A Phase 1b/2 Open-Label, Dose Escalation & Expansion Study of Orally Administered Viracta (VRx)-3996 & Valganciclovir in Subjects With Epstein-Barr Virus-Associated Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 52
- 主要终点
- Number (Proportion) of Participants With Adverse Events (AEs)
研究概览
简要总结
A two part, Phase 1b/2 study to define a recommended Phase 2 dose of VRx-3996 in combination with valganciclovir (Phase 1b) designed to evaluate the efficacy of this combination in relapsed/refractory Epstein-Barr Virus Associated Lymphoma (EBV+ lymphomas).
详细描述
The purpose of this study is to determine whether VRx-3996 in combination with valganciclovir is safe, determine the side effect profile, and to determine whether this therapy may help patients with EBV-related lymphomas. The study has two phases. Goals of the first phase include determining a safe and tolerable dose that can be administered in phase 2. Goals of the second phase include further evaluating the safety and tolerability of VRx-3996 in combination with valganciclovir, evaluating how the drugs are metabolized in the body, evaluating response rates and other exploratory objectives that will help the researchers evaluate how these drugs work in the body. Participants will receive daily oral doses of the two study drugs and will have multiple study visits where they will have blood collected, physical examinations, and other medical monitoring. Following completion of the Ph2, the study will enroll additional patients into a Tablet Pharmacokinetic (PK) cohort to investigate the PK parameters of the tablet formulation.
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
- •Relapsed/refractory, pathologically confirmed Epstein-Barr Virus positive (EBV+) lymphoid malignancy or lymphoproliferative disease
- •Absence of available therapy with reasonable likelihood of cure or significant clinical benefit
- •Adequate hematologic, hepatic and renal function as defined by laboratory assessment
排除标准
- •Known primary central nervous system (CNS) lymphoma
- •Known CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks
- •Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- •Refractory graft versus host disease (GvHD) not responding to treatment
- •Known active hepatitis B virus infection
- •Circulating hepatitis C virus on quantitative polymerase chain reaction (qPCR)
- •Known history of human herpes virus (HHV)-6 chromosomal integration
- •Known history of HIV infection
研究组 & 干预措施
Phase 1b Dose Escalation
VRx-3996 (cohort 1) and valganciclovir
VRx-3996 (cohort 2) and valganciclovir
VRx-3996 (cohort 3) and valganciclovir
VRx-3996 (cohort 4) and valganciclovir
VRx-3996 (cohort 5) and valganciclovir
干预措施: VRx-3996 and valganciclovir (Combination Product)
Phase 2 Expansion - Capsule
VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)
干预措施: VRx-3996 and valganciclovir (Combination Product)
Phase 2 Expansion - Tablet
VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)
干预措施: VRx-3996 and valganciclovir (Combination Product)
结局指标
主要结局
Number (Proportion) of Participants With Adverse Events (AEs)
时间窗: Up to approximately 2 years
Number (percentage) of patients experiencing at least one treatment-emergent adverse event, defined as those untoward medical events with onset after the first dose of study drug or existing events that worsened after the first dose during the study
Number (Proportion) of Participants With Dose-Limiting Toxicities (DLTs) in Phase 1b
时间窗: Cycle 1 (28 days)
Number (percentage) of patients experiencing a DLT during the first cycle (28 days) of study treatment in Phase 1b, defined as an adverse event (AE) or clinically significant abnormal laboratory value that was at least possibly related to study drugs and was not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness. In addition, to be considered a DLT, the AE had to meet at least one of the following criteria: * Grade 4 anemia unexplained by underlying disease * Grade 4 febrile neutropenia * Grade 4 neutropenia lasting \>5 days * Any other Grade 4 hematologic toxicity (thrombocytopenia, neutropenia, febrile neutropenia, anemia) of any duration * Grade 4 or higher tumor lysis syndrome * Grade 3 or higher thrombocytopenia (with or without bleeding) * Any requirement for platelet transfusion * Grade 3 or higher non-hematologic toxicity despite adequate supportive care * Results in a dose hold of \>7 consecutive days
Overall Response Rate
时间窗: Up to approximately 2 years
Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the Lugano 2014 criteria (Cheson, Bruce D. et al. J Clin Oncology 2014;32(27):3059-68), where CR included complete metabolic response (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions, and PR included partial metabolic response (reduced FDG uptake compared with baseline) or radiologic response (target lesions ≤ 50% decrease in the sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites)
次要结局
- Half-life of Valganciclovir(Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1)
- Duration of Response(Up to approximately 2 years)
- Time to Response(Up to approximately 2 years)
- Progression-Free Survival(Up to approximately 2 years)
- Disease Control Rate(Up to approximately 2 years)
- Overall Survival(Up to approximately 2 years)
- Cmax (ng/mL) of VRx-3996(Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1)
- Cmax (ng/mL) of Valganciclovir(Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1)
- Area Under Curve (AUC) 0-t of VRx-3996(Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1)
- AUC 0-t of of Valganciclovir(Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1)
- Half-life of VRx-3996(Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1)