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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Refractory or Relapsed Lymphoid Haemopathy
• Intervention / Treatment: Drug: Sequential Packaging (SET); Drug: Transfusion graft; Drug: Prevention of GVHD; Drug: Care supports; Drug: Lymphocyte injection of prophylactic donor (PDLI)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Service d'hématologie Clinique Hôpital Saint Antoine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: Relapsed or refractory lymphoid hematological disorders; Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Cumulative incidence of death not related to relapse	Describe not related to relapse mortality	90 days and then 12 and 24 months after transplantation
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
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
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
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

Collaborators and Investigators

• Sponsor: Association for Training, Education, and Research in Hematology, Immunology, and Transplantation

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2017
• Primary Completion (ANTICIPATED): July 30, 2023
• Study Completion (ANTICIPATED): July 30, 2023

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (ACTUAL): March 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 22, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Haploidentical transplant; Allogenic cell stem transplant; Sequential chemotherapy
• Additional Relevant MeSH Terms: Hematologic Diseases
• Other Study ID Numbers: 2016-A00861-50

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No