
treatment or any procedure specified in the protocol, even if the event is not 
considered to be related to the study. 
 
Abnormal laboratory values or diagnostic test results constitute adverse events only 
if they induce clinical signs or symptoms or require treatment or further diagnostic 
tests. 
10.4.2. 
Serious Adverse Event (SAE) 
A serious adverse event is an undesirable sign, symptom or medical condition which: 
 
• Is fatal or life-threatening; 
 
• Requires or prolongs inpatient hospitalization; 
 
 
• Results in persistent or significant disability/incapacity; 
 
 
• Constitutes a congenital anomaly or birth defect; or 
 
 
• Jeopardizes the participant and requires medical or surgical intervention to 
prevent one of the outcomes listed above. 
 
 
Events not considered to be serious adverse events are hospitalizations for: 
 
• Routine treatment or monitoring of the studied indication, not associated 
with any deterioration in condition, or for elective procedures. 
• Admission for closer monitoring for known side effects of therapy such as 
cytokine release syndrome and neurological events do not qualify as an SAE.   
 
• Elective or pre-planned treatment for a pre-existing condition that did not 
worsen. 
 
 
• Emergency outpatient treatment for an event not fulfilling the serious 
criteria outlined above and not resulting in inpatient admission. 
 
 


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• Respite care. 
 
 
10.4.3. 
Expectedness 
Expected:  Expected adverse events are those that have been previously identified as 
resulting from administration of the agent.  For the purposes of this study, an adverse 
event is considered expected when it appears in the current adverse event list, the 
Investigator’s Brochure, the package insert or is included in the informed consent 
document as a potential risk. 
 
Unexpected:  An adverse event is considered unexpected when it varies in nature, 
intensity or frequency from information provided in the current adverse event list, 
the Investigator’s Brochure, the package insert or when it is not included in the 
informed consent document as a potential risk. 
 
10.4.4. 
Attribution 
Attribution is the relationship between an adverse event or serious adverse event 
and the study treatment.  Attribution will be assigned as follows: 
 
• Definite – The AE is clearly related to the study treatment. 
 
• Probable – The AE is likely related to the study treatment. 
 
 
• Possible – The AE may be related to the study treatment. 
 
 
• Unlikely – The AE is doubtfully related to the study treatment. 
 
 
• Unrelated – The AE is clearly NOT related to the study treatment. 
 
 
10.5. 
Reporting Procedures 
 
10.5.1. General Considerations 
Investigators should use correct medical terminology/concepts when reporting Aes 
or SAEs, and avoid colloquialisms and abbreviations.  If known at the time of 
reporting, a diagnosis should be reported rather than individual signs and symptoms 
(e.g. record only liver failure or hepatitis rather than jaundice, asterixis, and elevated 
transaminases).  However, if a constellation of signs and/or symptoms cannot be 
medically characterized as a single diagnosis or syndrome at the time of reporting, it 
is acceptable to report the information that is currently available.  If a diagnosis is 
subsequently established, it should be reported as follow-up information. 
 


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All deaths that occur during the protocol-specified AE reporting period, regardless of 
attribution, will be reported to relevant bodies including Kite Pharmacovigilance, 
Vanderbilt,  and CIBMTR.  When recording a death, the event or condition that 
caused or contributed to the fatal outcome should be reported as the single medical 
concept.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, report “Unexplained Death.”  Deaths that occur during the protocol 
specified adverse event reporting period that are attributed by the investigator solely 
to progression of disease should be recorded only in the study eCRF and not reported 
as an SAE. 
 
A pre-existing medical condition is one that is present prior to initiation of protocol 
specified treatment.  Such conditions should be reported as medical and surgical 
history.  A pre-existing medical condition should be re-assessed throughout the trial 
and reported as an AE or SAE only if the frequency, severity, or character of the 
condition worsens during the study.  When reporting such events, it is important to 
convey the concept that the pre-existing condition has changed by including 
applicable descriptors (e.g., “more frequent headaches”). 
Any AE that results in transfer to the Intensive Care Unit (ICU) should be documented 
and reported as an SAE.  If a patient is hospitalized to undergo a medical or surgical 
procedure as a result of an AE, the event responsible for the procedure, not the 
procedure itself, should be reported as the SAE.  For example, if a patient is 
hospitalized to undergo coronary bypass surgery, record the heart condition that 
necessitated the bypass as the SAE. 
 
Hospitalizations for the following reasons do not require reporting: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for pre-existing conditions; or 
 
• Hospitalization or prolonged hospitalization required to allow efficacy 
measurement for the study; or 
 
 
• Hospitalization or prolonged hospitalization for scheduled therapy of the 
target disease of the study. 
 
 
10.5.2. Serious Adverse Events 
All serious adverse events, regardless of causality to study drug, will be reported to 
the Principal Investigator and the Study Coordinator at the institution. 
 
All serious adverse events must be reported to the Study Coordinator within 24 hours 
of the investigator becoming aware of the event.  Events should be reported using 
the Vanderbilt SAE form, located in the packet of supplemental forms.  This form 
must be fully completed and emailed (preferred), faxed, or scanned to the Study 
Coordinator. 


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The Study Coordinator will disseminate information regarding serious adverse events 
to the participating site as described in FDA guidance only in the case that the 
event(s) is/are unexpected, and is/are believed to be related (i.e., possibly, probably 
or definitely) to the study device/medication.  The Study Coordinator will be 
responsible for reporting of events to supporters, as appropriate (outlined below). 
 
10.5.3. Institutional Review Board 
All adverse events and serious adverse events will be reported to the IRB per current 
institutional standards.  If an adverse event requires modification of the informed 
consent, these modifications will be provided to the IRB with the report of the 
adverse event.  If an adverse event requires modification of the study protocol, these 
modifications will be provided to the IRB as soon as is possible. 
 
10.5.4. Reporting to Supporters 
Vanderbilt University Medical Center will notify the funder of any serious adverse 
event (SAE) that occurs during the reporting period as defined above in Section 10.2.  
Within 2 working days after the Study Coordinator initially receives the safety 
information from the site, the Study Coordinator will report the SAE (on the 
MedWatch, funder, or Vanderbilt SAE form approved by the study team and funder) 
to a point of contact specified by the funder – for example to Kite/Gilead via email at 
.  Follow-up SAE reports received by the Study Coordinator 
should be sent within 2 working days to the funder using the same procedure used 
for transmitting the initial report. 
 
10.6. Adverse Events of Special Interest (AESI) 
Selected non-serious and serious adverse events are also known as Adverse Events of Special 
Interest (AESI).  In this trial, adverse events of special interest include: 
 
• 
Neurological events ≥ Grade 3. 
 
• 
Hematological severe infections ≥ Grade 3, 
 
 
• 
Autoimmune events, and 
 
 
• 
Secondary malignancy events, 
 
 
• 
Cytokine release syndrome ≥ Grade 3.  
 
 
Within the reporting period outlined above in Section 10.2 and according to SAE reporting 
procedures outlined in Section 10.5, all adverse events of special interest (AESI) meeting the 
following criteria must be reported in an EXPEDITED manner by the site to the Study 


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Coordinator within 24 hours of the investigator becoming aware of the event – regardless of 
attribution to participation in the study: 
 
• 
AESI that is a non-serious adverse event (AE) ≥ Grade 3, or 
 
• 
AESI that is a serious adverse event (SAE) of any grade. 
 
11. STATISTICAL CONSIDERATIONS 
 
11.1. General Analysis Plan  
No formal hypothesis will be tested in this study. Data analysis will be descriptive. No group 
comparisons will be made.  Continuous variable will be summarized using the minimum value, 
maximum value, 25th, 50th (median), and 75th percentiles as well as the mean and standard 
deviation.  Categorical variables will be summarized in frequency tables. [13-15] See appendix E 
for detailed statistical considerations. 
 
 
 


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11.2. Study Endpoints 
 
 
11.2.1. Primary Endpoints 
 
1. Number of subjects that remain an outpatient at 3, 7 and 30 days after 
YESCARTA infusion.  
 
2. Time to requirement for inpatient hospitalization after YESCARTA infusion. 
 
 
11.2.2. Secondary Endpoints 
 
1. Incidence of Aes and clinically significant changes in safety lab values. 
2. Incidence/grade of adverse events. 
 
3. Incidence/grade of CRS and ICANS. 
  
4. Incidence of steroid and/or tocilizumab administration. 
  
5. YESCARTA treatment response rate. 
  
6. Time to intervention defined as the time interval between when the call was 
made to admit the subject for an adverse event of interest and the time that 
specific intervention was given. 
  
7. Rate of use of tocilizumab, corticosteroids, vasopressors.  
 
 
11.2.3. Exploratory Endpoints 
 
1. Levels of inflammatory cytokines in subject’s serum before and after YESCARTA 
infusion. 
 
2. Investigation for potential predictive markers for grade 3 or higher toxicity or 
need for hospitalization.  
 
 
3. Modified NF symptom burden score for days 1-3 for each subject (appendix D) 
  
4. Subject reported outcomes measured by Subject-Reported Outcomes 
Measurement Information System (PROMIS) [16, 17]. 
 
 


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11.3. Sample Size 
Twenty subjects will receive YESCARTA treatment at a maximum of two sites. Subjects 
who are unable to proceed with CART infusion and monitoring for 14 days on study will 
be replaced. 
 
12. DATA SAFETY AND MONITORING 
 
12.1. Data Management and Reporting 
Participating institutions will collaborate with Vanderbilt for patient accrual.  The Vanderbilt 
University Office of Research will be used as a central location for data processing and 
management.  Vanderbilt University, with collaboration from a consortium of institutional 
partners, has developed a software toolset and workflow methodology for electronic collection 
and management of research and clinical trial data.  REDCap (Research Electronic Data Capture) 
is a secure, web-based application that is flexible enough to be used for a variety of types of 
research.  REDCap provides an intuitive user interface that streamlines project development 
and improves data entry through real-time validation rules (with automated data type and 
range checks).  REDCap also provides easy data manipulation (with audit trails for reporting, 
monitoring and querying patient records) and an automated export mechanism to common 
statistical packages (SPSS, SAS, Stata, R/S-Plus).  In addition to traditional data capture 
functionality, REDCap’s survey capabilities are a powerful tool for building and managing online 
surveys.  The research team can create and design surveys in a web browser and engage 
potential respondents using a variety of notification methods.  All data collection projects rely 
on a thorough, study-specific data dictionary, defined by all members of the research team in 
an iterative, self-documenting process.  This iterative development and testing process results 
in a well-planned and individualized data collection strategy. 
 
REDCap servers are housed in a local data center at Vanderbilt, and all web-based information 
transmission is encrypted.  REDCap was developed specifically around HIPAA-Security 
guidelines and is recommended to Vanderbilt researchers by both our Privacy Office and 
Institutional Review Board.  REDCap has been disseminated for local use at more than 940 
other academic/non-profit consortium partners in 75 countries.  Vanderbilt leads the REDCap 
Consortium, which currently supports more than 99,000 projects and 128,000 users.  More 
information about the consortium and system security can be found at 
http://www.projectredcap.org/.  
 
12.2. Auditing and Monitoring 
The Vanderbilt-Ingram Cancer Center (VICC) oversees patient safety and data monitoring for its 
investigator-initiated and NIH-NCI funded clinical trials through its Data and Safety Monitoring 
Committee (DSMC).  The purpose of the DSMC is to ensure the efficient implementation and 
management of the VICC Data and Safety Monitoring Plan (DSMP).  The Committee maintains 
authority to intervene in the conduct of studies as necessary to ensure clinical research 
performed at VICC achieves the highest quality standards. 
 


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The VICC DSMC meets on a quarterly basis and ad hoc to discuss data and safety monitoring of 
clinical trials and to oversee the VICC DSMP.  Internal audits for compliance with adverse event 
reporting, regulatory and study requirements, and data accuracy and completion are conducted 
according to the VICC DSMP according to study phase and risk.  The committee reviews all 
serious adverse events (SAE) on Vanderbilt sponsored investigator-initiated studies on a 
quarterly basis and provides DSMC SAE review reports to the Vanderbilt IRB. 
 
The trial additionally will be monitored by the VICC Multi-Institutional Coordinating Center.  The 
actual frequency of monitoring will depend on the enrollment rate and performance of the site. 
Monitoring will be conducted through onsite and/or remote monitoring, teleconferences with 
the Investigator and site staff, and appropriate communications by mail, fax, email, or 
telephone.  The purpose of monitoring is to ensure that the study is conducted in compliance 
with the protocol, standard operating procedures (SOPs), and other written instructions, and to 
ensure the quality and integrity of the data. 
 
During scheduled monitoring visits, investigators and the investigational site staff must be 
available to discuss the progress of the trial, make necessary corrections to case report form 
entries, respond to data clarification requests, provide required regulatory documents, and 
respond to any other trial-related inquiries of the monitor. 
 
12.3. Data Handling and Record Keeping 
An electronic case report form (eCRF) is required and must be completed for each included 
participant.  The completed dataset should not be made available in any form to third parties, 
except for authorized representatives of appropriate Health/Regulatory Authorities, without 
written permission from Vanderbilt. 
 
To enable evaluations and/or audits from health authorities and Vanderbilt, the site 
investigator agrees to keep records including: The identity of all participants (sufficient 
information to link records; e.g., hospital records), all original signed informed consent forms, 
copies of all source documents, and detailed records of drug disposition.  To comply with 
international regulations, the records should be retained by the investigator in compliance with 
regulations. 
 
Queries resulting from review of the eCRFs will be generated for the site and corrections will be 
made by the study site personnel.  This will be done on an ongoing basis. 
 
13. REGULATORY CONSIDERATIONS 
 
13.1. Protocol Review and Amendments 
Information regarding study conduct and progress will be reported to the Institutional Review 
Board (IRB) per current institutional standards. 
 
The trial will not be initiated until there is approval by the local IRB of the protocol, informed 
consent document and any other material used to inform the patient about the nature of the 


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trial.  The IRB should be duly constituted according to local regulatory requirements.  The 
investigator will inform the IRB of the progress of the trial at least yearly. 
 
Any changes to the protocol will be made in the form of a written amendment and must be 
approved by the sponsor-investigator and the local IRB prior to local implementation.  All 
amendments will also be submitted as necessary to the FDA by the sponsor-investigator (or 
designee). 
 
Protocol changes to eliminate an immediate hazard to a trial patient may be implemented by 
the investigator immediately.  The investigator must then immediately inform the local IRB; and 
the sponsor-investigator (or designee), who will communicate as appropriate with the FDA. 
 
The sponsor-investigator (or designee) is responsible for the coordination and development of 
all protocol amendments and will disseminate this information to the participating centers. 
 
13.2. Informed Consent 
The investigator (or designee) will explain to each participant the nature of the study, its 
purpose, the procedures involved, the expected duration, the potential risks and benefits 
involved and any discomfort it may entail.  Each participant will be informed that participation 
in the study is voluntary, that s/he may withdraw from the study at any time, and that 
withdrawal of consent will not affect subsequent medical treatment or relationship with the 
treating physician(s) or institution.  The informed consent will be given by means of a standard 
written statement, written in non-technical language, which will be IRB approved.  The 
participant should read and consider the statement before signing and dating it and will be 
given a copy of the document.  No patient will enter the study or have study-specific 
procedures done before his/her informed consent has been obtained. 
 
In accordance with the Health Information Portability and Accountability Act (HIPAA), the 
written informed consent document (or a separate document to be given in conjunction with 
the consent document) will include a subject authorization to release medical information to 
the study sponsor and supporting agencies and/or allow these bodies, a regulatory authority, or 
Institutional Review Board access to subjects’ medical information that includes all hospital 
records relevant to the study, including subjects’ medical history. 
 
13.3. Confidentiality 
It is the responsibility of the investigator to ensure that the confidentiality of all patients 
participating in the trial and all of their medical information is maintained.  Case report forms 
(CRFs) and other documents submitted to regulatory authorities must not contain the name of 
a trial patient.  All patients in the trial will be identified by a unique identifier which will be used 
on all CRFs and any other material submitted to regulatory authorities.  All case report forms 
and any identifying information must be kept in a secure location with access limited to the 
study staff directly assisting with the trial. 
 
13.4. Study Termination 


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The sponsor-investigator reserves the right to terminate the study at any site and at any time.  
Reasons for study termination may include, but are not limited to, the following: 
• Investigator non-compliance with the protocol, GCP or regulatory requirements. 
• Insufficient enrollment. 
• Safety concerns. 
• Decision by suppliers to modify or discontinue the availability, development or 
manufacture of protocol-indicated treatment. 
• A request to discontinue the study by the IRB or recognized regulatory authority. 
 
14. STUDY COORDINATION 
 
14.1. Trial Compliance 
This is an investigator-initiated study.  The Principal Investigator, Olalekan O. Oluwole, MD, 
MPH (who may also be referred to as the Sponsor-Investigator), is conducting the study and 
acting as the sponsor.  Therefore, the legal and ethical obligations of the Principal Investigator 
include both those of a sponsor and those of a principal investigator. 
 
Vanderbilt is the Coordinating Center for this study.  All aspects of the study will be carefully 
monitored by the Coordinating Center for compliance with applicable government regulations 
with respect to current GCP and standard operating procedures. 
 
14.2. Changes to Protocol and Informed Consent Document 
Any change to the protocol or informed consent document must be reviewed and approved by 
the investigator before being submitted to the Institutional Review Board/Independent Ethics 
Committee at participating institutions.  Amendments should not be implemented until all 
necessary approvals have been obtained, except when necessary to eliminate an immediate 
hazard to study subjects. 
 
14.3. Protocol Deviations 
The Coordinating Center is responsible for implementing and maintaining quality assurance and 
quality control to ensure that studies are conducted according to the protocol, GCP, and all 
applicable regulatory requirements.  A protocol deviation is any noncompliance with the 
protocol.  Noncompliance can be on the part of the study participant, the investigator, or the 
study site staff.  Deviations to the protocol are not permitted except when necessary to 
eliminate an immediate hazard to study subjects. 
 
14.4. Monitoring and Quality Assurance 
As the Coordinating Center, Vanderbilt has responsibilities to health authorities to take all 
reasonable steps to ensure the proper conduct of the study with regard to ethics, protocol 
adherence, integrity, validity of the data recorded on the CRFs, and adherence to regulations 
regarding Good Clinical Practice (GCP) and the protection of human subjects. 
 
In accordance with applicable regulations, GCP, and Coordinating Center procedures, sites will 
be contacted prior to the start of the study to review with site staff the protocol, study 


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requirements, and their responsibilities to satisfy regulatory, ethical, and Coordinating Center 
requirements. 
 
During the course of the study, the Coordinating Center will routinely monitor sites for protocol 
compliance, compare CRFs with original source documents from individual subjects, assess drug 
accountability, and ensure that the study is being conducted according to the pertinent 
regulatory requirements.  The review of subject medical records will be performed in a manner 
to ensure that subject confidentiality is maintained.  Monitoring visits will primarily be 
conducted remotely, and sites are required to provide the appropriate source documentation 
in order to allow for proper oversight per GCP.  Investigators must agree to cooperate with the 
Coordinating Center to ensure that any problems detected are resolved. 
 
 


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14.5. Data Verification 
Data will be collected via eCRFs and entered into the database per Coordinating Center 
guidelines. The Coordinating Center will check data accuracy by performing source data 
verification.  Source data verification is a direct comparison of the entries made on the CRFs 
against the appropriate source documentation.  This will be conducted remotely, with the 
possibility of on-site verification periodically.  Discrepancies in the data will be brought to the 
attention of the investigator and/or the investigator’s staff.  Any necessary corrections will be 
made directly to the eCRFs or via queries by the investigator and/or the investigator’s staff. 
 
14.6. Study Documentation 
Each participating site is responsible for submitting copies of all relevant regulatory 
documentation to the Coordinating Center.  The required documents include but are not 
limited to the following: local IRB approvals (i.e., protocol, consent form, amendments, patient 
brochures, recruitment material, etc.), IRB membership rosters, summary of unanticipated 
problems or protocol deviations, and documentation of expertise of the investigators.  The 
Coordinating Center will provide each participating site with a comprehensive list of the 
necessary documents.  It is the responsibility of the participating sites to maintain copies of all 
documentation submitted to the Coordinating Center. 
 
The requirements for data management, submissions, and monitoring are outlined below.  The 
participating sites will submit all the research related information inclusive of: 
 
• Source documents (patient registration list, CRF info, toxicity assessments, tumor 
measurements / responses, etc.) are required to be provided within 30 days of visit or 
10 days in advance of a monitoring visit or audit, 
 
• Essential Documents (IRB approval documents, financial disclosure forms, 1572, 
delegation of authority log, protocol training, etc.) are required to be provided within 
one week of receiving the updated documents. 
 
Personnel from the VICC Clinical Trials Office will monitor the trial and may periodically visit the 
investigative site to assure proper conduct of the trial and proper collection of the data.  The 
investigators at other sites will allow the monitor to review all source documents used in the 
preparation of the case reports. 
 
14.7. Closure of the Study 
The Coordinating Center reserves the right to discontinue a site at any time during the study for 
medical or administrative reasons such as: 
• Unsatisfactory enrollment; 
• GCP noncompliance; 
• Inaccurate or incomplete data collection; 
• Falsification of records; 
• Failure to adhere to the study protocol. 
 


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14.8. Records Retention 
U.S. FDA regulations (21 CFR §312.62[c]) require that records and documents pertaining to the 
conduct of this study, including CRFs, consent forms, laboratory test results, and medication 
inventory records, must be retained by each Principal Investigator for 2 years after marketing 
application approval.  If no application is filed, these records must be kept 2 years after the 
study is discontinued and the applicable national and local health authorities are notified. 
 
Following closure of the study, each participating center will maintain a copy of all site study 
records in a safe and secure location.  The Coordinating Center will inform the investigator at 
such time that the records may be destroyed. 
 
14.9. Publication 
It is understood that any manuscript or releases resulting from the collaborative research must 
be approved by the sponsor-investigator and will be circulated to applicable participating 
sites/investigators prior to submission for publication or presentation. 
 
 
17. REFERENCES 
1. 
Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, Link BK, Hay A, Cerhan JR, Zhu L et 
al: Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 
study. Blood 2017, 130(16):1800-1808. 
2. 
Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, 
Timmerman JM et al: Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell 
lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. The Lancet Oncology 2019, 20(1):31-42. 


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3. 
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S 
et al: ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with 
Immune Effector Cells. Biology of blood and marrow transplantation : journal of the American Society for 
Blood and Marrow Transplantation 2019, 25(4):625-638. 
4. 
Borchman P, Tam, Constantine S., Jager, Ulrich, McGuirk, Joseph P., Holte, Harald, Waller, Edmund K., 
Jaglowski, Samantha M., Bishop, Michael R., Andreadis, Charalambos, Foley, Stephen Ronan, Westin, 
Jason R., Fleury, Isabelle, Ho, P. Joy, Mielke, Stephan, Salles, Gilles, Maziarz, Richard T., Anak, Ozlem, 
Pacaud, Lida Bututeishvili, del Corral, Chistopher, Awasthi, Rakesh, Agoulnik, Sergei, Tai, Feng, Schuster, 
Stephen J.: An Updated Analysis of JULIET, a Global Pivotal Phase 2 Trial of Tisagenlecleucelin Adult 
Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. In: 23rd Congress of EHA: 2018; 
Stockholm, Sweden: prIME Oncology; 2018. 
5. 
Abramson JS, Palomba ML, Gordon LL, Lunning MA, Wang ML, Arnason JE, Mehta A, Enkhtsetseg P, 
Maloney DG, Andreadis C et al: Pivotal Safety and Efficacy Results from Transcend NHL 001, a 
Multicenter Phase 1 Study of Lisocabtagene Maraleucel (liso-cel) in Relapsed/Refractory (R/R) Large B 
Cell Lymphomas. Blood 2019, 134(1):1. 
6. 
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi 
T, Lin Y et al: Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. The New 
England journal of medicine 2017, 377(26):2531-2544. 
7. 
Rossi J, Paczkowski P, Shen YW, Morse K, Flynn B, Kaiser A, Ng C, Gallatin K, Cain T, Fan R et al: Preinfusion 
polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL. 
Blood 2018, 132(8):804-814. 
8. 
Reid RM, Baran A, Friedberg JW, Phillips GL, 2nd, Liesveld JL, Becker MW, Wedow L, Barr PM, Milner LA: 
Outpatient administration of BEAM conditioning prior to autologous stem cell transplantation for 
lymphoma is safe, feasible, and cost-effective. Cancer medicine 2016, 5(11):3059-3067. 
9. 
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S 
et al: ASBMT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated 
with Immune Effector Cells. Biology of blood and marrow transplantation : journal of the American 
Society for Blood and Marrow Transplantation 2018. 
10. 
Ahn S, Rice TW, Yeung SJ, Cooksley T: Comparison of the MASCC and CISNE scores for identifying low-
risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in 
three continents. Supportive care in cancer : official journal of the Multinational Association of Supportive 
Care in Cancer 2018, 26(5):1465-1470. 
11. 
Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, 
Rolston K et al: Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: 
American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice 
Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 
2018, 36(14):1443-1453. 
12. 
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA: Recommendations for 
initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the 
Lugano classification. Journal of clinical oncology : official journal of the American Society of Clinical 
Oncology 2014, 32(27):3059-3068. 
13. 
Thall PF, Simon RM, Estey EH: Bayesian sequential monitoring designs for single-arm clinical trials with 
multiple outcomes. Statistics in medicine 1995, 14(4):357-379. 
14. 
Thall PF, Simon RM, Estey EH: New statistical strategy for monitoring safety and efficacy in single-arm 
clinical trials. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 
1996, 14(1):296-303. 
15. 
Thall PF, Sung HG: Some extensions and applications of a Bayesian strategy for monitoring multiple 
outcomes in clinical trials. Statistics in medicine 1998, 17(14):1563-1580. 
16. 
Chakraborty R, Sidana S, Shah GL, Scordo M, Hamilton BK, Majhail NS: Patient-Reported Outcomes with 
Chimeric Antigen Receptor T Cell Therapy: Challenges and Opportunities. Biology of blood and marrow 
transplantation : journal of the American Society for Blood and Marrow Transplantation 2019, 25(5):e155-
e162. 


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17. 
Shaw BE, Syrjala KL, Onstad LE, Chow EJ, Flowers ME, Jim H, Baker KS, Buckley S, Fairclough DL, Horowitz 
MM et al: PROMIS measures can be used to assess symptoms and function in long-term hematopoietic 
cell transplantation survivors. Cancer 2018, 124(4):841-849. 
 
 
 


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APPENDICES 
 
Appendix A: YESCARTA Patient and Caregiver Education   
 
Appendix B:  YESCARTA Caregiver Pre-Test 
 
Appendix C:  YESCARTA Caregiver Post-Test 
 
Appendix D:  Clinical Practice Guideline for Outpatient Management of Febrile Neutropenia in  
Patients Receiving Commercial CAR T-Cell Therapy 
 
Appendix E:  Detailed Statistical Considerations 
 
Appendix F:  PROMIS-29 Profile v2.1 
 
Appendix G: Biofourmis Wearable Device 
 
 
 
 
 
 
 
 
 
 


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Appendix A 
Vanderbilt University Medical Center 
YESCARTA Patient and Caregiver Education: Self-monitoring for CAR T toxicities 
 
Date: 
 
General consideration:  
You are part of patient’s care team and we need your help to monitor the patient’s wellbeing while not 
in the clinic or hospital. It is very important that you pay attention to any new symptoms or signs and 
report to us immediately. Below is the summary common symptoms/signs of CAR T therapy associated 
toxicities. This is NOT a complete list and you should not hesitate to call us with any new issue which 
may arise while at home.  
 
I.Vital Signs: equipment, testing, results  
• 
What equipment will you use?   
o 
Blood Pressure Cuff – used to take patient’s blood pressure and heart rate 
o 
Pulse Oximeter – used to measure patient’s oxygen and heart rate  
o 
Thermometer – used to take patient’s temperature  
• 
How often will take vitals for patient  
o 
Patient will have vital signs done during clinic visits at 8am  
o 
The caregiver will be responsible for vital signs at 6am, 12pm, 4:30, 10pm,   
• 
How will you report vital signs?   
o 
Patient will have a video conference call with night NP at 4:30pm and 10:00 PM ± 1 hour 
for at least first 14 days after Car-T infusion  
o 
Patient will call night NP at 6am to report 6am vital signs.  
 
Things to monitor at Home: 
II.Signs of Infection  
• 
Fever:  You will take your temperature 6am, 12pm, ≤10pm, 
o 
A temperature higher than 100.3 F is a reason to call at any time 
• 
Redness and/or tenderness around patient’s venous catheter site  
• 
Dizziness, shortness of breath, cough, altered mental status 
 
III.Cytokine Release Syndrome (CRS)  
• 
What is CRS?  
o 
This is an inflammatory process that impacts many organs. CRS typically occurs within 
first week after CAR-T infusion.   
• 
What are CRS symptoms?  
o 
Fever   
o 
Chills  
o 
Dizziness/lightheadedness 
o 
Shortness of breath 
o 
Altered mental status 
o 
Low blood pressure (Please call if systolic blood pressure drops below ____ mm Hg) 


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o 
Fast heart rate (Please call if hear rate is above 120 beats/min) 
o 
Low blood oxygen levels (Please call if pulse oxygen level fall below 90 %). 
• 
How do we treat CRS?   
o 
Intravenous fluids  
o 
Supplemental Oxygen  
o 
Tocilizumab (medication to reverse CRS)  
o 
Steroids.  
 
IV.Neurotoxicity  
• 
What is Neurotoxicity?  
o 
This is a collection of symptoms that impact patient’s mental status related to CAR T 
therapy administration.  
• 
What are Neurotoxicity symptoms?  
o 
Confusion  
o 
Headache 
o 
Delirium (confused thinking and reduced awareness of environment, for example to 
time and place; usually with rapid onset)  
o 
Difficulty finding words/speaking  
o 
Difficulty following commands  
o 
Memory lapses 
o 
Hallucinations (seeing or hearing things which does not exist) 
o 
Dizziness   
o 
Tremors  
o 
Seizures/ convulsions 
o 
Lethargy (lack of energy and enthusiasm).   
• 
How do we treat Neurotoxicity?   
o 
Steroids.   
 
V.  Monitoring  
• 
How will the patient be monitored?   
o 
You will be seen every day in our Outpatient Transplant Unit (OTU) at 8:00am and a nurse 
will visit the apartment at 4:30pm ± 1 hour daily for 14 days after your CAR-T infusion (Day 
0)  
o 
You will have your labs and vitals taken daily in clinic.   
o 
You will have a video conference telehealth visit with the night NP at 10pm. At that 
time, you will take your vital signs and answer questions.  
o 
You will take your vitals at 6am and then have a morning phone call with night NP to 
report overnight vital signs.   
o 
Once you are discharged from the OTU, you will transition to the CAR-T long term care 
clinic. This typically occurs between 14 and 30 days after CAR-T infusion.   
 
Official Use only  
 
 
 
 
 
 
Version date: 
Approved by: 


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Appendix B 
 
 
 
 
Vanderbilt University Medical Center 
YESCARTA Caregiver Pre-Test 
 
Date:  
 
Subject ID: 
1. What temperature is considered serious and warrants a call to Vanderbilt?  
a. 100.0°F 
b. 99.5°F 
c. 100.4°F 
d. 97.6°F 
2. Which symptom may mean the patient is experiencing neurotoxicity?  
a. Tremors 
b. Confusion 
c. Being extra sleepy 
d. All of the above 
3. What times do we need the patient to connect to the telehealth monitoring system?  
a. 10:00 PM 
b. 2:00 AM 
c. 6:00 AM 
d. None of the above  
4. Please perform 3 blood pressures on patient and write down values:  
a.     
b.     
c.     
5. Please take the patient’s temperature 3 times and write down values:  
a.   
b.     
c.     
6. Please take patient’s pulse oxygen levels and write down values: 
a.    
b.    
c.    
7. Please check patient’s heart rate and write down values:  
a.    
b.    
c.    
8. What symptom may mean the patient is experiencing cytokine release syndrome (CRS)?  
a. Chills 
b. Low blood pressure 
c. Fever 
d. All of the above 
Official Use only 
 
 
 
 
 
Appendix                 Version 
Date: 
Score: 
Pass/Fail 
Comment: 
Reviewer’s 
initials: 


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Appendix C 
Vanderbilt University Medical Center 
YESCARTA Caregiver Post-Test 
 
Date:  
 
Subject ID: 
1. What temperature is considered serious and warrants a call to Vanderbilt?  
a. 100.0°F 
b. 99.5°F 
c. 100.4°F 
d. 97.6°F 
2. Which symptom may mean the patient is experiencing neurotoxicity?  
a. Tremors 
b. Confusion 
c. Being extra sleepy 
d. All of the above 
3. What times do we need the patient to connect to the telehealth monitoring system?  
a. 10:00 PM 
b. 2:00 AM 
c. 6:00 AM 
d. None of the above  
4. Please perform 3 blood pressures on patient and write down values:  
a.     
b.     
c.     
5. Please take the patient’s temperature 3 times and write down values:  
a.   
b.     
c.     
6. Please take patient’s pulse oxygen levels and write down values: 
a.    
b.    
c.    
7. Please check patient’s heart rate and write down values:  
a.    
b.    
c.    
8. What symptom may mean the patient is experiencing cytokine release syndrome (CRS)?  
a. Chills 
b. Low blood pressure 
c. Fever 
d. All of the above  
Official Use only  
 
 
 
 
Score 
Pass/Fail 
Comment: 
Reviewer’s initials: 
 


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Appendix D 
Suggested Guideline for Outpatient Management of Febrile Neutropenia in  
Patients Receiving Immune Effector-Cell Therapy 
Modified Neutropenic Fever Symptom Burden (NFSB) score: Modified from MASCC 
Introduction: 
Prevention and appropriate management of febrile neutropenia (FN) is important because the rate 
of major complications (e.g., hypotension, acute renal, respiratory, and heart failure) in the 
context of FN is approximately 25% to 30%, and the mortality rate ranges up to 11%. Fever is a 
common toxicity associated with immune effector cell (IEC) therapy and may be indicative of an 
infectious process, cytokine release syndrome, or both. Patients receiving this therapy who 
present with fever (Tmax ≥100.4° F) and concomitant neutropenia (absolute neutrophil count 
≤500 cells/mm3) must be treated according to standard FN guidelines. However, fever in this 
population can at times be stable and otherwise asymptomatic and therefore, may warrant 
consideration of outpatient FN management. Several tools exist and have been validated to help 
determine whether oncology patients are at a low or high risk for medical complications as a 
result of an FN episode and are recommended for use in determining which patients are 
candidates for inpatient or outpatient FN treatment.  
 
Conditions/situations that are considered a contraindication to the outpatient management of FN 
and are therefore not eligible to be treated according to this guideline include: 
• Poor pulmonary function (FEV1/DLCO <50%, need for O2, COPD) 
• Mucositis 
• Known specific, active infection such as pneumonia or central line-associated 
bloodstream infection 
• Concern for infection with a resistant organism (ESBL, MRSA, VRE) 
 
Of note, IEC patients who are non-neutropenic and experience fever may also be treated 
according to this guideline per clinician discretion. 
 
Risk Assessment: 
The risk index table1 below has been established by the Vanderbilt Ingram Cancer Center 
Immune Effector-Cell Committee to identify patients who are candidates for outpatient 
management of FN based on their potential risk for medical complications.  
 
Modified Neutropenic Fever Symptom Burden (NFSB) score 
Characteristic 
Score 
Fever < 102°F 
2 
Fever ≥ 102°F 
5 
New or progressive symptoms based on ROS 
5 
Hypotension (systolic blood pressure ≤ 90mmHg or mean arterial pressure ≤ 65 
mmHG AND blood pressure/MAP within 80% of baseline value) 
5 
Hypoxia (02 < 90%) 
5 
Age > 65 years 
2 
Dehydration (IVF in last 24 hours) 
3 
Recent infection or antifungal prescription 
4 


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NOTE: Maximum score is 29; Scoring is cumulative 
 
 
 
Decision Tree: 
<5 points = Outpatient Management 
5-7 points = Admit to observation 
≥8 = Admit to inpatient 
 
1. Risk index table will be reviewed for purposes of validation after 5 patients have been assessed utilizing this scoring tool. 
 
Treatment:  
If the patient is deemed a potential candidate for outpatient treatment of FN, the following steps 
should be followed: 
1. The patient should present to VUMC for evaluation (clinic or emergency 
department, if after hours) within 1 hour of identification of fever.  
 Draw appropriate cultures (blood/urine)  
 Administer the first dose of IV broad-spectrum β-lactam antibiotic 
(cefepime or piperacillin-tazobactam as outlined in VUMC Empiric Anti-
Infective Algorithm for Febrile Neutropenia) 
 Obtain standard radiographic imaging (chest X-Ray) as outlined in VUMC 
Empiric Anti-Infective Algorithm for Febrile Neutropenia 
2. . 
 The clinic APP or inpatient nocturnist will then determine, with 
consultation from the SCT and/or IEC attending, if needed, if the patient is 
eligible for outpatient management (score ≥21 and no other 
contraindications) 
3. If eligible, the patient should begin usual FN treatment (cefepime, piperacillin-
tazobactam) via home infusion  
a) If home infusion or next clinic administration time will be delayed past 
when the next dose of IV antibiotics is due, the patient may begin an 
ORAL empiric antibiotic regimen with amoxicillin/clavulanate 1 g PO 
q12h (or clindamycin 600 mg PO q8h in case of penicillin allergy) and 
continue prophylactic levofloxacin until IV therapy is secured 
i. 
All patients will be given a 48-hour supply of 
amoxicillin/clavulanate or clindamycin along with all other IEC 
medications on the first day of lymphodepleting chemotherapy to 
use for this purpose 
4. The patient must be seen daily by a health care provider and have daily CBC with 
differential monitoring while receiving outpatient FN treatment 
5. For 72 hours following the onset of the febrile episode and initiation of outpatient 
FN management, the patient will be physically seen by a provider at the daily 
1630 visit/lab check 
6. Patients initially managed as outpatients for FN should be evaluated for admission 
if any of the following occur: 
a) Failure to defervesce after 24-48 hours of empiric antibiotic treatment 


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b) New or progressive signs/symptoms of infection (not attributable to other 
causes), including concomitant CRS and/or ICANS 
  
References: 
1. Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient Management of Fever and 
Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology 
and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin 
Oncol. 2018;36(14):1443-1453. 
2. Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for 
Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying 
Low-Risk Febrile Neutropenic Cancer Patients. J Clin Oncol. 2000;18(16):3038-3051. 
3. VUMC Empiric Anti-Infective Algorithm for Febrile Neutropenia. https://prd-medweb-
cdn.s3.amazonaws.com/documents/vasp/files/FN%20Algorithm%208_18.pdf


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Appendix E 
Detailed Statistical Considerations 
 
This is an open label, pilot clinical trial to evaluate the feasibility of safely delivering Axi-cel 
therapy in the outpatient setting.  The primary objective of this study is to collect data on a 
sample of 20 patients to provide data with which to plan a larger, more definitive trial.  
Sample size was chosen to complete accrual in 24 months. 
 
With 20 observations, categorical variables will be measured with a precision (1/2 of a 95% 
confidence interval) no larger than 20%. Similarly, the precision of measurement for 
continuous variables will be proportional to 0.447 standard deviations. 
 
Endpoints 
Many endpoints will be measures including patient characteristics, response to therapy by 
RECIST 1.0 criteria, progression-free (PFS) and overall (OS) survival. PFS is defined as the 
time from start of therapy to disease progression or death for any reason. OS is defined as the 
time from start of therapy to death for any reason.  Patients progression-free and alive (PFS) 
or alive (OS) at last follow-up will be censored. The distributions of PFS and OS will be 
estimated using the Kaplan-Meier (product limit) method. Adverse events according to 
ASTCT guidelines and CTCAE 5.0 criteria.1  Feasibility metrics include the proportion of 
planned doses delivered, 14-day incidence of hospitalization by type and overall, and the 
proportion of patients that were managed successfully via telemedicine (see above for more 
details) for more than 3 days post infusion.  95% confidence intervals will be estimated for 
all endpoints. 
 
General Analysis Plan 
Data analysis will be descriptive. No group comparisons will be made.  Continuous variable 
will be summarized using the minimum value, maximum value, 25th, 50th (median), and 75th 
percentiles as well as the mean and standard deviation.  Categorical variables will be 
summarized in frequency tables.   
 
Continuous Monitoring of Two Important Toxicities 
We will carefully monitor two toxicities, CRS and neurotoxicity.  Toxicity rates from 
published data for these events are 15% and 30% respectively.  Toxicity will be monitored 
simultaneously and independently in 20 patients using the Bayesian approach of Thall, 
Simon, Estey (1995, 1996) as extended by Thall and Sung (1998). 2-4 The probabilities of  
toxicity for the historical data for these two events are modeled by beta distributions 
(Beta(0.3, 1.7) and Beta(0.6, 1.4), respectively), representing 15% and 30% toxicity for an 
effective sample size of 2 patients.  The prior probabilities of toxicity for the experimental 
regimen are also modeled by beta distributions the same means as the corresponding beta 
distributions for the historical data, also with an effective sample size of  2 patients   


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Neurotoxicty.  Denoting the historical probabilities of toxicity for each endpoint by 
{p(OR,H) , p(TOX,H)}, the following decision criteria will be applied.  Stop if 
Prob{p(Neurotoxicity,H)  < p(Neurotoxicity,E)| data} > 0.75 provides the following 
monitoring rule, 
 
                                | Stop the trial if there are 
                                | this many toxicities total: 
                                |------------------------------------------------------------ 
# Patients              | # Toxicities 
| --------------------------------|------------------------------------------------------------ 
1-5                          | Never stop with this many patients 
6-7                          | 4-7 
8-9                          | 5-9 
10-11                     | 6-11 
12-13                     | 7-13 
14-15                     | 8-15 
16-17                     | 9-17 
18-19                     | 10-19 
20                           | Always stop with this many patients 
 
The monitoring rule becomes effective when 6 patients have been treated.  If the true 
neurotoxicity rate is 30%, this rule stops early 17% of the time.  For a 50% event rate, this rule 
stops 70% of the time.   
 
CRS. Denoting the historical probabilities of toxicity for each endpoint by {p(OR,H) , 
p(TOX,H)}, the following decision criteria will be applied.  Stop if Prob{p(CRS,H)  < p(CRS,E)| 
data} > 0.79 provides the following monitoring rule, 
 
                                | Stop the trial if there are 
                                | this many toxicities total: 
                                |------------------------------------------------------------ 
# Patients              | # Toxicities 
| --------------------------------|------------------------------------------------------------ 
1-5                          | Never stop with this many patients 
6-9                          | 3-9 
10-13                     | 4-13 
14-17                     | 5-17 
18-19                     | 6-19 
20                           | Always stop with this many patients 
  
  
This is for the event where 15% toxicity it expected and acceptable.  If the true toxicity is 15%, 
this rule stops the trial early 18% of the time.  If the true toxicity is 30%, this rule stops the study 
early (i.e., by an accrual of 19 patients) 69% of the time.  


Oluwole YESCARTA in the outpatient setting.  
05SEP23 
 
 
70 of 74
 
 
References  
 
1. 
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN et al. ASTCT Consensus 
Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune 
Effector Cells. Biology of blood and marrow transplantation : journal of the American Society for 
Blood and Marrow Transplantation 2019; 25(4): 625-638. e-pub ahead of print 2018/12/29; doi: 
10.1016/j.bbmt.2018.12.758 
 
2. 
Thall PF, Simon RM, Estey EH. Bayesian sequential monitoring designs for single-arm clinical 
trials with multiple outcomes. Statistics in medicine 1995; 14(4): 357-379. e-pub ahead of print 
1995/02/28;  
 
3. 
Thall PF, Simon RM, Estey EH. New statistical strategy for monitoring safety and efficacy in 
single-arm clinical trials. Journal of clinical oncology : official journal of the American Society of 
Clinical Oncology 1996; 14(1): 296-303. e-pub ahead of print 1996/01/01; doi: 
10.1200/jco.1996.14.1.296 
 
4. 
Thall PF, Sung HG. Some extensions and applications of a Bayesian strategy for monitoring 
multiple outcomes in clinical trials. Statistics in medicine 1998; 17(14): 1563-1580. e-pub 
ahead of print 1998/08/12;  
 
 
 
 
 








 
 
Appendix G: Biofourmis Wearable Device 
 
Introduction 
Subjects undergoing CART therapy are admitted to the hospital for 7 days or longer for close 
monitoring. During that time, the close monitoring consists of physical exam up to four times 
(One by physician, one by NP, twice by nurses) and vitals are measured at least six times (every 
4 hours x 24 hours).  
Biofourmis has FDA/IDE certified wearable devices that are already in use in the clinical setting 
This project explores how wearable devices might be of use in the research setting to enhance the 
close monitoring of patients and bridge the gap between the impatient and outpatient setting Data 
are collected for research purposes only. 
 
Data captured 
Body surface temperature, Respiratory rate, Heart rate, Blood Pressure, Oxygen saturation 
 
Devices 
1. Seven-day patch to be worn on the left anterior chest 
2. Blood Pressure cuff to be worn on the arm intermittently 
3. Pulse oximeter device to be worn on the digits intermittently 
Device Clearances: BP cuff and pulse oximeter are FDA approved while the patch is IDE 
approved 
 
Methods 
Subjects are trained to apply the devices which comprises of a patch that is applied on the left 
anterior chest and worn continuously, a blood pressure cuff that is applied intermittently on the 
arm, and a pulse oximeter applied intermittently to the digits. The BP cuff and pulse oximeter are 
applied at specific times (6am, 12 noon, 16:30 +/- 1 hour and 22:00) while the patch captures 
heart rate, temperature, and respiratory rate continuously. If patient fails to apply the BP cuff and 
pulse oximeter at the time stipulated, a vendor system generated reminder will go to them. Any 
alerts issued by vendor can be viewed by the PI and all authorized users of the program. Data are 
recorded in the device database and are for research only but are accessible by specific clinical 
trial staff.  
Between day -5 and day zero: Subjects are taught to apply and use devices 
Day zero: Subjects are given the devices and begin to wear them 
Day zero through day +14: Subjects use the devices as directed 
Day 14 – 21: Devices are returned to the vendor 
 
Data management 
This is an exploratory objective. We will track the frequency of abnormal vital signs, any alarms 
generated by system and time to resolution of the alarms. Data collected will be analyzed post 
hoc using machine learning to evaluate for any predictive pattern for hospitalization and other 
outcomes. 
 

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Name of participant: __________________________________________ Age: ___________ 
The following is given to you to tell you about this research study.  Please read this form with care and 
ask any questions you may have about this study.  Your questions will be answered.  Also, you will be 
given a copy of this consent form. 
Key information about this study:  
YESCARTA (also known as axicabtagene ciloleucel) is a treatment currently approved by the United 
States Food and Drug Administration (FDA) for various forms of lymphoma, a type of cancer involving 
cells of the immune system.  YESCARTA was initially approved in the U.S. in October 2017. 
YESCARTA is made from your own white blood cells, which will be modified in a laboratory to recognize 
and attack your lymphoma cells.  Because YESCARTA is a specialized and fairly new therapy, patients 
currently receiving YESCARTA at Vanderbilt and other medical centers are typically required to spend 
several days in the hospital – even if their treatment is well tolerated. 
In this study, we want to help understand if it is safe and feasible for participants to receive YESCARTA 
therapy in the outpatient setting, with fewer days spent as a patient in the hospital.  The key difference 
of receiving YESCARTA in this study, is the location where many of the follow-up safety visits after 
YESCARTA are conducted. 
If you participate in this study, you and a family member, friend or caregiver must stay in housing 
located close to Vanderbilt University Medical Center (VUMC) for up to 4 weeks after your YESCARTA 
treatment. You will utilize a wearable device called Everion for approximately 2 weeks after YESCARTA 
infusion to take some of these measurements (see separate Everion information).  If the caregiver 
becomes unable to assist, you will have pre-arranged another caregiver that will be available. It is 
anticipated this housing will be an apartment selected for the study located within 30 miles of the 
VUMC campus, where you will have appointments every day for at least 14 days after your YESCARTA 
Key Information: 
The first section of this document contains some key points that the research team thought you 
would find important. The study is described in more detail after this section. If you do not 
understand something, please ask someone.  
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treatment, and where you can quickly get specialized help if you have side effects from your therapy. 
You understand and agree to follow these requirements. 
 
For your safety, you cannot stay alone in the apartment.  A family member, friend, or caregiver must 
stay with you.  During this time, you and your companion must measure and record your vital signs 
(blood pressure, heart rate, breathing rate, oxygen saturation, and temperature) and conduct a remote 
telemedicine visit every day, with a nurse practitioner over the internet using an iPad or similar 
electronic device. 
 
You do not have to be in this study in order to receive YESCARTA.  In this study, there is no difference in 
the YESCARTA drug or dose of YESCARTA that you and your study doctor would otherwise have access to 
outside of this study. 
 

Since YESCARTA is made from your own white blood cells, your blood will be collected by a 
process called “leukapheresis” (loo-kah-fur-ee-sis), which will concentrate your white blood 
cells. 

Your blood cells will then be sent to a manufacturing center to make your YESCARTA. 

Before receiving YESCARTA, you will be scheduled for 3 days of chemotherapy (on Days -5, -4 
and -3) to prepare your immune system to receive YESCARTA. 

When your YESCARTA is ready, your study team will give it to you through a catheter placed into 
your vein (intravenous infusion).  Your YESCARTA infusion is scheduled to be completed on a 
single day (Day 0) and usually takes less than 30 minutes. 
 
Every day for 14 days (including weekends) after your YESCARTA treatment on Day 0, you will be 
scheduled for the following visits (as further described in the next section of this document): 
 

In the morning, you will travel to the clinic for bloodwork and an 8:00 am check-up visit. 

In the late afternoon between 3:30 to 5:30 pm, and in the late evening at about 10:00 pm, you 
will have a remote telemedicine visit with audio and video, using the internet, while you are in 
the apartment and a nurse practitioner is located elsewhere. 
 
Before and in between these in-person and remote visits, you and your companion will measure and 
record your vital signs (at about 6:00 am, 12:00 noon, 4:00pm, and 8:00 pm) using training and wearable 
devices you will receive as part of your participation in this study.  Before starting YESCARTA, you and 
your companion will be able to practice taking your vital signs and will have a practice telemedicine visit 
supervised by the study staff. 
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3 of 38 
 
For your safety, recording your vital signs and participating in the telemedicine visits is very important.  
If you and your companion are uncomfortable with the process, feel like you need additional training, or 
decide not to participate in the study, please tell your study team and study doctor so that you can 
receive more training or be considered for YESCARTA treatment outside of the study.  If you have 
serious side effects after receiving YESCARTA or are unable to fully complete the remote telemedicine 
visits, then you will most likely be hospitalized for your safety. 
 
Before getting YESCARTA, tell your study doctor about all your medical problems, including if you have 
or have had: 
 

Neurologic problems (such as seizures, stroke, or memory loss) 

Lung or breathing problems 

Heart problems 

Liver problems 

Kidney problems 

A recent or active infection. 
 
Tell your study doctor about all the medications you take, including prescription and over-the-counter 
medicines, vitamins, and herbal supplements. 
 
Your disease may or may not respond to the treatment.  You may have side effects from YESCARTA and 
feel worse.  The most common side effects of YESCARTA include: 
 

Fever (100.4°F/38°C or higher) 

Low white blood cells (can occur with a fever) 

Low red blood cells 

Low blood pressure (dizziness or lightheadedness, headache, feeling tired, short of breath) 

Fast heartbeat 

Confusion 

Difficulty speaking or slurred speech 

Nausea 

Diarrhea. 
 
YESCARTA may cause side effects that are life-threatening and can lead to death.  Call or see your study 
doctor or get emergency help right away if you experience any of the following: 
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
Fever (100.4°F/38°C or higher) 

Difficulty breathing 

Chills or shaking chills 

Confusion 

Dizziness or lightheadedness 

Severe nausea, vomiting, or diarrhea 

Fast or irregular heartbeat 

Severe fatigue or weakness. 
 
These are not all the possible side effects of YESCARTA.  Additional more detailed information about side 
effects is presented in the below section. 
 
Because YESCARTA treatment can cause sleepiness, confusion, weakness, temporary memory and 
coordination problems, you are advised to not drive, operate heavy machinery, or do other dangerous 
things for at least 8 weeks after your YESCARTA infusion.  You should also not donate blood, organs, 
tissues, and cells for transplantation after YESCARTA. 
 
This study is partially funded by Kite Pharma Inc. which is the pharmaceutical company that makes 
YESCARTA.  YESCARTA is an approved therapy for your disease, and YESCARTA will be provided as a 
standard of care therapy by your insurance.  You and/or your insurance will be responsible for the cost 
of other usual care you would receive even if you were not participating in this study. 
 
About 20 total combined patients are anticipated to enroll in this study at Vanderbilt. 
 
As discussed in detail below, if you enroll in this study, you must be willing and able to make numerous 
visits to the study site within about 28 days before and 30 days after receiving YESCARTA.  Additional 
long-term follow-up visits are intended at 2, 3, 6, and 12 months after your YESCARTA treatment. 
 
 
 
You are being asked to take part in this research study because you have been diagnosed with a form of 
lymphoma (a type of cancer involving cells of the immune system) and your study doctor feels your 
Detailed Information: 
The rest of this document includes detailed information about this study (in addition to the 
information listed above). 
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disease may possibly benefit from treatment with a therapy called YESCARTA (also known as 
axicabtagene ciloleucel). 
 
You do not have to be in this research study.  You may choose not to be in this study and get other 
treatments without changing your healthcare, services, or other rights.  You can stop being in this study 
at any time.  If we learn something new that may affect the risks or benefits of this study, you will be 
told so that you can decide whether or not you still want to be in this study.  Your medical record will 
contain a note saying you are in a research study and may contain some research information about 
you.  Anyone you authorize to receive your medical record will also get this information. 
 
YESCARTA is made using your own blood cells.  If you meet the requirements after screening tests for 
this study, you will be enrolled and have a procedure called leukapheresis.  This is a procedure where 
blood is taken from you and circulated through a machine that divides the cells in your blood (white 
blood cells, red blood cells and platelets).  During leukapheresis, white blood cells including T cells (a 
type of white blood cell that helps fight infection and cancer) are collected; and then all other remaining 
cells and plasma (the liquid part of the blood) are given back to you.  This process can take 
approximately 4 hours.  The T cells that are collected will then be sent to a manufacturing facility to be 
genetically modified in order to make YESCARTA. 
 
The genetic modification introduces a special chimeric antigen receptor (CAR) gene into the T cells 
outside of your body in a permanent and irreversible way, now called YESCARTA, so that they can help 
find your tumor cells.  After YESCARTA is made, it is sent back to your study doctor.  The study doctor 
will then have you come back into the clinic so that YESCARTA can be given back to you through an 
intravenous (IV) infusion.  The hope is that YESCARTA can then target and kill tumor cells. YESCARTA is 
standard of care for your condition, but follow-up monitoring is typically done in the hospital. In this 
research study, follow up monitoring being done in a home-setting, partly with wearable vitals 
monitoring devices, for research purposes. 
 
As described further below, this study has several parts: 
 

Screening (to check if you are eligible to be in this study). 

Leukapheresis (to collect white blood cells from you, in order to make your YESCARTA in a lab). 

Bridging therapy (if needed for your disease). 

Preparation for lymphodepletion (to check you are still eligible to proceed with the study). 

Lymphodepleting chemotherapy (on Days -5, -4 and -3) to prepare your immune system to 
receive YESCARTA. 
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
YESCARTA treatment (on Day 0). 

Post-treatment follow-up visits: 
 Days 1 to 14: 
Three visits every day, for 2 weeks: in-clinic visit, and two online telemedicine visit. 
 Day 21. 
 Day 30. 
 Month 2. 
 Month 3. 
 Month 6. 
 Month 12. 
 
Screening 
You will have the following done within 28 days prior to enrolling in the study, in order to determine if 
you meet the study requirements for participation: 

Review of your general medical history including information about your disease and what 
previous treatments you may have received. 

You will be asked about your level of activity. 

You will be asked to complete a questionnaire about your quality of life and state of health. 

Physical exam that includes obtaining your body weight, height, and vital signs (blood pressure, 
heart rate, breathing rate, oxygen saturation, and temperature). 

Assessment of your nervous system including questions to check your current mental status (ICE 
score). 

You will be asked about any problems you are having and the medicines you are taking including 
prescriptions and over-the-counter medicines. 

Collection of about ½ tablespoon of blood for routine laboratory testing.  If you are a woman 
capable of becoming pregnant, you will also have either a urine or blood pregnancy test. 

Echocardiogram (ECHO ultrasound of your heart) and electrocardiogram (ECG) to determine 
your heart’s performance. 

Existing (archival) tissue samples of your disease will be reviewed under a microscope to confirm 
the diagnosis of your disease. 

Possibly, if your study doctor determines you are showing symptoms, a spinal tap (lumbar 
puncture) using a needle inserted into your back will collect a small sample of cerebrospinal 
fluid (CSF), the fluid that surrounds your brain and spinal cord, to check if you have cancer cells 
in your central nervous system (CNS). This is standard of care. 
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
Possibly, a bone marrow aspirate/biopsy if your study doctor feels this is necessary (for 
example, if you have not already had this done within the previous 12 months prior to screening 
for this study). This is standard of care. 

Brain MRI (or brain CT scan if preferred brain MRI is not possible) and a positron emission 
tomography (PET)-CT scan of your neck, chest, abdomen, and pelvis to confirm the location and 
extent of your disease. This is standard of care.CT chest, abdomen and pelvis may be an 
alternative as decided by your doctor. 
 
 
Enrollment/leukapheresis 
If you meet all of the eligibility requirements for enrollment, you will then be scheduled to undergo 
leukapheresis (pronounced “loo-kah-fur-ee-sis“).  This is a collection of white blood cells from you, 
which are then used to make your YESCARTA in a laboratory. 
 
On the day of leukapheresis (or day before leukapheresis for the laboratory tests), the following will be 
performed: 

Measurement of your weight and vital signs. 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 

About ½ tablespoon of blood will be collected from you for routine laboratory testing. 

About 2 tablespoons of blood will be collected from you for additional laboratory testing for 
research purposes. 

Leukapheresis (over about 4 hours) to collect your white blood cells for research purposes. 
 
Note: because your YESCARTA must be custom made in a laboratory (using your white blood cells that 
are shipped to the laboratory), there is a rare but possible risk that a manufacturing problem could 
occur which might delay or possibly even prevent YESCARTA from being successfully made from your 
cells.  The risk of a YESCARTA manufacturing failure is estimated to be about 1 in 100 (1%). 
 
In case of a YESCARTA manufacturing failure, a second manufacturing of YESCARTA may be attempted.  
If you had to wait for YESCARTA therapy because of this, it is possible that you would need additional 
chemotherapy (such as bridging therapy discussed immediately below) while you waited, which may 
increase your risk of side effects (for example, if your disease got worse while waiting, or if you would 
otherwise not need such chemotherapy if your YESCARTA was ready to go). 
 
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Bridging Therapy (if needed) 
Before your upcoming YESCARTA treatment, you may first need some kind of additional treatment for 
your disease.  This is called "bridging" chemotherapy. 
 
Your study doctor will discuss what this involves, but bridging therapy often includes steroids (for 
example, dexamethasone or methylprednisolone) in combination with an antibody called rituximab or a 
combination of chemotherapy and rituximab. 
If you need bridging therapy, it will be administered after leukapheresis and completed prior to the start 
of your lymphodepleting chemotherapy. 
 
Preparation for Lymphodepletion 
Sometime between Day -9 and Day -6, you will have the following done as safety check before starting 
lymphodepleting chemotherapy: 

Physical exam including obtaining your body weight and vital signs. 

Review of any changes to your medical history and disease. 

You will be asked about your level of activity. 

You will be asked to complete a questionnaire about your quality of life and state of health. 

Assessment of your nervous system including questions to check your current mental status (ICE 
score). 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 

Collection of about ½ tablespoon of your blood for routine laboratory testing.  If you are a 
woman capable of becoming pregnant, you will also have either a urine or blood pregnancy test. 

PET-CT scan to recheck your disease (if you received bridging therapy as mentioned above, or if 
your most recent PET-CT scan is more than 28 days old). 
 
Day -5 to -3: Lymphodepleting chemotherapy with cyclophosphamide and fludarabine (Cy/Flu) 
After your leukapheresis procedure and prior to your upcoming YESCARTA treatment, you will receive 2 
chemotherapy medicines called fludarabine and cyclophosphamide.  Each day for 3 days, these 
chemotherapy medicines will be given through your vein.  These drugs are not intended to treat your 
cancer directly, but instead to help YESCARTA work with less interference from the cells in your immune 
system. 
 
To prepare your immune system to receive YESCARTA (upcoming on Day 0), you will have the following 
things done on the five days before receiving YESCARTA: 
 
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Day -5 

Collection of about ½ tablespoon of your blood for routine laboratory testing. 

Collection of about 2 tablespoon of more blood for additional laboratory testing for research 
purposes. 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 

You may be asked to have an optional tumor tissue biopsy for research purposes. 

You may be asked to have an optional spinal tap (lumbar puncture) using a needle inserted into 
your back to collect a sample of cerebrospinal fluid (CSF) from your nervous system. 

Vital signs. 

Intravenous (IV) infusion of chemotherapy: cyclophosphamide and fludarabine (Cy/Flu). 
 
Day -4 

Collection of about ½ tablespoon of your blood for routine laboratory testing. 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 

Vital signs. 

Intravenous (IV) infusion of chemotherapy: cyclophosphamide and fludarabine (Cy/Flu). 
 
Day -3 

Collection of about ½ tablespoon of your blood for routine laboratory testing. 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 

Vital signs. 

Intravenous (IV) infusion of chemotherapy: cyclophosphamide and fludarabine (Cy/Flu). 
 
Day -2 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 
 
Day -1 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 
 
In order to prepare for your upcoming remote telemedicine visits that are part of the research part of 
the study (that you will have after receiving YESCARTA on Day 0), you and your family member, friend or 
caregiver will be trained to operate the equipment needed to measure your vital signs (blood pressure, 
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heart rate, breathing rate, oxygen saturation, and temperature) and how to report this information at a 
practice telemedicine visit (conducted with an iPad or similar electronic device that uses the internet). 
You will utilize a wearable device called Everion, Vital Connect Patch, Blood Pressure cuff and Oximeter 
to take some of these measurements (see separate Everion information) as part of the research study.   
 
In order to participate in this study, you and your companion (who will stay with you for several days in 
the apartment) must be willing and able to obtain your vital signs and demonstrate the ability to 
complete a practice telemedicine visit as part of the research for this study.  If you, your companion or 
your study team determine this will not be possible, then you will stop participating in this study and be 
offered the option to instead receive YESCARTA outside the study (where your post-YESCARTA 
monitoring visits would typically involve staying in the hospital for several days as standard of care). 
 
Day 0: YESCARTA treatment 
In the morning at about 8:00 am, you will report to the clinic for the following: 

Physical exam including obtaining your vital signs. 

Assessment of your nervous system including questions to check your current mental status (ICE 
score). 

Questions about any problems you are having and any changes to the medicines you are taking 
including prescriptions and over-the-counter medicines. 

Collection of about ½ tablespoon of your blood for routine laboratory testing. 

About 2 tablespoons of blood will be collected from you for additional laboratory testing for 
research purposes. 

Approximately 1 hour prior to YESCARTA infusion, you will receive prophylactic medication 
acetaminophen, diphenhydramine and dexamethasone 

Intravenous infusion of YESCARTA over about 30 minutes. 
 
After your YESCARTA infusion, you will be monitored for about 2 hours.  If you are doing ok, you will be 
released and go to the apartment. 
 
Between 3:30 and 5:30 pm in the afternoon, , you and your companion will have a remote telemedicine 
check-in (conducted online typically with video, using the internet) with a nurse practitioner.  You will be 
in the apartment and the nurse will be located elsewhere.  You and the nurse practitioner (NP) will 
activate the telemedicine App in the electronic device you will use for the research study.  Your 
companion will obtain your vital signs (blood pressure, heart rate, breathing rate, oxygen saturation, 
and temperature) and provide the nurse with the information.  The nurse will also review your previous 
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11 of 38 
vital signs.  You will be asked questions to check your nervous system and current mental status (ICE 
score) and how you are doing.  If you are having problems, the nurse and a doctor working with the 
nurse may require that you return to the hospital for your safety.  If you are doing ok, you will stay in the 
apartment and return to the clinic in the morning. 
 
At approximately 10:00 pm in the evening, you and your companion will have a remote telemedicine 
check-in (conducted online typically with video, using the internet) with a nurse practitioner.  You will be 
in the apartment and the nurse will be located elsewhere.  You and the nurse practitioner (NP) will 
activate the telemedicine App in the electronic device you will use for the research study.  Your 
companion will obtain your vital signs (blood pressure, heart rate, breathing rate, oxygen saturation, 
and temperature) and provide the nurse with the information.  The nurse will also review your previous 
vital signs.  You will be asked questions to check your nervous system and current mental status (ICE 
score) and how you are doing.  If you are having problems, the nurse and a doctor working with the 
nurse may require that you return to the hospital for your safety.  If you are doing ok, you will stay in the 
apartment and return to the clinic in the morning. 
 
 
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Day 1 – Day 14 (every day for 14 days) 
 

Day 1 and 2 only: dexamethasone 10mg pill taken orally 

6:00 AM: 
Early in the morning, your family member, friend or caregiver staying with you in the apartment 
will obtain and record your vital signs (blood pressure, heart rate, breathing rate, oxygen 
saturation, and temperature).  You or your companion will call the nurse practitioner telephone 
line to report the information. You will utilize a wearable device called Everion, Vital Connect 
Patch, blood pressure cuff, and oximeter to take some of these measurements for research 
purposes (see separate Everion information).   
 

8:00 AM: 
Later in the morning, you will visit the outpatient clinic at 8am each day, including weekends.  
About ½ tablespoon of your blood will be collected for routine laboratory testing.  Your vital 
signs will be checked.  You will be asked about any side effects you are experiencing and about 
any changes to your medications.  Your vital signs log will be reviewed by a nurse with extra 
training (nurse practitioner) and your telemedicine equipment will be checked.  You will have a 
physical exam conducted by the nurse practitioner and doctor; they will review data and ask you 
questions to check your nervous system (ICE score).  You will be released back to the apartment 
by about 10am or shortly after if no criteria for hospitalization are met. 
 
In association with your daily clinic visit, the following additional items are scheduled to be 
performed on the following days: 
 Day 1:  You may be asked to have an optional spinal tap (lumbar puncture) using a 
needle inserted into your back to collect a sample of cerebrospinal fluid (CSF) 
from your nervous system as a standard of care procedure. 
 Day 2:  You may be asked to have an optional tumor tissue biopsy for research 
purposes. 
 Days 1, 2, 3, and 4:  About 2 tablespoons of additional blood will be collected for 
additional laboratory testing for research purposes. 
 Days 7 and 14:  About 2 tablespoons of additional blood will be collected for additional 
laboratory testing for research purposes. 
 

12:00 Noon: 
At mid-day, your family member, friend or caregiver staying with you in the apartment will 
obtain your vital signs (blood pressure, heart rate, breathing rate, oxygen saturation, and 
temperature) and record them in the logbook for research purposes.  You or your companion 
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13 of 38 
will call the nurse practitioner telephone line if pre-specified criteria for hospital admission are 
met. You will utilize a wearable device called Everion, Vital Connect Patch, blood pressure cuff, 
and oximeter to take some of these measurements (see separate Everion information) for 
research purposes.  
 

Between 3:30 PM and 5:30 PM and at 10:00 PM: 
You will have an online telemedicine visit (conducted remotely by iPad or similar electronic 
device) with a nurse practitioner. 
 
You and the nurse practitioner will activate the telemedicine App in the electronic device you 
will use for the study.  Your companion will obtain your vital signs (blood pressure, heart rate, 
breathing rate, oxygen saturation, and temperature) and provide the nurse with the 
information.  The nurse will also review your previous vital signs.  You will be asked questions 
about how you are doing, and your answers will be recorded.  A neurological assessment will be 
completed, and your ICE score calculated. 
 
For your safety, you will be admitted to the hospital (for observation or as inpatient, depending on 
the severity of symptoms) for any of the following: 
 
1. Fever ≥ 102◦F or higher, or fever 100.4 to < 102 with a change in status; for example, low blood 
pressure (hypotension), altered mental status, or other sign(s) of possible organ problems. 
 
2. Hemodynamic instability (including any of the following): 
 
 Low blood pressure requiring IV fluids; 
 
 Mean arterial pressure (MAP) < 20% of baseline; 
 
note: MAP is sometimes calculated as (systolic blood pressure + 2x diastolic pressure) / 3; 
[for example, a blood pressure of 83/50 mmHg might be reported with a MAP of 61 mmHg, 
by the following calculation: (83 + 2x50) / 3 = 183/3 = 61 mmHg]; 
 
 Systolic blood pressure (SBP) < 90 mmHg; 
 
 Heart rate (HR) > 130/min. 
 
3. Low blood oxygenation (hypoxia) with oxygen saturation (SpO2) < 90%. 
 
4. Abnormal neurological function (grade 1 or higher immune effector cell-associated neurotoxicity 
syndrome [ICANS]) based on questions about your mental status (ICE score). 
 
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14 of 38 
5. Other criteria at the discretion of your study doctor or the covering physician working with your 
nurse practitioner. 
 
Day 21 
Twenty-one days (or sometime between 18 and 24 days – i.e. ±3 days) after your YESCARTA treatment, 
you will visit the doctor’s office for the following to check how you are doing: 

Physical exam including obtaining your vital signs. 

Collection of about ½ tablespoon of your blood for routine laboratory testing. 

Questions about any side effects you are experiencing and about any changes to your 
medications. 
 
Day 30 
Thirty days (or sometime between 30 and 33 days – i.e. +0-3 days) after your YESCARTA treatment, you 
will visit the doctor’s office for the following to check how you are doing: 

Physical exam including obtaining your vital signs. 

Assessment of your nervous system including questions to check your current mental status (ICE 
score). 

Collection of about ½ tablespoon of your blood for routine laboratory testing. 

About 2 tablespoons of blood will be collected from you for additional laboratory testing for 
research purposes. 

Questions about any side effects you are experiencing and about any changes to your 
medications. 

You will be asked to complete a questionnaire about your quality of life and state of health. 

PET-CT scan to recheck your disease. 
 
2 months 
Two months (± 7 days) after your YESCARTA treatment, you will visit the doctor’s office for the following 
to check how you are doing: 

Physical exam including obtaining your vital signs. 

Assessment of your nervous system including questions to check your current mental status (ICE 
score). 
 
3 months 
Three months (± 7 days) after your YESCARTA treatment, you will visit the doctor’s office for the 
following to check how you are doing: 
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Physical exam including obtaining your vital signs. 

Collection of about ¼ tablespoon of your blood for routine laboratory testing. 

About 2 tablespoons of blood will be collected from you for additional laboratory testing for 
research purposes. 

Assessment of your nervous system including questions to check your current mental status (ICE 
score). 

You will be asked to complete a questionnaire about your quality of life and state of health. 

PET-CT scan to recheck your disease. 
 
6 months 
Six months (± 7 days) after your YESCARTA treatment, you will visit the doctor’s office for the following 
to check how you are doing: 

Physical exam including obtaining your vital signs. 

Collection of about 2 tablespoons of your blood for laboratory testing for research purposes. 

You will be asked to complete a questionnaire about your quality of life and state of health. 

PET-CT scan to recheck your disease. 
 
9 months 
Nine months (± 7 days) after your YESCARTA treatment 

You will be asked to complete a questionnaire about your quality of life and state of health. 
 
12 months 
Twelve months (± 7 days) after your YESCARTA treatment, about 2 tablespoons of your blood will be 
collected for laboratory testing for research purposes. 

You will be asked to complete a questionnaire about your quality of life and state of health. 
 
 
Side effects and risks that you can expect if you take part in this study: 
Throughout your participation in this study, you will be given medicines and treatments to help prevent 
or treat any side effects.  You will be made as comfortable as possible. 
 
You may experience all, some, or none of the adverse effects listed below.  If you do experience any of 
the listed adverse effects, the events often start during the first week after YESCARTA infusion and 
usually resolve completely within 1 to 4 weeks.  Occasionally some side effects may take longer to 
improve. 
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If significant new findings are found during the conduct of the study that could affect your willingness to 
continue to participate, information will be reported to you as soon as possible. 
 
Not all potential side effects (also known as adverse effects or adverse events) in humans are known.  In 
addition to the adverse effects noted below, there is a risk that you may experience new or unexpected 
adverse effects, some of which may have a delayed onset.  You may also experience side effects that are 
more severe than those reported to date.  If you have any side effects as a result of your participation in 
this study, please tell your study doctor. 
 
Your study doctor will closely monitor your health throughout this study.  Your study doctor will discuss 
with you any questions regarding risks, discomforts, and side effects. 
 
Important known risks of YESCARTA 
 
Cytokine release syndrome (CRS) is an important known risk associated with YESCARTA therapy.  CRS is 
a group of symptoms associated with systemic inflammation throughout the body.  CRS can be very 
serious, life-threatening and even cause death. 
 
Release of cytokines (proteins in certain cells of the body) by the immune system is normally involved in 
otherwise protective and desirable inflammation reactions in the body.  One way that cytokine release 
normally occurs in the body, is when T-cells of the immune system are activated.  Because YESCARTA 
treatment increases T-cell activity, there is a risk that YESCARTA therapy can cause too much cytokine 
release in the body, and possibly lead to cytokine release syndrome (CRS). 
 
If too many cytokines are released throughout the body in an uncontrolled way, this may result in a 
variety of adverse events including effects on your heart, stomach and intestines, liver, blood clotting, 
kidneys, lungs and skin.  You can experience symptoms of cytokine release syndrome (CRS) such as: 
 

Fever 

Chills 

Headache 

Nausea 

Vomiting 

Fatigue 

Joint pain 
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17 of 38 

Low blood pressure 

Rapid heart rate 

Low oxygen levels in the blood. 
 
In clinical trials, the onset of CRS was typically within 2 days after infusion of YESCARTA, with a range of 
onset from 1 to 12 days.  CRS typically resolved within approximately 7 days.  CRS has generally been 
manageable and reversible with supportive care measures and medications, although rarely fatal events 
have occurred.  Severe cases of CRS have occurred in clinical trial patients that required medications to 
maintain a normal blood pressure as well as placement of a breathing tube for mechanical ventilation 
(breathing machine). 
 
In a previous study in which 108 patients with lymphoma (relapsed/refractory B-cell non-Hodgkin 
lymphoma) received YESCARTA, cytokine release syndrome (CRS) occurred in 101 out of 108 (94%) 
patients.  In 14 out of 108 (13%) patients, CRS was considered ≥ Grade 3 (Lee grading system) and 
caused serious toxicity to body organs, required multiple drugs to maintain blood pressure (pressors), 
and the patients needed oxygen support for breathing (supplemental oxygen and/or mechanical 
ventilation with a breathing tube). 
 
After receiving YESCARTA on Day 0, if you experience cytokine release syndrome (CRS) between Day 0 
thru Day 14, you may be given a drug called tocilizumab (pronounced “toe-si-liz-oo-mab” and also 
known as ACTEMRA), which is approved for the treatment of CRS (as well as several types of arthritis).  
Tocilizumab is an antibody, which for CRS is recommended as an intravenous (IV) infusion into a vein, 
that helps against inflammation processes in the immune system that contribute to CRS. 
 
In patients receiving tocilizumab, the most common adverse reactions in at least 5 in 100 (5%) patients 
include: upper respiratory tract infections, nasopharyngitis (inflammation inside the nose and back of 
the throat), headache, high blood pressure (hypertension), increased liver enzyme (ALT) blood test, and 
injection site reactions.  Also, because of its activity in helping to slow or calm the immune system, an 
important additional side effect or risk of tocilizumab treatment is the possibility of serious infections.  
Serious infections leading to hospitalization or death including tuberculosis (TB), bacterial, invasive 
fungal, viral, and other opportunistic infections have occurred in patients receiving tocilizumab. 
 
Neurologic toxicities (side effects involving the nervous system) including fatal or life-threatening 
reactions have occurred in patients receiving YESCARTA.  Neurologic toxicities associated with YESCARTA 
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18 of 38 
treatment can occur at the same time as cytokine release syndrome (CRS) discussed above, or after CRS 
has improved or gone away. 
 
In one study involving YESCARTA, neurologic toxicities occurred in 87% of patients.  98% of all neurologic 
toxicities occurred within the first 8 weeks of YESCARTA infusion.  The middle (median) time to onset of 
neurologic toxicity was 4 days after starting YESCARTA (range of 1 to 43 days).  The middle (median) 
duration was 17 days for how long neurologic toxicities lasted.  Serious neurologic toxicity (Grade 3 or 
higher) consistent with a likely need for hospitalization occurred in 31% of patients. 
 
The most common neurologic toxicities associated with YESCARTA (and the percentage of patients who 
experienced such side effects) included: 
 

Encephalopathy (decreased brain function) (57%) 

Headache (44%) 

Tremor (rhythmic shaking due to a problem in the nervous system causing uncontrolled muscle 
contractions; typically in the hands, but possibly elsewhere like the arms, head, vocal cords, 
trunk, legs, and/or feet) (31%) 

Dizziness (21%) 

Aphasia (difficulty speaking or understanding speech) (18%) 

Delirium (disturbance in consciousness) (17%) 

Insomnia (difficulty sleeping) (9%) 

Anxiety (9%). 
 
Prolonged encephalopathy (decreased brain function) lasting up to 173 days was noted.  Serious events 
including leukoencephalopathy (inflammation of the white matter of the brain), myelitis (inflammation 
of the spinal cord which can lead to paralysis) and seizures have occurred with YESCARTA.  Fatal and 
serious cases of cerebral edema (fluid build-up around the brain causing pressure on the brain) have 
occurred in patients treated with YESCARTA. 
 
Neurologic events observed in clinical trial patients treated with YESCARTA have generally been 
manageable and reversible with supportive care measures and administration of medications.  Severe 
neurologic events have occurred that required placement of a breathing tube for mechanical ventilation 
(breathing machine) and care of the patient in the intensive care unit.  If you develop a neurologic 
event(s) after YESCARTA therapy, you should not drive or operate heavy or potentially dangerous 
machinery until at least 4 weeks after the neurologic event(s) have been deemed completely resolved 
by your study doctor. 
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19 of 38 
 
Brain swelling (cerebral edema) and spinal cord swelling (spinal cord edema) are serious neurologic risks 
associated with YESCARTA.  Death due to brain swelling has been reported rarely in studies involving 
chimeric antigen receptor (CAR) T cell products, including YESCARTA.  Symptoms may include headache, 
nausea, vomiting, changes in vision, inability to speak or think clearly, severely decreased brain function 
that can lead to lethargy and coma (loss of consciousness), difficulty breathing, weakness or paralysis, 
permanent disability, and death.  Brain and spinal cord swelling require aggressive treatment including 
placing a breathing tube for mechanical ventilation (breathing machine), administration of medications, 
or very rarely, surgery to decrease the swelling or pressure.  The exact cause of brain and spinal cord 
swelling in connection with treatment of CAR T cell products like YESCARTA is not fully understood at 
this time. 
 
After receiving YESCARTA on Day 0, you will be monitored for neurologic toxicities.  If you experience 
neurologic side effects between Day 0 thru Day 28, you may be given an anti-seizure medicine called 
levetiracetam (pronounced “lev-eh-teer-ASS-eh-tam” and also known as KEPPRA).  Levetiracetam is an 
approved drug for the treatment of various forms of epilepsy.  For patients receiving YESCARTA therapy, 
a main purpose of levetiracetam medication is to help prevent moderate neurologic symptoms from 
becoming more severe – for example, to help avoid or to control the possible side effect of seizure. 
 
The most common side effects of levetiracetam in adult patients include: somnolence (sleepiness or 
drowsiness), asthenia (abnormal weakness or lack of energy), infection, and dizziness. 
 
As outlined below (with percentages shown for each event) data regarding side effects, also called 
adverse reactions, associated with YESCARTA treatment are available from a previous study in which 
108 patients with lymphoma (relapsed/refractory B-cell non-Hodgkin lymphoma) received YESCARTA. 
 
The most common adverse reactions occurring in at least 20 out of 100 patients (≥20%) receiving 
YESCARTA included: 
 

Cytokine release syndrome (CRS, systemic inflammation) (94%) 

Fever (86%) 

Hypotension (low blood pressure) (57%) 

Encephalopathy (decreased brain function) (57%) 

Tachycardia (rapid heart rate) (57%) 

Fatigue (46%) 

Headache (45%) 
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
Decreased appetite (44%) 

Chills (40%) 

Diarrhea (38%) 

Febrile neutropenia (fever associated with a low white blood cell count) (34%) 

Infections (of unspecified cause) (26%) 

Nausea (34%) 

Hypoxia (low oxygen in the blood) (32%) 

Tremor (rhythmic shaking due to a problem in the nervous system causing uncontrolled 
muscle contractions; typically in the hands, but possibly elsewhere like the arms, head, vocal 
cords, trunk, legs, and/or feet) (31%) 

Cough (30%) 

Vomiting (26%) 

Dizziness (21%) 

Constipation (23%) 

Cardiac arrhythmias (abnormal heart rhythm) (23%). 
 
Less common adverse reactions occurring in at least 10 but less than 20 out of 100 patients  
(≥10% but <20%) receiving YESCARTA included: 
 

Edema (swelling caused by fluid build-up) (19%) 

Motor dysfunction (such as muscle spasms and/or muscle weakness) (19%) 

Dyspnea (shortness of breath) (19%) 

Aphasia (difficulty speaking or understanding speech) (18%) 

Pain in extremity (for example, in fingers, toes, arms, and/or legs) (17%) 

Delirium (disturbance in consciousness) (17%) 

Viral infection (16%) 

Weight decreased (16%) 

Hypogammaglobulinemia (low levels of antibodies [proteins] that help fight infections 
(15%) 

Back pain (15%) 

Hypertension (high blood pressure) (15%) 

Abdominal pain (14%) 

Muscle pain (14%) 

Bacterial infections (13%) 

Pleural effusion (fluid around the lungs) (13%) 
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
Renal insufficiency (decreased kidney function; typically with increased blood creatinine) 
(12%) 

Dry mouth (11%) 

Dehydration (11%) 

Arthralgia (joint pain) (10%) 

Thrombosis (abnormal blood clotting) (10%). 
 
 
 
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Serious adverse reactions occurred in fifty-two percent (52%) of patients.  The most common 
serious adverse reactions occurring in more than 2 in 100 patients (>2%) receiving YESCARTA 
included: 
 

Encephalopathy (decreased brain function) 

Fever 

Lung infection 

Febrile neutropenia (fever and low white blood cell count; increased risk of infection) 

Cardiac arrhythmia (abnormal heart rhythm) 

Cardiac failure (heart failure) 

Urinary tract infection (UTI) 

Renal insufficiency (decreased kidney function; typically with increased blood creatinine) 

Aphasia (difficulty speaking or understanding speech) 

Cardiac arrest (heart stops beating) 

Clostridium difficile infection (typically causing severe diarrhea and colitis, a serious 
inflammation of the colon) 

Delirium (disturbance in consciousness) 

Hypotension (low blood pressure) 

Hypoxia (low oxygen in the blood). 
 
The most common adverse reactions Grade 3 or higher (indicating severity often needing 
hospitalization) occurring in at least 10 in 100 patients (≥ 10%) receiving YESCARTA included: 
 

Febrile neutropenia (fever associated with a very low white blood cell count) (31%) 

Encephalopathy (decreased brain function) (29%) 

Fever (16%) 

Infections (unspecified cause) (16%) 

Hypotension (low blood pressure) (15%) 

Cytokine release syndrome (CRS, systemic inflammation) (13%) 

Lung infections (possibly viral or bacterial) (~13%) 

Hypoxia (low oxygen in the blood) (11%). 
 
Other clinically important adverse reactions occurring in less than 10 in 100 patients (<10%) treated 
with YESCARTA included: 
 

Coagulopathy (changes in the ability of blood to clot) (2%) 

Cardiac failure (heart failure) (6%) 
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
Cardiac arrest (heart stops beating) (4%) 

HLH/MAS (hemophagocytic lymphohistiocytosis / macrophage activation syndrome) (life-
threatening multi-organ failure associated with widespread inflammation throughout the 
body due to malfunctioning immune system (1%) 

Hypersensitivity (allergic reaction) (1%) 

Fungal infections (5%) 

Ataxia (loss of control of body movements) (6%) 

Seizure (burst of uncontrolled electrical activity in the brain; can cause abnormal 
movements like stiffness, twitching or limpness, or less obvious symptoms like altered 
sensations or states of awareness) (4%) 

Dyscalculia (difficulty understanding or calculating numbers; sign of brain dysfunction) (2%) 

Myoclonus (sudden muscle contraction/jerk) (2%) 

Pulmonary edema (fluid in the lungs) (9%) 

Rash (9%) 

Capillary leak syndrome (fluid or proteins leak into surrounding tissues) (3%). 
 
Laboratory abnormalities Grade 3 (severe or medically significant but not immediately-life-
threatening) or Grade 4 (life-threatening requiring urgent intervention) occurring in at least  
10 in 100 patients (≥ 10%) after YESCARTA treatment included: 
 

Lymphopenia (reduced lymphocytes, a type of white blood cells; increased risk of infection) 
(100%) 

Leukopenia (reduced white blood cells; increased risk of infection) (96%) 

Neutropenia (low neutrophils, a type of white blood cells; increased risk of infection) (93%) 

Anemia (decreased red blood cells that carry oxygen through the body; can cause fatigue 
and weakness) (66%) 

Thrombocytopenia (decreased platelets needed for blood clotting; increased risk of 
bleeding) (58%) 

Hypophosphatemia (low phosphate) (50%) 

Hyponatremia (low sodium) (19%) 

Hyperuricemia (uric acid increased) (13%) 

Direct bilirubin increased (can indicate poor liver function) (13%) 

Hypokalemia (low potassium) (10%) 

Alanine aminotransferase (ALT) increased (elevated liver enzyme; can indicate liver stress 
or liver injury) (10%). 
 
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Difficulty swallowing, spinal cord swelling (spinal cord edema) and partial or total loss of use of limbs 
have been reported for patients not participating in clinical trials.  Because these reactions were 
reported voluntarily from a population of unknown size, estimates of frequency cannot be made. 
 
It is possible that YESCARTA may not work to control your disease.  Also, because of the side effects of 
YESCARTA discussed above, and potentially other side effects we don’t know about yet, it is possible 
that YESCARTA therapy may make you feel worse, or even contribute to your death. 
 
After your cells are collected to make YESCARTA, a specific virus called a retrovirus will be used to insert 
a gene into your cells in the laboratory in order to make your custom YESCARTA.  The retrovirus has 
been disabled to prevent it from multiplying or growing on its own and infecting your body after 
YESCARTA is infused into you, but there is a theoretical concern that the retrovirus used to make 
YESCARTA could cause an infection. 
 
Researchers have wondered whether a transferred gene might sometimes land in a place in a cell where 
it can cause harm.  This happened to two children in another study (which did not involve YESCARTA but 
did use a similar technology), where genes were inserted into stem cells.  After getting the gene transfer 
into their stem cells, the children developed leukemia (a type of blood cell cancer).  A group of experts 
looked at all the test results and concluded that gene transfer caused the leukemia by causing some cells 
to grow out of control.  The children appeared to be responding to treatment of the leukemia, but their 
long-term health is unknown at this time.  In this study, genes are transferred to your mature white 
blood cells (not stem cells, which occurred in the children), and this has not knowingly resulted in 
leukemia. 
 
Risks of Lymphodepleting Chemotherapy 
 
You should discuss precautions, benefits and risks associated with the lymphodepleting chemotherapy 
drugs cyclophosphamide and fludarabine (Cy/Flu) with your study doctor prior to participating in this 
study.  You may experience all, some or none of the events listed below: 
 

Low blood counts: 
 Decrease in the number of white blood cells (neutropenia and/or lymphopenia); this 
increases the risk of infection, which may be life-threatening. 
 Fever with a very low white blood cell count (febrile neutropenia). 
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 Decrease in the number of cells that clot the blood (thrombocytopenia), which may 
cause bleeding or bruising; this may be serious or life-threatening and may require a 
blood transfusion; there have been rare cases of fatal bleeding events. 
 Decrease in the number of cells that carry oxygen through the body (anemia), which can 
cause things like fatigue, weakness, dizziness, and shortness of breath. 

Electrolyte or mineral changes in the blood (for example, changes in sodium, calcium and/or 
phosphate). 
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Other risks associated with chemotherapy should be discussed with your study doctor prior to 
participating in this study. 
 
To help protect against the risk of bleeding in bladder (which might initially be noted as blood in the 
urine) caused by chemotherapy, you may receive a medication called mesna.  Some patients have 
reported a bad taste or experienced nausea and vomiting after receiving mesna.  Your study doctor will 
discuss mesna with you, but some other possible side effects of mesna include allergic reaction and a 
rare, but very serious, rash called Stevens-Johnson syndrome (SJS).  Cases of SJS are often a reaction to 
medication and start with flu-like symptoms, followed by a painful rash that spreads and blisters.  The 
top layer of affected skin then dies, sheds and begins to heal after several days.  SJS is a medical 
emergency that usually requires hospitalization for wound care, pain management, and control of skin 
regrowth.  It can take weeks to months to recover.  Stevens-Johnson syndrome and a more severe form 
of the condition called toxic epidermal necrolysis (TEN), which typically involves more than 30% of the 
skin surface, can both cause death. 
 
Risks of Procedures 
 
Blood Collection 
Pain, redness, soreness, bruising, or infection may occur at the needle stick site. Rarely some people 
faint. The study doctor may put some cream (called EMLA) on your skin to numb the area so you will not 
feel the needle stick as much. The numbing cream may make your skin or the area have a change in skin 
color, but this is rare. 
Intravenous (IV) Catheter 
Prior to beginning YESCARTA, your study doctor may need to insert an intravenous (IV) catheter for the 
delivery of chemotherapy and YESCARTA and to take blood samples.  IV catheters can usually be placed 
in a hand, arm, or leg.  These are known as “peripheral” IVs.  IVs placed in the central circulation, like the 
internal jugular vein (neck) or subclavian vein (just beneath the collar bone), are known as” central 
lines.”  You should discuss this with your study doctor.  For both types of intravenous catheter, the area 
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will be numbed (with an anesthetic) before the catheter is inserted.  During the insertion, you could feel 
a pinch and shortly thereafter bleeding, redness, or a bruise could develop.  Rarely, an infection could 
occur if not kept clean.  For central catheters, although rare, they can sometimes cause collapse of a 
lung or cause bleeding.  Lung collapse is usually treated by putting a tube into your chest for a few days 
to allow your lung to expand.  Pressure is placed on any area that might bleed. 
 
Leukapheresis 
Leukapheresis is the first step in the process of treating you with YESCARTA.  During this procedure, your 
own white cells are removed from your blood in order to prepare them for your YESCARTA treatment.  
During leukapheresis, you may experience tingling in your face and lips due to the medicine used to 
keep your blood from clotting during the procedure.  The nurses may give you a calcium-containing 
antacid, like TUMS, to chew that helps to take away this tingling.  Rarely, people may experience 
lightheadedness or dizziness.  You will likely be asked to drink plenty of water so you are well hydrated, 
and that you eat prior to the procedure to help prevent lightheadedness or dizziness.  Rare 
complications of leukapheresis include lowered blood pressure, bleeding, or infection at the entry site of 
the IV. 
 
Echocardiography (ECHO) 
An ECHO is a test that shows how the heart moves as it beats.  During an ECHO test, ultrasound (high-
frequency sound waves) from a hand-held wand placed on your chest provides pictures of the heart’s 
valves and chambers and helps doctors evaluate the pumping action of the heart.  You should feel no 
major discomfort during the test.  You may feel coolness on your skin from the gel on the wand and a 
slight pressure of the wand on your chest. 
 
Electrocardiogram (ECG) 
An ECG is a test that measures the heart’s electrical activity.  You will typically be asked to lie flat on a 
table and several small electrode pads (like stickers) will be placed on your body.  This test takes about 
10 minutes.  The test may cause some redness or itching where the pads are placed. 
 
Lumbar Puncture 
A lumbar puncture (also known as spinal tap) may be done to sample cerebrospinal fluid (CSF), which is 
the fluid that surrounds your brain and spinal cord, to help determine if your disease is affecting the 
brain.  In order to collect cerebrospinal fluid (CSF), you may be asked to undergo lumbar puncture 
before and after YESCARTA treatment, as well as anytime your condition or disease affects your nervous 
system in such a way that doctors feel information from a lumbar puncture is necessary for your safety. 
 
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A lumbar puncture is done by inserting a thin, hollow needle between 2 of the vertebrae (bones) in your 
lower back.  Prior to the lumbar puncture, medicine (local anesthetic) is typically given to help numb the 
area.  Lumbar puncture may cause headache, local pain or discomfort, bleeding, or infection.  While 
rare, the procedure may also cause bleeding into the fluid surrounding the spinal cord and brain or an 
abnormal movement of your brain inside your skull (herniation), either of which can be fatal.  After the 
procedure you may develop a headache that may be accompanied by nausea, vomiting, and dizziness. 
 
Bone Marrow Aspirate and Biopsy 
A bone marrow aspirate and biopsy if necessary to obtain more information about your disease may be 
performed using a hollow needle to remove some liquid bone marrow and a small core of bone marrow.  
Before the biopsy, medicine is given (local anesthetic) to help numb the area where the needle will be 
inserted.  The procedure may cause discomfort, pain, bleeding, scarring, or infection at the site of the 
aspirate/biopsy. 
 
Tumor Tissue Biopsy 
Before and after YESCARTA treatment, you may be asked to have a tumor tissue biopsy, which is a 
procedure that involves removing samples of tumor surgically or percutaneously (through the skin) 
using a hollow “core” needle.  To undergo a biopsy, you will be given medication to help numb the area 
and reduce pain.  A small cut may then be made in the skin.  The biopsy may cause some pain and 
discomfort or bleeding.  It is possible, but not likely, that you could get an infection.  In very rare cases, 
people might have an allergic reaction to the numbing medicine.  The allergic reaction could include 
rash/hive, flushing of the face, itching, wheezing, and tightness in the throat.  There may be a small scar 
from the biopsy. 
 
Magnetic Resonance Imaging (MRI) 
An MRI is a type of scan using magnets to make a picture of the body and identify areas that could be 
injured or suspicious for diseases such as cancer.  An MRI of your brain is intended during screening to 
help ensure you do not have detectable cancer in your central nervous system or brain.  Some people 
cannot have an MRI because they have some type of metal in their body.  For example, if you have a 
heart pacemaker, artificial heart valves, metal implants such as metal ear implants, pieces or fragments 
of bullets or shrapnel, chemotherapy or insulin pumps, or any other metal such as metal clips or rings, 
you cannot have an MRI. 
 
During an MRI, you will lie in a small closed area usually inside a large magnetic tube.  Some people are 
scared or anxious in small places (claustrophobic).  The MRI scanner makes loud banging noises while 
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taking a measurement, so either ear plugs or specially designed headphones will be used to reduce the 
noise. 
 
PET-CT Scan 
Positron emission tomography (PET) scanning uses radioactive glucose (sugar) to study how organs and 
tissues in the body are functioning.  Abnormal cells in the body use glucose at a different rate than 
normal cells, allowing the scanner to create a detailed picture of how your body is working.  A CT scan, 
also called computerized tomography (CT), is an X-ray procedure where a high-speed scanner is used to 
take multiple images or pictures of your body.  A computer then creates images of your body 
incorporating the 2 scans (PET plus CT).  Procedures such as PET-CT scans will be used during this study 
to examine your response to treatment. 
 
You will be asked to lie still on a table, and you may have to hold your breath for a few seconds to avoid 
blurring the pictures.  You may hear slight buzzing, clicking, and/or whirring sounds as the CT scanner 
moves around your body.  You may experience some discomfort, anxiety, or fatigue from lying inside the 
scanner.  The contrast dye used to improve the image quality may cause you to get a metallic taste in 
your mouth, to feel warm throughout your body for a few moments, and rarely cause nausea or 
vomiting.  Before you begin, it is very important to tell the team performing these scans if you have any 
allergies to drugs or food (like shellfish). 
 
Radiation Risks: 
This research study may involve exposure to radiation from up to 1 CT scan of the head, and 5 PET/CT 
scans or 5CT scans of the Chest, Abdomen, and Pelvis. This radiation exposure is not necessary for your 
medical care and is for research purposes only. The total amount of radiation that you will receive by 
participating in this study is equal to your body receiving about 14% more than the amount allowed in a 
year for people who are exposed to radiation as part of their work. Please tell your doctor if you have 
taken part in other research studies or received any other medical care recently involving radiation. If 
you are pregnant or breast feeding, you SHOULD NOT participate in this research study. 
 
To help protect your bladder from the effects of the injected radioactive substances, you should drink 
plenty of fluids and empty your bladder every two hours for at least the first six hours after you have 
each PET/CT scan. 
 
 
 
Comment about Risk of Outpatient Therapy 
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Outpatient therapy is associated with the potential risk of delay in being able to administer intervention 
for specific side effects or complications that may arise during therapy. These include but are not limited 
to tocilizumab for cytokine release syndrome, corticosteroids neurological events, and antibiotics for 
fever.  
 
This risk is mitigated by the following processes 
1. Participants are housed within a mile radius of Vanderbilt and we have an established system to 
rapidly get them to the hospital (bypassing the emergency room) and start intervention within 1 
hour 
2. Vanderbilt has a track record of safety with myeloablative transplant in the outpatient setting 
3. A dedicated phone line that goes directly to a nurse practitioner 24 hours a day 
4. Wearable devices that report vital signs in real time with alerts and data available immediately 
to study personnel 
5. Home health nurse visit to participants 
6. Telemonitoring visit in the night 
 
VitalConnect Patch: 
VitalConnect Patch is used for cardiac monitoring. The adhesives in this product may cause adverse skin 
reactions. Discomfort or irritation may occur; if this occurs the patch may be removed. 
 
Everion Arm Band 
Wearing the arm band may cause discomfort. In addition, wearing multiple monitoring devices may also 
be uncomfortable. 
 
Reproductive Health/Sexual Activity and Pregnancy 
 
Some medications have the potential to cause side effects in the reproductive system of women or men 
that could cause harm, including birth defects, in subsequent pregnancies.  There has not been enough 
study of YESCARTA to be able to predict the risks to pregnant women, the developing fetus, or to the 
breast-feeding child. 
 
Therefore, women and female partners of male patients should not attempt pregnancy, and women 
should not be pregnant or breast-feeding for at least 6 months after conditioning chemotherapy 
(lymphodepleting chemotherapy).  Women of childbearing potential must have a negative pregnancy 
test prior to enrollment because of the potentially dangerous effects of the conditioning chemotherapy 
on the fetus and the unknown risks from YESCARTA. 
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If sexually active with the ability to become pregnant or to cause pregnancy, both women and men 
participating in this study must agree to use an effective birth control method as discussed with and 
directed by their study doctor, for at least 6 months after completion of conditioning chemotherapy. 
If you become pregnant and/or are breast-feeding within 6 months of conditioning chemotherapy, it is 
important that you tell your study nurse/doctor immediately. 
 
If you are male and your partner becomes pregnant within 6 months after you complete conditioning 
chemotherapy, it is important that you tell your study nurse/doctor immediately. 
If you are female and known to be post-menopausal, you are not required to use contraception while in 
this study.  Rarely, women considered to be post-menopausal become pregnant. 
 
In the event of pregnancy, the study team may request additional information about the pregnancy or 
the outcome of the pregnancy in an effort to better understand the effects of YESCARTA treatment on a 
pregnancy and/or the fetus. 
 
Risks that are not known: 
Patients receiving YESCARTA are typically required to spend several days in the hospital, even if their 
YESCARTA treatment is well tolerated.  Because patients in this study will receive YESCARTA in the 
outpatient setting, with fewer time required at the hospital, there may be risks that we do not know 
about at this time. 
 
Good effects that might result from this study: 
The benefits to science and humankind that might result from this study: Taking part may help patients 
with cancer get better or more accessible care in the future. 
 
Payments for your time spent taking part in this study or expenses: 
You will not be compensated for your participation. 
 
Costs to you if you take part in this study: 
If you agree to take part in this research study, you and/or your insurance will not have to pay for the 
tests and treatments that are being done only for research.  However, you are still responsible for 
paying for the usual care you would normally receive for the treatment of your illness.  This includes 
treatments and tests you would need even if you were not in this study.  These costs will be billed to you 
and/or your insurance. You should learn before participating in this study which part of the research-
related care will be free, which costs your insurer will pay for, and which costs will be your responsibility. 
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You have the right to ask what it may cost you to take part in this study.  If you would like assistance, 
financial counseling is available through the Vanderbilt Financial Assistance Program.  The study staff 
can help you contact this program.  You have the right to contact your insurance company to discuss the 
costs of your routine care (non-research) further before choosing to be in the study.  You may choose 
not to be in this study if your insurance does not pay for your routine care (non-research) costs and your 
doctor will discuss other treatment plans with you. 
 
Payment in case you are injured because of this research study: 
If it is determined by Vanderbilt and the Sponsor-Investigator (with Funder input) that an injury 
occurred, then you and/or your insurance may be billed for the cost of immediate medical care provided 
at Vanderbilt to treat the injury. You will be responsible for any copayments or deductibles associated 
with the treatment of that injury. 
 
There are no plans for Vanderbilt or the Funder(s) to pay for the costs of any additional care.  There are 
no plans for Vanderbilt or the Funder(s) to give you money for the injury. 
 
Who to call for any questions or in case you are injured: 
If you should have any questions about this research study or if you feel you have been hurt by being a 
part of this study, please feel free to contact Vanderbilt-Ingram Cancer Center at (877) 936-8422 or 
(615) 322-5000 and ask for Olalekan Oluwole, MD, MPH. 
 
For additional information about giving consent or your rights as a person in this study, to discuss 
problems, concerns, and questions, or to offer input, please feel free to call the VUMC Institutional 
Review Board Office at (615) 322-2918 or toll free at (866) 224-8273. 
 
Reasons why the study doctor may take you out of this study:  
Your study doctor might take you out of the study for reasons such as: 

You are unable to tolerate the treatment, or you have a side effect which the study doctor feels 
should end the treatment. 

Your disease spreads or gets worse (progresses). 

You have another serious illness or need major surgery. 

You do not follow the study doctor’s instructions. 

The study doctor feels it is not in your best interest for you to continue in the study or decides to 
stop the study. 
 
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If you are removed from the study, the reason will be explained to you. 
 
What will happen if you decide to stop being in this study? 
If you decide to stop being part of the study, you should tell your study doctor.  Deciding to not be part 
of the study will not change your regular medical care in any way. 
 
Clinical Trials Registry:  
A description of this clinical trial will be available on www.clinicaltrials.gov, as required by U.S. Law.  This 
website will not include information that can identify you.  At most, the website will include a summary 
of the results.  You can search this Web site at any time. 
 
Clinical Trials Reporting Program. 
Vanderbilt’s NCI-Designated Cancer Center or the Sponsor registers National Cancer Institute (NCI)-
supported clinical trials with NCI though their Clinical Trials Reporting Program (CTRP) to provide study 
related information.  The data provided will include the following identifiable information that may 
identify you: birth month/year and five-digit zip code.  NCI uses the data to manage and enhance the 
nation’s investment in cancer research. 
 
Confidentiality: 
All efforts within reason will be made to keep your personal information in your research record 
confidential but total confidentiality cannot be guaranteed.  Your information and samples will be given 
a code.  Dr. Oluwole, his staff, and other authorized people will be the only people who know your 
personal information. 
 
Study data will be recorded in a Vanderbilt electronic database which is maintained by a research 
coordinator and data manager at Vanderbilt.  The electronic database is password protected in order to 
help protect your identity.  Your study records will be locked up in the clinical trials office. 
 
Vanderbilt may share your information, without identifiers, to others or use it for other research 
projects not listed in this form.  Vanderbilt, Dr. Oluwole and his staff will comply with any and all laws 
regarding the privacy of such information.  There are no plans to pay you for the use or transfer of this 
de-identified information. 
 
 
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Disclosures that you consent to in this document are not protected.  This includes putting research data 
in the medical record or sharing research data for this study or future research.  Disclosures that you 
make yourself are also not protected. 
 
 
Privacy: 
Any samples and information about you may be made available to others to use for research.  To 
protect your privacy, we will not release your name.  You will not receive any benefit as a result of the 
tests done on your samples.  These tests may help us or other researchers learn more about the causes, 
risks, treatments, or how to prevent this and other health problems.  
 
Your samples may be used to make new products or tests.  These may have value and may be developed 
and owned by the study staff, Vanderbilt University, Vanderbilt University Medical Center, and/or 
others.  If this happens, there are no plans to provide money to you. 
 
Authorization to Use/Disclose Protected Health Information 
What information is being collected, used, or shared? 
To do this research, we will need to collect, use, and share your private health information.  By signing 
this document, you agree that your health care providers (including both Vanderbilt University Medical 
Center and others) may release your private health information to us, and that we may use any and all 
of your information that the study team believes it needs to conduct the study.  Your private 
information may include things learned from the procedures described in this consent form, as well as 
information from your medical record (which may include information such as HIV status, drug, alcohol 
or STD treatment, genetic test results, or mental health treatment). 
 
Who will see, use or share the information? 
The people who may request, receive or use your private health information include the study sponsor 
Vanderbilt Medical Center and its agents or contractors, study safety monitors and auditors, data 
managers and other agents and contractors used by the study team, researchers and study team 
members.  Additionally, we may share your information with other people at Vanderbilt, for example if 
needed for your clinical care or study oversight.  Also, your records may be seen by people from 
regulatory authorities (like the US Food and Drug Administration [FDA]), auditors, and the IRB.  By 
signing this form, you give permission to the research team to share your information with others 
outside of Vanderbilt University Medical Center.  This may include the funder of the study and its agents 
or contractors, outside providers, and government agencies.  We try to make sure that everyone who 
sees your information keeps it confidential, but we cannot guarantee that your information will not be 
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shared with others.  If your information is disclosed by your health care providers or the research team 
to others, federal and state confidentiality laws may no longer protect it. 
 
Do you have to sign this Authorization? 
You do not have to sign this Authorization, but if you do not, you may not join the study. 
 
How long will your information be used or shared? 
Your Authorization for the collection, use, and sharing of your information does not expire.  Additionally, 
you agree that your information may be used for similar or related future research studies. 
 
What if you change your mind? 
You may change your mind and cancel this Authorization at any time.  If you cancel, you must contact 
the Principal Investigator in writing to let him know using the contact information provided in this 
consent form.  Dr. Oluwole’s mailing address is: 
 
Olalekan Oluwole, MD, MPH 
Vanderbilt University Medical Center 
3927 The Vanderbilt Clinic 
1301 Medical Center Drive 
Nashville, TN 37232 
 
Your cancellation will not affect information already collected in the study, or information that has 
already been shared with others before you cancelled your authorization. 

If you decide not to take part in this research study, it will not affect your treatment, payment or 
enrollment in any health plans or affect your ability to get benefits.  You will get a copy of this form after 
it is signed. 
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STATEMENT BY PERSON AGREEING TO BE IN THIS STUDY 
I have read this consent form and the research study has been explained to me verbally.  All my 
questions have been answered, and I freely and voluntarily choose to take part in this study. 
 
 
 
Date 
 
 
 
Signature of patient/volunteer  
 
 
 
 
Consent obtained by:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name and Title  
 
 
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Consent for Genetic Research 
 
The purpose of this study is to look at genes (DNA) and how they affect health and disease.  Genes are 
the instruction manual for your body.  The genes you get from your parents decide what you look like 
and how your body behaves.  They can also tell us a person’s risk for certain diseases and how they will 
respond to treatment. 
 
Patients with similar diseases do not always obtain the same benefit from the same treatment.  
Therefore, a goal is to help understand why patients respond differently to treatment, and to then 
develop treatment that provides maximum benefit for individual patients. 
 
As part of the study, your tumor biopsy tissue, bone marrow biopsy and aspirate, cerebrospinal fluid 
(CSF), blood and/or fluid samples will be collected to better understand your disease.  It is possible that 
genetic testing may be conducted on some or all of this material.  You are being asked for your 
permission to allow this. 
 
It is possible that genetic testing on these samples could help to learn more about: 

The effect of treatment on your body 

Why some people respond to treatment and others do not 

Why some people have side effects 

The causes of the disease. 
 
What we learn about you from research on your samples is unlikely to be put in your health record.  No 
one else (like a relative, boss, or insurance company) will be given your test results. 
 
One risk of giving samples for this research may be the release of your name that could link you to the 
stored samples and/or the results of the tests run on your samples.  This may cause problems with 
insurance or getting a job.  To help prevent this, these samples will be given a code.  Only the study staff 
will know the code.  The name that belongs to the code will be kept in a locked file or in a computer with 
a password.  Dr. Oluwole and his staff helping with the study will have access to your name. 
 
Health insurance companies and group health plans may not use your genetic information when making 
decisions regarding your eligibility or premiums.  Employers with 15 or more employees may not use 
your genetic information that comes from this research when making a decision to hire, promote, or fire 
you or when setting the terms of your employment. 
 
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Your sample may be used to make DNA that will be kept for an unknown length of time (maybe years) 
for future research.  Samples will be destroyed when no longer needed.  Your samples may be used to 
make new products, tests or findings.  These may have value and may be developed and owned by the 
study staff, Vanderbilt University, Vanderbilt University Medical Center, and/or others.  If this happens, 
there are no plans to provide money to you. 
 
Your samples and information about you may be shared with others to use for research.  To protect 
your privacy, we will not release your name.  You will not receive any benefit as a result of the tests 
done on your samples.  These tests may help us learn more about the causes, risks, treatments, or how 
to prevent this and other health problems. 
 
At any time, you may ask to have your sample destroyed.  You should contact Dr. Oluwole to have your 
sample destroyed and no longer used for research.  His mailing address is: 
 
Olalekan Oluwole, MD, MPH 
Vanderbilt University Medical Center 
3927 The Vanderbilt Clinic, 1301 Medical Center Drive 
Nashville, TN 37232 
 
We will not be able to destroy research data that has already been gathered using your sample.  Also, if 
your identity was removed from the samples, we will not be able to locate and destroy them.  There will 
be no costs to you for any of the tests done on your samples.  You will not be paid for the use of your 
samples. 
 
Please check Yes or No to the questions below: 
 
My blood/tissue/fluid samples may be used for current gene research in cancer related to YESCARTA: 
 
 
 Yes 
 
My blood/tissue/fluid samples may be stored/shared for future gene research in cancer: 
 
 
 Yes  
 No 
 
My blood/tissue/fluid samples may be stored/shared for future gene research for other health problems  
(such as arthritis, heart disease, etc): 
 
 
 Yes  
 No 
 
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38 of 38 
My optional paired samples of tumor and CSF samples on Day -5 (before lymphodepleting chemo) and 
Day 2 (48 hours post CAR T infusion) may be used for future gene research in cancer: 
 
 
 Yes  
 No 
   
Signature: ______________________________________ Date: ___________ 
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