Golcadomide, Poseltinib, and Rituximab for Optimized Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma (Go-Pro-DLBCL)
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
概览
简要总结
This trial is a proof-of-concept, pilot study, phase I/II clinical trial aimed at generating preliminary data on the combination of golcadomide, poseltinib, and rituximab.
详细描述
This is a single arm, open-label, phase I/II trial of Poseltinib in combination with golcadomide and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. Considering (1) the combination of BTK inhibitor, lenalidomide, and rituximab has demonstrated efficacy in R/R DLBCL, (2) golcadomide, a CELMoD, exhibits potent immunomodulatory activity compared to IMiDs such as lenalidomide, and (3) poseltinib is a potent, covalent BTK inhibitor with more than twice the selectivity for BTK compared to other BTK inhibitors, we anticipate that this combination will yield promising results in R/R DLBCL.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must satisfy the following criteria to be enrolled in the study
- •Subject is ≥ 19 years of age at the time of signing the informed consent form (CRF).
- •Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- •Subject has histologically confirmed (per local evaluation) diagnosis of aggressive large B-cell lymphoma according to 2022 WHO classification, specifically:
- •A. DLBCL, NOS (including GCB and ABC types) B. DLBCL/high grade B-cell lymphoma, with MYC and BCL2 rearrangements C. High grade B-cell lymphoma, NOS D. T-cell/histiocyte-rich large B-cell lymphoma E. EBV-positive DLBCL
- •Relapsed or refractory disease following at least 1 prior line of therapy (must include an anthracycline-based treatment), and ineligible for hematopoietic stem cell transplantation.
- •Subjects must have measurable disease defined by at least one fluorodeoxyglucose (FDG)-avid lesion for FDG-avid subtype and one bi-dimensionally measurable (\> 1.5 cm in longer diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Subject must have the following laboratory values:
排除标准
- •The presence of any of the following will exclude a subject from enrollment:
- •Subject who has had prior treatment with golcadomide.
- •Subject who has had prior treatment with BTK inhibitor.
- •Subject has life expectancy ≤ 2 months.
- •Subject has received any of the following:
- •A. Major surgery (as defined by the Investigator) within 28 days of initiating study treatment. Subjects must have recovered from any clinically significant effects of recent surgery.
- •B. Radiation therapy within 28 days prior to initiating study treatment. C. Use of any systemic anti-cancer treatment (approved or investigational) within 28 days or 5 half-lives prior to starting study treatment, whichever is shorter. (Participation in another interventional clinical trial concurrent with this study is not permitted, except for those who have completed treatment with the prior investigational agent(s) and are currently in long-term follow up)
- •Subject has previously received solid organ transplantation.
- •Subject has undergone allogeneic SCT within 1 year prior to initiating study treatment or autologous SCT within 3 months prior to initiating study treatment.
- •A. Subject who had received prior SCT should not have any Grade \>1 treatment-related toxicity.
研究组 & 干预措施
Treatment arm
golcadomide + poseltinib + rituximab (GoPro)
干预措施: Golcadomide + Poseltinib + Rituximab (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: The evaluation time frame is from baseline up to 18 months.
The primary endpoint was the Overall response rate, defined as the proportion of participants who achieved either CMR or PMR according to the Lugano criteria 2014. The primary analysis will be conducted in the efficacy evaluable population. A one-sample exact binomial test (one-sided, α=0.05) will be used to compare the observed ORR against the null hypothesis value of 30%. If the lower bound of the exact one-sided 95% CI for the observed ORR exceeds 30%, the null hypothesis will be rejected, suggesting that the combination therapy demonstrates meaningful efficacy.
次要结局
- Progression-free survival (PFS)(The evaluation time frame extends from baseline to 1 year and 3 year after the last patient in.)
- Overall survival (OS)(The evaluation time frame extends from baseline to 3 years after the last patient in.)
- Complete metabolic response (CMR) rate(The evaluation time frame is from baseline up to 18 months.)
- Duration of response (DOR)(The evaluation time frame extends from baseline to 1 year and 3 years after the last patient in.)
- Recommended poseltinib dose(through study part 1 completion, up to 8 weeks.)
- Safety(from C1D1 to end of trial, assessed up to 3 years after the last patient in.)
研究者
JaMin Byun
M.D. Ph.D.
Seoul National University Hospital