- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT07917624
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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: XinXin XX Cao
- Puhelinnumero: +86-18618315968
- Sähköposti: caoxinxin@126.com
Opiskelupaikat
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Beijing, Kiina
- 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,
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Ottaa yhteyttä:
- XinXin XX Cao, doctor
- Puhelinnumero: +86-18618315968
- Sähköposti: caoxinxin@126.com
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Ennaltaehkäisy
- Jako: Ei satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
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Kokeellinen: 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. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Two-year cumulative recurrence rate of CNS
Aikaikkuna: The cumulative proportion of patients who experienced central nervous system recurrence within 2 years after starting the trial drug treatment.
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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.
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Progression-Free Survival (PFS)
Aikaikkuna: From enrollment to the end of treatment until 2 years
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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
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Overall survival (OS)
Aikaikkuna: From enrollment to the end of treatment until 1 years
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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
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Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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FACT-G (Functional Assessment of Cancer Therapy-General)
Aikaikkuna: From enrollment to the end of treatment until 3 years
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Score of FACT-G (Functional Assessment of Cancer Therapy-General) |
From enrollment to the end of treatment until 3 years
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Correlation between circulating free DNA (cfDNA) and efficacy
Aikaikkuna: From enrollment to the end of treatment until 3 years
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Correlation between circulating free DNA (cfDNA) and efficacy |
From enrollment to the end of treatment until 3 years
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Yhteistyökumppanit ja tutkijat
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Neoplasmat
- Immuunijärjestelmän sairaudet
- Neoplasmat histologisen tyypin mukaan
- Lymfaattiset sairaudet
- Lymfoproliferatiiviset häiriöt
- Immunoproliferatiiviset häiriöt
- Lymfooma, non-Hodgkin
- Lymfooma, B-solu
- Lymfooma
- Hemic- ja imusuutteet
- Lymfooma, suuri B-solu, diffuusi
- Orgaaniset kemikaalit
- Heterosykliset yhdisteet, 1-rengas
- Heterosykliset yhdisteet
- Heterosykliset yhdisteet, 2-rengas
- Heterosykliset yhdisteet, sulatettu rengas
- Karboksyylihapot
- Piperidiinit
- Ftalimidit
- Ftaalihapot
- Hapot, karbosyklinen
- Piperidonit
- Isoindoles
- Lenalidomidi
- N- (2-amino-5-fluorobentsyyli) -4- (n- (pyridiini-3-akryyli) aminometyyli) bentsamidi
Muut tutkimustunnusnumerot
- 26/174-0500
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