A Phase 2b, Open-label, Multicenter, Randomized Parallel-Group, Two-Stage, Study of an Immunotherapeutic Treatment DPX-Survivac and Pembrolizumab, With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (VITALIZE)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 102
- 试验地点
- 49
- 主要终点
- Objective response rate (ORR) in each of the study arms
研究概览
简要总结
This is a Phase 2b, randomized, open label study to assess the safety and efficacy of DPX-Survivac and pembrolizumab, with and without low-dose cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.
详细描述
This is a Phase 2b, randomized, open label study to assess the safety and efficacy of DPX-Survivac and pembrolizumab, with and without low-dose cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.
The study will enroll up to 102 subjects. Eligible subjects will be randomized (1:1) to receive:
- Arm 1: DPX-Survivac, pembrolizumab and intermittent, low-dose CPA; or,
- Arm 2: DPX-Survivac and pembrolizumab
All subjects will receive two 0.5 mL doses of DPX-Survivac 3 weeks apart on day 7 (D7) and D28 followed by up to twelve 0.1 mL doses of DPX-Survivac, 8 weeks apart (Q8W).
All subjects will receive pembrolizumab intravenously (IV) at a flat dose of 200 mg starting at D7 and on day 1 of each 3-week cycle thereafter (i.e., D28, D49, D70 etc.) (Q3W).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥ 18 years of age who are willing and able to provide written informed consent
- •Have an ECOG performance status of ≤
- •Subjects with an ECOG performance status of 2 may be enrolled with Medical Monitor approval.
- •Pathologically confirmed diagnosis of DLBCL, as defined by the 2016 World Health Organization classification including DLBCL NOS high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, Epstein-barr virus (EBV) positive DLBCL, and T cell rich B cell lymphoma (TCRBCL). Subjects with DLBCL transformed from indolent lymphoma (except for Richter's transformation) are eligible.
- •Subjects must have progressive disease following at least two (2) lines of prior systemic therapy for DLBCL; prior treatment must have included an anthracycline and rituximab (or another CD20-targeted agent).
- •Subjects must have failed or be ineligible for ASCT or CAR-T
- •Have at least one bi-dimensionally measurable lesion per Lugano (2014)
- •Willing to provide pre-treatment and on-treatment tumor biopsy tissue.
- •Meet protocol-specified laboratory requirements
- •Life expectancy > 3 months.
排除标准
- •Primary CNS lymphoma or active secondary CNS involvement and/or lymphomatous meningitis
- •Chemotherapy, immunotherapy, major surgery, or investigational agent treatment within 28 days of D0 or 5 half-lives, whichever is shorter
- •Radiotherapy within 14 days of day 0
- •Autologous stem cell transplant (ASCT) within ˂100 days prior to D0
- •Chimeric antigen receptor T cell (CAR-T) therapy within ˂28 days prior to D0
- •Diagnosis of immunodeficiency disorder or history of active autoimmune disease that has required systemic treatment in the past 2 years
- •Uncontrolled significant active infections (controlled Hepatitis B, Hepatitis C, or HIV may be eligible)
- •Prior history of malignancy other than eligible lymphoma sub-types, unless the subject has been free of the disease for ≥ 2 years prior to the start of study treatment
研究组 & 干预措施
Arm 1: DPX-Survivac, pembrolizumab, CPA
Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. CPA will be self-administered 50 mg BID for 7 days on and 7 days off starting on D0.
干预措施: DPX-Survivac (Drug)
Arm 1: DPX-Survivac, pembrolizumab, CPA
Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. CPA will be self-administered 50 mg BID for 7 days on and 7 days off starting on D0.
干预措施: Pembrolizumab (Drug)
Arm 1: DPX-Survivac, pembrolizumab, CPA
Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. CPA will be self-administered 50 mg BID for 7 days on and 7 days off starting on D0.
干预措施: CPA (Drug)
Arm 2: DPX-Survivac, pembrolizumab
Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. Subjects randomized to Arm 2 will not receive CPA.
干预措施: DPX-Survivac (Drug)
Arm 2: DPX-Survivac, pembrolizumab
Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. Subjects randomized to Arm 2 will not receive CPA.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Objective response rate (ORR) in each of the study arms
时间窗: Approximately 24 months
Centrally evaluated using Lugano (2014)
次要结局
- Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms(Approximately 24 months)
- Time to response in each of the study arms(Approximately 24 months)
- Duration of response (DOR) in each of the study arms(Approximately 24 months)
- Progression-Free Survival in each of the study arms(Approximately 48 months)
- Complete response (CR) rate in each of the study arms(Approximately 24 months)
- Changes in Patient Reported Outcomes using the FACT-Lym Assessment(Approximately 24 months)
- Disease control rate (DCR) in each of the study arms(Approximately 24 months)
- Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment(Approximately 24 months)