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

ConditionLarge B-cell Lymphoma
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorRuijin Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Experimental: LME-Guided Combination TherapyExperimental treatment 1 intervention
Group B: Active Comparator: Glofitamab MonotherapyActive comparator 1 intervention

Trial outcomes

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.

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.

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ruijin Hospital

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: