Phase II Study Testing Prophylaxis Feasibility of Graft Versus Host Disease With Only High Dose Cyclophosphamide Post-transplantation for Patients Eligible to a Reduced-intensity Conditioning Regiment Prior to Allogenic Transplantation With a Compatible Familial or Non-familial Donor.
Overview
- Phase
- Phase 2
- Intervention
- Fludarabine
- Conditions
- Graft Versus Host Disease
- Sponsor
- Nantes University Hospital
- Enrollment
- 47
- Locations
- 1
- Primary Endpoint
- Incidence of grade 3 and 4 acute GVHD cortico-resistant
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
Acute or chronic graft versus host disease is still the major complication of stem cells transplantation regarding morbidity and mortality.
Recently, high dose cyclophosphamide utilization early after post-transplantation (day+ 3 and +4) not only for patients with HLA- haploidentical donor but also for patients with Human Leukocyte Antigen (HLA)-compatible donor, showed a great control of graft versus host disease after transplantation, allowing to consider stopping immunosuppressive treatment after the transplantation (Neoral=cyclosporine, cell-cept=mycophenolate mofetil). Indeed, this step has already been completed in myeloablative transplantation in adult patients.
This approach could enable to avoid in the end several complications related to long term immunosuppressive drugs administration, while promoting quicker immunity recovery.
Detailed Description
The BALTIMORE conditioning regiment will be used in this study with peripheral stem cell transplantation and fludarabine will be replaced by clofarabine for myeloid diseases (Acute Myeloide Leukemia, Myelodysplasia , myelofibrosis, Chronic Myeoloid Leukemia..) because of better antitumoral activity in this setting.
Investigators
Eligibility Criteria
Inclusion Criteria
- •adults ≤ 70 years old
- •indication to stem cells transplantation with reduced-intensity conditioning regimen
- •with a HLA-compatible familial 10/10 or non-familial donor
- •Written signed informed consent form
- •woman with childbearing potential under efficient control birth method during the trial and up to 12 months after cyclophosphamide stop
- •men under efficient control birth method during the trial and up to 6 months after cyclophosphamide stop
- •Negative serology to B and C hepatitis and to HIV
- •Affiliated to social security
Exclusion Criteria
- •- Eligible to myeloablative contioning regimen
- •Other progressive malignancy disease or history of prior other malignancy in the last two years, with the exception of: curatively treated basal cell carcinoma or carcinoma in situ of the cervix
- •Progressive mental illness disease
- •Pregnant or Breastfeeding woman
- •woman with childbearing potential without any efficient control birth
- •Serious concomitant infection and not controlled
- •Contra-indications to allogenic transplantation, especially:
- •Cardiac: left ventricular ejection fraction \<45% assessed by transthoracic echography or isotopic method (isotopic gamma-angiography)
- •Respiratory: DLCO limiting fludarabine and busulfan use (DLCO\< 40% of theorical value)
- •Renal: creatinine clearance \< 60ml/min (MDRD method)
Arms & Interventions
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
Intervention: Fludarabine
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
Intervention: Full body irradiation
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
Intervention: Cyclophosphamide
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
Intervention: stem cell transplantation
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
Intervention: nuclear cells
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
Intervention: Clofarabine
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
Intervention: Full body irradiation
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
Intervention: Cyclophosphamide
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
Intervention: stem cell transplantation
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
Intervention: nuclear cells
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Fludarabine
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Full body irradiation
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Cyclophosphamide
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: stem cell transplantation
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: nuclear cells
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Thymoglobulin Injectable Product
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Clofarabine
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Full body irradiation
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Cyclophosphamide
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: stem cell transplantation
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: nuclear cells
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
Intervention: Thymoglobulin Injectable Product
Outcomes
Primary Outcomes
Incidence of grade 3 and 4 acute GVHD cortico-resistant
Time Frame: 100 days after transplantation
acute GVHD will be evaluated from International Mount Sinai criteria
Secondary Outcomes
- disease free survival (DFS)(one year, the last follow-up visit)
- Overall survival (OS)(one year, the last follow-up visit)
- Chimerism(1, 2, 3, 6 and 12 months after transplantation)
- graft and relapse free survival(one year)
- Infections frequency(one year)
- Engraftment(one year)
- Identification of ghost factors associated with GVHD(one year)
- non relapse mortality (NRM)(last follow-up visit)
- Immune reconstitution(3, 6 and 12 months after transplantation)
- Adverse events of grade 3 and 4 after transplantation(one year)
- chronic GVHD(one year)
- compare OS between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare grade 2-4 and 3-4 acute GVHD between patients with ATG and patients without ATG(one year)
- compare chronic GVHD between patients with ATG and patients without ATG(one year)
- compare DFS between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare Relapse between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare NRM between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare Infections frequency between patients with ATG and patients without ATG(one year)