| Eligibility |
Key Inclusion Criteria:
- Patients who are diagnosed with relapsed/refractory B cell non-Hodgkin lymphoma ,
especially
- Diffuse Large B Cell Lymphoma, not other specified (DLBCL,NOS),
- Primary Mediastinal Large B Cell Lymphoma (PMBCL)
- Transformation Follicular Lymphoma (TFL)
- High grade B-cell lymphoma(HGBCL)
- High grade B-cell lymphoma (HGBCL) with MYC(myelocytomatosis oncogene) and
BCL2(B-cell lymphoma2) /BCL6 (B-cell lymphoma6) rearrangement
- Refractory diseases are defined as one of the following
- No response to last line of therapy: i. Progressive disease (PD) as best response
to most recent therapy regimen; ii. Stable disease (SD) as best response to most
recent therapy regimen
- Not candidate for autologous stem cell transplant (ASCT) or refractory post-ASCT:
i. Disease progression (PD) or relapsed =12 months of ASCT (must have biopsy
proven recurrence in relapsed individuals) ii. If salvage therapy is given
post-ASCT, the individual must have had no response to or relapsed after the last
line of therapy
- Individuals must have received adequate prior therapy including at a minimum:
- anti-CD20 monoclonal antibody unless investigator determines that tumor is
CD20-negative and
- an anthracycline containing chemotherapy regimen
- Immunohistochemical staining shows at least two of B cell surface receptor antigen
CD19,CD20, BCMA are positive(including weak, medium and strong positive)
- At least one measurable lesion during the screening based on the recommendation for
initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin
lymphoma.
- Life expectancy = 12 weeks
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Renal function: Serum creatinine = 1.5 upper limit of normal(ULN), or eGFR = 60
mL/min/1.73m2 [eGFR(estimated glomerular filtration
rate)=186×age^-0.203×SCr^-1.154(mg/dl),female×0.742]
- Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate
aminotransferase (AST) = 5 ULN and ii: total bilirubin = 2 ULN, except in
individuals with Gilbert syndrome (in Gilbert's syndrome patients, those with
total bilirubin = 3 ULN and direct bilirubin = 1.5 ULN can be enrolled).iii:
International normalized ratio (INR) or prothrombin time (PT) =1.5 ULN Pulmonary:
Have the minimum level of pulmonary reserve, defined as = CTCAE (Common
Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen
saturation)= 91% on room air
- Cardiac: left ventricular ejection fraction (LVEF) =50% determined by
echocardiogram(ECG) or multigated acquisition scan (MUGA)
- Adequate bone marrow function, define as:
- absolute neutrophil count (ANC) =1 ×10^9/L
- absolute lymphocyte count (ALC)= 0.5 ×10^9/L
- Platelets =50 ×109/L;
- Hemoglobulin =80 g/L; patients with bone marrow involvement can be enrolled if
globulin>60 g/L
- Female of child-bearing age and male participants must agree to use effective
contraceptive methods until no CAR-T cells can be detected by PCR(polymerase chain
reaction) test.
Key Exclusion Criteria:
- Individuals who have antiCD45 or antiCD3 therapy
- Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases,
or with a history of primary or secondary CNS (central nervous system) lymphoma,
cerebrospinal fluid malignant cells or brain metastases
- Presence or history of CNS disorder such as seizure disorder, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS
involvement
- History of allogeneic stem cell transplantation
- Any of the following situations:
• HBsAg/ HBeAg positive; HBeAb/HBcAb positive and HBV(hepatitis B virus) DNA copies
above the lower test limit;
- HCV(hepatitis C virus) RNA positive
- HIV(human immunodeficiency virus) positive or treponema pallidum positive
- Presence of active or life-threatening fungal, bacterial, viral, or other infection
that is uncontrolled or requiring IV antimicrobials for management.
- Individuals presence of unstable angina or myocardial infarction within 6 months of
screening, or other severe/uncontrolled diseases during the screening (eg. Unstable or
uncompensated respiratory, cardiac, hepatic or renal disease)
- Presence of uncontrolled arrhythmia with treatment
- Pregnancy or breastfeeding women
Other protocol defined inclusion/exclusion criteria may apply.
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