MedPath

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

Phase 4
Completed
Conditions
Large B-cell Lymphoma
Diffuse Large B-cell Lymphoma
Interventions
Procedure: Telemedicine Visit
Procedure: Vital sign measurements
Procedure: Out-Patient Clinic Visit
Procedure: Blood pressure and pulse oximeter
Registration Number
NCT05108805
Lead Sponsor
Vanderbilt-Ingram Cancer Center
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
Inclusion Criteria

Not provided

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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
YESCARTA in the Outpatient SettingOut-Patient Clinic VisitParticipants will receive YESCARTA therapy in the outpatient setting
YESCARTA in the Outpatient SettingTelemedicine VisitParticipants will receive YESCARTA therapy in the outpatient setting
YESCARTA in the Outpatient SettingVital sign measurementsParticipants will receive YESCARTA therapy in the outpatient setting
YESCARTA in the Outpatient SettingBlood pressure and pulse oximeterParticipants will receive YESCARTA therapy in the outpatient setting
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient SettingTelemedicine VisitPatients 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.
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient SettingVital sign measurementsPatients 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.
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient SettingOut-Patient Clinic VisitPatients 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.
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient SettingBlood pressure and pulse oximeterPatients 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.
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient SettingAxicabtagene CiloleucelPatients 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.
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient SettingCyclophosphamidePatients 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.
YESCARTA (Axicabtagene Ciloleucel) in the Outpatient SettingFludarabinePatients 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.
Primary Outcome Measures
NameTimeMethod
Number of Participants That Received YESCARTAApproximately 6 weeks

The number of participants that received YESCARTA as outpatient therapy

Participants That Required Hospitalization at 72 Hours Post Infusionat 72 hours

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

Participants That Required Hospitalization at 7 Days Post Infusionat 7 days

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

Participants That Required Hospitalization at 14 Days Post Infusionat 14 days

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

Participants That Required Hospitalization at 30 Days Post Infusionat 30 days

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

Secondary Outcome Measures
NameTimeMethod
Count of Risk Factors That Preclude Out-patient Administration of YESCARTAApproximately 30 days

Reasons as to why a participant did not receive YESCARTA in the out-patient setting

Participants That Experienced Cytokine Release Syndrome EventsApproximately 30 days

Count of participants that had cytokine release syndrome events

Participants That Experienced Immune Effector Cell-associated Neurotoxicity Syndrome EventsApproximately 30 days

Count of participants that had an immune effector cell-associated neurotoxicity syndrome event

Incidence of Steroid Administration During YESCARTAApproximately 30 days

Count of participants that were administered steroids during treatment

Cost Per Patient of Administering YESCARTA in the Out-patient SettingApproximately 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.

Trial Locations

Locations (1)

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

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