| Eligibility |
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 ASCT at any time point
And
ECOG performance status 0-2.
Adequate hematologic, hepatic, renal and cardiac function evidenced by:
- 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 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 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, BTK
inhibitors, and Revlimid within 2 months or 5 half-lives whichever is shorter.
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