NCT05879744进行中（未招募）1 期
A Phase 1, Open-label, Dose Escalation and Dose Expansion Study of CLN-978 in Patients With Relapsed/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 90
- 试验地点
- 6
- 主要终点
- Safety and tolerability of CLN-978 based on AEs, AESIs, and SAEs
研究概览
简要总结
CLN-978-001 is a Phase 1, open-label, dose escalation and dose expansion study of CLN-978 in patients with Relapse/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Eastern Cooperative Oncology Group (ECOG) PS ≤ 2
- •Documented diagnosis of one of the below CD19+ B-cell neoplasms according to WHO classification (Swerdlow et al., 2016) or WHO classification 2008:
- •Diffuse large B-cell lymphoma - de novo or transformed
- •High-grade B-cell lymphoma
- •Primary mediastinal large B-cell lymphoma
- •Follicular lymphoma
- •Mantle cell lymphoma
- •Marginal zone lymphoma (nodal, extranodal, or mucosa-associated)
- •Relapsed, progressive, and/or refractory disease after at least 2 lines of therapy.
- •For Part B expansion cohorts:
- •Cohort B1: R/R DLBCL that has relapsed after at least 2 prior therapies including a CD20 monoclonal antibody and anthracycline.
- •Cohort B2: R/R FL (grade 1-3a) that has relapsed after at least 2 prior therapies including CD20 monoclonal antibody and an alkylating agent.
- •Cohort B3: Other R/R B-NHL.
- •Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) scan or magnetic resonance imaging (MRI) AND baseline fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrating positive lesion(s) compatible with CT- or MRI-defined anatomical tumor sites.
- •Laboratory parameters including the following:
- •Lymphocyte count < 5 x 10^9/L
- •Platelet count ≥ 75 x 10^9/L
- •Absolute neutrophil count ≥ 1.0 x 10^9/L; growth factor support allowed in cases of documented bone marrow involvement
- •Hemoglobin ≥ 9 g/dL, with or without transfusion
- •Creatinine clearance ≥ 45 mL/min
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN), except patients with confirmed Gilbert's Syndrome
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN (unless attributed to hepatic involvement by lymphoma)
排除标准
- •Primary CNS lymphoma or known CNS involvement by lymphoma at study screening
- •Known past or current malignancy other than the inclusion diagnosis
- •Known clinically significant cardiac disease
- •Significant central nervous system disease
- •Prior organ allograft
- •Confirmed history or current autoimmune disorder or other disease requiring ongoing immune suppression
- •Active Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), or known Human Immunodeficiency Virus (HIV) infection
- •Live virus vaccines within 28 days of the first dose of CLN-978, during treatment, and until the end of last dose of CLN-978
- •Known active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection, including coronavirus disease of 2019 (COVID-19) infection, at the time of enrollment or within 7 days of the first dose of CLN-
- •Prior treatment with any of the following:
- •Allogeneic HSCT
- •Autologous HSCT within 30 days prior to the first dose of CLN-978
- •Chimeric antigen receptor T cell therapy (CAR-T) within 30 days prior to the first dose of CLN-978
- •Any investigational CD19 x CD3 T cell engager (TCE)
- •Unconjugated CD19 monoclonal antibody ≤ 4 weeks prior to the first dose CLN-978
- •Radio-conjugated or CD19 antibody-drug conjugate ≤ 12 weeks prior to the first dose CLN-978
- •Investigational or standard of care monoclonal antibodies, chemotherapy, or other investigational agent ≤ 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of CLN-978
- •Radiation therapy (XRT), with the exception of focal treatment for symptom control, ≤ 4 weeks of the first dose of CLN-978
- •Woman of child-bearing potential who is pregnant, breast-feeding, or plans to become pregnant
- •Male patients who plan to father a child or donate sperm within 120 days of last study drug administration
研究组 & 干预措施
Part A Dose Escalation
Experimental
Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts
干预措施: CLN-978 (Drug)
Part B Dose Expansion
Experimental
Patients with R/R DLBCL, R/R FL and other R/R B-NHL treated with CLN-978 at a dose selected from the Part A Dose Escalation arm.
干预措施: CLN-978 (Drug)
结局指标
主要结局
Safety and tolerability of CLN-978 based on AEs, AESIs, and SAEs
时间窗: 24 months
Incidence and severity of adverse events (AEs)/adverse events of special interest (AESIs)/serious adverse events (SAEs); incidence of dose interruptions and delays
Define dose regimen for CLN-978
时间窗: 24 months
Dose-limiting Toxicities (DLTs)
次要结局
- Assess preliminary efficacy of CLN-978 by duration of response in patients with selective histologies of R/R B-NHL(24 months)
- Select PK parameters of CLN-978: Cmax(24 months)
- Select PK parameters of CLN-978: AUC(24 months)
- Select PK parameters of CLN-978: Half-life(24 months)
- Assess preliminary efficacy of CLN-978 by overall response in patients with selective histologies of R/R B-NHL(24 months)
- Assess preliminary efficacy of CLN-978 by complete response in patients with selective histologies of R/R B-NHL(24 months)
- Immunogenicity of CLN-978 and potential impact on drug exposure(24 months)
研究者
研究点 (6)
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