Refractory or Relapsed Lymphoid Haemopathy Clinical Trial
— LY-SET-HAPLOOfficial title:
Sequential Chemotherapy Prior Conditioning Reduced Intensity: Study Routine Care in Haploidentical Allogeneic Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders
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
| Status | Active, not recruiting |
| Enrollment | 40 |
| Est. completion date | July 30, 2023 |
| Est. primary completion date | July 30, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 60 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| France | Service d'hématologie clinique Hôpital Saint Antoine | Paris |
| Lead Sponsor | Collaborator |
|---|---|
| Association for Training, Education, and Research in Hematology, Immunology, and Transplantation |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall survival (OS) | 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 | 2 years after transplantation | |
| Secondary | Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival | Describe the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse and relapse-free survival | 90 days and then 6, 12 and 24 months after transplantation | |
| Secondary | Cumulative incidence of death not related to relapse | Describe not related to relapse mortality | 90 days and then 12 and 24 months after transplantation | |
| Secondary | Cumulative incidence of acute and chronic graft against host disease (GVHD) | Describe the incidence of acute and chronic graft against host disease (GVHD) | 100 days and then 12 and 24 months after transplantation | |
| Secondary | Number of patients for whom PDLI was possible and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients | Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI) | 2 years after transplantation | |
| Secondary | Immune reconstitution post-transplantation in the peripheral blood | Immune reconstitution will be determined by CD4 lymphocyte, CD8, T regulators, Natural Killer cells and B cells levels in the peripheral blood | 30, 90 and 180 days after transplantation | |
| Secondary | Tolerance of this therapeutic strategy | 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 |
90 days and the 6, 12 and 24 month after transplantation |