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

NCT03079089 | Completed

• 1 other identifier: 2016-A00861-50
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Refractory or Relapsed Lymphoid Haemopathy

Keywords

Allogenic cell stem transplant; Sequential chemotherapy; Haploidentical transplant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

• Cumulative incidence of death not related to relapse

  90 days and then 12 and 24 months after transplantation

• Cumulative 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

  2 years after transplantation

• Immune reconstitution post-transplantation in the peripheral blood

  30, 90 and 180 days after transplantation

Study Arms (1)

Relapsed or refractory lymphoid hematological disorders

OTHER

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); Drug: Transfusion graft; Drug: Prevention of GVHD; Drug: Care supports; Drug: Lymphocyte injection of prophylactic donor (PDLI)

Interventions

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)

Relapsed or refractory lymphoid hematological disorders

Transfusion graft DRUG

Graft of peripheral stem cells is preferred at DO

Relapsed or refractory lymphoid hematological disorders

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)

Relapsed or refractory lymphoid hematological disorders

Care supports DRUG

According to the protocols of each center

Relapsed or refractory lymphoid hematological disorders

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.

Relapsed or refractory lymphoid hematological disorders

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Service d'hématologie clinique Hôpital Saint Antoine

Paris, France

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Patients with refractory or relaps lymphoid hematological disorders

Study Record Dates

• First Submitted: February 16, 2017
• First Posted: March 14, 2017
• Study Start: June 30, 2017
• Primary Completion: September 11, 2023
• Study Completion: September 11, 2023
• Last Updated: July 30, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)