| Eligibility |
Inclusion Criteria:
Patients must meet the following inclusion criteria in order to be eligible for
participation in this trial:
1. For the dose escalation cohort: Eligible patients will include those with r/r B-cell
lymphoma including LBCL (DLBCL, HGBCL, LBCL transformed from indolent lymphoma, and
PMBCL), FL, marginal zone lymphoma, and MCL after at least 2 prior systemic therapies
and Burkitt lymphoma after at least 1 prior systemic therapy. For the dose expansion
cohort: Patients with r/r LBCL (DLBCL, HGBCL, LBCL transformed from indolent lymphoma,
and PMBCL) and FL grade 3B will be eligible
2. Received at least 2 prior lines of therapy, including anti-CD20 antibody and
anthracycline therapy for LBCL, anti-CD20 antibody and alkylating agent or
lenalidomide therapy for FL, anti-CD20 antibody and alkylating agent or lenalidomide
or BTK inhibitor therapy for marginal zone lymphoma, and anti-CD20 antibody and
alkylating agent or BTK inhibitor therapy for MCL. Patients with Burkitt lymphoma may
be eligible after 1 line of prior therapy including anti-CD20 antibody and
anthracycline therapy.
3. Patients who have received prior CD19 CAR cell therapy using FMC63 antibody for
targeting CD19 are eligible and must be at least 6 weeks post CAR infusion and have
<5% of peripheral blood T cells expressing the prior CAR by flow cytometry assessment.
4. =18 years of age
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
6. At least one measurable lesion per the Lugano 2014 Classification53
7. At least two weeks or 5 half-lives, whichever is shorter, must have elapsed since any
prior systemic anti-cancer therapy prior to leukapheresis. For patients treated with
monoclonal antibody-based therapies, at least 4 weeks must have elapsed prior to
leukapheresis.
8. Toxicities due to prior therapy must be stable and recovered to =grade 1 (except for
clinically non-significant toxicities such as alopecia)
9. Absolute neutrophil count of =1.0×10^9/L
10. Absolute lymphocyte count of =0.1×10^9/L
11. Platelet count of =75×10^9/L
12. Creatinine clearance (as estimated by Cockcroft Gault) =45 mL/min
13. Serum alanine transaminase (ALT) / aspartate transaminase (AST) =5 times the upper
limit of normal (ULN)
14. Total bilirubin =2 mg/dL, except in patients with Gilbert's syndrome.
15. Cardiac ejection fraction =45% with no evidence of clinically significant pericardial
effusion
16. Baseline oxygen saturation =92% on room air
17. Women of childbearing potential must have a negative serum or urine pregnancy test
(women who have had hysterectomy and women who are over the age of 45 years and
Exclusion Criteria:
Patients will be excluded from participating in the trial if he/she has:
1. Active central nervous system (CNS) lymphoma including patients with detectable
cerebrospinal fluid malignant cells or brain metastases. Patients with prior CNS
lymphoma that has been effectively treated will be eligible if treatment was completed
at least one year prior to enrolment and there is no evidence of disease on MRI with
gadolinium contrast at the time of screening.
2. Any CAR cell therapy using non-FMC63 antibody.
3. History of Richter's transformation of chronic lymphocytic leukemia
4. Autologous stem cell transplantation within 6 weeks.
5. Allogeneic stem cell transplantation within 3 months or active graft versus host
disease.
6. Active autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus
erythematosus) requiring systemic immunosuppression/systemic disease modifying agents
within the last 1 year or inflammatory disease (including graft versus host disease)
requiring systemic immunosuppressive therapy. Physiological replacement of
corticosteroids of up to 7.5 mg of prednisone or equivalent per day, and topical and
inhaled corticosteroids are permitted.
7. History of any form of primary immunodeficiency that in the opinion of the
investigator may affect efficacy of the CAR-T product.
8. History of any one of the following cardiovascular conditions within the past 6
months: Class III or IV heart failure as defined by the New York Heart Association,
cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other
clinically significant cardiac disease.
9. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g.
cervix, bladder, breast) unless disease free for at least 2 years and treated with
curative intent. Patients with a prior history of malignancy whose natural history or
treatment (e.g. hormonal therapy) does not have the potential to interfere with either
the safety or efficacy assessment of the investigational regimen in the opinion of the
investigator may be included.
10. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
requiring intravenous antimicrobials for management. Simple urinary tract infection
and uncomplicated bacterial pharyngitis or localized skin infections are permitted if
responding to active treatment and after consultation with the Principal Investigator.
11. Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C
virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the
viral load is undetectable per quantitative PCR and/or nucleic acid testing.
12. History or presence of CNS disorders such as seizure disorder, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS
involvement
13. Patients with cardiac atrial or cardiac ventricular lymphoma involvement
14. Requirement for urgent therapy due to tumor mass effect such as bowel obstruction or
blood vessel compression
15. Any medical condition likely to interfere with assessment of safety or efficacy of
study treatment
16. Live vaccine =6 weeks prior to planned start of conditioning regimen
17. Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the conditioning chemotherapy on the fetus or infant.
18. Females of childbearing potential and males of child fathering potential who are not
willing to practice two methods of birth control from the time of consent through 6
months after infusion of the study drug
19. In the investigator's judgment, the patient is unlikely to complete all
protocol-required study visits or procedures, including follow-up visits, or comply
with the study requirements for participation.
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