A Phase 1/2 Study of Vadastuximab Talirine Administered in Sequence With Allogeneic Hematopoietic Stem Cell Transplant in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Seagen Inc.
- 入组人数
- 14
- 试验地点
- 11
- 主要终点
- Rate of MRD Negativity
研究概览
简要总结
This study will examine the safety and anti-leukemic profile of SGN-CD33A (vadastuximab talirine) in patients with relapsed chemo-resistant AML, who are given vadastuximab talirine in sequence with standard treatments before a planned stem cell transplant, or as maintenance therapy after a stem cell transplant. The main purpose of the study is to find the best dose and determine the anti-leukemic activity of vadastuximab talirine, given either pre- or post-allogeneic stem cell transplant (alloSCT) for adults with relapsed or refractory AML. This will be determined by assessing the safety and tolerability of vadastuximab talirine. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed/refractory acute myeloid leukemia (AML) except for acute promyelocytic leukemia
- •Eastern Cooperative Oncology Group status of 0 or 1
- •Adequate baseline renal and hepatic function
- •For Pre-allo Part A (before stem cell transplant): Relapsed or refractory AML (greater than 5% blasts)
- •For Pre-allo Part A (before stem cell transplant): Availability of an HLA matched related or unrelated donor
- •For Pre-allo Part A (before stem cell transplant): Eligible for an allogeneic hematopoietic stem cell transplant
- •For Post-allo Part B: Transplant must have been performed with active AML (greater than 5% blasts) using a conventional conditioning regimen and have achieved CR or CRi post-alloSCT (with ANC greater than or equal to 1,000 and platelet greater than or equal to 50,000)
- •For Post-allo Part B: Treatment must begin at least 42 days, but no more than 100 days post-transplant.
排除标准
- •Inadequate heart function
- •Inadequate lung function
- •Previous central nervous system leukemia
- •Any history of another metastatic malignancy
- •Anti-leukemia treatment within14 days of study drug (other than hydroxyurea or 6-mercaptopurine), immunosuppressive therapy (except for GVHD treatment/prophylaxis in Part B), or investigational agents
- •For Pre-allo Part A (before stem cell transplant): Partially matched donors (related or unrelated) and umbilical cord blood cells are excluded as the source of hematopoietic stem cells
- •For Pre-allo Part A (before stem cell transplant): Prior alloSCT
- •For Post-allo Part B: Active GVHD Grade 2 or higher
- •For Post-allo Part B:History of veno-occlusive disease requiring defibrotide
- •For Post-allo Part B: History of Grade 2 or higher hepatic GVHD
- •For Post-allo Part B: Concurrent use of corticosteroids equivalent of prednisone at a dose of greater than 0.5 mg/kg
研究组 & 干预措施
Pre-allo (before stem cell transplant)
Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
干预措施: Fludarabine (Drug)
Pre-allo (before stem cell transplant)
Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
干预措施: Melphalan (Drug)
Pre-allo (before stem cell transplant)
Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
干预措施: vadastuximab talirine (Drug)
Post-allo (after stem cell transplant)
Post-allo vadastuximab talirine
干预措施: vadastuximab talirine (Drug)
结局指标
主要结局
Rate of MRD Negativity
时间窗: 30 days
Rate of MRD (minimal residual disease) negativity at Day -1 (1 day prior to transplant) and Day 30 post-transplant (Part A only)
Incidence of Laboratory Abnormalities
时间窗: Approximately 1 year
Number (count) of participants that experienced a Grade 3 or higher laboratory toxicity (hematology and chemistry). Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event.
Incidence of Adverse Events
时间窗: Approximately 1 year
AE: Adverse events; TEAE: Treatment-emergent adverse event. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event. An AE is considered serious if it was fatal, life threatening, required hospitalization, was disabling/incapacitating, resulted in a birth defect or congenital anomally, or was otherwise considered to be medically significant.
1-year Survival Rate
时间窗: 12 months
1-year survival rate estimated using Kaplan-Meier methods The start date for overall survival is the day of alloSCT.
次要结局
- Best Response of CR or CRi(9 weeks)
- Duration of Response(9 weeks)
- Overall Survival(Approximately 96 weeks)