Post Transplant Cyclophosphamide (PTCY) as Sole Graft Versus Host Disease (GVHD) Prophylaxis for Matched Allotransplant: CYRIC
- Conditions
- Graft Versus Host Disease
- Interventions
- Radiation: Full body irradiationOther: stem cell transplantationOther: nuclear cells
- Registration Number
- NCT03263767
- Lead Sponsor
- Nantes University Hospital
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 47
- 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
-
- 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)
- Hepatic: transaminases >5 Uper Per Normal (UPN) or bilirubin> 2 UPN
-
Contra-indications to cyclophosphamide:
- Urinary tract infections
- Acute urothelial toxicity due to cytotoxic chemotherapy or to radiotherapy
- Obstruction of urines flow
- Pre-existing hemorrhagic cystitis
- Yellow fever vaccination
-
Cardiac condition preventing high dose cyclophosphamide utilization :
- New York Heart Association (NYHA) functional class II, III or IV
- Rhythmic, valvular or ischemic cardiomyopathy
-
Minor
-
Patient under guardianship or curatorship
-
Patient under judicial protection
-
Known or suspected hypersensitivity to cyclophosphamide
-
Known or suspected hypersensitivity to rabbit proteins
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LYMPHOID HEMOPATHY without ATG Fludarabine patients with lymphoid hemopathy LYMPHOID HEMOPATHY without ATG Full body irradiation patients with lymphoid hemopathy LYMPHOID HEMOPATHY without ATG stem cell transplantation patients with lymphoid hemopathy LYMPHOID HEMOPATHY without ATG nuclear cells patients with lymphoid hemopathy MYELOID HEMOPATHY without ATG Clofarabine patients with myeloid hemopathy MYELOID HEMOPATHY without ATG Full body irradiation patients with myeloid hemopathy MYELOID HEMOPATHY without ATG Cyclophosphamide patients with myeloid hemopathy MYELOID HEMOPATHY without ATG stem cell transplantation patients with myeloid hemopathy MYELOID HEMOPATHY without ATG nuclear cells patients with myeloid hemopathy LYMPHOID HEMOPATHY witH ATG Full body irradiation patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence LYMPHOID HEMOPATHY witH ATG stem cell transplantation patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence LYMPHOID HEMOPATHY witH ATG nuclear cells patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence MYELOID HEMOPATHY with ATG Full body irradiation patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence MYELOID HEMOPATHY with ATG stem cell transplantation patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence MYELOID HEMOPATHY with ATG nuclear cells patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence LYMPHOID HEMOPATHY witH ATG Thymoglobulin Injectable Product patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence MYELOID HEMOPATHY with ATG Thymoglobulin Injectable Product patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence LYMPHOID HEMOPATHY without ATG Cyclophosphamide patients with lymphoid hemopathy LYMPHOID HEMOPATHY witH ATG Fludarabine patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence LYMPHOID HEMOPATHY witH ATG Cyclophosphamide patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence MYELOID HEMOPATHY with ATG Clofarabine patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence MYELOID HEMOPATHY with ATG Cyclophosphamide patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
- Primary Outcome Measures
Name Time Method Incidence of grade 3 and 4 acute GVHD cortico-resistant 100 days after transplantation acute GVHD will be evaluated from International Mount Sinai criteria
- Secondary Outcome Measures
Name Time Method graft and relapse free survival one year time between Day O and relapse
Infections frequency one year time of occurring and frequency of viral (CytoMegalo Virus, Epstein Barr virus , BKV, adenovirus), bacterial, parasite and yeast infections, evaluated by Polymerase Chain Reaction (PCR), blood and urines cultures, biopsy if applicable
Engraftment one year chimerism
disease free survival (DFS) one year, the last follow-up visit blood and bone marrow analysis
Overall survival (OS) one year, the last follow-up visit clinical follow-up
Chimerism 1, 2, 3, 6 and 12 months after transplantation proportion of full and mixed donor chimerism
Identification of ghost factors associated with GVHD one year Statistical Models to Identify Subjects with Ghost Prognosis Factors Nguyen JM. 2015
non relapse mortality (NRM) last follow-up visit number of death unrelated to relapse or disease progression
Immune reconstitution 3, 6 and 12 months after transplantation lymphocytes, monocytes, T4, T8, Natural Killer (NK), B cells rates
Adverse events of grade 3 and 4 after transplantation one year time of occurring and frequency of grade 3 and grade 4 adverse events (CTCAE criteria)
chronic GVHD one year chronic GVHD will be assessed with NCI criteria for evaluation of chronic GVHD
compare OS between patients with ATG and patients without ATG one year, last follow-up visit OS
compare grade 2-4 and 3-4 acute GVHD between patients with ATG and patients without ATG one year acute GVHD will be evaluated from International Mount Sinai criteria
compare chronic GVHD between patients with ATG and patients without ATG one year chronic GVHD will be assessed with NCI criteria for evaluation of chronic GVHD
compare DFS between patients with ATG and patients without ATG one year, last follow-up visit DFS
compare Relapse between patients with ATG and patients without ATG one year, last follow-up visit Relapse
compare NRM between patients with ATG and patients without ATG one year, last follow-up visit NRM
compare Infections frequency between patients with ATG and patients without ATG one year time of occurring and frequency of viral (CytoMegalo Virus, Epstein Barr virus , BKV, adenovirus), bacterial, parasite and yeast infections, evaluated by Polymerase Chain Reaction (PCR), blood and urines cultures, biopsy if applicable
Trial Locations
- Locations (1)
Nantes Uh
🇫🇷Nantes, France