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.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
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 estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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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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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Outro: 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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Outro: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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Progression-free survival at 1 year post-transplant
Prazo: during the study and end of study
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during the study and end of study
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Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
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Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Prazo: End of study
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End of study
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Incidence of infection requiring inpatient treatment
Prazo: 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
Prazo: End of study
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End of study
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Cumulative incidence of non-relapse mortality at 1 year
Prazo: End of study
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End of study
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Overall survival and non-relapse mortality
Prazo: End of study
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End of study
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Incidence, grade, or pattern of graft-versus-host disease
Prazo: 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
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Antecipado)
Conclusão do estudo (Antecipado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
- Linfoma não-Hodgkin
- Linfoma de Hodgkin
- Macroglobulinemia de Waldenstrom
- linfoma folicular grau 1 estágio III
- linfoma folicular grau 2 estágio III
- linfoma folicular grau 1 estágio IV
- linfoma folicular grau 2 estágio IV
- Síndrome mielodisplásica
- linfoma folicular grau 1 recorrente
- linfoma folicular grau 2 recorrente
- linfoma linfocítico pequeno recorrente
- linfoma linfocítico pequeno estágio III
- linfoma linfocítico pequeno estágio IV
- leucemia linfocítica crônica refratária
- leucemia linfocítica crônica estágio III
- leucemia linfocítica crônica estágio IV
- doença do enxerto contra o hospedeiro
- Leucemia mielóide aguda
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
Termos MeSH relevantes adicionais
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Neoplasias
- Distúrbios Linfoproliferativos
- Doenças Linfáticas
- Distúrbios imunoproliferativos
- Doenças da Medula Óssea
- Doenças Hematológicas
- Condições pré-cancerosas
- Linfoma
- Síndromes Mielodisplásicas
- Leucemia
- Pré-leucemia
- Doença do Enxerto x Hospedeiro
Outros números de identificação do estudo
- UCL/10/0241
- UCL-10/0241 (Outro identificador: Sponsor)
- LRF-09041 (Número de outro subsídio/financiamento: Leukaemia & Lymphoma Research)
- EU-21081 (Outro identificador)
- CRUK-UCL-PROT4 (Outro identificador: Cancer Research UK & UCL Cancer Trials Centre)
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