A Phase Ib/IIa Single-arm, Open-label Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination With Dasatinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) Including Chronic Phase Patients Who Have Failed Initial Tyrosine Kinase Inhibitor (TKI) Therapy, Accelerated or Blast Phase, Ph+ Acute Myeloid Leukemia (AML) or High-risk Ph+ Myelodysplastic Syndrome (MDS)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy
研究概览
简要总结
The primary objective of the Phase Ib study is to determine the dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of BP1001 in combination with dasatinib in patients with with Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) including chronic phase patients who have failed initial tyrosine kinase inhibitor (TKI) therapy, accelerated or blast phase, Ph+ Acute Myeloid Leukemia (AML) or High-risk Ph+ Myelodysplastic Syndrome (MDS). The primary objective of the Phase IIa study is to assess the efficacy of the combination of BP1001 and dasatinib in patients with Ph+ CML, Ph+AML, or high-risk Ph+ MDS.
详细描述
The Grb2 gene has been mapped to the human chromosome region 17q22-qter, a region that is duplicated in leukemias and solid tumors, which may result in an increased copy number of the Grb2 gene product. As Grb2 is important for the transformation of murine hematopoietic cells, and the proliferation of human leukemia cells that express high levels of oncogenic tyrosine kinases, inhibition of Grb2 may have a significant impact on the natural history of leukemias. The study drug (BP1001) may be able to inhibit the cells from making Grb-2. Researchers hope that without this protein, the leukemia cells will die.
Researchers hope that the combination of BP1001 and Das will provide a benefit to Ph+ CML patients, including chronic phase patients who have failed initial TKI therapy, accelerated or blast phase Ph+ AML, and high-risk Ph+ MDS patients.
This is a Phase Ib/IIa, multicenter, study of BP1001 in combination with Das in participants with Ph+ CML, including chronic phase patients who have failed initial TKI therapy, accelerated or blast phase Ph+ AML, and high-risk Ph+ MDS.
This is a Phase Ib/IIa, multicenter, study of BP1001 in combination with dasatinib in participants with Ph+ CML who are in chronic phase who have failed initial TKI therapy, accelerated or blast phase, Ph+ AML or high-risk Ph+ MDS.
This trial will utilize a single arm, open label design to assess the safety profile, DLT, MTD, PK, and efficacy of BP1001 in combination with dasatinib.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BP1001 (varying dose) + Dasatinib
Phase 1b: BP1001 (varying dose levels) in combination with Das
干预措施: BP1001 (varying dose) (Drug)
BP1001 (varying dose) + Dasatinib
Phase 1b: BP1001 (varying dose levels) in combination with Das
干预措施: Dasatinib (Drug)
BP1001 (fixed dose) + Dasatinib
Phase IIa: BP1001 (fixed dose based on Phase 1b) in combination with Das
干预措施: BP1001 (fixed dose) (Drug)
BP1001 (fixed dose) + Dasatinib
Phase IIa: BP1001 (fixed dose based on Phase 1b) in combination with Das
干预措施: Dasatinib (Drug)
结局指标
主要结局
Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy
时间窗: 240 days
Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Efficacy of the combination of BP1001 and Das using molecular response (PCR) by bone marrow aspirate or biopsy
时间窗: 240 days
Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Efficacy of the combination of BP1001 and Das using hematologic response by bone marrow aspirate or biopsy and complete blood counts
时间窗: 240 days
Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Dose Limiting Toxicity of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria
时间窗: 240 days
Phase 1b portion of the study: Determine the dose limiting toxicity of BP1001 in combination with Das
Maximum Tolerated Dose of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria
时间窗: 240 days
Phase 1b portion of the study: Determine the maximum tolerated dose of BP1001 in combination with Das
次要结局
- Time to Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts(30 days)
- Duration of Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts from day of response to day of disease progression(30 days)
- Efficacy of the combination of BP1001 and Das using molecular response (PCR) by bone marrow aspirate or biopsy versus Das alone by historical outcome comparison(240 days)
- Time to Response using molecular response (PCR) using bone marrow biopsy or aspirate(30 days)
- Duration of Response using molecular response (PCR) using bone marrow biopsy or aspirate from day of response to day of disease progression(30 days)
- Safety of BP1001 in combination with Das using non-hematologic and hematologic parameters per NCI CTCAE criteria(30 days)
- Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy versus Das alone by historical outcome comparison(240 days)
- In vivo PK using plasma to compute half life and elimination(30 days)
- Time to Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate(30 days)
- Efficacy of the combination of BP1001 and Das using hematologic response by bone marrow aspirate or biopsy and complete blood counts versus Das alone by historical outcome comparison(240 days)
- Duration of Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate from day of response to day of disease progression(30 days)
- Overall Survival from date of study entry to study closure(240 days)