A Dose Escalating Study of CD19/CD22/BCMA CAR-T Therapy in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)

Shanghai Cell Therapy Group

Status and phase

Enrolling

Early Phase 1

Conditions

Non-Hodgkin Lymphoma, B-cell

Treatments

Biological: CD19/CD20/BCMA CAR T cells

Study type

Interventional

Funder types

Industry

Identifiers

NCT06446128

BZE2204-A-01

Details and patient eligibility

About

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous chimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA in patients with relapsed or refractory B cell non-Hodgkin lymphoma.

Full description

This is a single arm, open-label, dose escalation investigator initiated (IIT) study, the primary objective is to evaluate the safety and tolerability of CD19/CD22/BCMA CAR-T therapy in patients with B cell non-Hodgkin lymphoma, and determine the maximum tolerated dose (MTD). For the secondary objectives, pharmacokinetics(PK), survival of CAR-T cells in vivo, pharmacodynamics (PD) and efficacy in R/R B cell NHL will be evaluated.

This study flow comprises of a screening phase( ≤28 days prior to apheresis), apheresis phase (occur upon enrollment, ≤10 days prior to infusion), lymphodepletion phase (from Day -5 to Day -3) ,infusion of CD19/CD22/BCMA CAR-T cells on Day0, DLT assessments phase from Day1 to Day 28 and post-treatment follow-up phase (Day 29 and up to end of the study).

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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