Etude : LY-SET-HAPLO / LY-SET-HAPLO



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : LY-SET-HAPLO

Nom : LY-SET-HAPLO

Traitement : Métastasique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 03/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Sequential Chemotherapy Prior Conditioning Reduced Intensity: Study Routine Care in Haploidentical Allogeneic Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C81 - Lymphome de Hodgkin

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C85 - Lymphome non hodgkinien, de types autres et non précisés

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C84 - Lymphomes à cellules T/NK matures

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C86 - Autres types précisés de lymphomes à cellules T/NK

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C91 - Leucémie lymphoïde
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with a significant chance of healing in lymphoid hematological refractory or multiple relapses after chemotherapy. However, all patients with an indication of allo-HSC can not benefit because of two limitations: the toxicity of the treatment and graft shortage available.

For patients refractory or in relapses with an indication of allo-HSC, used the combinaison of an SET followed by the reduced-intensity allo-HSC (RIC) has shown some interesting results.

A post-transplant immune modulation with prophylactic injections of donor lymphocytes (PDLI) showed its effectiveness to decrease the risk of relapse while having a lower toxicity than chemotherapy

Intervention:
- Drug: Sequential Packaging (SET)
Sequential chemotherapy: - Thiotepa 5 mg/kg/day for 1 day (D-13) -Cyclophosphamide 400 mg/m²/day for 4 days (J-12 to J-9)- Etoposide 100 mg/m²/day for 4 days (J-12 to J-9) Repos days J-8 and J-6 Reduced-intensity conditioning (RIC)-Fludarabine 30 mg/m²/day for 5 days (J-5 to D-1)- Busulfan IV 3.2 mg/kg/day for 2 days (J-5 and J-4)- Anti-lymphocyte serum (Thymoglobuline) 2.5 mg / kg / day for 2 days (J-3 and J-2)
- Drug: Transfusion graft
Graft of peripheral stem cells is preferred at DO
- Drug: Prevention of GVHD
Cyclophosphamide 50mg/ kg/day on days D + 3 and D + 5 - Cyclosporine A (CSA; 3 mg / kg / day IV from D+6)
Mycophenolate mofetil (MMF; 30 mg/kg/ day, maximum x2 1g / day from day J+6)
- Drug: Care supports
According to the protocols of each center
- Drug: Lymphocyte injection of prophylactic donor (PDLI)
According to the protocols of each center. In the absence of clinical indication against-disease (GVHD), phasing MMF between days D + 35 and D + 56, then phasing APF between D + 62 and D + 90
PDLI: 3 injections from the D + 120 patients who discontinued immunosuppressive therapy for ≥ 1 month and having no active GVHD or history of acute GVHD grade> II.

current primary outcome:
Overall survival (OS) [ Time Frame: 2 years after transplantation ]
Describe efficacy and safety of the combination of an SET followed by the RIC with post-transplant immune modulation by PDLI in patients with refractory or relaps lymphoid hematological refractory or multiple relapses lymphoid hematological disorders

current secondary outcomes:
- Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival [ Time Frame: 90 days and then 6, 12 and 24 months after transplantation ]
Describe the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse and relapse-free survival
- Cumulative incidence of death not related to relapse [ Time Frame: 90 days and then 12 and 24 months after transplantation ]
Describe not related to relapse mortality
- Cumulative incidence of acute and chronic graft against host disease (GVHD) [ Time Frame: 100 days and then 12 and 24 months after transplantation ]
Describe the incidence of acute and chronic graft against host disease (GVHD)
- Number of patients for whom PDLI was possible and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients [ Time Frame: 2 years after transplantation ]
Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI)
- Study the post-transplant immune reconstitution in the peripheral blood [ Time Frame: 30, 90 and 180 days after transplantation ]
Describe the immune reconstitution like CD4 lymphocyte levels, CD8, T regulators, Natural Killer cells and B cells
- Tolerance of this therapeutic strategy [ Time Frame: 90 days and the 6, 12 and 24 month after transplantation ]
The tolerance will be evaluated by:
> The cumulative incidence of death not related to relapse at 90 days, 1 year and 2 years after transplantation
> The cumulative incidence of acute and chronic graft against host disease (GVHD)
> The incidence of advert events

Phase : NA

Stade : NA

NA
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Patients with an indication of allo-HSC for a lymphoid hematological malignancy like Hodgkin's lymphoma, non hodgkin's lymphoma b cell (mantle follicular, diffuse large cells, marginal zone,MALT) or T (peripheral T whithout specificity, anaplasic, angio-immunoblastic, natural killer cells, gamma / delta T cells, Sezary's syndrome, primitive cutaneous T), prolymphocytic leukemia, chronic lymphocytic leukemia, waldenström's disease and for which a therapeutic strategie combining a sequential chemotherapy followed by the reduced-intensity conditioning(SET RIC + PDLI) is decided
- Patients at least in partial response (standard criteria) after a rescue treatment the day of evaluation at 1 month before the conditioning
- Advanced age ≥ 18 to <60 years
- Cardiac ejection fraction of the left ventricle ≥ 45%
- Lung function - free diffusion capacity for carbon monoxide ≥ 50% of predicted value
- Creatinine clearance ≥ 50 ml / min depending on the CKD-EPI formula
- Availability of an HLA haploidentical donor in the family
- Collection of non-opposition



Critères de non-inclusion : - Invasion of uncontrolled CNS
- Availability of an HLA identical family donor who agreed to donate hematopoietic stem cells OR non-related donor HLA-compatible 10/10 on HLA-A alleles, B, C, and DRB1 DQB1 available and ready to give in 4 weeks to make a decision allograft
- Presence in the patient HLA-specific antibodies directed against an antigen HLA haploidentical donor family
- Karnofsky score <70%
- Patient HIV positive
- Hepatitis B or C or chronic active
- Uncontrolled infection at the time of start packing
- Contraindication to the use of treatments provided by the protocol
- Previous history of allo-HSC
- No beneficiary of a social security scheme.
- life expentancy estimated less than 1 month by investigator


NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03079089
Promoteur :
APHP
Type de sponsor : Institutionnel
75010 PARIS 10

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Docteur Charles HERBAUX

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Ouverture de l'essai : OUVERT

MAJ : 20/05/2019