- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02638467
Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Failing TKIs Therapy
Allogeneic Haematopoietic Stem Cell Transplantation From a Matched Donor in Patients With Chronic Myeloid Leukemia Failing to Gain Normal Hemopoiesis Under TKIs Therapy
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Italy/MB
-
Monza, Italy/MB, Italia, 20900
- Asst-Monza
-
-
MI
-
Milano, MI, Italia, 20132
- Ospedale San Raffaele
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Chronic Myeloid Leukaemia -CML- in chronic phase (CP)
- Failure to achieve at least a Major Cytogenetic Response (MCyR) after a minimum of 18 months of TKIs treatment
- Inability to tolerate 3 months of uninterrupted full dose TKIs therapy due to hematological toxicity
- A minimum of three treatment interruptions due to hematological toxicity Availability of a HLA-identical related donor (Matched Related Donor, MRD)
- Availability of unrelated donor (Matched Unrelated Donor, MUD) satisfying the criteria of a 10/10 antigen match at (Human Leukocyte Antigen) HLA-A, -B, -C and - DRB1, -DQB1 at high resolution typing, or 9/10 with a permissive - DP disparity according to Fleischhauer model (Crocchiolo et al, Blood 2009)
- Target graft size (bone marrow):
- bone marrow: > 3 x 106 CD34+ cells/kg BW recipient or > 3 x 108 nucleated cells/kg BW
- Karnofsky Index > 80 %
- Age ≥18 and ≤70 years
- Adequate contraception in female patients of child-bearing potential
- Written informed consent
Exclusion Criteria:
- Secondary malignancies
- A hematopoietic cell transplantation-specific comorbidity index (Sorror et al Appendix C) > 4
- Known and manifested malignant involvement of the Central Nervous System (CNS)
- Active infectious disease
- Active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis B virus (HCV) infection
- Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)
- Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
- Pleural effusion or ascites > 1.0 L
- Pregnancy or lactation
- Known hypersensitivity to Busilvex and/or fludarabine 11 Non-co-operative behaviour or non-compliance 12 Psychiatric diseases or conditions that might impair the ability to give informed consent
Plan de estudios
¿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: Bosutinib and Bone Marrow Transplant
Subjects will receive 400mg of bosutinib from day at least -45 to day -15 to assess the sensitivity of patient Chronic Myeloid Leukemia (CML) to this TKI.
Patients will be transplanted with the aim to transplant > 3 x 106 CD34+ cells/kg Body Weight (BW) recipient from bone marrow or > 3 x 108 nucleated cells/kg BW recipient from bone marrow.
Then, subjects will receive 400mg of bosutinib once daily from day +30 after transplant.
|
Subjects will receive 400mg of bosutinib once daily from day +30 after transplant, by mouth with food, preferably in the morning.
Bosutinib will also be administered from day at least -45 to day -15 to assess the sensitivity of patient CML to this TKI.
Otros nombres:
Samples of the unrelated stem cell graft shall be characterised with respect to the number of CD34 positive cells per kg body weight of the recipient. The number of transplanted CD34 positive cells per kg body weight (BW) of the recipient shall be recorded in the Case Report Form (CRF). If the transplant was cryopreserved the number of viable CD34 positive cells has to be determined after thawing and documented. The goal is to transplant > 3 x 106 CD34+ cells/kg BW recipient from bone marrow or > 3 x 108 nucleated cells/kg BW recipient from bone marrow |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Efficacy as assessed by the percentage of patients with Complete Cytogenetic Response (CCyR)
Periodo de tiempo: 12 months
|
The percentage of patients with Complete Cytogenetic Response (CCyR) will be calculated as the complement to the percentage of failures on the total number of patients treated, where failure includes the following events: no engraftment, death within 12 months, no CCyR at 12 months.
|
12 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Sobrevivencia promedio
Periodo de tiempo: 12 meses
|
12 meses
|
|
Percentage of patients with engraftment
Periodo de tiempo: 12 months
|
12 months
|
|
percentage of patients with complete chimerism (95%)
Periodo de tiempo: Day +28, +56 and +100
|
Day +28, +56 and +100
|
|
Evaluation of Major Cytogenetic Response (MCyR)
Periodo de tiempo: 12 months
|
Major Cytogenetic Response (MCyR) is < 36% Ph+ metaphases
|
12 months
|
Evaluation of molecular responses
Periodo de tiempo: 12 months
|
Molecular response is defined
|
12 months
|
Relapse incidence (RI)
Periodo de tiempo: 12 months
|
12 months
|
|
Incidence of non-relapse mortality (NRM)
Periodo de tiempo: Within day +28 and +360
|
Within day +28 and +360
|
|
Incidence and severity of acute and chronic graft vs. host disease (GvHD)
Periodo de tiempo: 12 months
|
12 months
|
|
Quality of Life (QoL)
Periodo de tiempo: 12 months
|
Evaluation of QoL with EQ-5D-5L (Italian - Version 2) and FACT-Leu (Italian -Version 4)
|
12 months
|
Overall Survival (OS)
Periodo de tiempo: 36 months
|
2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
|
36 months
|
Progression Free Survival (PFS)
Periodo de tiempo: 36 months
|
2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
|
36 months
|
Relapse Incidence (RI)
Periodo de tiempo: 36 months
|
2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
|
36 months
|
Chronic Graft-versus-host Disease (cGvHD)
Periodo de tiempo: 36 months
|
2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
|
36 months
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: CARLO GAMBACORTI-PASSERINI, MD, University of Milano Bicocca
Publicaciones y enlaces útiles
Publicaciones Generales
- Redaelli A, Bell C, Casagrande J, Stephens J, Botteman M, Laskin B, Pashos C. Clinical and epidemiologic burden of chronic myelogenous leukemia. Expert Rev Anticancer Ther. 2004 Feb;4(1):85-96. doi: 10.1586/14737140.4.1.85.
- Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR, Grosveld G. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983 Nov 17-23;306(5940):239-42. doi: 10.1038/306239a0.
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- alloCML
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 Bosutinib
-
PfizerTerminado
-
PfizerTerminadoParticipantes SaludablesPaíses Bajos
-
Kyoto UniversityPfizer; Kitasato University; Tokushima University; Tottori UniversityReclutamientoLa esclerosis lateral amiotróficaJapón
-
PfizerTerminadoNeoplasiasEstados Unidos
-
Children's Oncology GroupPfizer; Erasmus Medical Center; Dutch Childhood Oncology Group; Innovative Therapies...Activo, no reclutandoLeucemia mielógena crónica en fase acelerada | Leucemia mielógena crónica en fase crónica | Leucemia mielógena crónica en fase blástica | LMC positiva para el cromosoma FiladelfiaEstados Unidos
-
Wyeth is now a wholly owned subsidiary of PfizerTerminado
-
Wyeth is now a wholly owned subsidiary of PfizerTerminado