Efficacy and Safety of Chidamide Combined With PD-1 Inhibitor as Maintenance Therapy Following CAR-T Cell Treatment With TP53-Mutated Large B-Cell Lymphoma (LBCL) (CP-LBCL)
A Prospective, Single-Arm, Single-Center Study on the Efficacy and Safety of Chidamide Combined With PD-1 Inhibitor as Maintenance Therapy Following CAR-T Cell Treatment in Patients With TP53-Mutated Large B-Cell Lymphoma (LBCL)
This is a study for patients with a type of blood cancer called large B-cell lymphoma (LBCL) who have a mutation in a gene called TP53. This gene mutation often makes the cancer harder to treat with standard therapies.
CAR T-cell therapy is a treatment that uses a patient's own immune cells to fight cancer. However, some patients relapse (the cancer comes back) after CAR T-cell therapy. This study will test whether taking two drugs - chidamide (a tablet taken by mouth) and a PD-1 inhibitor (given by intravenous infusion) - as maintenance therapy after CAR T-cell therapy can help keep the cancer from coming back.
Participants in this study will receive CAR T-cell therapy, followed by maintenance treatment with chidamide combined with a PD-1 inhibitor. Doctors will closely monitor participants for how well the treatment works and for any side effects. The study will take place at a single hospital, and all participants will receive the same treatment.
The main goal of the study is to find out if this maintenance treatment is effective and safe for patients with TP53-mutant large B-cell lymphoma.
Tutkimuksen yleiskatsaus
Tila
Tila
Ehdot
Ehdot
Interventio / Hoito
Interventio / Hoito
Opintotyyppi
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Ilmoittautuminen
Vaihe
Vaihe
- Vaihe 4
Yhteystiedot ja paikat
Opiskeluyhteys
Opiskeluyhteys
- Nimi: Aibin Liang, Prof,MD,phD
- Puhelinnumero: +86-21-66113037
- Sähköposti: zll3032@163.com
Opiskelupaikat
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Kiina, 200065
- Rekrytointi
- Shanghai Tongji Hospital, Tongji University School of Medicine
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Ottaa yhteyttä:
- Ping Li, MD
- Puhelinnumero: +86-21-66113037
- Sähköposti: lilyforever76@126.com
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
- Histologically or pathologically confirmed relapsed/refractory aggressive large B-cell lymphoma;
- Documented TP53 mutation confirmed by genetic testing;
- Age 18-70 years, inclusive; both sexes eligible;
- Patient has elected and is able to complete a CAR T-cell therapy regimen;
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
- Life expectancy of at least 3 months;
- Adequate major organ function (within 7 days prior to initiation of study treatment):
(1) Hepatic function: ALT/AST <3 × the upper limit of normal (ULN), and total bilirubin ≤34.2 μmol/L; (2) Renal function: serum creatinine <220 μmol/L; (3) Pulmonary function: oxygen saturation ≥95% on room air; (4) Cardiac function: left ventricular ejection fraction (LVEF) ≥40%;
8. Patient is able to swallow and take oral medication;
9. Patient has adequate peripheral superficial venous access suitable for intravenous infusion;
10. Voluntary participation in the clinical study; full awareness and understanding of the study; written informed consent provided; willingness and ability to comply with and complete all study procedures.
Exclusion Criteria:
- Pregnant or breastfeeding women, or patients of childbearing potential who are unwilling to use contraception;
- Concurrent malignancy of another organ system requiring treatment;
- Uncontrolled coagulation disorder or active bleeding;
- Known human immunodeficiency virus (HIV) infection;
- Currently receiving other antineoplastic therapy (for lymphoma or any other type of tumor);
- Psychiatric illness, or any other known or suspected inability to fully comply with the study protocol;
- Inability to swallow capsules, or any disease significantly affecting gastrointestinal function, such as malabsorption syndrome, prior bariatric (weight-reduction) surgery, inflammatory bowel disease, or partial or complete bowel obstruction;
- Any other concurrent and uncontrolled medical condition that, in the investigator's judgment, would affect the patient's participation in the study.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseiden lukumäärä
Aseet ja interventiot
Osallistujaryhmä / ArmOsallistujaryhmä / Arm |
Interventio / HoitoInterventio / Hoito |
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Kokeellinen: Chidamide + PD-1 Inhibitor Maintenance
Participants will receive CAR T-cell therapy as planned by the treating physician. After CAR T-cell infusion, participants will receive maintenance therapy with oral chidamide combined with an intravenous PD-1 inhibitor, continued until disease progression, unacceptable toxicity, withdrawal of consent, or completion of the planned maintenance duration. Treatment response and adverse events will be monitored regularly. |
Chidamide is an oral subtype-selective histone deacetylase (HDAC) inhibitor. Participants will take chidamide orally at the dose of 20mg twice week and schedule specified in the protocol, starting after CAR T-cell infusion, and continuing until disease progression, unacceptable toxicity, or completion of the planned maintenance duration. Sintilimab is a humanized anti-programmed death-1 (PD-1) monoclonal antibody administered by intravenous infusion. Participants will receive it at the dose of 200mg/21days, in combination with oral chidamide, until disease progression, unacceptable toxicity, or completion of the planned maintenance duration. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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PFS
Aikaikkuna: From date of CAR-T cell infusion (Day 0) to date of documented disease progression or death from any cause, assessed every 3 months for up to 24 months]
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Progression-Free Survival |
From date of CAR-T cell infusion (Day 0) to date of documented disease progression or death from any cause, assessed every 3 months for up to 24 months]
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OS
Aikaikkuna: From date of CAR-T cell infusion (Day 0) to date of death from any cause, assessed every 3 months for up to 24 months]
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Overall Survival |
From date of CAR-T cell infusion (Day 0) to date of death from any cause, assessed every 3 months for up to 24 months]
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ORR
Aikaikkuna: From date of CAR-T cell infusion (Day 0) to Day 90 (±14 days), assessed by PET-CT or MRI according to Lugano 2014 criteria
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Overall Response Rate |
From date of CAR-T cell infusion (Day 0) to Day 90 (±14 days), assessed by PET-CT or MRI according to Lugano 2014 criteria
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Yhteistyökumppanit ja tutkijat
Sponsori
Sponsori
Julkaisuja ja hyödyllisiä linkkejä
Yleiset julkaisut
- Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.
- McGowan E, Lin Q, Ma G, Yin H, Chen S, Lin Y. PD-1 disrupted CAR-T cells in the treatment of solid tumors: Promises and challenges. Biomed Pharmacother. 2020 Jan;121:109625. doi: 10.1016/j.biopha.2019.109625. Epub 2019 Nov 13.
- Ni Y, Zhang Q, Tang X, Li X, Ye S, Lu Y, Liang A, Li P. Upregulation of CD19 by low-dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma. Discov Oncol. 2025 Jan 24;16(1):84. doi: 10.1007/s12672-025-01810-1.
- Zhu M, Han Y, Gu T, Wang R, Si X, Kong D, Zhao P, Wang X, Li J, Zhai X, Yu Z, Lu H, Li J, Huang H, Qian P. Class I HDAC inhibitors enhance antitumor efficacy and persistence of CAR-T cells by activation of the Wnt pathway. Cell Rep. 2024 Apr 23;43(4):114065. doi: 10.1016/j.celrep.2024.114065. Epub 2024 Apr 4.
- Wang C, Tan JYM, Chitkara N, Bhatt S. TP53 Mutation-Mediated Immune Evasion in Cancer: Mechanisms and Therapeutic Implications. Cancers (Basel). 2024 Sep 3;16(17):3069. doi: 10.3390/cancers16173069.
- St Martin Y, Franz JK, Agha ME, Lazarus HM. Failure of CAR-T cell therapy in relapsed and refractory large cell lymphoma and multiple myeloma: An urgent unmet need. Blood Rev. 2023 Jul;60:101095. doi: 10.1016/j.blre.2023.101095. Epub 2023 Apr 29.
- Sermer D, Batlevi C, Palomba ML, Shah G, Lin RJ, Perales MA, Scordo M, Dahi P, Pennisi M, Afuye A, Silverberg ML, Ho C, Flynn J, Devlin S, Caron P, Hamilton A, Hamlin P, Horwitz S, Joffe E, Kumar A, Matasar M, Noy A, Owens C, Moskowitz A, Straus D, von Keudell G, Rodriguez-Rivera I, Falchi L, Zelenetz A, Yahalom J, Younes A, Sauter C. Outcomes in patients with DLBCL treated with commercial CAR T cells compared with alternate therapies. Blood Adv. 2020 Oct 13;4(19):4669-4678. doi: 10.1182/bloodadvances.2020002118.
- Westin J, Sehn LH. CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift? Blood. 2022 May 5;139(18):2737-2746. doi: 10.1182/blood.2022015789.
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Opiskelun aloitus
Ensisijainen valmistuminen (Arvioitu)
Ensisijainen valmistuminen
Opintojen valmistuminen (Arvioitu)
Opintojen valmistuminen
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Ensimmäinen Lähetetty
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin päivitys julkaistu
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
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