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.
Panoramica dello studio
Stato
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Birmingham, Regno Unito
- Birmingham Heartlands Hospital
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Bristol, Regno Unito
- Bristol Royal Hospital for Children
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Cambridge, Regno Unito
- Addenbrooke's Hospital
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Glasgow, Regno Unito
- Beatson West of Scotland Cancer Centre
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Leeds, Regno Unito
- St James's University Hospital
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Leicester, Regno Unito
- Leicester Royal Infirmary
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London, Regno Unito
- University College Hospital London (UCLH)
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Manchester, Regno Unito
- Christie Hospital
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Nottingham, Regno Unito
- Nottingham City Hospital
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Sheffield, Regno Unito
- Royal Hallamshire Hospital
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Southampton, Regno Unito
- University Hospitals Southampton
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Altro: 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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Altro: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
|
Progression-free survival at 1 year post-transplant
Lasso di tempo: during the study and end of study
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during the study and end of study
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Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
|
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Lasso di tempo: End of study
|
End of study
|
|
Incidence of infection requiring inpatient treatment
Lasso di tempo: during the study and end of study
|
during the study and end of study
|
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Rate of reconstitution of T-cell subsets and viral-specific immunity
Lasso di tempo: End of study
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End of study
|
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Cumulative incidence of non-relapse mortality at 1 year
Lasso di tempo: End of study
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End of study
|
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Overall survival and non-relapse mortality
Lasso di tempo: End of study
|
End of study
|
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Incidence, grade, or pattern of graft-versus-host disease
Lasso di tempo: during the study and end of study
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during the study and end of study
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Ronjon Chakraverty, Professor, University College Hospital London; UCL Cancer Institute
Pubblicazioni e link utili
Collegamenti utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Anticipato)
Completamento dello studio (Anticipato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
- Linfoma non-Hodgkin
- Linfoma di Hodgkin
- Macroglobulinemia di Waldenstrom
- linfoma follicolare stadio III grado 1
- linfoma follicolare stadio III grado 2
- linfoma follicolare stadio IV grado 1
- linfoma follicolare in stadio IV grado 2
- Sindrome mielodisplasica
- linfoma follicolare ricorrente di grado 1
- linfoma follicolare ricorrente di grado 2
- piccolo linfoma linfocitico ricorrente
- piccolo linfoma linfocitico stadio III
- piccolo linfoma linfocitico stadio IV
- leucemia linfatica cronica refrattaria
- leucemia linfatica cronica stadio III
- leucemia linfocitica cronica in stadio IV
- malattia del trapianto contro l'ospite
- Leucemia mieloide acuta
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Neoplasie
- Malattie linfoproliferative
- Malattie linfatiche
- Disturbi immunoproliferativi
- Malattie del midollo osseo
- Malattie ematologiche
- Condizioni precancerose
- Linfoma
- Sindromi mielodisplastiche
- Leucemia
- Preleucemia
- Malattia del trapianto contro l'ospite
Altri numeri di identificazione dello studio
- UCL/10/0241
- UCL-10/0241 (Altro identificatore: Sponsor)
- LRF-09041 (Altro numero di sovvenzione/finanziamento: Leukaemia & Lymphoma Research)
- EU-21081 (Altro identificatore)
- CRUK-UCL-PROT4 (Altro identificatore: Cancer Research UK & UCL Cancer Trials Centre)
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