Efficacy and Safety of Methotrexate (MTX) or Thiotepa (for MTX-Intolerant Patients) Combined With R-CHOP and Orelabrutinib in the Treatment of Systemic DLBCL With Central Nervous System Involvement
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 23
- 主要终点
- Complete Response (CR)
研究概览
简要总结
This study is designed as an open-label, prospective, single-arm, single-center trial aimed at evaluating the efficacy and safety of MTX or Thiotepa combined with Orelabrutinib and standard chemotherapy regimens in the treatment of DLBCL patients with central nervous system involvement.
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
- 14 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fully understand the study and voluntarily sign the informed consent form.
- •Age: 14-80 years.
- •Expected survival of more than 3 months, as determined by the investigator.
- •Pathologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL) of B-cell origin through pathology or flow cytometry.
- •Central nervous system (CNS) involvement, confirmed by at least one of the following:
- •Symptoms related to CNS involvement.
- •Abnormal findings on imaging.
- •Pathological evidence (positive cerebrospinal fluid cytology, positive brain lesion biopsy or positive cerebrospinal fluid ctDNA).
- •Any non-hematologic toxicity related to prior treatments must have resolved to Grade 1 or normal levels (per NCI CTCAE Version 5.0), except for alopecia.
- •Bone marrow and organ function must meet the following criteria (without blood transfusion, G-CSF administration, or pharmacological correction within 14 days prior to screening):
- •Bone marrow function:
- •Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L. 2)Platelet count ≥ 50 × 10⁹/L. 3)Hemoglobin ≥ 60 g/L.
- •Liver function:
- •Total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN if liver metastasis is present).
- •AST and ALT ≤ 2.5 × ULN (≤ 5.0 × ULN if liver metastasis is present).
- •Coagulation function:
- •International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
- •Renal function: Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance rate ≥ 30 mL/min (calculated using the Cockcroft-Gault formula): Male: Cr (mL/min) = (140 - age) × weight (kg) / [72 × serum creatinine (mg/dL)]. Female: Cr (mL/min) = (140 - age) × weight (kg) / [85 × serum creatinine (mg/dL)].
- •Women of childbearing potential (WOCBP) and men with reproductive potential must agree to use effective contraception during the study and for 3 months after discontinuing treatment.
- •Good compliance, with willingness to adhere to visit schedules, dosing regimens, laboratory tests, and other study procedures.-
排除标准
- •Contraindications to any of the drugs included in the treatment regimen.
- •History of active liver disease, including viral or other hepatitis or liver cirrhosis (Hepatitis B is defined as HBV-DNA exceeding the upper limit of normal; active Hepatitis C is defined as seropositive for HCV antibodies, but patients with HCV-RNA negative results can be included).
- •Human immunodeficiency virus (HIV) infection.
- •Congestive heart failure classified as greater than NYHA Class II by the New York Heart Association; history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within the past six months.
- •Congenital long QT syndrome or QTc > 480 ms (Note: QTc must be calculated using Friederica's formula: QTcF = QT / (RR)^0.33).
- •Pregnant or breastfeeding women, or those planning to become pregnant during the study.
- •History of confirmed neurological or psychiatric disorders, or a history of substance abuse or drug addiction.
研究组 & 干预措施
MTX or Thiotepa(for MTX-Intolerant Patients) Combined with R-CHOP and Orelabrutinib therapy group
For DLBCL patients with central nervous system involvement, administer methotrexate (MTX) or thiotepa (for patients intolerant to MTX) combined with R-CHOP and orelabrutinib for six cycles, with each cycle lasting 21 days. Following the completion of induction therapy, proceed with consolidation therapy. If the patient undergoes autologous stem cell transplantation, maintain orelabrutinib for one year; if not, maintain orelabrutinib for two years unless disease progression or intolerable toxicity occurs.
干预措施: Orelabrutinib (Drug)
MTX or Thiotepa(for MTX-Intolerant Patients) Combined with R-CHOP and Orelabrutinib therapy group
For DLBCL patients with central nervous system involvement, administer methotrexate (MTX) or thiotepa (for patients intolerant to MTX) combined with R-CHOP and orelabrutinib for six cycles, with each cycle lasting 21 days. Following the completion of induction therapy, proceed with consolidation therapy. If the patient undergoes autologous stem cell transplantation, maintain orelabrutinib for one year; if not, maintain orelabrutinib for two years unless disease progression or intolerable toxicity occurs.
干预措施: RCHOP+MTX or Thiotepa (Drug)
结局指标
主要结局
Complete Response (CR)
时间窗: the end of Cycle 6 (up to approximately 24 weeks)
The CR rate is defined as the percentage of participants with CR, on the basis of investigator assessments, according to 2014 Lugano criteria.
次要结局
- Progression-Free Survival (PFS)(2 years)
- Overall Survival (OS)(up to approximately 4 years)
- The Overall Response Rate (ORR)(the end of Cycle 6 (up to approximately 24 weeks))