NCT01871727已完成3 期
A Clinical Study to Demonstrate Safety and Efficacy of E7777 in Persistent or Recurrent Cutaneous T-Cell Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 112
- 试验地点
- 22
- 主要终点
- Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)
研究概览
简要总结
The purpose of this trial is to assess the efficacy of E7777 in participants with recurrent or persistent Cutaneous T-Cell Lymphoma (CTCL) in Stage I - III participants as assessed by objective response rate (ORR). A lead-in dose-finding part was used to determine dose level 9 microgram per kilogram (mcg/kg) E7777 that is being used to test efficacy and safety.
详细描述
This is a multicenter, open-label study of E7777 in participants with recurrent or persistent CTCL. The study consists of an initial Lead-in part (to select recommended dose of E7777 for Main part), followed by the Main part (to test efficacy). Participants will move through three phases while on study: Pretreatment Phase, Treatment Phase, and Extension Phase and a Follow-up Period.
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
- •Participants must meet all of the following criteria to be included in the study:
- •Age greater than or equal to 18 years.
- •Histopathologic diagnosis of CTCL (mycosis fungoides [MF] or Sezary Syndrome [SS]), confirmed by skin biopsy, or lymph node, or blood assessment, of current disease.
- •CD25 assay-positive tumor, defined as detectable CD25 on greater than or equal to 20% of total lymphoid infiltrate in biopsied lesions by immunohistochemistry.
- •CTCL disease stage at study entry as follows, according to ISCL/EORTC (Olsen 2011).
- •Lead-In Part: Stage IA - IV, except participants with CNS involvement.
- •Main Study: Stage I - III
- •History of prior therapies for CTCL: must have had prior therapy, any number of prior therapies allowed.
- •Topical treatments (except topical chemotherapy) and steroids are not considered as prior therapies.
- •A minimum washout period of 4 weeks after previous CTCL therapy is recommended before the first dose of E
- •Participants must have recovered from any adverse effects from any previous CTCL therapy to Common Terminology Criteria for Adverse Events (CTCAE) Grade <2 before starting study drug. A shorter washout may be allowed if participant is experiencing progressive disease despite ongoing treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 in the Lead-In Part and performance status of 0 or 1 in the Main Study.
- •Life expectancy greater than or equal to 3 months in the Lead-In Part and greater than or equal to 12 months in the Main Study.
- •Adequate bone marrow reserves as evidenced by:
- •platelets greater than or equal to 100,000/mm^3 (100 x 10^9/L)
- •clinically stable hemoglobin greater than or equal to 9 gram per deciliter (g/dL) (90 g/L) and hematocrit greater than or equal to 27% without transfusion support
- •Normal hepatic function as evidenced by:
- •bilirubin <= 1.5* upper limit if normal (ULN) and alkaline phosphatase <=3.0*ULN
- •aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0*ULN
- •albumin >= 3.0 g/dL (30 g/L)
- •Adequate renal function as evidenced by serum creatinine less than or equal to 1.8 mg/dL (158 umol/L) or calculated creatinine clearance greater than or equal to 50 mL/min (per the Cockcroft-Gault formula) with less than 2+ protein or 24- hour urine creatinine clearance greater than or equal to 50 mL/minute with 24- hour urine protein less than 1gram.
- •Provide written informed consent prior to any study-specific screening procedures.
- •Females may not be lactating or pregnant at Screening or Baseline
- •All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically
- •Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partner must meet the criteria above
- •Exclusion Criteria
- •Participants who meet any of the following criteria will be excluded from the study:
- •Prior denileukin diftitox therapy
- •Use of topical steroids within 14 days of Day 1 of initial therapy is not allowed.Topical steroids or systemic low dose steroids of less than or equal to 10 milligram per day (mg/day) prednisone are allowed in participants with erythroderma who have been on corticosteroids for a prolonged period of time and where discontinuation may lead to rebound flare in disease. The concomitant steroid medication is allowed as long as the type of steroid, route of administration, and steroid dose remain the same as what the participant had been receiving for a prolonged period of time.
- •Active malignancy (except for CTCL, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix) within the past 24 months.
- •Serious intercurrent illness
- •Significant cardiac disease requiring ongoing treatment, including congestive heart failure (CHF), severe coronary artery disease (CAD), cardiomyopathy, uncontrolled cardiac arrhythmia, unstable angina pectoris, or myocardial infarction (MI)
- •Significant pulmonary symptoms or disease
- •History of uncontrolled seizure disorder or active central nervous system disease
- •Major surgery within 2 weeks of study enrollment
- •Significant or uncontrolled infections requiring systemic anti-infective therapy
- •Known human immunodeficiency virus (HIV) infection; known active hepatitis B or hepatitis C infection
- •Females who are pregnant (positive urine test) or breastfeeding
- •Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the participant's ability to safely complete the study.
排除标准
- 未提供
研究组 & 干预措施
E7777
Experimental
干预措施: E7777 9 mcg/kg (Drug)
结局指标
主要结局
Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)
时间窗: Cycle 1 (cycle length was 21 days)
DLTs as per NCI CTCAE v4.03 were defined as 1) serious infusion reaction (CTCAE) Grade 4 adverse event of "Infusion related reaction," or recurrent CTCAE Grade 3 despite administration of systemic steroid premedication after initial occurrence. Infusion reactions were defined as symptoms (example, fatigue, nausea, vomiting, arthralgia, myalgia, pyrexia, chills, rigors) occurring within 24 hours of E7777 infusion. 2) Capillary leak syndrome (CLS) CTCAE Grade 4 or Grade 3 (with exceptions). A CLS event was defined as the noted occurrence of at least 2 of the following: hypotension, edema, or serum albumin less than (\<) 3.0 gram per decilitre (g/dL). 3) Clinical visual impairment. 4) Any CTCAE Grade greater than or equal to (\>=) 4 adverse event (AE) that may represent an infusion reaction. 5) Any other Grade 3 or greater toxicity assessed as related to E7777 treatment and which in the opinion of a safety consultancy investigator panel, was a dose-limiting toxicity.
Lead-In Part: Maximum Tolerated Dose (MTD) of E7777
时间窗: Cycle 1 (cycle length was 21 days)
The MTD was defined as the safe dose level established in Lead-In Part. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the Lead-In Part.
Main Study Part: Objective Response Rate (ORR) by Independent Review Committee (IRC) Based on Olsen 2011 Criteria
时间窗: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) based on independent review committee on 2 assessments at least 3 weeks apart. The tumor response was based on global response score (GRS) Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites.
次要结局
- Lead-In Part: Duration of Response (DOR) Per Investigator Assessment(From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (Up to 1 year 2 months))
- Main Study Part: Duration of Response (DOR) Per Independent Review Committee(From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (Up to 3 years 6 months))
- Lead-In Part: Time to Response (TTR) Per Investigator Assessment(From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR (Up to 1 year 2 months))
- Main Study Part: Time to Response (TTR) Per Independent Review Committee(From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR (Up to 3 years 6 months))
- Lead-In Part and Main Study Part: ORR Per Investigator Assessment(From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months))
- Main Study Part: ORR Per IRC Based on Prince 2010 Criteria(From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months))
- Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the first dose of study drug up to 30 days after the last dose (Up to 3 years and 7 months))
- Lead-In Part: Maximum Serum Concentration (Cmax) of E7777(Cycles 1, 3, 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days))
- Main Study Part: Maximum Serum Concentration (Cmax) of E7777(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days))
- Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777(Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours Post-dose (Cycle length was 21 days))
- Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777(Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777(Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Main Study Part: Terminal Elimination Half-life (t1/2) of E7777(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)(Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Lead-In Part: Total Body Clearance (CL) of E7777(Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Main Study Part: Total Body Clearance (CL) of E7777(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777(Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days))
- Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1)
- Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1)
- Main Study Part: Number of Participants With Objective Skin Response(Up to 30 months)
- Main Study Part: Duration of Skin Response(Up to 30 months)
- Main Study Part: Time to Skin Response(Up to 30 months)
研究者
研究点 (22)
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