Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting

Safety and Feasibility Study of Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05108805

Enrollment

Registered

2021-11-05

Start date

2021-12-02

Completion date

2023-12-08

Last updated

2025-03-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diffuse Large B-cell Lymphoma, Large B-cell Lymphoma

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

Interventions

PROCEDURETelemedicine Visit

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.

PROCEDUREVital sign measurements

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.

PROCEDUREOut-Patient Clinic Visit

Physical exam and review of all available data

PROCEDUREBlood pressure and pulse oximeter

Participant and their family take their blood pressure and pulse oximeter

BIOLOGICALAxicabtagene Ciloleucel

Axicabtagene Ciloleuce given by IV

DRUGCyclophosphamide

Given IV

DRUGFludarabine

Given IV

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

(before leukapheresis) Age 18 years and above 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 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 Refractory after autologous stem cell transplant (ASCT) at any time point And Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Adequate hematologic, hepatic, renal and cardiac function evidenced by: * absolute neutrophil count (ANC) ≥1000/µL * Platelet ≥ 75,000/ µL * T-bilirubin ≤ 1.5 mg/dL * Normal serum creatinine or creatinine clearance ≥ 60 mL/min/1.73 m2 * Cardiac ejection fraction ≥ 50% * Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 5 times upper limit of normal (ULN). * At least 1 measurable lesion * Baseline oxygen saturation ≥92% on room air. * 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. * A caregiver who can be educated to operate equipment for vital signs monitoring. Caregiver Eligibility: Willingness to serve as a caregiver Ability to read, write and operate a phone Willingness to be taught to operate electronic device Willingness and ability to assist subject to wear electronic device such including patch, blood pressure machine, thermometer Pass caregiver assessment test 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.

Exclusion criteria

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. Known CD19 negative tumor. History of Richter's transformation of chronic lymphocytic leukemia (CLL). Autologous stem cell transplant with therapeutic intent within 6 weeks of planned YESCARTA infusion. History of allogeneic stem cell transplantation. Prior CAR therapy or other genetically modified T-cell therapy. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides. 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. 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. 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. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases. Patients with treated secondary CNS involvement of lymphoma are allowed. 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. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrolment. Requirement for urgent therapy due to tumor mass effects (e.g., blood vessel compression, bowel obstruction, or transmural gastric involvement). Primary immunodeficiency. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment. Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 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. 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. 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. 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. Must not have received immunomodulating agents including checkpoint inhibitors, Bruton tyrosine kinase (BTK) inhibitors, and Revlimid within 2 months or 5 half-lives whichever is shorter.

Design outcomes

Primary

Measure	Time frame	Description
Participants That Required Hospitalization at 30 Days Post Infusion	at 30 days	Number of subjects that were admitted to hospital at 30 days post infusion
Number of Participants That Received YESCARTA	Approximately 6 weeks	The number of participants that received YESCARTA as outpatient therapy
Participants That Required Hospitalization at 72 Hours Post Infusion	at 72 hours	Number of subjects that were admitted to hospital at 72 hours post infusion
Participants That Required Hospitalization at 7 Days Post Infusion	at 7 days	Number of subjects that were admitted to the hospital at 7 days post infusion
Participants That Required Hospitalization at 14 Days Post Infusion	at 14 days	Number of subjects that were admitted to the hospital at 14 days post infusion

Secondary

Measure	Time frame	Description
Count of Risk Factors That Preclude Out-patient Administration of YESCARTA	Approximately 30 days	Reasons as to why a participant did not receive YESCARTA in the out-patient setting
Participants That Experienced Cytokine Release Syndrome Events	Approximately 30 days	Count of participants that had cytokine release syndrome events
Participants That Experienced Immune Effector Cell-associated Neurotoxicity Syndrome Events	Approximately 30 days	Count of participants that had an immune effector cell-associated neurotoxicity syndrome event
Incidence of Steroid Administration During YESCARTA	Approximately 30 days	Count of participants that were administered steroids during treatment
Cost Per Patient of Administering YESCARTA in the Out-patient Setting	Approximately 30 days	Cost includes hospital clinic charges and CAR-T acquisition. It was pre-specified to report a single dollar amount that every participant was changed. The amount entered was the amount that each patient was charged. It was not planned to assess this amount separately for each participant.

Countries

United States

Participant flow

Participants by arm

Arm	Count
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting 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. Telemedicine Visit: A remote telemedicine visit with audio and video, using the internet with a nurse practitioner located elsewhere. The participant 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. Review of system questions are asked, and the answers given by subject recorded. Neurological assessment done, and ICE score calculated. Vital sign measurements: 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. Out-Patient Clinic Visit: Physical exam and review of all available data Blood pressure and pulse oximeter: Participant and their family take their blood pressure and pulse oximeter Axicabtagene Ciloleucel: Axicabtagene Ciloleuce given by IV Cyclophosphamide: Given IV Fludarabine: Given IV	25
Total	25

Arm

Count

YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting

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. Telemedicine Visit: A remote telemedicine visit with audio and video, using the internet with a nurse practitioner located elsewhere. The participant 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. Review of system questions are asked, and the answers given by subject recorded. Neurological assessment done, and ICE score calculated. Vital sign measurements: 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. Out-Patient Clinic Visit: Physical exam and review of all available data Blood pressure and pulse oximeter: Participant and their family take their blood pressure and pulse oximeter Axicabtagene Ciloleucel: Axicabtagene Ciloleuce given by IV Cyclophosphamide: Given IV Fludarabine: Given IV

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	T-cell expansion was not successful.	5

Baseline characteristics

Characteristic	YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	14 Participants
Age, Categorical Between 18 and 65 years	11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	23 Participants
Region of Enrollment United States	25 participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	16 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	6 / 25
other Total, other adverse events	21 / 25
serious Total, serious adverse events	6 / 25

Outcome results

Primary

Number of Participants That Received YESCARTA

The number of participants that received YESCARTA as outpatient therapy

Time frame: Approximately 6 weeks

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting	Number of Participants That Received YESCARTA	20 Participants

Primary

Participants That Required Hospitalization at 14 Days Post Infusion

Number of subjects that were admitted to the hospital at 14 days post infusion

Time frame: at 14 days

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting	Participants That Required Hospitalization at 14 Days Post Infusion	19 Participants

Primary

Participants That Required Hospitalization at 30 Days Post Infusion

Number of subjects that were admitted to hospital at 30 days post infusion

Time frame: at 30 days

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting	Participants That Required Hospitalization at 30 Days Post Infusion	19 Participants

Primary

Participants That Required Hospitalization at 72 Hours Post Infusion

Number of subjects that were admitted to hospital at 72 hours post infusion

Time frame: at 72 hours

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting	Participants That Required Hospitalization at 72 Hours Post Infusion	2 Participants

Primary

Participants That Required Hospitalization at 7 Days Post Infusion

Number of subjects that were admitted to the hospital at 7 days post infusion

Time frame: at 7 days

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient Setting	Participants That Required Hospitalization at 7 Days Post Infusion	19 Participants

Secondary

Cost Per Patient of Administering YESCARTA in the Out-patient Setting

Cost includes hospital clinic charges and CAR-T acquisition. It was pre-specified to report a single dollar amount that every participant was changed. The amount entered was the amount that each patient was charged. It was not planned to assess this amount separately for each participant.