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.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert 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.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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-
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Birmingham, Storbritannia
- Birmingham Heartlands Hospital
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Bristol, Storbritannia
- Bristol Royal Hospital for Children
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Cambridge, Storbritannia
- Addenbrooke's Hospital
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Glasgow, Storbritannia
- Beatson West of Scotland Cancer Centre
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Leeds, Storbritannia
- St James's University Hospital
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Leicester, Storbritannia
- Leicester Royal Infirmary
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London, Storbritannia
- University College Hospital London (UCLH)
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Manchester, Storbritannia
- Christie Hospital
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Nottingham, Storbritannia
- Nottingham City Hospital
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Sheffield, Storbritannia
- Royal Hallamshire Hospital
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Southampton, Storbritannia
- University Hospitals Southampton
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
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 studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Annen: CD4 DLI
Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
|
Patients will receive CD4 DLI between day 70 to 115 post transplant
|
|
Annen: No DLI
Patients will receive no DLI post transplant as trial treatment.
|
Patients will not receive DLI as trial treatment
|
Hva måler studien?
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
|
|
Incidence of infection requiring inpatient treatment
Tidsramme: 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
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
|
during the study and end of study
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Ronjon Chakraverty, Professor, University College Hospital London; UCL Cancer Institute
Publikasjoner og nyttige lenker
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Forventet)
Studiet fullført (Forventet)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
- Non-Hodgkins lymfom
- Hodgkins lymfom
- Waldenstrom makroglobulinemi
- stadium III grad 1 follikulært lymfom
- stadium III grad 2 follikulært lymfom
- stadium IV grad 1 follikulær lymfom
- stadium IV grad 2 follikulært lymfom
- Myelodysplastisk syndrom
- tilbakevendende grad 1 follikulær lymfom
- tilbakevendende grad 2 follikulær lymfom
- tilbakevendende små lymfatiske lymfomer
- stadium III små lymfatiske lymfomer
- stadium IV små lymfatiske lymfomer
- refraktær kronisk lymfatisk leukemi
- stadium III kronisk lymfatisk leukemi
- stadium IV kronisk lymfatisk leukemi
- graft versus host sykdom
- Akutt myeloid leukemi
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- UCL/10/0241
- UCL-10/0241 (Annen identifikator: Sponsor)
- LRF-09041 (Annet stipend/finansieringsnummer: Leukaemia & Lymphoma Research)
- EU-21081 (Annen identifikator)
- CRUK-UCL-PROT4 (Annen identifikator: Cancer Research UK & UCL Cancer Trials Centre)
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