A Phase I/II, Open-label, Dose-Escalating Study With a Proof of Concept Cohort to Evaluate the Safety, Tolerability and Efficacy of ARGX-110 in Combination With Azacytidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 主要终点
- Phase 2: Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to determine the maximum tolerated dose (MTD) of ARGX-110 and/or the recommended Phase II dose (RP2D) in combination with a standard dose of azacytidine (AZA) in Phase 1; and to evaluate efficacy of ARGX-110 when administered at a RP2D level established in Phase I in combination with a standard dose of AZA (proof-of concept) by evaluating overall response rate (ORR) in Phase 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- 否
入选标准
- •Signed informed consent form (ICF) indicating an understanding of the purposes, risks, and procedures required for the study and willingness and ability to participate in the study
- •Acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) (according to 2016 World Health Organization [WHO] classification definition of greater than or equal to [>=] 20 percent [%] blasts) (bone marrow) unsuitable for intensive treatment (including stem cell transplantation) with a curative intent, but eligible to receive azacytidine (AZA) treatment
- •Expected life expectancy >= 3 months, at the discretion of the investigator
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Women of childbearing potential having a negative serum pregnancy test at screening and within 48 hours before infusion of ARGX-110 on Day -14, and willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) during the study and for at least 3 months after the last study drug administration
排除标准
- •Prior or concurrent malignancy, except for the following: (1) adequately treated basal cell or squamous cell skin cancer; (2) carcinoma in situ of the cervix; (3) carcinoma in situ of the breast; (4) incidental histological finding of Prostate cancer (Tumour, Node, Metastasis [TNM] stage T1a or T1b), or; (5) Any other cancer from which the subject has been disease-free for more than 2 years
- •Any previous AML or MDS chemo- or radiotherapy (with the exception of hydroxyurea/Litalir for leukocyte control which should be discontinued by the first day of AZA, local radiation therapy, therapy for basal or squamous cell carcinoma of the skin)
- •Treatment with any investigational product within 4 weeks before the first administration of ARGX-110
- •Any known active or chronic infection, including human immunodeficiency virus (HIV) and hepatitis B or C virus infection
- •Any other concurrent disease or medical condition that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
研究组 & 干预措施
ARGX-110 with Azacytidine (AZA)
Phase 1: Participants will receive loading dose of ARGX-110 1 milligram per kilogram (mg/kg) body weight (cohort 1), 3 mg/kg body weight (cohort 2), 10 mg/kg body weight (cohort 3) or 20 mg/kg body weight (cohort 4) administered intravenously (IV) in combination with AZA standard dose of 75 milligram per meter square (mg/m^2) body surface area (BSA) administered subcutaneously (SC) / intravenously (IV). Phase 2: Participants will receive loading dose of ARGX-110 IV at a recommended dose for Phase 2 (RP2D) level from phase 1 in combination with AZA standard dose of 75 mg/m^2 BSA, administered SC/IV as per local practice.
干预措施: ARGX-110 (Drug)
ARGX-110 with Azacytidine (AZA)
Phase 1: Participants will receive loading dose of ARGX-110 1 milligram per kilogram (mg/kg) body weight (cohort 1), 3 mg/kg body weight (cohort 2), 10 mg/kg body weight (cohort 3) or 20 mg/kg body weight (cohort 4) administered intravenously (IV) in combination with AZA standard dose of 75 milligram per meter square (mg/m^2) body surface area (BSA) administered subcutaneously (SC) / intravenously (IV). Phase 2: Participants will receive loading dose of ARGX-110 IV at a recommended dose for Phase 2 (RP2D) level from phase 1 in combination with AZA standard dose of 75 mg/m^2 BSA, administered SC/IV as per local practice.
干预措施: AZA (Drug)
结局指标
主要结局
Phase 2: Overall Response Rate (ORR)
时间窗: Up to 3.6 years
ORR is defined as the sum of Complete remission (CR), CR with incomplete recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) at the ARGX-110 RP2D level that was established in Phase 1 according to established response criteria for Acute myeloid leukemia (AML).
Phase 1: Number of Participants with Dose Limiting Toxicity (DLT)
时间窗: Up to 3.6 years
DLTs will be defined as any of the following drug-related events: Any grade 3 or higher drug related non-hematological toxicity or; Grade 3 or higher IRRs or; inability to administer the next dose due to a drug-related adverse event or a delay of the administration of the next dose due to toxicities for more than 14 days despite adequate medication or; drug-related grade 4 febrile neutropenia or; drug-related grade 4 anemia which cannot be adequately treated.
次要结局
- Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve from Time Zero to Infinite (AUC[0-infinity]) of ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Elimination Half-Life (t1/2) of ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with Minimal Residual Disease (MRD) to ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Time to Response(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants Achieving Transfusion Independence (TI)(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with Adverse Events(Up to 3.6 years)
- Phase 1 and Phase 2: Trough Concentration (Ctrough) of ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of ARGX-110(Up to 3.6 years)
- Biomarker Assessment of ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with Anti-drug Antibodies (ADA) to ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with Complete Remission (CR)(Up to 3.6 years)
- Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCtau)(Up to 3.6 years)
- Phase 1 and Phase 2: Apparent Volume of Distribution (Vd/F) of ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with CR with Incomplete Recovery (CRi)(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with Morphologic Leukemia-free State (MLFS)(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with Partial remission (PR)(Up to 3.6 years)
- Phase 1 and Phase 2: Overall Survival (OS)(Up to 3.6 years)
- Phase 1 and Phase 2: Total Systemic Clearance (CL) of ARGX-110(Up to 3.6 years)
- Phase 1 and Phase 2: Time to Neutrophil Recovery(Up to 3.6 years)
- Phase 1: Levels of B Cells(Up to 3.6 years)
- Phase 1: Levels of NK Cells(Up to 3.6 years)
- Phase 1 and Phase 2: Number of Participants with 30 Day and 60 Day Mortality(30 and/or 60 days after the first administration)
- Phase 1 and Phase 2: Time to Transfusion Independence(Up to 3.6 years)
- Phase 1 and Phase 2: Duration of Transfusion Independence(Up to 3.6 years)
- Phase 1: Levels of T, B and NK Cells(Up to 3.6 years)
- Phase 1 and Phase 2: Duration of Response(Up to 3.6 years)
- Phase 1 and Phase 2: Relapse-Free Survival (RFS)(Up to 3.6 years)
- Phase 1 and Phase 2: Time to Platelet Recovery(Up to 3.6 years)