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.
Studieoversigt
Status
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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-
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Birmingham, Det Forenede Kongerige
- Birmingham Heartlands Hospital
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Bristol, Det Forenede Kongerige
- Bristol Royal Hospital for Children
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Cambridge, Det Forenede Kongerige
- Addenbrooke's Hospital
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Glasgow, Det Forenede Kongerige
- Beatson West of Scotland Cancer Centre
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Leeds, Det Forenede Kongerige
- St James's University Hospital
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Leicester, Det Forenede Kongerige
- Leicester Royal Infirmary
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London, Det Forenede Kongerige
- University College Hospital London (UCLH)
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Manchester, Det Forenede Kongerige
- Christie Hospital
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Nottingham, Det Forenede Kongerige
- Nottingham City Hospital
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Sheffield, Det Forenede Kongerige
- Royal Hallamshire Hospital
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Southampton, Det Forenede Kongerige
- University Hospitals Southampton
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-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Andet: 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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Andet: No DLI
Patients will receive no DLI post transplant as trial treatment.
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Patients will not receive DLI as trial treatment
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Progression-free survival at 1 year post-transplant
Tidsramme: during the study and end of study
|
during the study and end of study
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Tidsramme: End of study
|
End of study
|
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Incidence of infection requiring inpatient treatment
Tidsramme: 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
Tidsramme: End of study
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End of study
|
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Cumulative incidence of non-relapse mortality at 1 year
Tidsramme: End of study
|
End of study
|
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Overall survival and non-relapse mortality
Tidsramme: End of study
|
End of study
|
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Incidence, grade, or pattern of graft-versus-host disease
Tidsramme: during the study and end of study
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during the study and end of study
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Ronjon Chakraverty, Professor, University College Hospital London; UCL Cancer Institute
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Forventet)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- Non-Hodgkins lymfom
- Hodgkins lymfom
- Waldenstrom makroglobulinæmi
- stadium III grad 1 follikulært lymfom
- stadium III grad 2 follikulært lymfom
- stadium IV grad 1 follikulært lymfom
- stadium IV grad 2 follikulært lymfom
- Myelodysplastisk syndrom
- tilbagevendende grad 1 follikulært lymfom
- tilbagevendende grad 2 follikulært lymfom
- tilbagevendende lille lymfocytisk lymfom
- stadium III lille lymfatisk lymfom
- stadium IV lille lymfocytisk lymfom
- refraktær kronisk lymfatisk leukæmi
- stadium III kronisk lymfatisk leukæmi
- stadium IV kronisk lymfatisk leukæmi
- graft versus host sygdom
- Akut myeloid leukæmi
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- UCL/10/0241
- UCL-10/0241 (Anden identifikator: Sponsor)
- LRF-09041 (Andet bevillings-/finansieringsnummer: Leukaemia & Lymphoma Research)
- EU-21081 (Anden identifikator)
- CRUK-UCL-PROT4 (Anden identifikator: Cancer Research UK & UCL Cancer Trials Centre)
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