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Sequential Conditioning in Haploidentical Transplantation for Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders (LY-SET-HAPLO)

Primary Purpose

Refractory or Relapsed Lymphoid Haemopathy

Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Sequential Packaging (SET)
Transfusion graft
Prevention of GVHD
Care supports
Lymphocyte injection of prophylactic donor (PDLI)
Sponsored by
Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Refractory or Relapsed Lymphoid Haemopathy focused on measuring Allogenic cell stem transplant, Sequential chemotherapy, Haploidentical transplant

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Service d'hématologie clinique Hôpital Saint Antoine

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Relapsed or refractory lymphoid hematological disorders

Arm Description

Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Cumulative incidence of death not related to relapse
Describe not related to relapse mortality
Cumulative incidence of acute and chronic graft against host disease (GVHD)
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
Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI)
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
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

Full Information

First Posted
February 16, 2017
Last Updated
July 22, 2022
Sponsor
Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
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1. Study Identification

Unique Protocol Identification Number
NCT03079089
Brief Title
Sequential Conditioning in Haploidentical Transplantation for Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders
Acronym
LY-SET-HAPLO
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 30, 2017 (Actual)
Primary Completion Date
July 30, 2023 (Anticipated)
Study Completion Date
July 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Association for Training, Education, and Research in Hematology, Immunology, and Transplantation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory or Relapsed Lymphoid Haemopathy
Keywords
Allogenic cell stem transplant, Sequential chemotherapy, Haploidentical transplant

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Patients with refractory or relaps lymphoid hematological disorders
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Relapsed or refractory lymphoid hematological disorders
Arm Type
Other
Arm Description
Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI
Intervention Type
Drug
Intervention Name(s)
Sequential Packaging (SET)
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Transfusion graft
Intervention Description
Graft of peripheral stem cells is preferred at DO
Intervention Type
Drug
Intervention Name(s)
Prevention of GVHD
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Care supports
Intervention Description
According to the protocols of each center
Intervention Type
Drug
Intervention Name(s)
Lymphocyte injection of prophylactic donor (PDLI)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival (OS)
Description
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
Time Frame
2 years after transplantation
Secondary Outcome Measure Information:
Title
Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival
Description
Describe the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse and relapse-free survival
Time Frame
90 days and then 6, 12 and 24 months after transplantation
Title
Cumulative incidence of death not related to relapse
Description
Describe not related to relapse mortality
Time Frame
90 days and then 12 and 24 months after transplantation
Title
Cumulative incidence of acute and chronic graft against host disease (GVHD)
Description
Describe the incidence of acute and chronic graft against host disease (GVHD)
Time Frame
100 days and then 12 and 24 months after transplantation
Title
Number of patients for whom PDLI was possible and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients
Description
Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI)
Time Frame
2 years after transplantation
Title
Immune reconstitution post-transplantation in the peripheral blood
Description
Immune reconstitution will be determined by CD4 lymphocyte, CD8, T regulators, Natural Killer cells and B cells levels in the peripheral blood
Time Frame
30, 90 and 180 days after transplantation
Title
Tolerance of this therapeutic strategy
Description
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
Time Frame
90 days and the 6, 12 and 24 month after transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Service d'hématologie clinique Hôpital Saint Antoine
City
Paris
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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