A Phase III, Randomised, Open-label, Multicentre, Study of Surovatamig as Consolidation Therapy Versus Observation After First-line Induction Therapy in Participants With Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma With Unmutated IGHV (SOUNDTRACK-C1)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 420
- 试验地点
- 50
- 主要终点
- DOSRI- Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the therapeutic benefit and safety of subcutaneous (SC) Surovatamig monotherapy as consolidation therapy in patients with Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) with unmutated IGHV (uIGHV).
详细描述
This is a Phase III global, randomised, open-label, multicentre study. The study will consist of 2 sequential parts- the Dose Optimisation and Safety Run-in part and the Phase-III part.
During the dose optimisation and safety run-in part, Surovatamig will be initiated in 2 dose levels. This part will help to determine the recommended phase III dose (RP3D) of Surovatamig to be used in Phase III part. Phase III would comprise of 2 arms, Arm A where the Surovatamig dose (RP3D) will be administered as a consolidation therapy (post standard of care [SOC] induction therapy) and Arm B where participants will be observed. In Phase 3 participants will be randomized in a 1:1 ratio to Arm A or Arm B.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 18 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of CLL/SLL with genomic features defined by unmutated IGHV.
- •Treatment received and response at the end of 1L (first-line) finite therapy.
- •Participants with SLL (except those in CR in Phase III part) must have measurable disease (nodal or extranodal) with at least one measurable target lesion.
- •ECOG performance status of 0 to
- •Adequate haematologic, liver, renal and cardiac function.
- •Female participants: must be either women not of childbearing potential or must use a highly effective form of contraception.
- •Male participants who intend to be sexually active with females of childbearing potential must agree to use barrier contraception (eg, condoms).
排除标准
- •Suspected or confirmed transformation of CLL/SLL to a more aggressive form of lymphoma (ie, Richter's transformation, prolymphocytic leukaemia, or DLBCL).
- •Evidence of active or history of Central Nervous System (CNS) involvement by CLL/SLL.
- •History of or ongoing confirmed progressive multifocal leukoencephalopathy.
- •Participants who have any concurrent or history of malignancy.
- •Participants with:
- •Active or uncontrolled infection (including Epstein-Barr virus-EBV) requiring systemic therapy.
- •Participants with known history of Heamophagocytic lymphohistiocytosis (HLH).
- •Human Immunodeficiency Virus (HIV) infection, or participants with chronic or active infection with Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
- •Major cardiac abnormalities.
- •Prior CLL/SLL-specific therapies.
- •Requires chronic immunosuppressive therapy for active autoimmune/inflammatory condition or prior allogeneic stem cell or solid organ transplant.
- •Major surgical procedure.
- •Known hypersensitivity to surovatamig or any of the excipients of the product.
研究组 & 干预措施
DOSRI-Surovatamig Dose 2
Participants will receive Surovatamig Dose 2 SC for 6 cycles (each cycle is 28 days in length).
干预措施: Surovatamig (Drug)
Phase III-Arm A: Surovatamig SC
Participants will receive Surovatamig at RP3D subcutaneously for 6 cycles (each cycle is 28 days in length).
干预措施: Surovatamig (Drug)
Dose Optimisation and Safety run-in (DOSRI)- Surovatamig Dose 1
Participants will receive Surovatamig Dose 1 subcutaneously (SC) for 6 cycles (each cycle is 28 days in length).
干预措施: Surovatamig (Drug)
Phase III-Arm B: Observation
Participants will undergo observation for 24 weeks.
结局指标
主要结局
DOSRI- Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 5 years
To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV.
Phase III- Progression Free Survival (PFS)
时间窗: Until disease progression or death (up to 5 years)
PFS is defined as the time from date of randomisation until disease progression or death due to any cause, whichever occur first based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria, as assessed by independent review committee (IRC).
DOSRI- Number of participants with study intervention discontinuations, dose reductions and dose delays due to AEs
时间窗: Up to 5 years
To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV.
次要结局
- Objective Response Rate (ORR)(Up to 5 years)
- Complete Response rate (CR rate)(Up to 5 years)
- Duration of response (DoR)(Up to 5 years)
- DOSRI- PFS(Until disease progression or death (up to 5 years))
- Overall Survival (OS)(Up to 5 years)
- Serum concentrations of Surovatamig(At pre-defined intervals from date offirst dose (C1D1) up to 30 days from last dose (approximately 5 years))
- Maximum concentration observed (Cmax)(At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years))
- Time to Maximum Concentration (tmax)(At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years))
- Trough concentration (Ctrough)(At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years))
- Number of participants with Anti-drug antibodies (ADA)(At predefined intervals from the date of first dose to approximately 5 years)
- Phase III- PFS(Until disease progression or death (up to 5 years))
- Phase III- Number of participants with AEs and SAEs(Up to 5 years)