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.
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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Birmingham, Royaume-Uni
- Birmingham Heartlands Hospital
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Bristol, Royaume-Uni
- Bristol Royal Hospital for Children
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Cambridge, Royaume-Uni
- Addenbrooke's Hospital
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Glasgow, Royaume-Uni
- Beatson West of Scotland Cancer Centre
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Leeds, Royaume-Uni
- St James's University Hospital
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Leicester, Royaume-Uni
- Leicester Royal Infirmary
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London, Royaume-Uni
- University College Hospital London (UCLH)
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Manchester, Royaume-Uni
- Christie Hospital
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Nottingham, Royaume-Uni
- Nottingham City Hospital
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Sheffield, Royaume-Uni
- Royal Hallamshire Hospital
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Southampton, Royaume-Uni
- University Hospitals Southampton
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Autre: 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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Autre: 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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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
|
Progression-free survival at 1 year post-transplant
Délai: during the study and end of study
|
during the study and end of study
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
|
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Délai: End of study
|
End of study
|
|
Incidence of infection requiring inpatient treatment
Délai: 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
Délai: End of study
|
End of study
|
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Cumulative incidence of non-relapse mortality at 1 year
Délai: End of study
|
End of study
|
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Overall survival and non-relapse mortality
Délai: End of study
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End of study
|
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Incidence, grade, or pattern of graft-versus-host disease
Délai: during the study and end of study
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during the study and end of study
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Ronjon Chakraverty, Professor, University College Hospital London; UCL Cancer Institute
Publications et liens utiles
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Anticipé)
Achèvement de l'étude (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
- Lymphome non hodgkinien
- Lymphome de Hodgkin
- Macroglobulinémie de Waldenström
- Lymphome folliculaire stade III grade 1
- Lymphome folliculaire stade III grade 2
- Lymphome folliculaire de stade IV de grade 1
- lymphome folliculaire de stade IV grade 2
- Syndrome myélodysplasique
- lymphome folliculaire de grade 1 récurrent
- lymphome folliculaire de grade 2 récurrent
- petit lymphome lymphocytaire récurrent
- Lymphome lymphocytaire de stade III
- Lymphome lymphocytaire de stade IV
- leucémie lymphoïde chronique réfractaire
- leucémie lymphoïde chronique stade III
- leucémie lymphoïde chronique de stade IV
- maladie du greffon contre l'hôte
- Leucémie aiguë myéloïde
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
Termes MeSH pertinents supplémentaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Maladies de la moelle osseuse
- Maladies hématologiques
- Conditions précancéreuses
- Lymphome
- Syndromes myélodysplasiques
- Leucémie
- Préleucémie
- Maladie du greffon contre l'hôte
Autres numéros d'identification d'étude
- UCL/10/0241
- UCL-10/0241 (Autre identifiant: Sponsor)
- LRF-09041 (Autre subvention/numéro de financement: Leukaemia & Lymphoma Research)
- EU-21081 (Autre identifiant)
- CRUK-UCL-PROT4 (Autre identifiant: Cancer Research UK & UCL Cancer Trials Centre)
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