Phase 1, Open-label, Study of Voruciclib in Subjects With Relapsed and/or Refractory B Cell Malignancies or AML After Failure of Prior Standard Therapies and Voruciclib in Combination With Venetoclax in Subjects With Relapsed/Refractory AML
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 84
- 试验地点
- 12
- 主要终点
- Determine the safety and tolerability of voruciclib in combination with venetoclax in subjects with AML.
研究概览
简要总结
This is a Phase 1, open-label, dose escalation study to determine the safety and preliminary efficacy of voruciclib monotherapy in subjects with relapsed/refractory B cell malignancies or AML after failure of standard therapies or voruciclib in combination with venetoclax in subjects with relapsed or refractory AML
详细描述
This is a Phase 1, open-label, 3 + 3 dose escalation and expansion study to determine the safety and preliminary efficacy of voruciclib monotherapy in subjects with relapsed/refractory B cell malignancies or AML after failure of prior standard therapies or voruciclib in combination with venetoclax in subjects with relapsed or refractory AML. Escalation to the next higher dose level will depend on demonstrated safety and tolerability at each dose level.
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
- •Age ≥18 years
- •Histologically-confirmed diagnosis of Follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), chronic lymphocytic leukemia(CLL), diffuse large B-cell lymphoma (DLBCL), or AML
- •a. Subjects must have disease that has relapsed or is refractory to 2 or more prior regimens and in need of treatment due to progressive disease
- •Presence of measurable disease defined per the 2008 International workshop on CLL guidelines, or by 2014 Lugano criteria for non-Hodgkin lymphoma (does not apply for AML subjects)
- •Adequate hematologic parameters unless clearly due to the disease under study
- •Adequate renal and hepatic function, per laboratory reference range at screening
排除标准
- •History of pneumonitis of any cause
- •For CLL subjects: only known histological transformation to an aggressive lymphoma
- •For AML subjects:
- •Acute promyelocytic leukemia
- •Peripheral blast count > 25 × 10 9/L
- •Known central nervous system involvement
- •Significant cardiovascular disease
- •Significant screening ECG abnormalities
- •Subjects who require warfarin, anti-cancer therapeutics or investigational agents
- •Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of voruciclib therapy
- •Prior solid organ transplantation
- •Receipt of an allogeneic transplant within 6 months or an autologous transplant within the preceding 3 months; evidence of ongoing graft-versus-host disease (GVHD)
- •Prior therapy with a cyclin-dependent kinase (CDK9) inhibitor
- •Symptomatic/uncontrolled HIV infection/AIDS, or currently taking contraindicated medications for HIV control
- •Ongoing immunosuppressive treatment including calcineurin inhibitors at the time of the start of study treatment, including systemic or enteric corticosteroids except as follows:
- •Prior to the start of study treatment, subjects may be using systemic corticosteroids (≤20 mg/day of prednisone or equivalent), topical, or inhaled corticosteroids
- •During study therapy, subjects may use systemic, topical, or enteric corticosteroids, if needed
研究组 & 干预措施
voruciclib monotherapy and voruciclib in combination with venetoclax
voruciclib monotherapy - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level and disease type (AML or B-cell malignancies)
voruciclib and venetoclax - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level for AML subjects
干预措施: voruciclib monotherapy (Drug)
voruciclib monotherapy and voruciclib in combination with venetoclax
voruciclib monotherapy - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level and disease type (AML or B-cell malignancies)
voruciclib and venetoclax - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level for AML subjects
干预措施: voruciclib and venetoclax (Drug)
结局指标
主要结局
Determine the safety and tolerability of voruciclib in combination with venetoclax in subjects with AML.
时间窗: 2 years
Safety will be measured by the incidence of all AEs and SAEs, timing, grade \[CTCAE v4.03\] severity, seriousness, relatedness. Tolerability will be measured by the incidence of DLTs (dose limiting toxicities)
Determine the safety and tolerability of voruciclib
时间窗: 2 years
Safety will be measured by the incidence of all AEs and SAEs, timing, grade \[CTCAE v4.03\] severity, seriousness, relatedness. Tolerability will be measured by the incidence of DLTs (dose limiting toxicities)
次要结局
- Progression Free Survival (PFS)(2 years)
- Overall Response Rate (ORR)(2 years)
- Duration of Response (DOR)(2 years)
- Evaluate the PK of voruciclib(2 years)
- Evaluate the PK of voruciclib Cmax in combination with venetoclax Determined by the Area Under the Concentration time curve (AUC)(2 years)