此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

ACT34-CMI -- Adult Autologous CD34+ Cells

2021年1月8日 更新者：Lisata Therapeutics, Inc.

A DB, Randomized, Placebo-controlled Study of the Tolerability, Efficacy, Safety, and Dose Range of Intramyocardial CLBS14 for Reduction of Angina Episodes in Patients With Refractory Chronic Myocardial Ischemia (ACT34-CMI)

The purpose of this study is to evaluate the efficacy and safety of intramyocardial injections of CLBS14 in patients with refractory chronic myocardial ischemia.

研究概览

地位

完全的

条件

干预/治疗

详细说明

This is a double-blind, prospective, randomized, placebo-controlled trial to determine the tolerability, efficacy, safety and dose range of intramyocardial injections of adult autologous CD34+ cells mobilized with granulocyte colony stimulating factor (G-CSF) for the reduction of angina episodes in patients with refractory chronic myocardial ischemia.

研究类型

介入性

注册 (实际的)

321

阶段

  • 阶段2

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。

学习地点

  • 美国
    • Alabama
      • Birmingham、Alabama、美国、35211
        • Cardiology PC
    • Arizona
      • Phoenix、Arizona、美国、85054
        • Mayo Clinic Hospital
      • Phoenix、Arizona、美国、85005
        • Arizona Heart Institute
    • California
      • La Jolla、California、美国、92037
        • Scripps Memorial Hospital
      • Stanford、California、美国、94305
        • Stanford University Hospital and Clinics
    • District of Columbia
      • Washington、District of Columbia、美国、20010
        • Washington Hospital Center
    • Florida
      • Fort Lauderdale、Florida、美国、33308
        • Holy Cross Hospital
      • Gainesville、Florida、美国、32610
        • University of Florida Health Science Center
      • Jacksonville、Florida、美国、32209
        • University of Florida Health Science Center
      • Orlando、Florida、美国、32803
        • Central Florida Cardiology Group
    • Georgia
      • Atlanta、Georgia、美国、30342
        • Saint Joseph's Research Institute
    • Illinois
      • Chicago、Illinois、美国、60612
        • Rush University Medical Center
      • Chicago、Illinois、美国、60611
        • Northwestern University Medical Center, Bluhm Cardiovascluar Institute
    • Iowa
      • Iowa City、Iowa、美国、52242
        • University of Iowa Hospitals & Clinic
    • Massachusetts
      • Boston、Massachusetts、美国、02114
        • Massachusetts General Hospital
      • Boston、Massachusetts、美国、02135
        • Caritas Saint Elizabeth's Medical Center
    • Minnesota
      • Minneapolis、Minnesota、美国、55407
        • Abbott Northwestern Hospital
    • New York
      • New York、New York、美国、10032
        • New York Presbyterian Hospital - Columbia University Medical Center
      • New York、New York、美国、10065
        • New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University
    • Ohio
      • Cincinnati、Ohio、美国、45267
        • University of Cincinnati Medical Center
      • Cincinnati、Ohio、美国、45219
        • The Lindner Clinical Trial Center
      • Cleveland、Ohio、美国、44106
        • University Hospitals Case Medical Center
    • Pennsylvania
      • Pittsburgh、Pennsylvania、美国、15213
        • University of Pittsburgh Medical Center
    • Washington
      • Seattle、Washington、美国、98122
        • Swedish Heart & Vascular - Swedish Medical Center
    • Wisconsin
      • Madison、Wisconsin、美国、53792
        • University of Wisconsin Medical School
      • Milwaukee、Wisconsin、美国、53223
        • Comprehensive Cardiovascular Care Group

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

21年 至 80年 (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:

  • Canadian Cardiovascular Society (CCS) functional class III or IV chronic refractory angina
  • subjects without control of their angina symptoms, in spite of maximal tolerated doses of anti-anginal drugs, must be on optimal therapy for their angina and on a stable anti-anginal medication regimen for at least 1 month prior to entering the screening period of the study
  • identified as unsuitable for conventional revascularization
  • recent coronary angiogram (within the last 12 months) to document the coronary anatomy and to verify the revascularization procedures
  • subjects must have objective evidence of inducible ischemia or viable myocardium in the potential target injection zone
  • a left ventricular ejection fraction equal to or greater than 25% by ECHO or single photon emission computed tomography (SPECT) at screening
  • subjects must experience at minimum an average of 7 angina or anginal equivalent episodes per week
  • subjects must be able to complete a minimum of 3 minutes but nor more than 10 minutes on a treadmill following the Modified Bruce Protocol
  • subjects must experience angina or anginal equivalent episodes during the screening exercise treadmill test
  • female subjects must either be no longer capable of reproduction or using medically valid contraception to prevent pregnancy during the study
  • subjects must be willing and able to comply with specified follow-up evaluations

Exclusion Criteria:

  • predominant congestive heart failure
  • myocardial infarction within 60 days of treatment
  • successful or partially successful coronary revascularization procedures (any vessel) within 6 months of study enrollment
  • placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure in the past 90 days
  • documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment
  • history of moderate to severe aortic stenosis or severe aortic insufficiency; severe mitral stenosis or severe mitral insufficiency
  • prosthetic aortic valve replacement
  • evidence of any life-threatening arrhythmia that requires intervention on the 24-hour Holter monitor. Life-threatening arrhythmia that is successfully treated with an implantable cardioverter defibrillator (ICD) is not exclusionary.
  • splenomegaly and/or severe co-morbidity associated with a reduction in life expectancy of less than 1 year, such as chronic medical illness (ie, severe chronic obstructive pulmonary disease, renal failure or cancer [exceptions: in-situ skin cancer or fully removed skin cancer other than melanoma, in-situ cervical cancer, or cancer free for 5 years with no history of a stem cell transplant])
  • sickle cell disease or sickle cell trait
  • platelet count greater than 10% above the upper limit of normal or a platelet count below 100,000 if on Clopidogrel or 50,000 without Clopidogrel
  • hematocrit <30%
  • serum creatinine >2.5 mg/dL
  • any clinically significant laboratory abnormality on screening laboratories
  • currently enrolled in another IDE or IND that has not completed the protocol required primary follow-up period (excludes 15 year follow up of gene therapy trials)
  • history of alcohol or drug abuse within 3 months of screening
  • joint or peripheral vascular disease or neurologic disease that severely limits treadmill walking
  • chronic obstructive pulmonary disease that severely limits walking or FEV1 <30% predicted
  • females who are pregnant or lactating
  • female subjects who are capable of reproduction and will not use medically valid contraception to prevent pregnancy during the study
  • subjects who test positive for HIV, hepatitis B or hepatitis C, or are on chronic immunosuppressive medications or have had a prior stem cell transplant
  • subjects with a known hypersensitivity to E. coli-derived proteins, or to any component of Neupogen (Filgrastim) or G-CSF
  • subjects who have a significant psychiatric disorder or mental disability that could interfere with the subject´s ability to provide informed consent and/or comply with protocol procedures

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：随机化
  • 介入模型：并行分配
  • 屏蔽：三倍

武器和干预

参与者组/臂
干预/治疗
实验性的：CLBS14: Low-Dose Group
10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 1 x 10^5 (=100000) cells/kg bodyweight
生物：CLBS14 (low-dose)
Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 1 x 10^5 (=100000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.
其他名称：
  • G-CSF mobilized, autologous CD34+ cells
实验性的：CLBS14: High-Dose Group
10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 5 x 10^5 (=500000) cells/kg bodyweight
生物：CLBS14 (high-dose)
Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 5 x 10^5 (=500000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.
其他名称：
  • G-CSF mobilized, autologous CD34+ cells
安慰剂比较：Placebo injection
10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma
生物：placebo injection
Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Placebo will be delivered in 10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma into the target areas of myocardial ischemia.
其他名称：
  • 0.9% NaCl (saline) in 5% autologous plasma

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 Angina Episodes Per Week at 6 and 12 Months
大体时间：6 and 12 months
The number of angina episodes were collected via an electronic subject diary for four weeks at Baseline and at 6 and 12 months. The four-week angina episodes (per week mean) were used as the frequency for each visit. A lower number represents fewer angina episodes. A lower number is better.
6 and 12 months

次要结果测量

结果测量
措施说明
大体时间
Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
大体时间：Change from Baseline to 6 months and change from baseline to 12 months after treatment
A modified Bruce Protocol Exercise Treadmill Test was used to evaluate duration of exercise in all subjects.
Change from Baseline to 6 months and change from baseline to 12 months after treatment
Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels
大体时间：Baseline and 12 months after treatment

The Canadian Cardiovascular Society (CCS) Functional Classification of Angina is as follows:

  • Class I - Angina only during strenuous or prolonged physical activity
  • Class II - Slight limitation, with angina only during vigorous physical activity
  • Class III - Symptoms with everyday living activities, i.e., moderate limitation
  • Class IV - Inability to perform any activity without angina or angina at rest, i.e., severe limitation
Baseline and 12 months after treatment
Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
大体时间：Baseline to 6 months after treatment
Angina symptoms were evaluated based on the Seattle Angina Questionnaire (SAQ), which was used to analyze the following: physical limitations, angina stability, angina frequency, treatment satisfaction, and disease perception. The SAQ consisted of 11 questions with 5 or 6 possible responses. Responses were ordinal values (1-7, 10, 11, 97, depending on the type of question; no uniform ranges throughout); responses that corresponded to the lowest level of functioning (worse outcomes) were assigned values of 1, while responses that corresponded to higher functioning levels (better outcome) were assigned a higher ordinal value. If the response to any of these questions was 97 it was recoded as a missing value. Each scale can have a scored value ranging from 0 to 100. A larger number is better.
Baseline to 6 months after treatment
Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters
大体时间：Baseline to 6 months after treatment
The Short Form 36 (SF-36) health survey form was used to analyze physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, general mental health, and health transition. Responses were coded as ordinal numbers going from worst (=1) to best (=highest number). These ordinal scores were transformed into scales ranging from 0 to 100. Higher numbers are generally considered better.
Baseline to 6 months after treatment
Change in Anti-anginal Medication (ie, Nitroglycerin) Use
大体时间：Baseline to 6 months
The mean nitroglycerin use per week was analyzed at baseline and 6 months
Baseline to 6 months

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。

赞助

Lisata Therapeutics, Inc.

调查人员

  • 研究主任：Caladrius Study DIrector、Lisata Therapeutics, Inc.

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

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

2006年4月1日

初级完成 (实际的)

2008年3月1日

研究完成 (实际的)

2009年3月1日

研究注册日期

首次提交

2006年3月6日

首先提交符合 QC 标准的

2006年3月6日

首次发布 (估计)

2006年3月8日

研究记录更新

最后更新发布 (实际的)

2021年1月26日

上次提交的符合 QC 标准的更新

2021年1月8日

最后验证

2021年1月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 24779

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.

订阅