Large B-Cell Lymphoma (LBCL)
Conditions
Keywords
CD19/CD22, bispecific, CAR-T, Large B-cell Lymphoma
Brief summary
CAR-T cell therapy targeting CD19 has been shown to be effective in heavily-pretreated B-cell ALL or NHL, but relapses post-CAR-T are common, and CD19 antigen loss is one of the reasons. Thus, the investigators supposed that CD19/CD22 bispecific CAR-T cell therapy would be more effective and less relapses would occur in B- NHL. In this prospective phase 2 clinical trial, the investigators aim to explore the efficacy and safety of CD19/CD22 bispecific CAR-T cell therapy in relapsed/refractory Large B cell lymphoma.
Detailed description
Large B cell lymphoma (LBCL) is the most common aggressive subtype of non-Hodgkin lymphoma (NHL) in adults. While approximately 60% of patients can be cured with first-line therapy, a subset of patients experiences relapse or refractory disease (R/R). The prognosis for R/R LBCL patients is poor, with limited efficacy from traditional treatments such as autologous stem cell transplantation (ASCT) and novel targeted agents. Chimeric antigen receptor-T (CAR-T) cell therapy involves genetically engineering T cells to express chimeric antigen receptors (CARs) that target tumor-specific antigens, enabling precise elimination of tumor cells. CD19 is the most commonly targeted antigen in B-cell malignancies, however, antigen escape following CD19 CAR-T therapy can lead to disease relapse in some patients. Studies indicate that CD22 is widely expressed in B-cell malignancies and exhibits incomplete overlap with CD19 expression, suggesting that dual-target CAR-T therapy may more comprehensively eradicate tumor cells. Therefore, dual-target CAR-T therapy, particularly strategies targeting both CD19 and CD22, has emerged as a promising approach to overcome antigen escape and enhance therapeutic outcomes. In this prospective study, the investigators aimed to evaluate the efficacy and safety of CD19/CD22 bispecific CAR-T cell (CAR2219) therapy in patients with R/R LBCL.
Interventions
DRUGCD19/CD22 bispecific CAR-T cells
CD19/CD22-bispecific CAR-T cells were infused at the dosage of 2×10e6/kg
Sponsors
Beijing Tongren Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In this group, all patients will receive CD19/CD22 bispecific CAR-T cell therapy.
Eligibility
Sex/Gender
ALL
Age
14 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 14 years to 85 years, expected survival \> 3 months; * CD19 positive with or without CD22 positive Large B-cell lymphoma; * relapsed or refractory disease; * ECOG-PS score=0-2; * Having at least one measurable lesion; * Cardiac function: 1-2 levels; * Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; * kidney: Cr≤1.25ULN; * bone marrow: WBC ≥ 3.0×10e9/L, Hb ≥80 g/L, PLT ≥ 50×10e9/L; * No serious allergic constitution; * No other serious diseases that conflicts with the clinical program; * No other cancer history; * No serious mental disorder; * Informed consent is signed by a subject or his lineal relation.
Exclusion criteria
* Pregnant or lactating women (female participants of reproductive potential must have a negative serum or urine pregnancy test); * Uncontrolled active infection, HIV infection, syphilis serology reaction positive; * Active hepatitis B or hepatitis C infection; * With severe cardiac, liver, renal insufficiency, diabetes and other diseases; * Participate in other clinical research in the past 4 weeks; * Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| best overall response rate (ORR) as of 3 months post-CAR-T cells infusion | From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion | Overall response rate means sum of complete response rate and partial response rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Complete Response rate (CR) as of 3 months post-CAR-T cells infusion | From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion | CR was defined as complete response evaluated using PET-CT scan |
| Progression free survival (PFS) | From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion | PFS was defined from the date of CAR-T infusion to the date fo confirmed disease progression or death of any reason |
| overall survival (OS) | From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion | OS was defined from the date of CAR-T infusion to the date fo death |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion | measured using CTCAE version 5.0 |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORLiang Wang, M.D.
Beijing Tongren Hospital
Outcome results
None listed