AzTrials
AzTrials

Large B-cell LymphomaPhase 2NCT07602322

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

A Phase 2 study testing LME-Guided Combination Therapy Regimen and Glofitamab Monotherapy in people with Large B-cell Lymphoma, run by Ruijin Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Large B-cell Lymphoma
What is being tested?
LME-Guided Combination Therapy Regimen and Glofitamab Monotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteChina
Study dates
14 May 2026to 1 Nov 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.).
Show all 10Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Weili Zhao contact

+862164370045 ext. 610707

zwl_trial@163.com

China1 site

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

    Shanghai, Shanghai Municipality, 200020

    Weili Zhao, +862164370045 ext. 610707, zwl_trial@163.com

Other trials in China

About this study

Official title: An Exploratory, Two-Arm Study of LME Subtype-Guided Precision Combination Therapy Strategies in Patients With B-Cell Lymphoma After CD19 CAR-T Therapy Failure

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.

Read the detailed description

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). However, a substantial number of patients still experience treatment failure, and their prognosis is historically very poor, with limited standard treatment options available. Recent scientific evidence suggests that the tumor microenvironment-a complex ecosystem of immune cells, structural cells, and signals surrounding the lymphoma-acts as a critical barrier that drives resistance to CAR-T and other immunotherapies.

This prospective, open-label, randomized clinical trial introduces a "microenvironment-guided" precision immunotherapy approach. Researchers utilize a practical immunohistochemistry (IHC)-based classification system to categorize the lymphoma microenvironment (LME) of each patient into four distinct subtypes: Germinal Center-like (GC), Interstitial (IN), Mesenchymal (ME), and Depleted (DE). Each subtype corresponds to a specific immune suppression mechanism or survival pathway.

Participants will be randomly assigned in a 1:1 ratio to either an experimental group or a control group.

Control Group: Participants will receive monotherapy with glofitamab, a CD3xCD20 bispecific antibody.

Experimental Group: Participants will receive a tailored combination regimen built upon a glofitamab backbone. The additional therapies are specifically matched to their LME subtype to overcome their unique resistance mechanisms. The regimens include:

GC Type: Glofitamab + a BCL-2 inhibitor IN Type: Glofitamab + a PD-1 inhibitor + Lenalidomide ME Type: Glofitamab + local radiotherapy + a BTK inhibitor DE Type: Glofitamab + Chidamide (an HDAC inhibitor) By systematically matching therapies to the specific vulnerabilities of the patient's tumor microenvironment, this study aims to break CAR-T resistance, achieve deeper remissions, and establish a new biomarker-driven treatment paradigm for this challenging clinical scenario.

Being tested
LME-Guided Combination Therapy Regimen, Glofitamab Monotherapy
Keywords
Large B-Cell Lymphoma (LBCL), CAR-T Failure, Lymphoma Microenvironment (LME)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LME-Guided Combination Therapy RegimenCombination 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 MonotherapyDrug

    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 groups in NCT07602322
Study groupRoleWhat they receive
Experimental: LME-Guided Combination TherapyExperimentalParticipants 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).
Receives: Combination Product: LME-Guided Combination Therapy Regimen
Active Comparator: Glofitamab MonotherapyActive comparatorAll 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.
Receives: Drug: Glofitamab Monotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Objective Response Rate (ORR)

    ORR is defined as the proportion of participants who achieve a Best Overall Response of Complete Response (CR) or Partial Response (PR). Response will be assessed by a Blinded Independent Central Review (BICR) according to the Lugano 2014 classification criteria for lymphoma.

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

  2. Complete Response Rate (CRR)

    CRR is defined as the proportion of participants who achieve a Best Overall Response of Complete Response (CR), as assessed by the BICR according to the Lugano 2014 classification criteria.

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

  3. Duration of Response (DOR)

    DOR is defined as the time from the date of the first documented response (CR or PR) to the date of first documented disease progression (assessed by BICR per Lugano 2014 criteria) or death from any cause, whichever occurs first.

    Measured: 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.

  4. Overall Survival (OS)

    OS is defined as the time from the date of randomization to the date of death from any cause.

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

  5. Incidence and Severity of Adverse Events (AEs)

    Safety will be evaluated by monitoring the incidence, severity, and causality of adverse events. The severity of general AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be specifically graded using the ASTCT consensus criteria.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2026
  2. Study start14 May 2026 (estimated)
  3. Primary completion14 May 2028 (estimated)
  4. Study completion1 Nov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07602322
Sponsor's protocol ID
POST-CART-LME
Status last verified
May 2026
First submitted
15 May 2026
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LME-Guided Combination Therapy Regimen and Glofitamab Monotherapy in people with Large B-cell Lymphoma, run by Ruijin Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Weili Zhao (+862164370045 ext. 610707, zwl_trial@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07602322.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in