ACT34-CMI -- Adult Autologous CD34+ Cells
2021년 1월 8일 업데이트: 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.
연구 개요
상세 설명
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.
연구 유형
중재적
등록 (실제)
321
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
-
-
Alabama
-
Birmingham, Alabama, 미국, 35211
- Cardiology PC
-
-
Arizona
-
Phoenix, Arizona, 미국, 85054
- Mayo Clinic Hospital
-
Phoenix, Arizona, 미국, 85005
- Arizona Heart Institute
-
-
California
-
La Jolla, California, 미국, 92037
- Scripps Memorial Hospital
-
Stanford, California, 미국, 94305
- Stanford University Hospital and Clinics
-
-
District of Columbia
-
Washington, District of Columbia, 미국, 20010
- Washington Hospital Center
-
-
Florida
-
Fort Lauderdale, Florida, 미국, 33308
- Holy Cross Hospital
-
Gainesville, Florida, 미국, 32610
- University of Florida Health Science Center
-
Jacksonville, Florida, 미국, 32209
- University of Florida Health Science Center
-
Orlando, Florida, 미국, 32803
- Central Florida Cardiology Group
-
-
Georgia
-
Atlanta, Georgia, 미국, 30342
- Saint Joseph's Research Institute
-
-
Illinois
-
Chicago, Illinois, 미국, 60612
- Rush University Medical Center
-
Chicago, Illinois, 미국, 60611
- Northwestern University Medical Center, Bluhm Cardiovascluar Institute
-
-
Iowa
-
Iowa City, Iowa, 미국, 52242
- University of Iowa Hospitals & Clinic
-
-
Massachusetts
-
Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital
-
Boston, Massachusetts, 미국, 02135
- Caritas Saint Elizabeth's Medical Center
-
-
Minnesota
-
Minneapolis, Minnesota, 미국, 55407
- Abbott Northwestern Hospital
-
-
New York
-
New York, New York, 미국, 10032
- New York Presbyterian Hospital - Columbia University Medical Center
-
New York, New York, 미국, 10065
- New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University
-
-
Ohio
-
Cincinnati, Ohio, 미국, 45267
- University of Cincinnati Medical Center
-
Cincinnati, Ohio, 미국, 45219
- The Lindner Clinical Trial Center
-
Cleveland, Ohio, 미국, 44106
- University Hospitals Case Medical Center
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, 미국, 15213
- University of Pittsburgh Medical Center
-
-
Washington
-
Seattle, Washington, 미국, 98122
- Swedish Heart & Vascular - Swedish Medical Center
-
-
Wisconsin
-
Madison, Wisconsin, 미국, 53792
- University of Wisconsin Medical School
-
Milwaukee, Wisconsin, 미국, 53223
- Comprehensive Cardiovascular Care Group
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
21년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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
|
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.
다른 이름들:
|
|
실험적: 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
|
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.
다른 이름들:
|
|
위약 비교기: Placebo injection
10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma
|
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.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of Angina Episodes Per Week at 6 and 12 Months
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
기간: 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
기간: Baseline and 12 months after treatment
|
The Canadian Cardiovascular Society (CCS) Functional Classification of Angina is as follows:
|
Baseline and 12 months after treatment
|
|
Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
기간: 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
기간: 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
기간: Baseline to 6 months
|
The mean nitroglycerin use per week was analyzed at baseline and 6 months
|
Baseline to 6 months
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 연구 책임자: Caladrius Study DIrector, Lisata Therapeutics, Inc.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Losordo DW, Henry TD, Davidson C, Sup Lee J, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Traverse JH, Amrani D, Ewenstein BM, Riedel N, Story K, Barker K, Povsic TJ, Harrington RA, Schatz RA; ACT34-CMI Investigators. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res. 2011 Aug 5;109(4):428-36. doi: 10.1161/CIRCRESAHA.111.245993. Epub 2011 Jul 7.
- Henry TD, Schaer GL, Traverse JH, Povsic TJ, Davidson C, Lee JS, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Patel AN, Riedel N, Junge C, Hunt A, Kereiakes DJ, White C, Harrington RA, Schatz RA, Losordo DW; ACT. Autologous CD34+ Cell Therapy for Refractory Angina: 2-Year Outcomes From the ACT34-CMI Study. Cell Transplant. 2016;25(9):1701-1711. doi: 10.3727/096368916X691484. Epub 2016 May 4.
- Povsic TJ, Losordo DW, Story K, Junge CE, Schatz RA, Harrington RA, Henry TD. Incidence and clinical significance of cardiac biomarker elevation during stem cell mobilization, apheresis, and intramyocardial delivery: an analysis from ACT34-CMI. Am Heart J. 2012 Nov;164(5):689-697.e3. doi: 10.1016/j.ahj.2012.06.022.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2006년 4월 1일
기본 완료 (실제)
2008년 3월 1일
연구 완료 (실제)
2009년 3월 1일
연구 등록 날짜
최초 제출
2006년 3월 6일
QC 기준을 충족하는 최초 제출
2006년 3월 6일
처음 게시됨 (추정)
2006년 3월 8일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2021년 1월 26일
QC 기준을 충족하는 마지막 업데이트 제출
2021년 1월 8일
마지막으로 확인됨
2021년 1월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .