Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
A Phase 1/2a, Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
研究概览
详细说明
The ZX-101A-101 study will consist of 2 parts:
- Part 1: ZX-101A Dose Escalation
- Part 2: ZX-101A Dose Expansion
The Part 1 (dose escalation) of the study is designed to determine the safety and tolerability of ZX-101A administered orally once daily in 28-day cycles. The Part 2 (dose expansion) of the study is designed to further investigate the safety, tolerability, pharmacokinetics and pharmacodynamic and clinical activities of ZX-101A administered orally once daily in 28-day cycles at the selected recommended Phase 2 dose (RP2D).
Results of clinical findings in patients in the dose-escalation portion of the study will be reviewed to identify conditions (or genetic characteristics) most likely to respond to ZX-101A. These select types of hematologic malignancies will be enrolled in cohorts in the dose-expansion part of the study.
Male or female patients who are 18 years of age or older with relapsed/resistant or refractory advanced hematologic malignancies (CLL/SLL, iNHL, and other NHL subtypes) will be included in the study provided that all inclusion and exclusion criteria are satisfied.
Up to three cohorts are planned in Part 2 - Dose Expansion of the study: 1) relapsed/resistant or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), 2) relapsed/resistant or refractory indolent Non- Hodgkin's Lymphoma (iNHL), and based on emerging data from Part 1-Dose Expansion, a third cohort consisting of other types of NHL may be included.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Arizona
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Gilbert、Arizona、美国、85234
- Banner MD Anderson Cancer Center
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Tucson、Arizona、美国、85715
- Acrc/Arizona Clinical Research Center, Inc.
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California
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Long Beach、California、美国、90804
- Innovative Clinical Research Institute
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New Jersey
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Brick、New Jersey、美国、08724
- New Jersey Center for Cancer Research
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Ohio
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Toledo、Ohio、美国、43614
- University of Toledo Precision Oncology Research
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Washington
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Seattle、Washington、美国、98109
- Seattle Cancer Care Alliance
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Males and females who are ≥ 18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Failed at least 2 prior systemic standard therapies.
- Histopathological confirmed diagnosis of CLL/SLL, indolent NHL,and other NHL subtypes.
- Documented active disease that is relapsed/resistant or refractory requiring treatment after established therapy shown to have clinical benefit.
- Acceptable bone marrow, kidney, and liver function.
- No transfusion or cytokine support for ≥ 2 weeks before initiating study treatment.
- Ability to swallow and retain oral medications (see exclusion criteria #20 below).
- Negative serum pregnancy test in women of childbearing potential at Screening.
- Women of childbearing potential and men who partner with a woman of childbearing potential must agree to use effective contraceptive methods.
- Men must agree to no sperm donations during the study and for 3 months after the last dose of ZX-101A.
- Understands the requirements of the study (e.g. periodic imaging studies, periodic blood sampling, bone marrow studies), is willing to comply with all study procedures and signed the Institutional Review Board (IRB)-approved informed consent.
Exclusion Criteria:
- Received investigational study drug within 28 days (or 5 half-lives, whichever is longer).
- Concurrent participation in another therapeutic treatment trial.
- Received approved anti-cancer drugs within 21 days (42 days for nitrosoureas) or 5 half-lives, whichever is longer.
- Ongoing immunosuppression for chronic conditions.
- Known active hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection.
- Any concurrent uncontrolled illness.
- Has not recovered from adverse events from prior anti-cancer treatment (with exception of alopecia).
- Pregnant or breast-feeding or planning to conceive or father children within the projected duration of the study.
- Major surgery within 4 weeks prior to first dose of study treatment.
- Radiation treatment within 2 weeks prior to first dose of study treatment.
- Gastrointestinal dysfunction, including motility or malabsorption syndromes or inflammatory bowel disease which could limit absorption of study drug.
- Active or prior pneumonitis or interstitial lung disease.
Other inclusion and exclusion criteria may apply.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:顺序分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:ZX-101A Dose Level 1
Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle
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Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
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实验性的:ZX-101A Dose Level 2
2-times the SD of ZX-101A administered orally once daily in a 28-day cycle
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Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
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实验性的:ZX-101A Dose Level 3
3-times the SD of ZX-101A administered orally once daily in a 28-day cycle
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Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
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实验性的:ZX-101A Dose Level 4
4-times the SD of ZX-101A administered orally once daily in a 28-day cycle
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Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
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实验性的:ZX-101A Dose Level 5
5-times the SD of ZX-101A administered orally once daily in a 28-day cycle
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Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
大体时间:From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days.
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To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.
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From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days.
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Safety and tolerability of ZX-101A
大体时间:From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days.
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To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2
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From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Peak Plasma Concentration of ZX-101A
大体时间:Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A
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Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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Area under the plasma concentration of ZX-101A
大体时间:Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A
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Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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Half-life of ZX-101A
大体时间:Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A
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Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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Phospho-AKT (p-AKT) levels in whole blood
大体时间:Days 1 and 2 of Cycle 1 (each cycle is 28 days)
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To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.
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Days 1 and 2 of Cycle 1 (each cycle is 28 days)
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客观缓解率(ORR)
大体时间:长达 2 年
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评估由特定疾病反应标准确定的客观反应率 (ORR)
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长达 2 年
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反应持续时间 (DoR)
大体时间:长达 2 年
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检查反应持续时间 (DoR),定义为从第一次记录反应的日期到第一次记录进行性疾病 (PD) 或因任何原因死亡的日期的时间
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长达 2 年
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无进展生存期 (PFS)
大体时间:长达 2 年
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检查无进展生存期 (PFS),定义为从首次接受研究治疗的日期到首次记录 PD 或因任何原因死亡的日期的时间
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长达 2 年
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总生存期(OS)
大体时间:长达 2 年
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检查总生存期 (OS),定义为从首次接受研究治疗的日期到因任何原因死亡的时间
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长达 2 年
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合作者和调查者
调查人员
- 研究主任:Xiaolin Qin, PhD、Zenshine Pharmaceutical, Inc.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
慢性淋巴细胞白血病的临床试验
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Shenzhen Second People's Hospital招聘中白血病 | 骨髓的 | 慢性的 | BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia) | 积极的中国
ZX-101A的临床试验
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Nanjing Zenshine Pharmaceuticals招聘中
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Nanjing Zenshine Pharmaceuticals尚未招聘
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Nanjing Zenshine Pharmaceuticals完全的