An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 102
- 试验地点
- 62
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas
详细描述
Patients with EBV-associated lymphomas have inferior outcomes with standard-of-care therapies compared to those with EBV-negative disease. Nanatinostat is a selective class I HDAC inhibitor which induces EBV lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. This open-label, multicenter, multinational, single-arm, Phase 2 basket study employs a Simon's 2-stage design to allow termination of enrollment into cohorts where treatment appears futile, and will include the following cohorts of patients with EBV+ relapsed/refractory lymphomas:
- Diffuse large B-cell lymphoma (DLBCL)
- Extranodal natural killer/T-cell lymphoma (ENKTL)
- Peripheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS)
- Hodgkin lymphoma (HL)
- Post-transplant lymphoproliferative disorders (PTLD)
- Human immunodeficiency virus (HIV)-associated lymphomas (HIV-L)
- EBV+ lymphomas other than the above
The study was terminated prematurely and did not reach its target enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •EBV+ DLBCL, NOS and PTCL, NOS, and AITL: Relapsed/refractory disease following 1 or more prior systemic therapy(ies) with curative intent.
- •For EBV+ PTLD patients: Relapsed/refractory disease following 1 prior therapy and must have received at least 1 course of an anti-CD20 immunotherapy. For patients with EBV+ PTLD only, age 12 years and older and weighing greater than 40 kg (Adolescent, Adult, Older Adult) are allowed
- •For other EBV+ relapsed/refractory lymphoma: Following at least 1 course of an anit-CD20 immunotherapy and at least 1 course of anthracycline-based chemotherapy (unless contraindicated)
- •No available therapies in the opinion of the Investigator
- •Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T therapy
- •Measurable disease per Cheson 2007
- •ECOG performance status 0, 1, 2
- •Adequate bone marrow function
排除标准
- •Presence or history of CNS involvement by lymphoma
- •Systemic anticancer therapy or CAR-T within 21 days
- •Antibody (anticancer) agents within 28 days
- •Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant
- •Less than 90 days from prior allogeneic transplant.
- •Daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1
- •Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir.
- •Active infection requiring systemic therapy (excluding viral upper respiratory tract infections).
研究组 & 干预措施
Nanatinostat with Valganciclovir
Patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week with valganciclovir 900 mg orally once daily.
Up to 10 PTCL patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week.
干预措施: Nanatinostat in combination with valganciclovir (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
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 2007 International Working Group (IWG) criteria, where CR included complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy with all lymph nodes and nodal masses having regressed on computed tomography to normal size, and PR included at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, no increase should have been observed in the size of other nodes, liver, or spleen, and splenic and hepatic nodules must have regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.
次要结局
- Duration of Response (DOR)(Up to approximately 2 years)
- Time to Next Anti-Lymphoma Treatment (TTNLT)(Up to approximately 3 years)
- Time to Progression (TTP)(Up to approximately 3 years)
- Progression-Free Survival (PFS)(Up to approximately 3 years)
- Overall Survival (OS)(Up to approximately 3 years)
- Number (Percentage) of Participants With Adverse Events (AEs)(Up to approximately 2 years)
- Pharmacokinetic (PK) Parameter - Time to Maximum Plasma Concentration [Tmax](Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days))
- Pharmacokinetic (PK) Parameter - Maximum Plasma Concentration [Cmax](Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days))
- Pharmacokinetic Parameter - Area Under the Plasma Concentration-Time Curve [AUC0-t](Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days))
- Pharmacokinetic (PK) Parameter - Half-Life [t1/2](Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days))