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

NCT ID: NCT03079089

Last Updated: 2024-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-30
• Study Completion Date: 2023-09-11

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: OTHER

Sequential Packaging (SET)

Intervention Type: 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

Intervention Type: DRUG

Graft of peripheral stem cells is preferred at DO

Prevention of GVHD

Intervention Type: 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

Intervention Type: DRUG

According to the protocols of each center

Lymphocyte injection of prophylactic donor (PDLI)

Intervention Type: 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.

Interventions

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)

Intervention Type: DRUG

Transfusion graft

Graft of peripheral stem cells is preferred at DO

Intervention Type: 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)

Intervention Type: DRUG

Care supports

According to the protocols of each center

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Pr Mohamad MOHTY

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Service d'hématologie clinique Hôpital Saint Antoine

Paris, , France

Countries

France

Other Identifiers

2016-A00861-50

Identifier Type: -

Identifier Source: org_study_id