A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Participants With Chronic Leukemia
2017年6月12日 更新者:MedImmune LLC
A Phase I, Multicenter, Dose-Escalation Study of CAT-8015 in Patients With Relapsed or Refactory Chronic Lymphocytic Leukemia (CLL) Prolymphocytic Leukemia (PLL), or Small Lymphocytic Leukemia (SLL)
This was a multicenter, Phase 1, standard 3+3 dose-escalation study to evaluate the safety and anti-neoplastic activity of moxetumomab pasudotox in relapsed or refractory participants with chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL) or Small Lymphocytic Lymphoma (SLL).
研究概览
地位
终止
条件
详细说明
This was a multicenter, Phase 1, standard 3+3 dose-escalation study to evaluate the safety and anti-neoplastic activity of CAT-8015 in relapsed or refractory participants with CLL, PLL, or SLL.
Participants in the initial dose cohort were to receive CAT-8015 at a dose of 5 microgram per kilogram (mcg/kg) CAT-8015, increasing to 10 mcg/kg in the second dose cohort, and then increasing by 10 mcg/kg increments in subsequent cohorts (that is, to doses of 20, 30, 40, 50, 60 mcg/kg, etc) until a maximum tolerated dose (MTD) was identified.
Following identification of the MTD, the MTD cohort was to be expanded to 16 participants.
研究类型
介入性
注册 (实际的)
11
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Confirmed diagnosis of B-Cell Leukemia [(chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), or Small lymphocytic leukemia (SLL)]
- Measurable Disease
- Disease characteristics: Participants with CLL or SLL are eligible if they have failed 2 or more prior courses of standard chemo and/or biologic therapy (example, Rituxan) and PLL will be eligible if they have failed at least one prior standard chemotherapeutic regimen. Medical indications for treatment include progressive disease-related symptoms, progressive cytopenias due to marrow involvement, progressive or painful splenomegaly or adenopathy, rapidly increasing lymphocytosis, autoimmune hemolytic anemia or thrombocytopenia and increased frequency of infections.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Participants with other cancers who meet eligibility criteria and have had less than 5 years of disease-free survival will be considered on a case-by-case basis
- Life expectancy of greater than 6 months, as assessed by the principal investigator
- Must be able to understand and sign the informed consent
- Must be at least 18 years old
- Female and Male participants agree to use an approved method of contraception during the study
Exclusion Criteria:
- History of allogeneic bone marrow transplant.
- Documented and ongoing central nervous system involvement with their malignant disease [history of central nervous system (CNS) involvement is not an exclusion criterion]
- Pregnant or breast-feeding females
- Participants who plasma contains either a significant level of antibody to CAT-8015 as measured by ELISA, or antibody that neutralizes the binding of CAT-8015 to CD22 as measured by a competition ELISA.
- HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs)
- Hepatitis B surface antigen positive
- Uncontrolled, symptomatic, intercurrent illness including but not limited to: infections requiring systemic antibiotics, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements.
- Hepatic function: Serum transaminases [either alanine aminotransferase (ALT) or aspartate aminotransferase (AST)] or direct bilirubin greater than or equal to Grade 2, unless bilirubin is due to Gilbert's disease
- Renal function: Serum creatinine clearance is less than or equal to 60 millilitre per minute (mL/min) as estimated by Cockcroft-Gault formula
Hematologic function:
- The ANC less than 1000/cubic millimeter (cmm), or platelet count less than 50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (that is, potentially reversible with anti-neoplastic therapy).
- A participant will not be excluded because of pancytopenia greater than or equal to Grade 3, or erythropoietin dependence, if it is due to disease, based on the results of bone marrow studies.
- Baseline coagulopathy greater than or equal to grade 3 unless due to anticoagulant therapy
Pulmonary function:
- Participants with less than 50 percent (%) of predicted forced expiratory volume (FEV-1) or less than 50% of predicted diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin concentration and alveolar volume. Note: Participants with no prior history of pulmonary illness are not required to have pulmonary function test (PFTs). FEV1 will be assessed after bronchodilator therapy.
Recent prior therapy:
- Cytotoxic chemotherapy, corticosteroids (except stable doses of prednisone), whole body electron beam radiation therapy, hormonal, biologic or other standard or any investigational therapy of the malignancy for 3 weeks prior to entry into the trial.
- Less than or equal to 1 month prior monoclonal antibody therapy (that is, rituximab)
- Participants who are receiving or have received radiation therapy less than 3 weeks prior to study entry will not be excluded providing the volume of the bone marrow treated is less than 10% and also the participant has measurable disease outside the radiation report.
- Any history of prior pseudomonas - exotoxin immunotoxin administrator
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
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:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:CAT-8015 5 microgram per kilogram (mcg/kg)
Participants received a single intravenous infusion of 5 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.
|
Participants received a single intravenous infusion of 5 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.
|
实验性的:CAT-8015 10 mcg/kg
Participants received a single intravenous infusion of 10 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.
|
Participants received a single intravenous infusion of 10 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.
|
实验性的:CAT-8015 20 mcg/kg
Participants received a single intravenous infusion of 20 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.
|
Participants received a single intravenous infusion of 20 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.
|
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 |
---|---|---|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
大体时间:From start of study drug administration until 30 days after the last dose of study drug
|
An adverse event (AE) events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug.
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received moxetumomab pasudotox.
Treatment-emergent were events between administration of investigational product and Day 28 that were absent before treatment or that worsened relative to pretreatment state.
|
From start of study drug administration until 30 days after the last dose of study drug
|
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
大体时间:From start of study drug administration until 30 days after the last dose of study drug
|
The vital sign abnormalities which require an action or intervention by the investigator, or a finding judged by the investigator were reported as an adverse event.
TEAEs were events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug.
|
From start of study drug administration until 30 days after the last dose of study drug
|
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)
大体时间:From start of study drug administration until 30 days after the last dose of study drug
|
AEs observed in participants with clinically significant ECG abnormalities were assessed.
|
From start of study drug administration until 30 days after the last dose of study drug
|
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
大体时间:From start of study drug administration until 30 days after the last dose of study drug
|
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event.
Treatment-emergent were events between first dose of study drug and 30 days after the last dose that were absent before treatment or that worsened relative to pretreatment state.
Number of participants with grade 3 or higher treatment-emergent adverse events for laboratory abnormalities were reported as clinically relevant laboratory changes.
|
From start of study drug administration until 30 days after the last dose of study drug
|
Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR)
大体时间:Up to 2 years of post-treatment follow-up
|
Objective response rate defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria.
|
Up to 2 years of post-treatment follow-up
|
Best Overall Objective Tumor Response
大体时间:Up to 2 years of post-treatment follow-up
|
Antitumor activity was assessed by best overall objective tumor response.
|
Up to 2 years of post-treatment follow-up
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox
大体时间:Predose, 0.25 (During Infusion), 0.5 (End of Infusion), 1, 1.5, 2, 4, 8 and 12 hours postdose on Day 1 and 5; Predose and End of Infusion on Day 3
|
The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.
|
Predose, 0.25 (During Infusion), 0.5 (End of Infusion), 1, 1.5, 2, 4, 8 and 12 hours postdose on Day 1 and 5; Predose and End of Infusion on Day 3
|
Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox
大体时间:Predose, 0.25 (During Infusion), 0.5 (End of Infusion), 1, 1.5, 2, 4, 8 and 12 hours postdose on Day 1 and 5; Predose and End of Infusion on Day 3
|
The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.
|
Predose, 0.25 (During Infusion), 0.5 (End of Infusion), 1, 1.5, 2, 4, 8 and 12 hours postdose on Day 1 and 5; Predose and End of Infusion on Day 3
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Number of Participants With Positive Neutralizing Antibodies
大体时间:Up to end of treatment (4-6 weeks after the last dose)
|
Participants tested for immunogenicity to moxetumomab pasudotox prior to enrollment, before each cycle and at end of study.
The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of moxetumomab pasudotox to its target, cluster of differentiation 22 (CD22), coated onto enzyme linked immunosorbent assay (ELISA) plates.
It was used as a direct surrogate for biological activity based on the mechanism of action of this drug.
Significant level of neutralizing antibody activity defined as the capacity of test plasma to inhibit greater than (>)50 percentage (%) of the binding of CAT-8015 to CD22 using an ELISA-based method.
|
Up to end of treatment (4-6 weeks after the last dose)
|
Percentage Change From Baseline in Cluster of Differentiation 22 (CD22) Expression
大体时间:End of treatment (4-6 weeks after the last dose)
|
Participants demonstrated CD22 expression on malignant cells at Screening and CD22 is a regulatory molecule that prevents the over activation of the immune system and the development of autoimmune diseases.
|
End of treatment (4-6 weeks after the last dose)
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2007年3月7日
初级完成 (实际的)
2008年4月7日
研究完成 (实际的)
2008年4月7日
研究注册日期
首次提交
2007年12月21日
首先提交符合 QC 标准的
2007年12月21日
首次发布 (估计)
2008年1月7日
研究记录更新
最后更新发布 (实际的)
2017年7月6日
上次提交的符合 QC 标准的更新
2017年6月12日
最后验证
2017年6月1日
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.
CAT-8015 5 mcg/kg的临床试验
-
MedImmune LLC终止
-
Center for International Blood and Marrow Transplant...MedImmune LLC; National Marrow Donor Program; Pediatric Blood and Marrow Transplant Consortium; St...终止