Hematopoietic Stem Cell Transplantation, Graft Versus Host Disease
Conditions
Brief summary
The purpose of this trial is to assess whether an adaptation of cyclosporine (CsA) dose according to a longitudinal calcineurin (CN) activity monitoring would prevent the onset of graft-versus-host disease (GVHD).
Detailed description
Our previous studies established a correlation between increased calcineurin (CN) activity and the risk of developing severe acute GVHD in allogeneic stem cell transplant recipients receiving immunosuppressive therapy with calcineurin inhibitors. This proof-of-concept trial is aiming at evaluating CALCIneurin activity as a monitoring biomarker of efficacy of cyCLOsporine - (CALCICLO) - for the prophylaxis of acute GVHD. Our aim is to assess whether a longitudinal monitoring of CN activity would permit to adapt and optimize the dose of CsA that would prevent the onset of severe acute GVHD, yet still maintaining an acceptable tolerability profile.
Interventions
BEHAVIORALDose adaptation according to CN activity monitoring
The protocol of the CALCICLO trial consisted in a CsA dose adaptation during the first 100 days following transplantation. This dose adaptation was performed according to both residual CsA blood and CN activity levels only if the safety of vital functions - especially renal, liver, and neurological - was preserved as assessed by clinical evaluations and laboratory analyses such as creatinine clearance higher than 40 ml/min, serum bilirubin lower than 40 µM and absence of neurological signs. According to the protocol, CsA blood levels and CN activity were measured concomitantly at least once a week from day 0 to day 15, twice a week from day 16 to day 35 and then once a week until day 100.
Cyclosporine (CsA)
Sponsors
Agence de La Biomédecine
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients were between the age of 12 and 60 years * Patients planned to receive an allogeneic HSCT following a myeloablative conditioning regimen
Exclusion criteria
* Transplant from a syngeneic donor * Evidence of refractory disease * Nonmyeloablative conditioning * Any participation to a study with a new investigational drug within the previous 3 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary end point is the acute grade II to IV GVHD-free survival 100 days after transplantation. | 100 days after transplantation. |
Secondary
| Measure | Time frame |
|---|---|
| Safety was a secondary endpoint. It was assessed through clinical assessments including vital signs, creatinine clearance, the presence or not of neurological signs evocative of, or consistent with CsA toxicity, creatinine clearance and serum bilirubin. | 100 days after transplantation |
Countries
France
Outcome results
None listed