Post Transplant Cyclophosphamide (PTCY) as Sole Graft Versus Host Disease (GVHD) Prophylaxis for Matched Allotransplant: CYRIC

• Status: Recruiting
• Trial end date: 2023-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nantes University Hospital
• Treatments: Clofarabine; Cyclophosphamide; Fludarabine; Thymoglobulin

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