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临床试验/NCT02011945
NCT02011945已完成1 期

A Phase 1B Dose Escalation Study to Investigate the Safety, Tolerability and Preliminary Efficacy for the Combination Dasatinib (BMS-354825) Plus Nivolumab (BMS-936558) in Patients Chronic Myeloid Leukemia (CML)

Bristol-Myers Squibb13 个研究点 分布在 4 个国家目标入组 35 人开始时间: 2014年2月7日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
发起方
入组人数
35
试验地点
13
主要终点
Incidence of Adverse Events (AEs)

研究概览

简要总结

The purpose of this study is to find a dose of Nivolumab that can be safely added to Dasatinib in patients with Chronic Myeloid Leukemia.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Single Group
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

入选标准

  • Confirmed diagnosis of Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase :
  • With historically documented Ph+ cells
  • ≥2 prior Tyrosine Kinase Inhibitors (TKI) therapies for CML
  • Currently progressing, resistance to or with a suboptimal response to their most recent therapy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score 0 - 1

排除标准

  • Blast phase CML
  • Known Abl-kinase mutation resistant to Dasatinib (e.g. T315I or T315A)

研究组 & 干预措施

dasatinib Only

Experimental

dasatinib 100 mg QD(CP) or 140 mg QD (AP)

干预措施: Dasatinib (Drug)

Dose Level 2

Experimental

Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

干预措施: Nivolumab (Drug)

Dose Level 1

Experimental

Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

干预措施: Dasatinib (Drug)

Dose Level 1

Experimental

Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

干预措施: Nivolumab (Drug)

Dose Level 2

Experimental

Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

干预措施: Dasatinib (Drug)

结局指标

主要结局

Incidence of Adverse Events (AEs)

时间窗: Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days

Any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product.

Incidence of Serious Adverse Events (SAEs)

时间窗: Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing

Any untoward medical occurrence that at any dose: results in death, is life threatening, requires in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a important medical event.Requires inpatient hospitalization or causes prolongation of existing hospitalization, results.

Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology

时间窗: Up to 40 Months

The number of participants with a shift in laboratory test results from baseline to Grade 3-4 in hematology

Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests

时间窗: Up to 40 Months

The number of participants with an abnormal Liver function test. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)

Incidence of Laboratory Abnormalities in Specific Thyroid Tests

时间窗: Up to 40 Months

Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)

Incidence of Dose Limiting Toxicities (DLT)

时间窗: Week 3 to week 6

DLT will be determined based on the incidence and intensity of drug related adverse events (AEs). The following drug-related AEs (whether related to one or both agents) occurring during the first 6 weeks of combined treatment with both dasatinib plus nivolumab (ie, Weeks 3 to 8, inclusive) would be considered DLTs: * Grade 4 hematologic AE lasting \> 7 days despite appropriate medical intervention, except as noted below; * Grade 3 or Grade 4 nonhematologic AE irrespective of duration; * Grade 2 nonhematologic AE lasting \> 7 days despite appropriate medical intervention (exception: asymptomatic laboratory values of Grade 2 which do not require medical intervention); * Any toxicity managed by discontinuation of nivolumab; * Grade ≥ 2 AE not controlled by medical intervention and requiring dasatinib treatment interruption for \> 28 consecutive days; * Grade ≥ 2 AE not controlled by medical intervention and requiring missing 2 consecutive doses of nivolumab.

次要结局

  • Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants(upto 36 Months)
  • Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants(upto 36 Months)
  • Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants(upto 36 Months)
  • Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants(upto 36 Months)
  • Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants(upto 36 Months)
  • Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants(upto 36 Months)
  • Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants(Up to 36 Months)
  • Time to Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants(Up to 36 Months)
  • Time to Major Molecular Response (MMR) - CML-AP Participants(Up to 36 Months)
  • Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants(Up to 36 Months)
  • Duration of Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants(Up to 36 Months)
  • Duration of Major Molecular Response (MMR) - CML-AP Participants(Up to 36 Months)
  • Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants(Up to 36 Months)
  • Time to Molecular Response 4.5(MR4.5) - CML-CP Prior Dasatinib Participants(Up to 36 Months)
  • Time to Molecular Response 4.5(MR4.5) - CML-AP Participants(Up to 36 Months)
  • Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants(Up to 36 Months)
  • Duration of Molecular Response 4.5 (MR4.5) - CML-CP Prior Dasatinib Participants(Up to 36 Months)
  • Duration of Molecular Response 4.5 (MR4.5) - CML-AP Participants(Up to 36 Months)

研究者

发起方
Bristol-Myers Squibb
申办方类型
Industry
责任方
Sponsor

研究点 (13)

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