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A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)

30 de diciembre de 2021 actualizado por: Janssen Pharmaceutical K.K.

A Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Subjects With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)

The purpose of this study is to evaluate efficacy of ibrutinib in Japanese participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response [CR] and partial response [PR] defined by National Institutes of Health [NIH] consensus development project criteria [2014]).

Descripción general del estudio

Estado

Terminado

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

19

Fase

  • Fase 3

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

      • Anjo-shi, Japón, 446-8602
        • Anjo Kosei Hospital
      • Bunkyo-ku, Japón, 113-8677
        • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
      • Hiroshima, Japón, 730-8619
        • Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
      • Hyogo, Japón, 650-0047
        • Kobe City Medical Center General Hospital
      • Isehara, Japón, 259-1193
        • Tokai University Hospital
      • Izumi, Japón, 594-1101
        • Osaka Women's and Children's Hospital
      • Kumamoto, Japón, 860-0008
        • National Hospital Organization Kumamoto Medical Center
      • Kurashiki, Japón, 710-8602
        • Kurashiki Central Hospital
      • Maebashi, Japón, 371-0821
        • Gunmaken Saiseikai Maebashi Hospital
      • Nagoya, Japón, 453-8511
        • Japanese Red Cross Nagoya Daiichi Hospital
      • Nishinomiya, Japón, 663-8501
        • The Hospital of Hyogo College of Medicine
      • Okayama, Japón, 700-8558
        • Okayama University Hospital
      • Osaka, Japón, 545-8586
        • Osaka City University Hospital
      • Sapporo-shi, Japón, 060-8648
        • Hokkaido University Hospital
      • Setagaya-ku, Japón, 157-8535
        • National Center for Child Health and Development

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

12 años y mayores (Niño, Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as modified National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): a) Dependent disease, defined as, when glucocorticoid (prednisolone doses greater than or equal to [>=] 0.25 milligram per kilogram per day (mg/kg/day)or >=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. In case of inability to taper the dose to less than or equal to (<=)0.25 mg/kg/day or <=0.5 mg/kg every other day (prednisolone doses) due to recurrence or progression of cGVHD manifestations, it is considered as steroid-dependent disease if the lowest tapering dose of the second occasion is equal or higher than the lowest tapering dose of the first occasion; b) Refractory disease, defined as, when cGVHD manifestations progress despite the use of a regimen containing glucocorticoid (prednisolone at >=1 mg/kg/day for at least 1 week) or persist without improvement despite continued treatment with glucocorticoid (prednisolone at >=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks
  • Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting ibrutinib
  • At the time of trial enrollment, participants may be receiving other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting ibrutinib
  • Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment
  • Karnofsky or Lansky (participants less than [<]16 years) performance status >=60

Exclusion Criteria:

  • Active acute graft versus host disease (GVHD)
  • More than 3 previous systemic treatments for cGVHD. Treatment with glucocorticoids is considered a treatment for cGVHD and should be included in determining the number of previous treatments
  • History of treatment with a tyrosine kinase inhibitor (example [e.g.] imatinib), purine analogs, or other cancer chemotherapy in the 4 weeks prior to starting ibrutinib. Participants may have received ibrutinib pre-transplant for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma
  • History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib

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: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Ibrutinib
Participants will receive 420 milligram (mg) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
Participants will receive 420 mg (3 * 140 mg capsules) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
Otros nombres:
  • PCI-32765
  • JNJ-54179060

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage of Participants who Achieve Complete Response (CR) or Partial Response (PR) (i.e. Overall Response Rate [ORR])
Periodo de tiempo: Approximately up to 4.5 years
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR). Response is defined by the National Institutes of Health (NIH) Consensus Development Project Criteria (2014) and must occur, in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death. CR: Resolution of all manifestations in each organ or site. PR: Improvement in at least 1 organ or site without progression in any other organ or site. cGVHD Progression: Clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Approximately up to 4.5 years

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage of Participants with Sustained Response
Periodo de tiempo: Approximately up to 4.5 years
Percentage of participants with sustained response is defined as rate of NIH defined CR or PR that was sustained for at least 20 weeks.
Approximately up to 4.5 years
Duration of Response (DOR)
Periodo de tiempo: From the date of initial documentation of a response to the date of first documented evidence of progressive cGVHD or death, whichever occurs first (approximately up to 4.5 years)
DOR is defined as the duration of time from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurs first.
From the date of initial documentation of a response to the date of first documented evidence of progressive cGVHD or death, whichever occurs first (approximately up to 4.5 years)
Percentage of Participants with cGVHD response at Each Timepoint of Efficacy Evaluation
Periodo de tiempo: Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and every 12 weeks (q12w) thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Percentage of Participants with cGVHD response at each timepoint of efficacy evaluation (cGVHD response rate) is defined as percentage of participants with NIH defined CR or PR at each timepoint.
Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and every 12 weeks (q12w) thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Change in the Amount of Corticosteroid Required Per Participant Over Time
Periodo de tiempo: Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Change in the amount of corticosteroid required per participant over time will be monitored across the study.
Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Improvement in Symptom Burden Measured by the Lee cGVHD Symptom Scale
Periodo de tiempo: Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Lee cGVHD Symptom Scale is a participant-reported symptom scale. It includes a total of 30 items within the following 7 domains: Skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, mental and emotional for evaluating overall response. Response options range from 0 to 4 and includes: "not at all" (0), "Slightly" (1), "Moderately" (2), "Quite a bit" (3), and "extremely" (4), and yield an overall score. A change greater than or equal to (>=) 7 points on the Lee cGVHD Symptom Scale will be considered significant and relates to improvement in quality of life (QoL).
Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Periodo de tiempo: From signing Informed Consent Form until 30 days after the last dose of study treatment (approximately up to 4.5 years)
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
From signing Informed Consent Form until 30 days after the last dose of study treatment (approximately up to 4.5 years)
Number of Participants with Clinical Laboratory Abnormalities
Periodo de tiempo: Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment (approximately up to 4.5 years)
Number of participants with clinical laboratory abnormalities will be reported.
Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment (approximately up to 4.5 years)
Area Under the Plasma Concentration-Time Curve from Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-last) is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Area Under the Plasma Concentration-Time Curve from Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-24) is defined as the area under the plasma concentration-time curve from time zero to 24 hours.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Cmax is defined as the maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Elimination Half-Life (t1/2) of Ibrutinib
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-last) of Metabolite PCI-45227
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-last) is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-24) of Metabolite PCI-45227
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-24) is defined as the area under the plasma concentration-time curve from time zero to 24 hours.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Cmax of Metabolite PCI-45227
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Cmax is defined as the maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Tmax of Metabolite PCI-45227
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
t1/2 of Metabolite PCI-45227
Periodo de tiempo: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1

Colaboradores e Investigadores

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

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.

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 (Actual)

1 de mayo de 2018

Finalización primaria (Actual)

29 de noviembre de 2021

Finalización del estudio (Actual)

29 de noviembre de 2021

Fechas de registro del estudio

Enviado por primera vez

16 de marzo de 2018

Primero enviado que cumplió con los criterios de control de calidad

16 de marzo de 2018

Publicado por primera vez (Actual)

22 de marzo de 2018

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

3 de enero de 2022

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

30 de diciembre de 2021

Última verificación

1 de diciembre de 2021

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • CR108443
  • 54179060GVH3001 (Otro identificador: Janssen Pharmaceutical K.K., Japan)

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

producto fabricado y exportado desde los 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. .

Ensayos clínicos sobre Ibrutinib

3
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