Sequential Conditioning in Haploidentical Transplantation for Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders

Not Applicable

Completed

• Conditions: Refractory or Relapsed Lymphoid Haemopathy
• Interventions: Drug: Sequential Packaging (SET); Drug: Transfusion graft; Drug: Prevention of GVHD; Drug: Care supports; Drug: Lymphocyte injection of prophylactic donor (PDLI)

• Registration Number: NCT03079089
• Lead Sponsor: Association for Training, Education, and Research in Hematology, Immunology, and Transplantation

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-02-16
• Study First Submitted QC: 2017-03-08
• Study First Posted: 2017-03-14
• Study Start: 2017-06-30
• Primary Completion: 2023-09-11
• Study Completion: 2023-09-11
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Relapsed or refractory lymphoid hematological disorders	Lymphocyte injection of prophylactic donor (PDLI)	Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI
Relapsed or refractory lymphoid hematological disorders	Care supports	Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI
Relapsed or refractory lymphoid hematological disorders	Sequential Packaging (SET)	Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI
Relapsed or refractory lymphoid hematological disorders	Transfusion graft	Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI
Relapsed or refractory lymphoid hematological disorders	Prevention of GVHD	Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
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
Cumulative incidence of death not related to relapse	90 days and then 12 and 24 months after transplantation	Describe not related to relapse mortality
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)
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
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

Trial Locations

Locations (1)

Service d'hématologie clinique Hôpital Saint Antoine; 🇫🇷 Paris, France