Clinical trial NCT03263767: Post Transplant Cyclophosphamide (PTCY) as Sole Graft Versus Host Disease (GVHD) Prophylaxis for Matched Allotransplant: CYRIC
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Keywords: Peripheral haemopoietic stem cell transplant
High dose cyclophosphamide
acute GVHD
allogenic transplantation
RIC (reduced-intensity conditioning)
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2017-08-28
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)
  * 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

Primary outcomes:
measure: Incidence of grade 3 and 4 acute GVHD cortico-resistant
timeFrame: 100 days after transplantation
Secondary outcomes:
measure: Engraftment
timeFrame: one year
measure: Engraftment
timeFrame: one year
measure: disease free survival (DFS)
timeFrame: one year, the last follow-up visit
measure: Overall survival (OS)
timeFrame: one year, the last follow-up visit
measure: graft and relapse free survival
timeFrame: one year
measure: chronic GVHD
timeFrame: one year
measure: non relapse mortality (NRM)
timeFrame: last follow-up visit
measure: Chimerism
timeFrame: 1, 2, 3, 6 and 12 months after transplantation
measure: Immune reconstitution
timeFrame: 3, 6 and 12 months after transplantation
measure: Identification of ghost factors associated with GVHD
timeFrame: one year
measure: Adverse events of grade 3 and 4 after transplantation
timeFrame: one year
measure: Infections frequency
timeFrame: one year
measure: compare OS between patients with ATG and patients without ATG
timeFrame: one year, last follow-up visit
measure: compare grade 2-4 and 3-4 acute GVHD between patients with ATG and patients without ATG
timeFrame: one year
measure: compare chronic GVHD between patients with ATG and patients without ATG
timeFrame: one year
measure: compare DFS between patients with ATG and patients without ATG
timeFrame: one year, last follow-up visit
measure: compare Relapse between patients with ATG and patients without ATG
timeFrame: one year, last follow-up visit
measure: compare NRM between patients with ATG and patients without ATG
timeFrame: one year, last follow-up visit
measure: compare Infections frequency between patients with ATG and patients without ATG
timeFrame: one year
Other outcomes:
Locations:
city: Nantes
country: France
facility: Nantes Uh
Study officials:
References: