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

NCT ID: NCT00948727

Last Updated: 2009-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2008-06-30

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.

Conditions

Hematopoietic Stem Cell Transplantation; Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Dose adjustment according CN activity

Group Type: EXPERIMENTAL

Dose adaptation according to CN activity monitoring

Intervention Type: BEHAVIORAL

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)

Intervention Type: DRUG

Cyclosporine (CsA)

Interventions

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.

Intervention Type: BEHAVIORAL

Cyclosporine (CsA)

Cyclosporine (CsA)

Intervention Type: DRUG

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agence de La Biomédecine

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Department Clinical Research of developpement

Principal Investigators

Sylvia Sanquer, Pharm.D.

Role: STUDY_DIRECTOR

AP-HP, Hôpital Necker-Enfants Malades

Locations

Chu Henri Mondor

Créteil, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 15077026 (View on PubMed)

Other Identifiers

P021004

Identifier Type: -

Identifier Source: org_study_id