ACT34-CMI -- Adult Autologous CD34+ Cells
8 de janeiro de 2021 atualizado 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
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 estudo
Intervencional
Inscrição (Real)
321
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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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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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
21 anos a 80 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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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.
Outros nomes:
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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.
Outros nomes:
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Comparador de Placebo: 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.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of Angina Episodes Per Week at 6 and 12 Months
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Diretor de estudo: Caladrius Study DIrector, Lisata Therapeutics, Inc.
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- 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.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de abril de 2006
Conclusão Primária (Real)
1 de março de 2008
Conclusão do estudo (Real)
1 de março de 2009
Datas de inscrição no estudo
Enviado pela primeira vez
6 de março de 2006
Enviado pela primeira vez que atendeu aos critérios de CQ
6 de março de 2006
Primeira postagem (Estimativa)
8 de março de 2006
Atualizações de registro de estudo
Última Atualização Postada (Real)
26 de janeiro de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
8 de janeiro de 2021
Última verificação
1 de janeiro de 2021
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 24779
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .