An Open-Label, Single-arm, Phase Ib/II Study of AEB071 (a Protein Kinase C Inhibitor) and Everolimus (mTOR Inhibitor) in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 4
- 主要终点
- Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle
研究概览
简要总结
Study of the safety and efficacy of AEB071 and EVEROLIMUS in patients with CD79-mutant or ABC subtype Diffuse Large B-Cell Lymphoma.
The trial did not progress into Phase II due to the suboptimal tolerability of the combination treatment of sotrastaurin and everolimus in the Phase Ib part of the study. There were no serious safety concerns associated with this combination.
详细描述
This is a Phase Ib dose escalation and Phase II study in patients with DLBCL harboring mutations in CD79A/B or of the ABC subtype. Pre-screening for mutations in CD79A/B or the ABC subtype will be required, as it is anticipated that both patient groups may receive clinical benefit from the combination of AEB071 and EVEROLIMUS.
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
- •Male or female ≥18 years of age.
- •Diffuse DLBCL with activating mutations in CD79 (A or B subunits) or ABC-subtype DLBCL (CD79 wildtype or CD79 mutant). DLBCL that arose from transformed indolent lymphoma is allowed.
- •Prior treatment and relapse following chemotherapy and autologous bone marrow or stem cell transplant. Patients who are not transplant eligible or who did not respond to chemotherapy may be considered for the study following a single regimen of chemotherapy such as R-CHOP or R-EPOCH. There is no limit to number of prior therapies allowed.
- •May be treated with localized radiation as long as measurable or evaluable disease remains at untreated sites.
- •WHO performance status of ≤
- •A representative FFPE tumor sample must be available for molecular testing along with a corresponding pathology report. An archival tumor sample may be submitted. However, if not available, a new tumor biopsy obtained for the purpose of this study must be submitted instead.
排除标准
- •Treatment with strong inducers or inhibitors (medications and herbal supplements) of cytochrome P450 3A4/5 (CYP3A4/5), or CYP3A4/5 substrates with a QT prolongation risk that cannot be discontinued at least 7 half-lives (or if the half-life is unknown,14 days) prior to study drug treatment.
- •Impaired cardiac function or clinically significant cardiac diseases.
- •Impairment of GI function or GI disease that could interfere with the absorption of AEB071 or everolimus.
- •Severe systemic infections, current or within the two weeks prior to initiation of AEB
- •Kown history of HIV.
- •Poorly controlled diabetes as defined by a fasting serum glucose > 2.0 x ULN.
- •Evidence of current CNS involvement.
- •Significant symptomatic deterioration of lung function.
研究组 & 干预措施
AEB071 and EVEROLIMUS
AEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study
干预措施: AEB071 (Drug)
AEB071 and EVEROLIMUS
AEB071 and EVEROLIMUS will be taken together in this open-label non-randomized study
干预措施: Everolimus (Drug)
结局指标
主要结局
Phase Ib- Incidence of dose limiting toxicities (DLT) during the first cycle
时间窗: 12 months
Estimate the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the AEB071and EVEROLIMUS combination therapy in patients with DLBCL.
Phase II- Overall response rate (ORR) = complete response (CR) + partial response (PR) according to the non-Hodgkin's Lymphoma International Working Group criteria
时间窗: 12 months
Assess the preliminary evidence for anti-tumor activity at RP2D for AEB071 and EVEROLIMUS in patients with a CD79 mutation and those wild-type for the mutation but of the ABC subtype
次要结局
- Duration of Response (DOR)(24 months)
- Overall Survival (OS)(24 months)
- Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs) assessments of clinical laboratory values and vital sign measurements.(24 months)
- Concentration-time profiles of Pharmacokinetics (PK) parameters - Phase Ib(24 months)
- Best Overall Response (BOR)(24 months)
- Progression Free survival (PFS)(24 months)