The Study of Zanubrutinib Combined With Rituximab in the Treatment of Secondary Hemophagocytic Lymphohistiocytosis in B-cell Lymphoma
概览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- The First Affiliated Hospital of Soochow University
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- response rate of HLH after 4 weeks of treatment
概览
简要总结
For patients who met the inclusion criteria, treatment regimens were administered: Rituximab 375 mg/m², intravenously, once weekly for 4 weeks.
Zanubrutinib 160 mg, orally, twice daily for 4 weeks. Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
详细描述
For patients who met the inclusion criteria, treatment regimens were administered:
Rituximab 375 mg/m², intravenously, once weekly for 4 weeks (may be extended or adjusted according to clinical response).
Zanubrutinib: 160 mg, orally, twice daily for 4 weeks as for rutuximab. Dose can be adjusted or extended according to tolerance and efficacy.
When ≥3 grade hematological or intolerable non-hematological toxicity occur, zanubrutinib or rituximab will be suspended, and the dose will be reduced or resumed according to the toxicity grade after recovery. The dose of zanubrutinib should be adjusted according to the manufacturer's label with concomitant use of strong CYP3A inhibitor/inducer.
Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
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
- •According to the diagnostic criteria of HLH-04, the patients meet the diagnostic criteria of HLH;
- •HLH patients with definite or highly suspected evidence of B-cell lymphoma; Or HLH patients whose bone marrow flow cytometry show an increased proportion of CD20-positive B cells;
- •Age of 14-80 years old, both sexes;
- •Predicted survival beyond 1 month;
- •Baseline serum creatinine ≤1.5 times ULN; Fibrinogen could be corrected to ≥0.6g/L by infusion;
- •Negative serum HIV antibody; Either negative for HCV antibodies or positive for HCV antibodies but negative for HCV RNA. HBV surface antigen and HBV core antibody were negative. If any of the above was positive, HBV DNA titer in peripheral blood should be tested, and the titer was less than 1×10\^3 copies /ml;
- •Left ventricular ejection fraction (LVEF) ≥50% measured by echocardiography;
- •The patient have no serious and uncontrollable infections, such as pulmonary infection, intestinal infection, and sepsis;
- •Women of childbearing age must be confirmed to be not pregnant by pregnancy test and willing to take effective measures to prevent pregnancy during the study period and ≥12 months after the last dose; Pregnant and lactating women cannot participate; All male subjects took contraceptive measures during the trial and ≥3 months after the last dose;
- •Patients should be able to sign informed consent.
排除标准
- •Patients with known severe allergy to rituximab, zanubrutinib, or other BTK inhibitors;
- •Severe active infections (including bacterial, viral or fungal infections) or uncontrolled co-infections;
- •Severe organ dysfunction including NYHA class III-IV heart failure or severe arrhythmia; Liver function: ALT or AST \>5 times the upper limit, or severe cirrhosis; Renal function: CrCl \<30 mL/min or severe renal insufficiency;
- •Combined with other malignant tumors and the expected survival time was less than 3 months;
- •Have received other experimental drugs and had not completed the drug washout period;
- •Pregnant or lactating women, or unwilling to use effective contraception;
- •any condition that would not be suitable for participation in the study or that might affect adherence, follow-up, or safety assessment, as judged by the investigator.
研究组 & 干预措施
intervention group
Rituximab 375 mg/m², intravenously, once weekly for 4 weeks (may be extended or adjusted according to clinical response).
Zanubrutinib: 160 mg, orally, twice daily for 4 weeks as for rutuximab. Dose can be adjusted or extended according to tolerance and efficacy.
When ≥3 grade hematological or intolerable non-hematological toxicity occur, zanubrutinib or rituximab will be suspended, and the dose will be reduced or resumed according to the toxicity grade after recovery. The dose of zanubrutinib should be adjusted according to the manufacturer's label with concomitant use of strong CYP3A inhibitor/inducer.
Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
干预措施: Rituximab (Drug)
intervention group
Rituximab 375 mg/m², intravenously, once weekly for 4 weeks (may be extended or adjusted according to clinical response).
Zanubrutinib: 160 mg, orally, twice daily for 4 weeks as for rutuximab. Dose can be adjusted or extended according to tolerance and efficacy.
When ≥3 grade hematological or intolerable non-hematological toxicity occur, zanubrutinib or rituximab will be suspended, and the dose will be reduced or resumed according to the toxicity grade after recovery. The dose of zanubrutinib should be adjusted according to the manufacturer's label with concomitant use of strong CYP3A inhibitor/inducer.
Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
response rate of HLH after 4 weeks of treatment
时间窗: after 4 weeks
RR will be evaluated according to the response evaluation criteria recommended by the International Histiocyte Society.
OS at week 8
时间窗: after 8 weeks
overall survival after 8 weeks of treatment
次要结局
- OS(at 4/8/12/24 weeks)
- AE(till the end of 4 weeks)
研究者
Xuefeng He
professor
The First Affiliated Hospital of Soochow University