Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers (ProT4)
Multicenter Randomized Phase II Study to Evaluate the Efficacy of Prophylactic Transfer of CD4 Lymphocytes After T-cell Depleted Reduced Intensity HLA-Identical Sibling Transplantation for Haematological Cancers
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving alemtuzumab before transplant and cyclosporine after transplant, may stop this from happening.
PURPOSE: This randomized phase II trial is studying donor lymphocyte infusion after stem cell transplant in preventing cancer relapse or cancer progression in patients with follicular lymphoma, small lymphocytic non-Hodgkin lymphoma, or chronic lymphocytic leukemia.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- To evaluate the effect of prophylactic transfer of donor CD4 cells after T-cell depleted reduced-intensity HLA-identical sibling transplantation upon the risk of relapse or progression in patients with haematological cancers (e.g. NHL, HL, CLL/PLL, PCM, AML, ALL, MDS or CMML depending on the disease status).
Secondary
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the risk of graft-versus-host disease (GvHD) in these patients.
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the rates of conversion to full donor chimerism in peripheral blood in these patients.
- To determine the effect of prophylactic transfer of donor CD4 cells upon immune reconstitution in these patients.
- To evaluate the impact of prophylactic transfer of donor CD4 cells upon non-relapse mortality and overall survival of these patients.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV, melphalan IV, and alemtuzumab IV as reduced intensity conditioning for T-cell depletion followed by a reduced-intensity HLA-identical sibling stem cell transplantation on day 0. Withdrawal of cyclosporine immunosuppression therapy commence at day 40 with tapering over a period of 3-4 weeks, according to the discretion of the PI. Patients are reassessed between day 70-90 post-transplantation. Patients with stable engraftment, no significant graft-versus-host disease, and no early relapse or progression are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive an allogeneic CD4 donor lymphocyte infusion (DLI) at a dose of 1 x10^6 CD4 cells/kg body weight without any other medication once between day 100-120.
- Arm II: Patients receive no further treatment.
Patients undergo blood sample collection for chimerism studies and translational research.
After completion of study treatment, patients are followed up periodically for 1 years and then annually.
Peer Reviewed and Funded or Endorsed by Bloodwise.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Birmingham, Reino Unido
- Birmingham Heartlands Hospital
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Bristol, Reino Unido
- Bristol Royal Hospital for Children
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Cambridge, Reino Unido
- Addenbrooke's Hospital
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Glasgow, Reino Unido
- Beatson West of Scotland Cancer Centre
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Leeds, Reino Unido
- St James's University Hospital
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Leicester, Reino Unido
- Leicester Royal Infirmary
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London, Reino Unido
- University College Hospital London (UCLH)
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Manchester, Reino Unido
- Christie Hospital
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Nottingham, Reino Unido
- Nottingham City Hospital
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Sheffield, Reino Unido
- Royal Hallamshire Hospital
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Southampton, Reino Unido
- University Hospitals Southampton
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
At registration (pre-transplant)
Haematological cancer which can be ONE OF the following:
- Non-Hodgkin's lymphoma (NHL) in CR or PR
- Hodgkin's lymphoma (HL) in CR or PR
- Chronic (Pro-)lymphocytic leukaemia (CLL/PLL) in CR or PR
- Plasma cell myeloma (PCM) in CR, VGPR or PR
- Acute myeloid leukaemia (AML) in CR
- Acute lymphoblastic leukaemia (ALL) in CR
- Myelodysplastic syndrome (MDS) < 10% blasts in bone marrow
- Chronic myelomonocytic leukaemia (CMML) < 10% blasts in bone marrow
- Have undergone disease reassessment within 8 weeks prior to registration
HLA-identical sibling transplant to be performed using one of the following reduced intensity alemtuzumab-containing conditioning regimens:
- Fludarabine-busulphan-alemtuzumab
- Fludarabine-melphalan-alemtuzumab
- BCNU-etoposide-cytarabine-melphalan (BEAM)-alemtuzumab
- CCNU-etoposide-cytarabine-melphalan (LEAM)-alemtuzumab
- Aged ≥18 years, and <70 years
- Written informed consent
Exclusion Criteria
- Women who are pregnant or breast-feeding
- Life expectancy of <8 weeks
- Currently taking part in any other interventional clinical research study (involving any IMP, ATMP or cellular therapy)
- Organ dysfunction: Creatinine >200μmol/l, Bilirubin >50μmol/l, or AST/ALT > 3x ULN
Post-transplant
- Active acute GvHD
- Prior grade II-IV GvHD
- Relapse or progressive disease
- Primary or secondary graft failure
- Other cellular therapies
- Requirement for ongoing immunosuppression
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Otro: CD4 DLI
Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
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Patients will receive CD4 DLI between day 70 to 115 post transplant
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Otro: No DLI
Patients will receive no DLI post transplant as trial treatment.
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Patients will not receive DLI as trial treatment
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Progression-free survival at 1 year post-transplant
Periodo de tiempo: during the study and end of study
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during the study and end of study
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Periodo de tiempo: End of study
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End of study
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Incidence of infection requiring inpatient treatment
Periodo de tiempo: during the study and end of study
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during the study and end of study
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Rate of reconstitution of T-cell subsets and viral-specific immunity
Periodo de tiempo: End of study
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End of study
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Cumulative incidence of non-relapse mortality at 1 year
Periodo de tiempo: End of study
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End of study
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Overall survival and non-relapse mortality
Periodo de tiempo: End of study
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End of study
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Incidence, grade, or pattern of graft-versus-host disease
Periodo de tiempo: during the study and end of study
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during the study and end of study
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Ronjon Chakraverty, Professor, University College Hospital London; UCL Cancer Institute
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
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
Palabras clave
- Linfoma no Hodgkin
- Linfoma de Hodgkin
- Macroglobulinemia de Waldenström
- linfoma folicular de grado 1 en estadio III
- linfoma folicular de grado 2 en estadio III
- linfoma folicular de grado 1 en estadio IV
- linfoma folicular de grado 2 en estadio IV
- Síndrome mielodisplásico
- linfoma folicular grado 1 recurrente
- linfoma folicular grado 2 recurrente
- linfoma de linfocitos pequeños recurrente
- Linfoma de linfocitos pequeños en estadio III
- Linfoma de linfocitos pequeños en estadio IV
- leucemia linfocítica crónica refractaria
- leucemia linfocítica crónica en estadio III
- leucemia linfocítica crónica en estadio IV
- Enfermedad de injerto contra huésped
- Leucemia mieloide aguda
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
Términos MeSH relevantes adicionales
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Enfermedades de la médula ósea
- Enfermedades hematológicas
- Condiciones precancerosas
- Linfoma
- Síndromes mielodisplásicos
- Leucemia
- Preleucemia
- Enfermedad de injerto contra huésped
Otros números de identificación del estudio
- UCL/10/0241
- UCL-10/0241 (Otro identificador: Sponsor)
- LRF-09041 (Otro número de subvención/financiamiento: Leukaemia & Lymphoma Research)
- EU-21081 (Otro identificador)
- CRUK-UCL-PROT4 (Otro identificador: Cancer Research UK & UCL Cancer Trials Centre)
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