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Completed

NCT Number: NCT03079089

Sequential Conditioning in Haploidentical Transplantation for 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

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Key information

Conditions

Refractory or Relapsed Lymphoid Haemopathy

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Service d'hématologie clinique Hôpital Saint Antoine

Paris, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sequential Packaging (SET)

Drug

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)

Transfusion graft

Drug

Graft of peripheral stem cells is preferred at DO

Prevention of GVHD

Drug
  • 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)

Care supports

Drug

According to the protocols of each center

Lymphocyte injection of prophylactic donor (PDLI)

Drug

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 outcomes

  1. Overall survival (OS)

    Time frame: 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 outcomes

  1. Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival

    Time frame: 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

  2. Cumulative incidence of death not related to relapse

    Time frame: 90 days and then 12 and 24 months after transplantation

    Describe not related to relapse mortality

  3. Cumulative incidence of acute and chronic graft against host disease (GVHD)

    Time frame: 100 days and then 12 and 24 months after transplantation

    Describe the incidence of acute and chronic graft against host disease (GVHD)

  4. Number of patients for whom PDLI was possible and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients

    Time frame: 2 years after transplantation

    Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI)

  5. Immune reconstitution post-transplantation in the peripheral blood

    Time frame: 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

  6. Tolerance of this therapeutic strategy

    Time frame: 90 days and the 6, 12 and 24 month after transplantation

    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

Sponsors and collaborators

Lead sponsor

Association for Training, Education, and Research in Hematology, Immunology, and Transplantation

Other

Registry information

Official study 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

Acronym: LY-SET-HAPLO

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
Mar 14, 2017
Registry last updated
Jul 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.