A Phase 1b Dose-escalation Study of SGN-CD33A in Combination With Standard-of-care for Patients With Newly Diagnosed Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Seagen Inc.
- 入组人数
- 116
- 试验地点
- 13
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) by itself (monotherapy) or in combination with other standard treatments. The main purpose of this study is to find the best dose and schedule for SGN-CD33A when given in combination with standard induction treatment, in combination with standard consolidation treatment, or by itself for maintenance treatment. This will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of SGN-CD33A. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed.
详细描述
The study will be conducted in the following distinct parts:
Part A: Induction dose escalation - 7+3 combined with SGN-CD33A (Day 1 and Day 4 dosing)
Part B: Consolidation dose escalation - consolidation combined with SGN-CD33A; up to 4 cycles of consolidation therapy will be administered after SGN-CD33A (Day 1 of each cycle).
Part C: Maintenance - SGN-CD33A Monotherapy; Up to 24 patients with and up to 24 patient without prior allogeneic stem cell transplant will be treated with SGN-CD33A. Both arms will enroll simultaneously. SGN-CD33A will be administered on Day 1 of each 6-week cycle for up to 8 cycles.
Part D: Induction plus consolidation - induction/consolidation combined with SGN-CD33A; patients who achieve a CR/CRi (with or without a second induction) will receive up to 4 cycles of consolidation therapy administered after SGN-CD33A (Day 1 of each cycle).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •All subtypes of Acute Myeloid leukemia (except for acute promyelocytic leukemia)
- •Eastern Cooperative Oncology Group status of 0 or 1
- •Adequate baseline renal and hepatic function
- •Central venous access
- •Part specific requirements: eligible to receive induction; achieved CR/CRi with standard induction and eligible to receive consolidation; in CR with documented blood count recovery for maintenance
排除标准
- •Previous treatment for MDS or MPN for dose escalation cohorts
- •Inadequate lung function
- •Inadequate heart function
研究组 & 干预措施
Induction with SGN-CD33A
7+3 (Standard dose cytarabine for induction and daunorubicin) + SGN-CD33A
干预措施: Standard dose cytarabine for induction (Drug)
Induction with SGN-CD33A
7+3 (Standard dose cytarabine for induction and daunorubicin) + SGN-CD33A
干预措施: SGN-CD33A (Drug)
Induction with SGN-CD33A
7+3 (Standard dose cytarabine for induction and daunorubicin) + SGN-CD33A
干预措施: Daunorubicin (Drug)
Consolidation with SGN-CD33A
High dose cytarabine for consolidation + SGN-CD33A (28-day cycles)
干预措施: SGN-CD33A (Drug)
Consolidation with SGN-CD33A
High dose cytarabine for consolidation + SGN-CD33A (28-day cycles)
干预措施: High dose cytarabine for consolidation (Drug)
SGN-CD33A Maintenance
SGN-CD33A Monotherapy (42-day cycles)
干预措施: SGN-CD33A (Drug)
Induction and Consolidation with SGN-CD33A
7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
干预措施: Standard dose cytarabine for induction (Drug)
Induction and Consolidation with SGN-CD33A
7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
干预措施: SGN-CD33A (Drug)
Induction and Consolidation with SGN-CD33A
7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
干预措施: Daunorubicin (Drug)
Induction and Consolidation with SGN-CD33A
7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
干预措施: High dose cytarabine for consolidation (Drug)
结局指标
主要结局
Incidence of adverse events
时间窗: Through 1 month following last dose
Incidence of laboratory abnormalities
时间窗: Through 1 month following last dose
Incidence of dose-limiting toxicity (DLT)
时间窗: Through 1 month following last dose
次要结局
- Complete remission (CR) rate at the end of induction(Through 1 month following last dose)
- Blood concentrations of SGN-CD33A and metabolites(Up to approximately 3 years)
- Incidence of antitherapeutic antibodies (ATA)(Up to approximately 3 years)
- Leukemia-free survival(Up to approximately 3 years)
- Overall survival(Up to approximately 3 years)
- Rate of minimal residual disease (MRD) clearance(Up to approximately 3 years)