LME-Guided Precision Combination Therapy in B-cell Lymphoma Patients After CD19 CAR-T Failure

Sponsor
Ruijin Hospital
Study ID
NCT07602322
Phase
PHASE2
Status
Not Yet Recruiting

Notify me when recruiting opens

Save your spot on the interest list for this study. We'll keep your details with this study so our team can follow up when recruiting opens.

Not yet recruiting

Add your contact details and location so we can keep your interest tied to this study.

Conditions

  • Large B-cell Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • LME-Guided Combination Therapy Regimen — COMBINATION_PRODUCT
    Participants in this arm receive a tailored combination therapy based on their baseline Lymphoma Microenvironment (LME) subtype identified via immunohistochemistry (IHC). The regimens are built on a glofitamab backbone: GC Type: Glofitamab + BCL-2 inhibitor (e.g., Lisaftoclax/Venetoclax) IN Type: Glofitamab + PD-1 inhibitor (e.g., Tislelizumab) + Lenalidomide ME Type: Glofitamab + Local Radiotherapy + BTK inhibitor (e.g., Zanubrutinib) DE Type: Glofitamab + HDAC inhibitor (e.g., Chidamide)
  • Glofitamab Monotherapy — DRUG
    Participants receive glofitamab as a single agent. Administered intravenously. Cycle 1 uses a step-up dosing schedule (e.g., 2.5mg on Day 1, 10mg on Day 8), followed by a target dose (e.g., 30mg) on Day 15 and every 3 weeks thereafter. Pretreatment with obinutuzumab 1000mg is given one week prior to the first dose.

Study Details

This study evaluates a personalized treatment strategy for patients with large B-cell lymphoma (LBCL) whose disease has relapsed or not responded after CD19 CAR-T cell therapy. Researchers believe that the area surrounding the tumor, called the lymphoma microenvironment (LME), plays a major role in why treatments fail. In this study, researchers will classify patients into four different LME subtypes (GC, IN, ME, or DE) using a standard lab test on their tumor samples. Patients will then be randomly assigned to one of two groups. The control group will receive a standard single-drug therapy (glofitamab). The experimental group will receive a tailored combination therapy based specifically on their tumor's LME subtype. The main hypothesis of this study is that customizing the treatment based on the tumor's microenvironment will significantly improve how long patients live without their disease getting worse (progression-free survival) compared to the standard single-drug approach.

Key Dates

First listed
May 22, 2026
Start date
May 14, 2026
Status verified
May 2026
Primary completion
May 14, 2028
Completion
Nov 1, 2028

Study Design

Enrollment
60 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental: LME-Guided Combination Therapy
    Participants receive a tailored combination therapy based on their baseline Lymphoma Microenvironment (LME) subtype identified via immunohistochemistry (IHC). The specific regimens are: GC Type: Glofitamab combined with a BCL-2 inhibitor. IN Type: Glofitamab combined with a PD-1 inhibitor and lenalidomide. ME Type: Glofitamab combined with local radiotherapy and a BTK inhibitor. DE Type: Glofitamab combined with chidamide (an HDAC inhibitor).
  • Active Comparator: Active Comparator: Glofitamab Monotherapy
    All participants in this control arm receive single-agent therapy with the CD3xCD20 bispecific antibody glofitamab. The drug will be administered according to the approved product label and standard clinical practice.

Primary Outcome Measure

Progression-Free Survival (PFS) [ Time Frame: From the date of randomization until the first documented disease progression or death from any cause, whichever occurs first, assessed up to approximately 24 months. ]

Central Contacts

Related Studies