Refractory or Relapsed Lymphoid Haemopathy
Conditions
Keywords
Allogenic cell stem transplant, Sequential chemotherapy, Haploidentical transplant
Brief summary
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
Interventions
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)
Graft of peripheral stem cells is preferred at DO
* 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)
DRUGCare supports
According to the protocols of each center
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.
Sponsors
Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Patients with refractory or relaps lymphoid hematological disorders
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of death not related to relapse | 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) | 100 days and then 12 and 24 months after transplantation | Describe the incidence of acute and chronic graft against host disease (GVHD) |
| Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival | 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 |
| Immune reconstitution post-transplantation in the peripheral blood | 30, 90 and 180 days after transplantation | Immune reconstitution will be determined by CD4 lymphocyte, CD8, T regulators, Natural Killer cells and B cells levels in the peripheral blood |
| Tolerance of this therapeutic strategy | 90 days and the 6, 12 and 24 month after transplantation | The tolerance will be evaluated by: 1. The cumulative incidence of death not related to relapse at 90 days, 1 year and 2 years after transplantation 2. The cumulative incidence of acute and chronic graft against host disease (GVHD) 3. The incidence of advert events |
| Number of patients for whom PDLI was possible and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients | 2 years after transplantation | Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI) |
Countries
France
Outcome results
None listed