Application of Zanubrutinib-based Combination Regimens in the Treatment of Newly-diagnosed Diffuse Large B-cell Lymphoma: A Phase II, Prospective, Single-center, Single-arm Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Best complete remission rate (CRR)
研究概览
简要总结
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Currently, the first-line treatment regimen based on R-CHOP can only achieve clinical cure for 50% to 60% of patients. Previous studies have shown that patients with high-risk factors have a poor response to R-CHOP treatment and need further improvement. These high-risk factors include: IPI score ≥2 points, ABC subtype, double-expressing lymphoma, double-hit lymphoma, CD5-positive DLBCL, MCD subtype, N1 subtype, A53 subtype, extranodal lesions ≥2, special site involvement, such as central nervous system CNS, breast, testis, ovary, uterus, bone marrow, vitreoretinal, paraspinal, paranasal sinuses and intravascular, etc. Patients with DLBCL accompanied by high-risk factors also have a significantly increased risk of secondary CNS infiltration during recurrence. In previous RCHOP+X research strategies, only the combination of polatuzumab achieved significant 2-year PFS benefits in the overall population. None of the other studies achieved significant PFS benefits in the overall population. Therefore, the latest version of the CSCO guidelines recommends the Pola-R-CHP regimen as the first-line treatment for primary DLBCL. However, there is still considerable room for improvement in the survival of DLBCL patients with high-risk factors in clinical practice. Therefore, the strategy of the Pola-R-CHP-based combined with X regimen in high-risk DLBCL patients with specific risk factors can be explored subsequently.
The Phoenix study for young double expression of lymphoma patients, R - CHOP combined with BTK inhibitors can significantly improve the patient's survival, the subsequent omics data analysis indicates that MCD subtype, N1 subtypes and BN2 subtype can significantly benefit from BTK inhibitors. In addition, given that the proportion of MCD subtypes is high in most extranodal DLBCL patients and secondary CNS involvement is prone to occur, BTK inhibitors can effectively penetrate the blood-brain barrier (BBB) and have both preventive and therapeutic effects on CNS lesions. Therefore, exploring the application of BTK inhibitor zanubrutinib combined with R-CHOP or Pola-R-CHP regimens in high-risk DLBCL patients with specific risk factors (or zanubrutinib combined with rituximab and high-dose MTX in primary central nervous system DLBCL) has good application prospects. It is conducive to further improving the prognosis of such high-risk patients. Therefore, this study aimed to explore the efficacy and safety of the BTK inhibitor zanubrutinib combined with Pola-R-CHP regimen (or zanubrutinib combined with rituximab and high-dose MTX in primary central nervous system DLBCL, etc.) in patients of DLBCL with specific risk factors (IPI score two points or more, ABC subtypes, double expressor lymphoma, double hit lymphoma, CD5 positive DLBCL, MCD subtypes, N1 subtypes, A53 subtypes, extranodal lesions of 2 or more, special locations involved, such as the central nervous system (CNS, breast, testes).
详细描述
This study aimed to explore the efficacy and safety of the BTK inhibitor zanubrutinib combined with Pola-R-CHP regimen (or zanubrutinib combined with rituximab and high-dose MTX in primary central nervous system DLBCL, etc.) in patients of DLBCL with specific risk factors (IPI score two points or more, ABC subtypes, double expressor lymphoma, double hit lymphoma, CD5 positive DLBCL, MCD subtypes, N1 subtypes, A53 subtypes, extranodal lesions of 2 or more, special locations involved, such as the central nervous system (CNS, breast, testes).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed diffuse large B-cell lymphoma (DLBCL);
- •Have a "measurable lesions" ;
- •Have at least one of the following risk factors, including: IPI score ≥2 points, ABC subtype, double-expressor lymphoma, double-hit lymphoma, CD5-positive DLBCL, MCD subtype, N1 subtype, A53 subtype, extranodal lesions ≥2, special site involvement, such as central nervous system CNS, breast, testis, ovary, uterus, bone marrow, vitreoretinal, paraspinal, paranasal sinuses and intravascular, etc.
- •ECOG score 0-3;
- •Expected survival time for 3 months or more;
- •White blood cell count ≥3 x 10e9/L, the platelet count≥50 x 10e9/L; 1.5 mg/dL or less of serum creatinine, creatinine clearance≥50 ml/min; ALT, AST 3 x ULN or less, total bilirubin 2 x ULN or less.
排除标准
- •(the subject should not have any one of the following):
- •currently suffering from other malignant tumor;
- •ever received any treatments for lymphoma, except for short-term use of corticosteroids;
- •Allergic to any kind of study drug;
- •Active infection or uncontrol of HBV infection, HIV/AIDS or other serious infectious diseases;
- •Pregnancy and lactation women of childbearing age and are reluctant to take contraception subjects;
- •Researchers think that the subject does not fit to participate in this study.
研究组 & 干预措施
treatment arm (for DLBCL patients witout central nervous system lesions)
zanubrutinib combined with Pola-R-CHP regimen: zanubrutinib 160mg bid d1-d21/C1-C6; polatuzumab 1.8mg/kg d1/C1-C6; rituximab 375mg/㎡, iv, d1/C1-C6; cyclophosphamide 750mg/㎡, iv, d1/C1-C6; doxorubicin 50mg/㎡, iv, d1/C1-C6; predinisone 60mg/㎡ d1-5/C1-C6.
干预措施: Zanubrutinib+Pola-R-CHP (Drug)
结局指标
主要结局
Best complete remission rate (CRR)
时间窗: From the start of the first cycle of treatment up to 24 weeks (when all six cycles of treatment was completed)
Response assessment was done after every two cycles of treatment. Best CRR was defined as the CRR during all the six cycles of treatment.
次要结局
- best overall response rate (ORR)(From the start of the first cycle of treatment up to 24 weeks (when all six cycles of treatment was completed).)
- Two-year progression free survival (PFS) rate(From the start of the first cycle of treatment up to 24 months after initiation of treatment for the last enrolled patient.)
- Two-year overall survival (OS) rate(From the start of the first cycle of treatment up to 24 months after initiation of treatment for the last enrolled patient.)
研究者
LIANG WANG
Director of department of hematology, Beijing Tongren Hospital
Beijing Tongren Hospital