Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ly-set-haplo
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03079089
Recruitment Status : Recruiting
First Posted : March 14, 2017
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Pr Mohamad MOHTY, 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


Condition or disease Intervention/treatment Phase
Refractory or Relapsed Lymphoid Haemopathy Drug: Sequential Packaging (SET) Drug: Transfusion graft Drug: Prevention of GVHD Drug: Care supports Drug: Lymphocyte injection of prophylactic donor (PDLI) Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Patients with refractory or relaps lymphoid hematological disorders
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : June 30, 2017
Estimated Primary Completion Date : June 15, 2020
Estimated Study Completion Date : June 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Disorders

Arm Intervention/treatment
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.





Primary Outcome Measures :
  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 Outcome Measures :
  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:

    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03079089


Contacts
Layout table for location contacts
Contact: Remy DULERY, PH 01.49.28.26.20 remy.dulery@aphp.fr
Contact: Mohamad MOHTY, PUPH 01.49.28.26.20 mohamad.mohty@inserm.fr

Locations
Layout table for location information
France
Service d'hématologie clinique Hôpital Saint Antoine Recruiting
Paris, France
Contact: Rémy DULERY, PH    01.49.28.26.20    remy.dulery@aphp.fr   
Contact: Mohamad MOHTY, PUPH    01.49.28.26.20    mohamad.mohty@inserm.fr   
Sponsors and Collaborators
Association for Training, Education, and Research in Hematology, Immunology, and Transplantation

Layout table for additonal information
Responsible Party: Pr Mohamad MOHTY, Principal investigator, Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
ClinicalTrials.gov Identifier: NCT03079089     History of Changes
Other Study ID Numbers: 2016-A00861-50
First Posted: March 14, 2017    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pr Mohamad MOHTY, Association for Training, Education, and Research in Hematology, Immunology, and Transplantation:
Allogenic cell stem transplant
Sequential chemotherapy
Haploidentical transplant
Additional relevant MeSH terms:
Layout table for MeSH terms
Hematologic Diseases