A Phase III, Multicentre, Open-Label, Randomised Study Evaluating the Efficacy and Safety of R-mini-CHOP x2 Followed by AZD0486 Versus R-mini-CHOP x6 in Elderly or Unfit Participants With Newly Diagnosed Large B-cell Lymphoma (SOUNDTRACK-D2)
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
- 68
- 主要终点
- SRI - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.
研究概览
简要总结
The purpose of this study is to measure the efficacy and safety of R-mini-CHOP × 2 followed by AZD0486 compared with R-mini-CHOP × 6 in elderly or unfit participants newly diagnosed with LBCL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 130 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants are either 80 years of age or older, OR 65 to 79 years of age or older and classified as unfit per sGA, and otherwise not considered candidates for full-dose R-CHOP per investigator assessment;
- •Histologically confirmed diagnosis of previously untreated LBCL as per WHO-HEM5 (excluding plasmablastic lymphoma) and follicular large cell lymphoma;
- •FDG-avid and measurable disease as per Lugano and Ann Arbor staging;
- •Stage I bulky (7.5 cm and greater) to Stage IV;
- •ECOG performance status 0 to 2;
- •Adequate bone marrow, liver, renal and cardiac function.
- •The above is a summary, other inclusion criteria details may apply.
- •As judged by the investigator, any evidence of diseases which make it undesirable for the participant to participate in the study, or that would jeopardise compliance with the protocol
- •Diagnosis of post-transplant lymphoproliferative disease, plasmablastic lymphoma, Richter's transformation, prior history of or concurrent indolent lymphoma (including de novo transformed or composite lymphoma).
- •History of CNS involvement by their B-NHL or history of clinically relevant CNS medical condition
- •Known history of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
- •Active or uncontrolled infection
- •Major cardiac abnormalities
- •Prior anti-lymphoma therapy except for corticosteroids for symptom control
- •Requires chronic immunosuppressive therapy for active autoimmune/inflammatory condition, with some exceptions
- •The above is a summary, other
排除标准
- •details may apply.
研究组 & 干预措施
Phase III Arm A: R-mini-CHOP and AZD0486
2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP3D.
干预措施: R-mini-CHOP (Drug)
Phase III Arm B: R-mini-CHOP
6 cycles of R-mini-CHOP per SoC regimen.
干预措施: R-mini-CHOP (Drug)
Phase III Arm A: R-mini-CHOP and AZD0486
2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP3D.
干预措施: AZD0486 (Drug)
Safety Run in: R-mini-CHOP and AZD0486
2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP2D.
干预措施: AZD0486 (Drug)
Safety Run in: R-mini-CHOP and AZD0486
2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP2D.
干预措施: R-mini-CHOP (Drug)
结局指标
主要结局
SRI - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.
时间窗: Up to 1 year
Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
SRI - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.
时间窗: Up to 1 year
AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
SRI - Determination of the recommended Phase III dose (RP3D)
时间窗: Up to 1 year
The RP3D will be the dose of AZD0486 selected for the Phase 3 part based on safety data compiled during the Safety Run-In part
Phase 3 - To demonstrate the superiority of R-mini-CHOP x2 followed by AZD0486 compared to R-mini-CHOP x6 regimen.
时间窗: Up to 7 years
Progression-free Surival (PFS), based on Lugano 2014 Response Criteria.
次要结局
- Phase 3 - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.(Up to 7 years)
- Phase 3 - Time to First Subsequent Therapy or Death (TFST)(Up to 7 Years)
- Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.(Up to 7 years)
- Safety Run-In and Phase 3 - ORR(Up to 7 years)
- Safety Run-In and Phase 3 - CR Rate(Up to 7 years)
- Safety Run-In and Phase 3 - DoR(Up to 7 years)
- Safety Run-In and Phase 3 - DoCR(Up to 7 years)
- Safety Run-In and Phase 3 - PFS(Up to 7 years)
- Safety Run In and Phase 3 - OS(Up to 7 years)
- Phase 3 - Time from randomisation to second progression or death (PFS2)(Up to 7 years)
- Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: serum concentration of study drug(Up to 7 years)
- Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Maximum plasma concentration of the study drug (Cmax).(Up to 7 years)
- Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Concentration of study drug reached before next dose (Ctrough).(Up to 7 years)
- Safety Run-In and Phase 3 - To determine the immunogenicity of AZD0486(Up to 7 years)
- Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6(Up to 7 years)
- Phase 3 - Efficacy evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6(Up to 7 years)