Cyclosporine Dose Adjustment According to Calcineurin Activity After Allogeneic Hematopoietic Stem-cell Transplantation

Graft Versus Host Disease Clinical Trial

— CALCICLO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00948727
• Other study ID #: P021004
• Status: Completed
• Phase: Phase 2
• First received: July 28, 2009
• Last updated: September 30, 2009
• Start date: January 2004
• Est. completion date: June 2008

Study information

• Verified date: July 2009
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: June 2008
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 85 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation

Intervention

Behavioral:
• Dose 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.

Drug:
• Cyclosporine (CsA)
Cyclosporine (CsA)

Locations

Country	Name	City	State
France	Chu Henri Mondor	Créteil

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Agence de La Biomédecine

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end point is the acute grade II to IV GVHD-free survival 100 days after transplantation.		100 days after transplantation.	Yes
Secondary	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	Yes