Clinical trial NCT00948727: Cyclosporine Dose Adjustment According to Calcineurin Activity After Allogeneic Hematopoietic Stem-cell Transplantation
Official title: Reduction of Acute and Chronic Graft-versus-host Disease After Allogeneic Hematopoietic Stem-cell Transplantation by Adapting Cyclosporine Doses According to Calcineurin Activity : a Proof-of-concept Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematopoietic Stem Cell Transplantation
Graft Versus Host Disease
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Agence de La Biomédecine
First posted: 2009-07-29
Enrollment: 39
Sex: ALL
Minimum age (years): 12
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: The primary end point is the acute grade II to IV GVHD-free survival 100 days after transplantation.
timeFrame: 100 days after transplantation.
Secondary outcomes:
measure: 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.
timeFrame: 100 days after transplantation
Other outcomes:
Locations:
city: Créteil
country: France
facility: Chu Henri Mondor
Study officials:
affiliation: AP-HP, Hôpital Necker-Enfants Malades
name: Sylvia Sanquer, Pharm.D.
role: STUDY_DIRECTOR
References:
citation: Sanquer S, Schwarzinger M, Maury S, Yakouben K, Rafi H, Pautas C, Kuentz M, Barouki R, Cordonnier C. Calcineurin activity as a functional index of immunosuppression after allogeneic stem-cell transplantation. Transplantation. 2004 Mar 27;77(6):854-8. doi: 10.1097/01.tp.0000114612.55925.22.