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

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

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).

Study Overview

• Status: Completed
• Conditions: Hematopoietic Stem Cell Transplantation; Graft Versus Host Disease
• Intervention / Treatment: Behavioral: Dose adaptation according to CN activity monitoring; Drug: Cyclosporine (CsA)

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94000
    • CHU Henri Mondor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 85 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose adjustment according CN activity

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)

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Agence de La Biomédecine
• Investigators: Study Director: Sylvia Sanquer, Pharm.D., AP-HP, Hôpital Necker-Enfants Malades

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: July 28, 2009
• First Submitted That Met QC Criteria: July 28, 2009
• First Posted (Estimate): July 29, 2009

Study Record Updates

• Last Update Posted (Estimate): October 1, 2009
• Last Update Submitted That Met QC Criteria: September 30, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: P021004