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

NCT07602322 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: POST-CART-LME
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Large B-cell Lymphoma

Keywords

Large B-Cell Lymphoma (LBCL); CAR-T Failure; Lymphoma Microenvironment (LME)

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from the date of randomization to the date of first documented disease progression (PD) or death from any cause, whichever occurs first. Disease response and progression will be assessed by a Blinded Independent Central Review (BICR) according to the Lugano 2014 classification criteria for lymphoma.

  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.

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  From the date of randomization until the first documented disease progression or death from any cause, assessed up to approximately 24 months.

• Complete Response Rate (CRR)

  From the date of randomization until the first documented disease progression or death from any cause, assessed up to approximately 24 months.

• Duration of Response (DOR)

  From the date of first documented response (Complete Response or Partial Response) until the first documented disease progression or death from any cause, assessed up to approximately 24 months.

• Overall Survival (OS)

  From the date of randomization until the date of death from any cause, assessed up to approximately 24 months.

• Incidence and Severity of Adverse Events (AEs)

  From the first dose of study treatment until 90 days after the last dose of study treatment, assessed up to approximately 24 months.

Study Arms (2)

Experimental: LME-Guided Combination Therapy

EXPERIMENTAL

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).

Combination Product: LME-Guided Combination Therapy Regimen

Active Comparator: Glofitamab Monotherapy

ACTIVE COMPARATOR

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.

Drug: Glofitamab Monotherapy

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)

Experimental: LME-Guided Combination Therapy

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.

Active Comparator: Glofitamab Monotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, regardless of gender.
• Histologically confirmed large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL, not otherwise specified) or high-grade B-cell lymphoma.
• Received prior CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.
• Confirmed stable disease (SD) or progressive disease (PD) at the most recent imaging assessment (according to Lugano 2014 criteria) following CAR-T therapy.
• Able to provide a formalin-fixed paraffin-embedded (FFPE) tumor tissue sample (fresh biopsy or archival specimen obtained before CAR-T therapy or after recent progression) with sufficient quantity and quality for immunohistochemistry (IHC) testing.
• Confirmed CD20-positive tumor cells by central laboratory IHC testing.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Adequate organ function (including bone marrow, liver, kidney, and heart).
• Women of childbearing potential must agree to use highly effective contraception during the study and for a specified period after the last dose of study drug; male patients must agree to use effective contraception during the study and for a specified period after the last dose.
• Voluntarily agreed to participate in the study, signed the written informed consent form, and willing to comply with the study visit schedule and other protocol requirements.

You may not qualify if:

• Prior treatment with glofitamab resulting in disease progression.
• Known severe allergic reactions to any components of the study drugs.
• Active central nervous system (CNS) lymphoma involvement.
• Presence of a severe, uncontrolled active infection.
• Presence of severe cardiovascular or cerebrovascular diseases, uncontrolled diabetes, or uncontrolled hypertension that, in the investigator's judgment, makes the patient unsuitable for study participation.
• History of or current other malignancies (exceptions: adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, etc.).
• Pregnant or breastfeeding women.
• Positive for human immunodeficiency virus (HIV) antibody, or active hepatitis B virus (HBV) infection (HBsAg positive with HBV-DNA \> 1x10\^3 copies/mL), or active hepatitis C virus (HCV) infection (HCV antibody positive and HCV-RNA positive).
• Any medical or psychiatric condition that might interfere with study execution or result interpretation, or place the patient at unacceptable risk.
• Received other anti-tumor therapies (including chemotherapy, radiotherapy, immunotherapy, etc.) within 2 weeks prior to study enrollment, or have not recovered from toxicities of prior therapies to ≤ Grade 1 or baseline levels (excluding alopecia or other irreversible but non-clinically significant toxicities).

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai,

Shanghai, Shanghai Municipality, 200020, China

Location

Central Study Contacts

Weili Zhao

CONTACT

+862164370045; zwl_trial@163.com

Study Design

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

Model Details: This study uses a parallel-group design with a biomarker-driven experimental arm. Participants are randomly assigned in a 1:1 ratio to either the control arm or the experimental arm. Participants in the control arm receive a single standard therapy (glofitamab monotherapy). Participants in the experimental arm receive one of four distinct combination therapies; the specific combination is determined by their baseline Lymphoma Microenvironment (LME) subtype (GC, IN, ME, or DE), which is identified via immunohistochemistry (IHC) profiling prior to treatment.

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: May 22, 2026
• Study Start: May 14, 2026
• Primary Completion (Estimated): May 14, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)