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Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

10 de julio de 2014 actualizado por: H. Lee Moffitt Cancer Center and Research Institute

A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

The purpose of this study was to test whether a new drug named visilizumab would decrease the severity of graft-versus-host disease in patients treated with a mismatched donor. Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as the "study treatment".

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

The protocol plan was a two stage, controlled, phase II study to assess safety and compare the grade of acute graft-versus-host disease (GVHD) with visilizumab, or Anti-thymocyte Globulin (ATG) in combination with tacrolimus + methotrexate in patients at high risk of GVHD after transplant from unrelated donors mismatched for 1-2 alleles of any type at human leukocyte antigen (HLA) A, B, C and DRB1.

The study design included two stages. The first stage of the trial was to enroll 15 patients on a single arm to be treated with "study treatment" (visilizumab, tacrolimus and methotrexate) to assess for treatment safety and exclude intolerable GVHD. The second stage of the trial was to include a random control group of patients treated with the current "standard treatment" (ATG, tacrolimus, and methotrexate) or "study treatment". The purpose of this comparison was to determine if the "study treatment" visilizumab causes less severe side effects and if it is more potent in reducing graft-versus-host disease symptoms than the "standard treatment".

Tipo de estudio

Intervencionista

Inscripción (Actual)

8

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

  • Estados Unidos
    • Florida
      • Tampa, Florida, Estados Unidos, 33612
        • H. Lee Moffitt Cancer Center & Research Institute

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

18 años a 60 años (Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • One of the following diagnoses with histological confirmation by the Pathology Department at H. Lee Moffitt Cancer Center:
  • Acute Lymphocytic Leukemia (ALL) in complete remission 1 (CR1) with t(9:22) or t(4:11), or any ALL beyond CR1
  • Acute Myelogenous Leukemia (AML) with high risk cytogenetics in CR1 as defined by Bloomfield any AML beyond CR1
  • Myelodysplastic Syndrome (MDS) with International Prognostic Scoring System (IPSS) score > 1
  • Chronic myelomonocytic leukemia (CMML)
  • Chronic Myelogenous Leukemia (CML) with Imatinib-refractory chronic phase, or beyond chronic phase by morphology or cytogenetics
  • Myelofibrosis
  • Severe aplastic anemia
  • Chemosensitive Non-Hodgkin's lymphoma and Hodgkin's disease that are not candidate to autologous transplant due to prior autologous transplantation
  • Multiple Myeloma patient not candidate for autologous stem cell transplantation
  • Karnofsky performance status ≥ 70% (adult)
  • Normal organ and marrow function as defined below:
  • Hepatic: Total bilirubin must be less than or equal to 2mg/dL (Gilbert and other syndromes with increased indirect bilirubin are allowed); serum transaminases must be less than two times the upper limit of normal
  • Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb), forced expiratory volume-one second (FEV1), forced vital capacity (FVC) must be greater than 50% predicted
  • Cardiac: Left ventricular ejection fraction at rest must be greater than 50%
  • Renal: Creatinine clearance (measured or calculated) must be equal or greater than 50 ml/min/1.73m^2

Exclusion Criteria:

  • Anti thymocyte globulin (ATG) or anti T cell therapy in prior 45 days
  • Splenectomized patients;
  • A positive pregnancy test administered to all females of childbearing potential prior to allogeneic stem cell transplant
  • Inability to comply with follow up as determined by the patient's physician
  • HIV-I/II infection prior to hematopoietic stem cell (HSC) transplantation, confirmed by nucleic acid test (NAT)
  • Uncontrolled bacterial or fungal infection
  • History of documented invasive aspergillosis or cytomegalovirus (CMV) pneumonia
  • Presence of any of the following comorbid conditions:
  • History of myocardial infarction
  • Congestive heart failure (even if symptomatically controlled)
  • Peripheral vascular disease (including intermittent claudication or history of bypass for arterial insufficiency)
  • Untreated thoracic or abdominal aneurysm (6cm or more)
  • History of any cerebrovascular accident including transient ischemic attacks
  • Dementia
  • History of peptic ulcer disease requiring treatment
  • Connective tissue/rheumatologic disorders
  • Diabetes unless being managed with dietary changes only
  • Hemiplegia/paraplegia
  • History of solid tumor excluding skin or cervical carcinoma after curative resection

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: Prevención
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: First Study Stage: Study Treatment
Visilizumab, Tacrolimus and Methotrexate.
Droga: Visilizumab
3 mg/m^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).
Droga: Tacrolimus
0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.
Droga: Methotrexate
15 mg/m^2 intravenously (IV) on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Droga: Tacrolimus
0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.
Droga: Methotrexate
15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Comparador activo: Second Study Stage: Standard Treatment
Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.
Droga: Tacrolimus
0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.
Droga: Methotrexate
15 mg/m^2 intravenously (IV) on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Droga: Tacrolimus
0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.
Droga: Methotrexate
15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Droga: Antithymocyte globulin (ATG)
1 mg/kg IV over 6 hours on Day 3 before transplant; 3.25 mg/kg IV over 4 hours on days 2 and 1 before transplant.
Otros nombres:
  • Thymoglobulin-ATG

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days
Periodo de tiempo: 100 days

Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned.

Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II
100 days

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of Epstein-Barr Virus (EBV) Reactivation
Periodo de tiempo: 3 months
Number of participants who reactivated EBV. Patients had their plasma tested once weekly using the TaqMan polymerase chain reaction (PCR) for quantitative determination of EBV-DNA for 6 weeks. Plasma levels > 1000 copies per ml plasma were scored as positive.
3 months
Incidence of Rituximab Response to Reactivated EBV Without PTLD
Periodo de tiempo: 100 days

Participants who developed plasma EBV-DNA of >1000 copies/mL on any tests received rituximab.

Incidence of Rituximab Response: Reactivated EBV participants whose plasma titers cleared after rituximab, without post-transplant lymphoproliferative disorder (PTLD).
100 days
Overall Survival (OS)
Periodo de tiempo: At 2 years and 5 years
Median OS in days. Survival was measured from the time of transplant to the time of death.
At 2 years and 5 years
Pharmacodynamics of Visilizumab - Test 1
Periodo de tiempo: At 1 - 2 hours
Mean Cmax (±SD)
At 1 - 2 hours
Pharmacodynamics of Visilizumab - Test 2
Periodo de tiempo: Up to 205 hours
Mean terminal half-life (±SD)
Up to 205 hours

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

H. Lee Moffitt Cancer Center and Research Institute

Colaboradores

National Cancer Institute (NCI)
National Institutes of Health (NIH)

Investigadores

  • Investigador principal: Lia Perez, MD, H. Lee Moffitt Cancer Center and Research Institute

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

Enlaces Útiles

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 diciembre de 2007

Finalización primaria (Actual)

1 de diciembre de 2013

Finalización del estudio (Actual)

1 de diciembre de 2013

Fechas de registro del estudio

Enviado por primera vez

21 de julio de 2008

Primero enviado que cumplió con los criterios de control de calidad

21 de julio de 2008

Publicado por primera vez (Estimar)

23 de julio de 2008

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

18 de julio de 2014

Última actualización enviada que cumplió con los criterios de control de calidad

10 de julio de 2014

Última verificación

1 de abril de 2014

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • MCC-15033
  • R01CA132197-06A2 (Subvención/contrato del NIH de EE. UU.)

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. .

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