Treatment for relapsed or refractory aggressive B-cell lymphoma using bispecific antibodies and CAR-T therapy
A Phase 2 Clinical Study of CD20×CD3 Bispecific Antibody-Based Salvage Therapy Followed by CAR-T With or Without ASCT in R/R Aggressive B-Cell Lymphoma
This study is testing a new treatment for patients with aggressive B-cell lymphoma that combines a special antibody and CAR-T therapy to see if it helps them feel better and live longer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 25 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Institute of Hematology & Blood Diseases Hospital, China Academic / other |
| Drugs / interventions | chemotherapy, glofitamab, CAR-T |
| Locations | 1 site (Tianjin) |
| Trial ID | NCT06996132 on ClinicalTrials.gov |
What this trial studies
This clinical trial involves two sequential treatment phases for patients with relapsed or refractory aggressive B-cell lymphoma. In the first phase, participants receive two cycles of glofitamab, potentially combined with other selected agents. Those who qualify then proceed to the second phase, where they receive CAR-T cell therapy, either alone or in combination with autologous stem cell transplantation, followed by additional glofitamab treatment if necessary. The study aims to evaluate the efficacy of this combined therapeutic approach in improving patient outcomes.
Who should consider this trial
Good fit: Ideal candidates are patients with relapsed or refractory aggressive B-cell lymphoma who have undergone at least two prior lines of therapy.
Not a fit: Patients with early-stage aggressive B-cell lymphoma or those who have not received prior treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new effective option for patients with aggressive B-cell lymphoma who have not responded to previous therapies.
How similar studies have performed: Other studies have shown promising results with CAR-T therapies and bispecific antibodies in similar patient populations, indicating a potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Patients with relapsed/refractory aggressive B-cell lymphoma, including the following subtypes: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), or transformed large B-cell lymphoma.
2. Relapsed or refractory disease, meeting criteria for one of the following cohorts:
Cohort 1 (Relapsed/Refractory Disease):
1. ≥2 prior lines of therapy (including both anti-CD20 monoclonal antibody and anthracycline-based chemotherapy) with documented progression following last treatment; OR
2. Failure of first-line immunochemotherapy (containing anti-CD20 antibody and anthracycline) defined by any of:
* Relapse/progression within 12 months of treatment completion; OR
* Progressive disease during first-line therapy; OR
* Stable disease as best response after 4 cycles; OR
* Partial response as best response after 6 cycles.
Cohort 2 (Early Treatment Failure):
* Persistent metabolic activity (Deauville 5) on PET-CT after 2 cycles of first-line immunochemotherapy; OR
* Biopsy-proven residual disease following initial therapy.
3. Age ≥18 years and ≤65 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
5. Hematologic parameters at screening must meet the following (unless due to bone marrow involvement):
* Absolute neutrophil count (ANC) ≥1×10⁹/L,
* Platelet count (PLT) ≥75×10⁹/L.
6. Biochemical parameters at screening must meet the following:
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN);
* Total bilirubin (TBIL) ≤1.5×ULN (unless due to Gilbert's syndrome or non-hepatic causes);
* Serum creatinine (Cr) ≤2×ULN OR creatinine clearance ≥40 mL/min.
7. Left ventricular ejection fraction (LVEF) within institutional normal range by echocardiography.
8. Baseline oxygen saturation \>92% on room air.
9. Life expectancy ≥3 months as assessed by the investigator.
Exclusion Criteria:
1. Confirmed primary central nervous system lymphoma;
2. Prior autologous or allogeneic hematopoietic stem cell transplantation;
3. Active HBV or HCV infection, defined as HBV-DNA or HCV-RNA levels above the upper limit of detection.
4. Uncontrolled comorbidities include infectious diseases, cardiovascular/cerebrovascular disorders, coagulopathies, and connective tissue diseases.
5. History of epilepsy or other central nervous system disorders;
6. Pregnancy or lactation;
7. HIV infection;
8. History of other malignancies unless:
1. Disease-free for ≥5 years, or
2. Previously cured of the following:
* Non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma, or related localized cutaneous malignancies)
* Carcinoma in situ of cervix
9. Other conditions deemed ineligible by investigators.
Where this trial is running
Tianjin
- Institute of Hematology & Blood Diseases Hospital — Tianjin, China (Recruiting)
Study contacts
- Principal investigator: Dehui Zou — Institute of Hematology & Blood Diseases Hospital, China
- Study coordinator: Wei Liu
- Email: liuwei@ihcams.ac.cn
- Phone: 86-022-23608461
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.