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Prophylactic Strategies for Mitigating Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma

Therapeutic Strategies for Preventing Central Nervous System Recurrence in Patients With Central High-risk Diffuse Large B-cell Lymphoma: A Prospective, Multicenter, Non-randomized Cohort Study

Background: The central nervous system (CNS) recurrence rate of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is as high as 15% - 20%, and the prognosis is extremely poor once it occurs. Current intrathecal injection and high-dose methotrexate prophylaxis are ineffective and have significant toxicity. Lenalidomide, BTK inhibitors, and sidaribine all can penetrate the blood-brain barrier, and each has shown a signal of reducing the risk of CNS recurrence in previous studies, but there is still a lack of prospective concurrent comparative data.

Objective: To preliminarily evaluate the efficacy and safety of using these three oral drugs (lenalidomide, BTK inhibitors, and sidaribine) in combination with first-line immunotherapy chemotherapy for high-risk DLBCL patients to prevent CNS recurrence during the same period or after chemotherapy.

Method: This study is a phase II exploratory, open-label, non-randomized concurrent multi-cohort study, combined with historical external controls. A total of 87 patients with DLBCL diagnosed by histopathology and having at least one CNS high-risk factor (CNS-IPI ≥ 4 points, specific extranodal involvement (such as testis, breast, adrenal gland, kidney, uterus, bone marrow, bone), and extranodal invasion sites ≥ 2) are planned to be enrolled. Patients can choose to enter the lenalidomide group, BTK inhibitor group (ibrutinib, zanubrutinib, or obinutinib) or sidaribine group based on their disease characteristics and economic conditions, and the preventive treatment lasts for 1 year. The primary endpoint is the 2-year cumulative CNS recurrence rate (competitive risk model analysis), and the secondary endpoints include progression-free survival time, overall survival time, CNS disease-free survival time, and safety.

Significance: This study is the first to prospectively compare the CNS preventive value of these three drugs with different mechanisms in high-risk DLBCL patients, which is expected to provide key exploratory data for this field and lay the foundation for future confirmatory studies.

Studieoversikt

Studietype

Intervensjonell

Registrering (Antatt)

87

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

      • Beijing, Kina
        • Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College,
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 80 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • 1. The diagnosis of diffuse large B-cell lymphoma, non-specific type or indolent lymphoma that has undergone large B-cell transformation, has been confirmed by histopathological examination; according to the 2016/2022 WHO classification, advanced B-cell lymphoma with dual expression/dual therapy is allowed; 2. Age between 18 and 80 years; 3. Proposed or currently receiving first-line standard immunotherapy, and planning to complete at least 6 cycles; 4. Baseline examination including brain-enhanced MR and cerebrospinal fluid cytology/flow cytometry by lumbar puncture was conducted to rule out CNS invasion; 5. Has at least one high-risk factor for CNS recurrence: CNS-IPI score ≥ 4 points; or involving specific extranodal sites (such as testis, breast, adrenal gland, kidney, uterus, bone marrow, high-risk bones); or extranodal invasion sites ≥ 2; 6. ECOG physical status score 0-2; 7. The subject can understand the study protocol and is willing to participate in this study, and signs a written informed consent.

Exclusion Criteria:

  • 1. Any evidence indicating the presence of CNS parenchymal, meningeal or intraocular lymphoma at the time of enrollment; 2. Having a history of myocardial infarction within 6 months prior to enrollment; suffering from New York Heart Association (NYHA) grade 3 or 4 congestive heart failure, or having a history of NYHA grade 3 or 4 congestive heart failure in the past, unless the left ventricular ejection fraction (LVEF) was ≥ 50% in the echocardiography (ECHO) screening conducted within 1 month before entering the study; 3. Pregnant or lactating women (baseline pregnancy test positive or not undergoing pregnancy test for women of childbearing age. Postmenopausal women must be at least 12 months post-menopause); 4. Having an uncontrollable infection; 5. Any other situation that the investigator deems the patient is not suitable to participate in this trial.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Forebygging
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Patients with diffuse large B-cell lymphoma who meet the criteria for high-risk central nervous syst

At least one of the following high-risk factors for CNS recurrence must be present: CNS-IPI score ≥ 4; or involving specific extranodal sites (such as testis, breast, adrenal gland, kidney, uterus, bone marrow, high-risk bones); or having ≥ 2 extranodal invasion sites.

The dosage of lenalidomide is 25mg each time, once daily, taken with food or on an empty stomach. It is administered continuously from day 1 to day 21, with each 28-day period as one cycle. For elderly patients (aged > 75 years) or those with reduced renal function (creatinine clearance rate < 60 ml/min), the starting dose is reduced to 15mg. During the lenalidomide treatment, aspirin 100mg once daily or low molecular weight heparin is used to prevent thrombosis. The preventive drugs can be initiated simultaneously with chemotherapy or started 4-6 weeks after the completion of chemotherapy for continuous prevention, which is determined by the investigator. After the chemotherapy, it enters the single-agent maintenance stage, with the total prevention medication duration of 1 year (counting from the first administration), or until disease progression, intolerable toxicity occurs, or informed consent is withdrawn.

The BTK inhibitor group includes drugs such as Zanubrutinib, Obinutinib, and Ibrutinib. Their specific usage is as follows: Zanubrutinib, 160mg each time, taken twice daily before or after meals; Ibrutinib, 560mg each time, once daily, taken before or after meals; Obinutinib, 150mg each time, once daily, taken before or after meals. Preventive drugs can be initiated simultaneously with chemotherapy or started 4-6 weeks after the completion of chemotherapy, depending on the decision of the researchers. After the completion of chemotherapy, it enters the single-agent maintenance stage. The total preventive medication duration is 1 year (counting from the first administration), or until disease progression, intolerable toxicity occurs, or informed consent is withdrawn.

Chidamide is administered at a dose of 20mg every 21 days. The medication is taken on days 1, 4, 8, and 11 of each cycle, 30 minutes after meals. The preventive medication can be initiated simultaneously with chemotherapy or started 4-6 weeks after the completion of chemotherapy, depending on the decision of the investigator. After the chemotherapy is completed, it enters the single-agent maintenance phase. The total preventive medication duration is 1 year (counting from the first administration), or until disease progression, intolerable toxicity occurs, or informed consent is withdrawn.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Two-year cumulative recurrence rate of CNS
Tidsramme: The cumulative proportion of patients who experienced central nervous system recurrence within 2 years after starting the trial drug treatment.

The cumulative proportion of patients who experienced central nervous system recurrence within 2 years after starting the trial drug treatment.

The cumulative proportion of patients who experienced central nervous system recurrence within 2 years after starting the trial drug treatment.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-Free Survival (PFS)
Tidsramme: From enrollment to the end of treatment until 2 years

From the time the experimental drug was administered until the date of the first recorded disease progression (in the central nervous system or systemically), recurrence, or death for any reason.

From enrollment to the end of treatment until 2 years
Overall survival (OS)
Tidsramme: From enrollment to the end of treatment until 1 years

OS was defined as the time from cytarabine and thalidomide initiation to death or last follow-up.

From enrollment to the end of treatment until 1 years

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
FACT-G (Functional Assessment of Cancer Therapy-General)
Tidsramme: From enrollment to the end of treatment until 3 years

Score of FACT-G (Functional Assessment of Cancer Therapy-General)

From enrollment to the end of treatment until 3 years
Correlation between circulating free DNA (cfDNA) and efficacy
Tidsramme: From enrollment to the end of treatment until 3 years

Correlation between circulating free DNA (cfDNA) and efficacy

From enrollment to the end of treatment until 3 years

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. november 2026

Primær fullføring (Antatt)

31. oktober 2028

Studiet fullført (Antatt)

1. november 2028

Datoer for studieregistrering

Først innsendt

30. oktober 2026

Først innsendt som oppfylte QC-kriteriene

30. oktober 2026

Først lagt ut (Faktiske)

4. november 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

4. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

30. oktober 2026

Sist bekreftet

1. oktober 2026

Mer informasjon

Begreper knyttet til denne studien

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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