Clinical trial · Interventional
Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma
A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)
NCT04002401CI-TRIAL-00074145ZUMA-14completedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Refractory Large B-cell Lymphoma | — | UNRESOLVED | — |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Axicabtagene Ciloleucel | Biological | Axicabtagene Ciloleucel | ALIAS |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Fludarabine | Drug | Fludarabine | ALIAS |
| Rituximab | Drug | Rituximab | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Axicabtagene Ciloleucel and Rituximab Combination
- description
- Participants will receive rituximab 375 mg/m\^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m\^2 over 30 minutes and cyclophosphamide 500 mg/m\^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10\^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m\^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133.
- interventionNames
- Biological: Axicabtagene Ciloleucel
- Drug: Rituximab
- Drug: Fludarabine
- Drug: Cyclophosphamide
Primary outcomes (1)
- measure
- Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators
- timeFrame
- First infusion date up to maximum duration of 32.7 months
- description
- CR rate is defined as the incidence of a CR per the IWG Lugano Classification as determined by study investigators. CR rate: percentage of participants with CR \[complete metabolic response (CMR); complete radiological response (CRR)\]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology. 95% confidence interval (CI) was calculated by Clopper-Pearson method.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Key Inclusion Criteria: * Histologically confirmed large B-cell lymphoma * Chemotherapy-refractory disease, defined as one or more of the following: * No response to first-line therapy (primary refractory disease) * No response to second or greater lines of therapy OR * Refractory after autologous stem cell transplant (ASCT) * At least 1 measureable lesion according to the Lugano Classification (Cheson 2014). * Individuals must have received adequate prior therapy, including at a minimum: * Anti-CD20 monoclonal antibody * An anthracycline-containing chemotherapy regimen * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate renal, hepatic, pulmonary, and cardiac function Key Exclusion Criteria: * Known CD19 negative or CD20 negative tumor * History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL) * Prior CAR therapy or other genetically modified T-cell therapy * Prior organ transplantation including prior allogeneic stem cell transplant (SCT) * Prior CD19 targeted therapy * Clinically significant infection or cardiopulmonary disease * Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed) * History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases * History of autoimmune disease * History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months Note: Other protocol defined Inclusion/Exclusion criteria may apply.
References
Publications (2)
- DERIVEDStrati P, Leslie L, Shiraz P, Budde LE, Oluwole OO, Ulrickson M, Ramakrishnan A, Zhang T, Sun J, Milletti F, Kanska J, Shen R, Neumann F, Xu H, Patel K. Axicabtagene ciloleucel in combination with rituximab for refractory large B cell lymphoma: the phase 2, single-arm ZUMA-14 trial. Nat Cancer. 2026 Feb;7(2):304-315. doi: 10.1038/s43018-025-01102-1. Epub 2026 Jan 5. PMID 41492094
- DERIVEDErnst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2. PMID 34515338