Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)Phase 2NCT07489989
Enhancing CAR-T Cell Therapy Efficacy in B-cell Lymphoma Via Chidamide and PD-1 Inhibitor Combination.
A Phase 2 study testing CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance in people with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL), run by Daihong Liu at 1 site in China.
Trial summary
B-cell non-Hodgkin lymphoma (B-NHL) is one of the most common malignancies in China, with approximately 100,000 new cases diagnosed annually. Although immunochemotherapy, novel small-molecule targeted agents, and hematopoietic stem cell transplantation have significantly improved outcomes for patients with B-cell… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)
- What is being tested?
- CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 15 May 2025to 15 May 2027
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -
- The patient must meet all of the following inclusion criteria:
- Histologically or cytologically confirmed CD19 and/or CD22-positive large B-cell lymphoma (LBCL) according to the WHO 2016 classification, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), and related entities, with one of the following:
- Partial response (PR) after induction therapy with a standard first-line chemotherapy regimen (e.g., R-CHOP for 4-6 cycles); or
- Complete response (CR) after standard first-line induction therapy, but with high-risk features present at initial diagnosis.
- Presence of high-risk features at initial diagnosis, defined as at least one of the following:
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- High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements ("double-hit" or "triple-hit") confirmed by fluorescence in situ hybridization (FISH);
- High-grade B-cell lymphoma with 11q aberration (Burkitt-like lymphoma with 11q aberration);
- International Prognostic Index (IPI) score of 2-5; age-adjusted IPI (aa-IPI) score of 2-3; or National Comprehensive Cancer Network-IPI (NCCN-IPI) score of 4-8;
- CD5 positivity by immunohistochemistry;
- Dual expression of MYC and BCL2 by immunohistochemistry (recommended thresholds: MYC ≥ 40% and BCL2 ≥ 50%);
- TP53 mutation detected by gene sequencing;
- Molecular subtype MCD or N1 by next-generation sequencing (NGS);
- Relapsed/refractory B-cell lymphoma, meeting one of criteria ①-④ plus criterion ⑤:
- Less than 50% tumor reduction or disease progression after ≥4 cycles of standardized chemotherapy;
- Relapse within 6 months after achieving CR with standard regimen;
- ≥2 relapses after CR;
- Relapse after hematopoietic stem cell transplantation;
- Must have received adequate prior therapy, including at least an anti-CD20 monoclonal antibody and anthracycline-containing combination chemotherapy.
- Age 18 to 85 years, male or female.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Expected survival of >3 months from the date of signing informed consent.
- Hemoglobin (HGB) ≥60 g/L (transfusion permitted).
- Absolute neutrophil count (ANC) ≥1,000/μL and platelet count ≥45,000/μL.
- Adequate hepatic, renal, cardiac, and pulmonary function, meeting all of the following:
- Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN) (except for patients with Gilbert's syndrome);
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
- Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (CCr) ≥60 mL/min (estimated by Cockcroft-Gault formula);
- Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO), with no pericardial effusion and no clinically significant arrhythmias;
- Baseline oxygen saturation by pulse oximetry >92% on room air;
- No clinically significant pleural effusion.
Who cannot join
- Patients eligible for CAR-T cell immunotherapy must NOT meet any of the following exclusion criteria:
- Prior treatment with any form of chimeric antigen receptor (CAR) T-cell therapy or other genetically modified T-cell therapy.
- History of severe immediate-type hypersensitivity reaction to aminoglycoside antibiotics or other drugs.
- Known history of human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
- (Active HBV infection is defined as meeting all of the following: a) HBV DNA ≥ 2000 IU/mL; b) ALT ≥ 2 × upper limit of normal (ULN); c) hepatitis not attributable to other causes such as the underlying disease or medications. Patients with active HBV at initial diagnosis who achieve non-active HBV status after adequate anti-HBV treatment may be eligible under continued effective anti-HBV therapy.)
- Non-hematologic malignancy-related hepatic or renal impairment, including any of the following: ALT > 3 × ULN, AST > 3 × ULN, total bilirubin (TBIL) > 2 × ULN, or creatinine clearance < 30 mL/min.
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- History of myocardial infarction, percutaneous coronary intervention (including coronary angioplasty or stenting), unstable angina, active arrhythmia, or other clinically significant cardiovascular disease within the past 12 months.
- Any other serious medical condition that, in the opinion of the investigator, may interfere with the study treatment or increase risk to the patient (e.g., poorly controlled diabetes, active peptic ulcer disease, severe respiratory or circulatory disease, severe autoimmune disease, congenital immunodeficiency, uncontrolled severe infection, or other conditions with high risk of clinical deterioration).
- History of severe immediate-type hypersensitivity reaction to any medication required during the treatment process, or history of severe allergy to biologics (including antibiotics).
- Female patients who are pregnant or breastfeeding (preconditioning chemotherapy regimen poses potential risk to the fetus or infant).
- In the opinion of the investigator, the patient is unlikely to comply with all required study visits, procedures, or long-term follow-up; has poor willingness or ability to participate and cooperate fully; or has insufficient compliance (as judged by the patient and/or family).
- History of other malignancy, unless the patient has been disease-free and has received no antitumor therapy for at least 3 years (exceptions: non-melanoma skin cancer, and carcinoma in situ of the cervix, bladder, or breast).
- Receipt of a live vaccine within 6 weeks prior to initiation of the preconditioning regimen.
- Major surgery (excluding lymph node biopsy) within the past 14 days, or anticipated need for major surgery during the treatment period.
- Any other serious physical or psychiatric illness, or clinically significant laboratory abnormality, that may increase the risk associated with study participation, interfere with the interpretation of study results, or render the patient unsuitable for participation in the opinion of the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
About this study
Official title: Chidamide-based Combination With PD-1 Blockade: A Synergistic Strategy to Improve CAR-T Cell Therapy Outcomes for B-cell Lymphoma.
B-cell non-Hodgkin lymphoma (B-NHL) is one of the most common malignancies in China, with approximately 100,000 new cases diagnosed annually. Although immunochemotherapy, novel small-molecule targeted agents, and hematopoietic stem cell transplantation have significantly improved outcomes for patients with B-cell malignancies, nearly half of patients still experience drug resistance and relapse. In high-risk aggressive B-cell lymphoma, the 5-year survival rate remains around 50%. Previous clinical guidelines recommended autologous hematopoietic stem cell transplantation as first-line consolidation therapy for high-risk patients; however, multiple studies have demonstrated that even after autologous transplantation, nearly half of these patients relapse and succumb to the disease.
Chimeric antigen receptor T (CAR-T) cell therapy has achieved objective response rates of approximately 50% in relapsed/refractory lymphoma, particularly in B-cell subtypes. Nevertheless, limitations such as tumor immune antigen escape, immunosuppressive effects of the tumor microenvironment (TME) on CAR-T cells, and T-cell exhaustion continue to restrict the durability and efficacy of CAR-T-mediated cytotoxicity.
This study evaluates the incorporation of chidamide (an HDAC inhibitor) combined with a PD-1 inhibitor as maintenance therapy following CAR-T cell immunotherapy in patients with relapsed/refractory high-risk aggressive B-cell lymphoma. By implementing an "early intervention" strategy-prompt administration of CAR-T cell therapy after induction treatment for relapsed/refractory high-risk aggressive B-cell lymphoma-and subsequent maintenance with chidamide plus a PD-1 inhibitor, the approach aims to reduce relapse rates and improve overall survival. These strategies are intended to address the current unmet clinical need for improved outcomes in relapsed/refractory high-risk aggressive B-cell lymphoma, where prognosis remains poor despite existing therapies.
- Being tested
- CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance
- Keywords
- Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL), CAR-T therapy, Chidamide, PD-1 inhibitor
- Medical subject headings
- Recurrence, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor MaintenanceDrug
Patients will receive maintenance therapy consisting of Chidamide combined with a PD-1 inhibitor following CAR-T cell infusion. This intervention is designed to upregulate target antigen expression on tumor cells and mitigate antigen escape. By synergistically enhancing the cytotoxic activity and persistence of CAR-T cells, the regimen aims to reduce the risk of relapse and improve long-term clinical outcomes
| Study group | Role | What they receive |
|---|---|---|
| CAR-T + Chidamide/PD-1 Maintenance in R/R High-Risk DLBCL | Experimental | Not described Receives: Drug: CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year progression free survival rate (1-year-PFSR)
Measured: 1 years after treatment
Secondary outcomes (9)
overall survival (OS)
Measured: 2 years after treatment
progression free survival (PFS)
Measured: 2 years after treatment
time to progression (TTP)
Measured: 2 years after treatment
disease free survival (DFS)
Measured: 2 years after treatment
duration of response (DOR)
Measured: 2 years after treatment
event free survival (EFS)
Measured: 2 years after treatment
recurrence rate
Measured: 2 years after treatment
safety
Evaluate post-CAR-T cell infusion adverse events by analyzing the number of cases, incidence rates, and severity grades of the following key immunotherapy-related toxicities as recorded:
Cytokine release syndrome (CRS) Immune effector cell-associated neurotoxicity syndrome (ICANS) Hematologic toxicity Organ toxicity
and other immune-related adverse events associated with CAR-T cell therapy.
Measured: 2 years after treatment
CAR-T cell kinetic parameters in peripheral blood
CAR gene copy number Peak CAR-T cell concentration (Cmax) Time to peak concentration (Tmax) Area under the concentration-time curve from day 0 to day 28 (AUC₀-₂₈d / AUC₂₈d)
Measured: 2 years after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2026
- Study start15 May 2025
- Primary completion15 May 2027 (estimated)
- Study completion15 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daihong Liu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Daihong Liu, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07489989
- Sponsor's protocol ID
- M2025-222-01
- Status last verified
- May 2025
- First submitted
- 18 Mar 2026
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chidamide-based Combination With PD-1 Blockade: A Synergistic Strategy to Improve CAR-T Cell Therapy Outcomes for B-cell Lymphoma.
- ClinicalTrials.gov ID
- NCT07489989
- Acronym / sponsor ID
- M2025-222-01
- Keywords
- Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL), CAR-T therapy, Chidamide, PD-1 inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Daihong LiuUniversity, hospital or other
- Study start
- 15 May 2025 (actual)
- Primary completion
- 15 May 2027 (estimated)
- Study completion
- 15 May 2027 (estimated)
- First posted
- 24 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
B-cell non-Hodgkin lymphoma (B-NHL) is one of the most common malignancies in China, with approximately 100,000 new cases diagnosed annually. Although immunochemotherapy, novel small-molecule targeted agents, and hematopoietic stem cell transplantation have significantly improved outcomes for patients with B-cell malignancies, nearly half of patients still experience drug resistance and relapse. In high-risk aggressive B-cell lymphoma, the 5-year survival rate remains around 50%. Previous clinical guidelines recommended autologous hematopoietic stem cell transplantation as first-line consolidation therapy for high-risk patients; however, multiple studies have demonstrated that even after autologous transplantation, nearly half of these patients relapse and succumb to the disease.
Chimeric antigen receptor T (CAR-T) cell therapy has achieved objective response rates of approximately 50% in relapsed/refractory lymphoma, particularly in B-cell subtypes. Nevertheless, limitations such as tumor immune antigen escape, immunosuppressive effects of the tumor microenvironment (TME) on CAR-T cells, and T-cell exhaustion continue to restrict the durability and efficacy of CAR-T-mediated cytotoxicity.
This study evaluates the incorporation of chidamide (an HDAC inhibitor) combined with a PD-1 inhibitor as maintenance therapy following CAR-T cell immunotherapy in patients with relapsed/refractory high-risk aggressive B-cell lymphoma. By implementing an "early intervention" strategy-prompt administration of CAR-T cell therapy after induction treatment for relapsed/refractory high-risk aggressive B-cell lymphoma-and subsequent maintenance with chidamide plus a PD-1 inhibitor, the approach aims to reduce relapse rates and improve overall survival. These strategies are intended to address the current unmet clinical need for improved outcomes in relapsed/refractory high-risk aggressive B-cell lymphoma, where prognosis remains poor despite existing therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-T + Chidamide/PD-1 Maintenance in R/R High-Risk DLBCL | Experimental | Drug: CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- -
- Histologically or cytologically confirmed CD19 and/or CD22-positive large B-cell lymphoma (LBCL) according to the WHO 2016 classification, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), and related entities, with one of the following:
- Presence of high-risk features at initial diagnosis, defined as at least one of the following:
- Age 18 to 85 years, male or female.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Key exclusion criteria (15 listed)
- Patients eligible for CAR-T cell immunotherapy must NOT meet any of the following exclusion criteria:
- (Active HBV infection is defined as meeting all of the following: a) HBV DNA ≥ 2000 IU/mL; b) ALT ≥ 2 × upper limit of normal (ULN); c) hepatitis not attributable to other causes such as the underlying disease or medications. Patients with active HBV at initial diagnosis who achieve non-active HBV status after adequate anti-HBV treatment may be eligible under continued effective anti-HBV therapy.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor MaintenancePatients will receive maintenance therapy consisting of Chidamide combined with a PD-1 inhibitor following CAR-T cell infusion. This intervention is designed to upregulate target antigen expression on tumor cells and mitigate antigen escape. By synergistically enhancing the cytotoxic activity and persistence of CAR-T cells, the regimen aims to reduce the risk of relapse and improve long-term clinical outcomes | Drug | CAR-T + Chidamide/PD-1 Maintenance in R/R High-Risk DLBCL |
Primary outcome
1-year progression free survival rate (1-year-PFSR)
Time frame: 1 years after treatment
9 secondary outcomes
overall survival (OS)
Time frame: 2 years after treatment
progression free survival (PFS)
Time frame: 2 years after treatment
time to progression (TTP)
Time frame: 2 years after treatment
disease free survival (DFS)
Time frame: 2 years after treatment
duration of response (DOR)
Time frame: 2 years after treatment
event free survival (EFS)
Time frame: 2 years after treatment
recurrence rate
Time frame: 2 years after treatment
safety
Time frame: 2 years after treatment
CAR-T cell kinetic parameters in peripheral blood
Time frame: 2 years after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance in people with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL), run by Daihong Liu 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 31 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 24 Mar 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 Li-Ping Dou, Dr. (86-010-66937232, lipingruirui@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year progression free survival rate (1-year-PFSR) (time frame: 1 years after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Mar 2026.