ACT34-CMI -- Adult Autologous CD34+ Cells
8 de enero de 2021 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
321
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Alabama
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Birmingham, Alabama, Estados Unidos, 35211
- Cardiology PC
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Arizona
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Phoenix, Arizona, Estados Unidos, 85054
- Mayo Clinic Hospital
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Phoenix, Arizona, Estados Unidos, 85005
- Arizona Heart Institute
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California
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La Jolla, California, Estados Unidos, 92037
- Scripps Memorial Hospital
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Stanford, California, Estados Unidos, 94305
- Stanford University Hospital and Clinics
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20010
- Washington Hospital Center
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Florida
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Fort Lauderdale, Florida, Estados Unidos, 33308
- Holy Cross Hospital
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Gainesville, Florida, Estados Unidos, 32610
- University of Florida Health Science Center
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Jacksonville, Florida, Estados Unidos, 32209
- University of Florida Health Science Center
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Orlando, Florida, Estados Unidos, 32803
- Central Florida Cardiology Group
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Georgia
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Atlanta, Georgia, Estados Unidos, 30342
- Saint Joseph's Research Institute
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Illinois
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Chicago, Illinois, Estados Unidos, 60612
- Rush University Medical Center
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Chicago, Illinois, Estados Unidos, 60611
- Northwestern University Medical Center, Bluhm Cardiovascluar Institute
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Iowa
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Iowa City, Iowa, Estados Unidos, 52242
- University of Iowa Hospitals & Clinic
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Estados Unidos, 02135
- Caritas Saint Elizabeth's Medical Center
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55407
- Abbott Northwestern Hospital
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New York
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New York, New York, Estados Unidos, 10032
- New York Presbyterian Hospital - Columbia University Medical Center
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New York, New York, Estados Unidos, 10065
- New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45267
- University of Cincinnati Medical Center
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Cincinnati, Ohio, Estados Unidos, 45219
- The Lindner Clinical Trial Center
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Cleveland, Ohio, Estados Unidos, 44106
- University Hospitals Case Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- University of Pittsburgh Medical Center
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Washington
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Seattle, Washington, Estados Unidos, 98122
- Swedish Heart & Vascular - Swedish Medical Center
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53792
- University of Wisconsin Medical School
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Milwaukee, Wisconsin, Estados Unidos, 53223
- Comprehensive Cardiovascular Care Group
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
21 años a 80 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: 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
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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.
Otros nombres:
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Experimental: 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
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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.
Otros nombres:
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Comparador de placebos: Placebo injection
10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma
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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.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Angina Episodes Per Week at 6 and 12 Months
Periodo de tiempo: 6 and 12 months
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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.
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6 and 12 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
Periodo de tiempo: Change from Baseline to 6 months and change from baseline to 12 months after treatment
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A modified Bruce Protocol Exercise Treadmill Test was used to evaluate duration of exercise in all subjects.
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Change from Baseline to 6 months and change from baseline to 12 months after treatment
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Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels
Periodo de tiempo: Baseline and 12 months after treatment
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The Canadian Cardiovascular Society (CCS) Functional Classification of Angina is as follows:
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Baseline and 12 months after treatment
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Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
Periodo de tiempo: Baseline to 6 months after treatment
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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.
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Baseline to 6 months after treatment
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Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters
Periodo de tiempo: Baseline to 6 months after treatment
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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.
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Baseline to 6 months after treatment
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Change in Anti-anginal Medication (ie, Nitroglycerin) Use
Periodo de tiempo: Baseline to 6 months
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The mean nitroglycerin use per week was analyzed at baseline and 6 months
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Baseline to 6 months
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Director de estudio: Caladrius Study DIrector, Lisata Therapeutics, Inc.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de abril de 2006
Finalización primaria (Actual)
1 de marzo de 2008
Finalización del estudio (Actual)
1 de marzo de 2009
Fechas de registro del estudio
Enviado por primera vez
6 de marzo de 2006
Primero enviado que cumplió con los criterios de control de calidad
6 de marzo de 2006
Publicado por primera vez (Estimar)
8 de marzo de 2006
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
26 de enero de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
8 de enero de 2021
Última verificación
1 de enero de 2021
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Enfermedades cardíacas
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Arteriosclerosis
- Enfermedades arteriales oclusivas
- Enfermedad coronaria
- Enfermedad de la arteria coronaria
- Isquemia miocardica
- Isquemia
- Efectos fisiológicos de las drogas
- Factores inmunológicos
- Adyuvantes, Inmunológicos
- Lenograstim
Otros números de identificación del estudio
- 24779
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .