An Open-Label, Dose-Escalation Phase I/II Study of PRI-724 for Patients With Advanced Myeloid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 6
- 主要终点
- DLT (Dose Limiting Toxicity)
研究概览
简要总结
PRI-724 is a new investigational drug being studied to treat subjects with cancer who have advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling pathway that cancer cells need to grow and spread (metastasize).
详细描述
PRI-724 is a new investigational drug being studied to treat subjects with cancer who have advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling pathway that cancer cells need to grow and spread (metastasize).
Purpose:
- To test the safety of PRI-724 when taken intravenously (through the vein).
- To observe whether PRI-724 can slow or stop the progression of leukemia.
- To find the Maximum Tolerated Dose (highest safe dose) in the first two parts of the study.
- To find the dose of PRI-724 that should be used in the third part of the study and possible future clinical trials that will study effectiveness and additional safety.
- To test the safety of combining PRI-724 with an approved cancer drug called dasatinib in treating chronic myeloid leukemia (CML).
- To evaluate whether the combination of PRI-724 with the approved cancer drug dasatinib slows or stops the progression of chronic myeloid leukemia (CML).
- To test the safety of combining PRI-724 with an approved cancer drug called Cytarabine in treating acute myelogenous leukemia (AML).
- To evaluate whether the combination of PRI-724 with the approved cancer drug Cytarabine slows or stops the progression of acute myelogenous leukemia (AML).
- To measure how much PRI-724 appears and remains in the blood after infusion.
- To measure several signals called biomarkers associated with cancer in the blood to see if PRI-724 affects those signals.
Study Design:
This will be a single center, open-label escalating-dose cohort study with 3 parts: Part I during which the MTD will be determined in acute group patients; Part II during which the MTD will be determined in non-acute group patients; and Part III during which safety and tolerability of escalating doses of PRI-724 will be assessed in combination with dasatinib for CML patients or low dose ara-C therapy for AML patients ≥ 65 years of age.
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
Part III Arm A
Once the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each.
Escalating doses of PRI-724, beginning 2 dose levels below the Part I MTD will be administered in combination with low dose ara-C therapy (20 mg SC BID × 10d q 28d) for AML patients ≥ 65 years of age.
干预措施: PRI-724 (Drug)
Part III Arm B
Once the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each.
Escalating doses of PRI-724, beginning 2 dose levels below the Part I MTD will be administered in combination with dasatinib (140 mg PO daily) to Acute Group patients with CML-AP or BC.
干预措施: PRI-724 (Drug)
Part I
Single-agent MTD (or maximum dose to be studied) of PRI-724 will be determined in escalating dose cohorts of Acute Group patients. The MTD cohort will be expanded up to 10 patients to further evaluate tolerability.
干预措施: PRI-724 (Drug)
Part II
Single-agent MTD (or maximum dose to be studied) of PRI-724 will be determined in escalating dose cohorts of Non-Acute Group patients. Dosing will begin 2 dose levels below the Part I MTD. The MTD cohort will be expanded up to 10 patients to further evaluate tolerability.
干预措施: PRI-724 (Drug)
Part III Arm C
Once the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each.
Escalating doses of PRI-724, beginning 1 dose level below the Part II MTD will be administered in combination with dasatinib (100 mg PO daily) to Non-Acute Group patients with CML-CP.
干预措施: PRI-724 (Drug)
结局指标
主要结局
DLT (Dose Limiting Toxicity)
时间窗: 1 year
Observance of 1 DLT in first 3 patients during 3+3 phase will result in the enrollment of an additional 3 patients. Observance of 2+ DLTs in 6 patients during 3+3 phase will result in the next lower dose being expanded. Observance of DLTs in 33% of patients in 10 patient MTD expansion will result in the next lower dose being expanded. MTD will only be established in a dose level where 0/3 pts or 1/6 pts have a DLT observed in first 2 cycles of therapy. Two types of DLTs will be observed: non-hematologic and hematologic.
次要结局
- Preliminary Efficacy Endpoints(1 year)