Axicabtagene Ciloleucel CAR T-cells in Patients With Relapsed or Refractory Primary Mediastinal B-cell Lymphoma

NCT06912529 | Terminated Phase 2 DMC

• 2 other identifiers: UniMS23_00182024-510972-19-00
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II study will evaluate the efficacy, safety and tolerability of second-line treatment with axicabtagene ciloleucel in primary mediastinal B-cell lymphoma patients (PMBCL).

Conditions

B-cell Lymphoma Refractory; B-cell Lymphoma Recurrent

Outcome Measures

Primary Outcomes (1)

• Complete metabolic response (CMR)

  Complete metabolic response at 3 months from axicabtagene ciloleucel infusion (without additional anticancer therapy). Assessment of response will be based on the Lugano classification.

  3 months from axicabtagene ciloleucel infusion

Secondary Outcomes (10)

• Best response rate

  between day 30 and 12 months from axicabtagene ciloleucel infusion

• Duration of complete metabolic response (DOCMR)

  3 months from axicabtagene ciloleucel infusion

• Time to first response

  time from axicabtagene ciloleucel infusion after which the first response (CMR without additional anticancer therapy/PMR at 30 days, 3 months, 6 months and 12 months) has ocurredhas occurred

• Relapse rate (RR)

  3 months from axicabtagene ciloleucel infusion

• Progression-free survival (PFS)

  until last visit of patient, assessed up to 24 months

Study Arms (1)

Treatment arm

EXPERIMENTAL

While completing the screening process corticoid therapy may be continued up 7 days prior to leukapheresis. After leukapheresis, one cycle of any therapy can be given as bridging therapy to reduce tumor burden if clinically necessary. Lymphodepletion (LD) can be started after PET-CT-based staging. LD consists of lymphocyte depleting chemotherapy with fludarabine and cyclophosphamide (FC) applied on day -5 to day -3 followed by administration of axicabtagene ciloleucel on day 0. Patients will be observed as inpatients until at least day 10. Once the patient is discharged, outpatient visits including PET-CT-based staging are required on day 30 (±2 days), day 100 (±7 days), month 6 and 12 after axicabtagene ciloleucel administration.

Procedure: Leukapheresis; Drug: Bridging Therapy; Drug: Lymphodepletion; Genetic: Axicabtagene Ciloleucel

Interventions

Leukapheresis PROCEDURE

Axicabtagene ciloleucel is prepared from the patient's peripheral blood mononuclear cells, which are obtained via a standard leukapheresis procedure.

Also known as: apheresis

Treatment arm

Bridging Therapy DRUG

Bridging therapy refers to treatment used to control a patient's disease or disease related inflammation prior to lymphodepletion.

Treatment arm

Lymphodepletion DRUG

Patients will receive a non-myeloablative lymphodepleting regimen consisting of fludarabine and cyclophosphamide (FC) to induce lymphocyte depletion and create an optimal environment for expansion of axicabtagene ciloleucel in vivo.

Treatment arm

Axicabtagene Ciloleucel GENETIC

Patient will receive the axicabtagene ciloleucel infusion in the hospital followed by daily monitoring in the hospital.

Also known as: axi-cel

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent form (ICF) according to ICH/EU GCP and national regulations
• Age \> 18 years
• ECOG performance status \< 2
• Histologically confirmed primary mediastinal B-cell lymphoma (PMBCL)
• based on the 2022 World Health Organization (WHO) (R. Allagio et al.)
• classification by local pathology laboratory assessment
• Patients must have received adequate first-line therapy including:
• An anti-CD20 monoclonal antibody (rituximab), and
• CHOP or CHOP-like chemotherapy Note: CHOP-like chemotherapy corresponds to CHOEP, ACVBP or EPOCH or COPADEM. Patients who received dose-reduced CHOP (e.g., mini-CHOP) are excluded except for dose reductions of vincristine due to peripheral neuropathy. Patients who have received additional drugs in combination with CHOP or CHOP-like regimen are eligible.
• Relapsed or refractory disease after first-line chemoimmunotherapy, documented by PET-CT:
• Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse
• Refractory disease defined as:
• Progressive disease (PD) during first-line therapy
• Stable disease (SD) as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP) and biopsy-proven residual disease, or
• Partial response (PR) as best response after at least 6 cycles, and biopsy-proven residual disease

You may not qualify if:

• Patients who received more than one prior line of systemic therapy
• Prior CD19-targeted therapy
• History of another primary malignancy that has not been in remission for at least 2 years (except for non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast)). A maintenance treatment is not allowed
• History or presence of non-malignant CNS disorder, such as seizure disorder requiring anti-convulsive therapy, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema with confirmed structural defects by appropriate imaging. History of stroke or transient ischemic attack within 12 months prior to enrollment.
• History of acute or chronic active hepatitis B or C infection. If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing
• Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a CD4 count \> 200 cells/μl
• Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal catheter). Dedicated venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
• Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antimicrobials at the time of enrollment
• Presence of cardiac atrial or ventricular lymphoma involvement
• History of any one of the following cardiovascular conditions within the past 12 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• History of any medical condition including but not limited to autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression and/or systemic disease modifying agents within the last year. Endocrine conditions that require maintenance with physiologic dose steroids are allowed
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed
• History of severe immediate hypersensitivity reaction to any of the agents used in this study, including aminoglycosides, cyclophosphamide, fludarabine or tocilizumab
• Treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
• FCBP who are pregnant or breastfeeding

Sponsors & Collaborators

• Universität Münster: lead
• Kite, A Gilead Company: collaborator

Study Sites (1)

Medizinische Klinik A Hämatologie, Hämostaseologie, Onkologie und Pneumologie Universitätsklinikum Münster

Münster, 48149, Germany

Location

MeSH Terms

Interventions

Leukapheresis; Blood Component Removal; axicabtagene ciloleucel

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Georg Lenz, Prof

  Universität Münster

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: April 4, 2025
• Study Start: March 13, 2025
• Primary Completion: July 25, 2025
• Study Completion: July 25, 2025
• Last Updated: September 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)