NCT07839247尚未招募2 期
Zanubrutinib Plus Lenalidomide for Frail Elderly Patients With Newly Diagnosed Primary CNS Lymphoma: a Prospective, Single-arm, Phase II Clinical Study
Xiaohui Ren1 个研究点 分布在 1 个国家目标入组 33 人开始时间: 2026年9月25日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- CRR
研究概览
简要总结
This is a prospective, single-arm, phase II clinical study evaluating the efficacy and safety of Zanubrutinib (a BTK inhibitor) plus Lenalidomide (an immunomodulatory drug) in frail elderly patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The study plans to enroll 33 patients who are aged ≥ 70 years and classified as frail, a population for whom standard first-line treatment regimens, high-dose methotrexate-based chemotherapy, may be "unfit". This study includes screening phase, induction phase, consolidation phase and maintenance phase. The screening period is defined as within 1 week prior to the first dose. During induction, participants will receive Zanubrutinib 160 mg orally twice daily continuously and Lenalidomide 25 mg orally once daily on days 1-21 of each 28-day cycle for three cycles. Participants who achieve a partial response (PR) or complete response (CR) after induction will receive three additional 28-day consolidation cycles of the same regimen. Participants who achieve a CR after consolidation will continue maintenance treatment with Zanubrutinib and Lenalidomide until disease progression. Treatment response will be assessed throughout the study using the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria and assessed every 3 months. The primary endpoint is the complete response rate (CRR) at the end of induction therapy. Secondary endpoints include overall response rate (ORR) at the end of induction therapy, CRR and ORR at the end of consolidation therapy, One-year and two-year progression-free survival (PFS) rates, Duration of response (DOR), overall survival (OS), adverse event (AE) and serious adverse event (SAE). Exploratory liquid-biopsy analyses will be performed to evaluate treatment response and prognosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 70 years.
- •patients classified as "Frail"according to the simplified Geriatric Assessment (sGA):
- •-ADL ≤ 4 residual functions, or
- •IADL ≤ 5 residual functions, or
- •CIRS: ≥ 1 comorbidity of grade 3-4 or > 8 comorbidities of grade 2, or
- •Age ≥ 80 years with "UNFIT" profile "UNFIT" profile: ADL = 5 residual functions or IADL = 6-7 residual functions, or CIRS: 0 comorbidity of grade 3-4 and 5-8 comorbidities of grade
- •Voluntary provision of written informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Considered able to safely undergo lumbar puncture.
- •Life expectancy of ≥ 3 months, as judged by the investigator.
- •Histologically confirmed diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system (CNS).
- •Hematologic function: absolute neutrophil count ≥ 1.5 x 10^9/L, hemoglobin ≥ 90 g/L, and platelet count ≥ 80 x 10^9/L.
- •Hepatic function: serum total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and serum alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x ULN.
- •Renal function: creatinine clearance ≥ 30 mL/min, as estimated using the Cockcroft-Gault formula, or serum creatinine ≤ 1.5 x ULN.
- •Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
- •Female participants of childbearing potential must have a negative pregnancy test within 7 days before the first dose and agree not to donate oocytes for reproductive purposes throughout the treatment and follow-up periods. Their male sexual partners must use condoms during sexual intercourse.
- •Male participants with female partners of childbearing potential must use condoms during sexual intercourse throughout the study and refrain from donating or cryopreserving sperm during this period.
- •Participants with stable and adequately controlled comorbidities may be enrolled, including those with hypertension (blood pressure ≤ 160/100 mmHg), type 2 diabetes mellitus (HbA1c ≤ 8%), or mild coronary artery disease without myocardial infarction within the preceding 6 months.
排除标准
- •Any disease or condition that may impair drug absorption (e.g., active inflammatory gastrointestinal disease, active gastric ulcer, chronic diarrhea, dysphagia, prior gastrectomy, gastroparesis, or short bowel syndrome).
- •Known hypersensitivity to zanubrutinib, lenalidomide, or any excipient contained in either drug.
- •Active bleeding within 1 month before treatment; a need for therapeutic anticoagulation during the study (e.g., warfarin or other vitamin K antagonists); or any condition associated with an increased risk of bleeding or coagulopathy (e.g., high-risk esophageal varices or active ulcer disease).
- •High risk of thrombosis.
- •Concurrent participation in another interventional clinical study (participation in noninterventional observational studies is permitted).
- •Major surgery within 4 weeks before treatment or an incompletely healed surgical incision.
- •Treatment with systemic corticosteroids within 4 weeks before treatment.
- •Another active malignancy or a history of another malignancy within 5 years before the initiation of study treatment, except for malignancies adequately treated with curative intent, such as basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast.
- •Receipt of any vaccine, including but not limited to a vaccine against COVID-19, influenza, pneumonia, herpes zoster, or hepatitis B, within 4 weeks before the first dose.
- •Requirement for treatment with a moderate or strong CYP3A4/5 inhibitor or inducer within 2 weeks before the first dose or during the study;
- •Stroke or intracranial hemorrhage within 6 months before the first dose.
- •Known liver disease, including but not limited to alcoholic liver disease, cirrhosis, active hepatitis B virus (HBV) infection (detectable HBV DNA), active hepatitis C virus (HCV) infection (detectable HCV RNA), or other active hepatitis. Participants with HBV DNA below the limit of detection or cured HCV infection are not excluded. Participants with HBV or HCV infection may be enrolled after antiviral therapy, provided that HBV DNA is below the limit of detection or HCV RNA is undetectable, as applicable.
- •Active syphilis.
- •Human immunodeficiency virus (HIV) infection
- •Epstein-Barr virus (EBV) infection
- •An active infection requiring systemic treatment or unexplained fever with a body temperature ≥ 38.5℃ within 1 week before treatment;
- •Any of the following cardiac or cardiovascular criteria:
- •（1）A heart rate-corrected QT interval calculated using Fridericia's formula (QTcF) > 470 ms in females or > 450 ms in males, or other risk factors for QT-interval prolongation or arrhythmic events (e.g., hypokalemia or a personal or family history of long QT syndrome); （2）A clinically significant arrhythmia or other cardiovascular disease requiring clinical intervention, including but not limited to acute myocardial infarction, unstable angina, or coronary artery bypass grafting within 6 months before treatment; congestive heart failure of New York Heart Association (NYHA) class II or higher; left ventricular ejection fraction (LVEF) < 50%; hypertension not controlled with medication (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg); atrial fibrillation of European Heart Rhythm Association (EHRA) class ≥ 2b; or primary cardiomyopathy.
- •18. Prior organ transplantation or allogeneic stem cell transplantation.
- •19. Prior or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, or radiation pneumonitis considered by the investigator to render the patient unsuitable for the study.
- •20. An autoimmune disease requiring systemic treatment within the previous 2 years.
- •21. Incomplete clinical data (e.g., no pathology report or inability to undergo MRI or PET/CT assessment).
- •22. Pregnant (positive pregnancy test before dosing) or breastfeeding.
- •23. Any other disease, psychiatric disorder, metabolic abnormality, physical examination finding, or clinically significant laboratory abnormality that, in the investigator's judgment, may compromise the participant's adherence to the study requirements, expose the participant to an unacceptable risk, interfere with the interpretation of the study results, or otherwise render the participant unsuitable for treatment with the study drugs.
- •24. Any other circumstance that, in the investigator's judgment, renders the patient unsuitable for participation in the study.
研究组 & 干预措施
Zanubrutinib plus lenalidomide
Experimental
干预措施: Zanubrutinib (Drug)
Zanubrutinib plus lenalidomide
Experimental
干预措施: Lenalidomide (Drug)
结局指标
主要结局
CRR
时间窗: From the first day of treatment to the completion of induction treatment (3 months)
complete response rate
次要结局
- CRR(From the first day of treatment to the completion of consolidation treatment (6 months))
- ORR(From the first day of treatment to the completion of induction treatment (3 months))
- ORR(From the first day of treatment to the completion of consolidation treatment (6 months))
- PFS(1-year and 2-year PFS rates, and the time interval from the start of treatment to tumor progression or death from any cause (up to 24 months).)
- DOR(Time from documentation of tumor response (CR or PR) to disease progression or death (up to 24 months).)
- OS(The percentage of surviving patients out of the total number of included patients (specifically assessed as 1- and 2-year OS rate in study objectives) (up to 24 months).)
- AE(From the first day of treatment until 30 days after the last treatment (up to 24 months))
- SAE(from the first day of treatment until 30 days after the last treatment (up to 24 months))
研究者
Xiaohui Ren
Deparment of neurosurgery, Beijing tiantan hospital
Beijing Tiantan Hospital
研究点 (1)
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