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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00948727
Recruitment Status : Completed
First Posted : July 29, 2009
Last Update Posted : October 1, 2009
Agence de La Biomédecine
Information provided by:
Assistance Publique - Hôpitaux de Paris

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).

Condition or disease Intervention/treatment Phase
Hematopoietic Stem Cell Transplantation Graft Versus Host Disease Behavioral: Dose adaptation according to CN activity monitoring Drug: Cyclosporine (CsA) Phase 2

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  (Clinical Trial)
Actual Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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 Start Date : January 2004
Actual Primary Completion Date : September 2006
Actual Study Completion Date : June 2008

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)

Primary Outcome Measures :
  1. The primary end point is the acute grade II to IV GVHD-free survival 100 days after transplantation. [ Time Frame: 100 days after transplantation. ]

Secondary Outcome Measures :
  1. 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. [ Time Frame: 100 days after transplantation ]

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Ages Eligible for Study:   12 Years to 85 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00948727

Chu Henri Mondor
Créteil, France, 94000
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Agence de La Biomédecine
Study Director: Sylvia Sanquer, Pharm.D. AP-HP, Hôpital Necker-Enfants Malades

Responsible Party: Thérèse NGOUE, Department Clinical Research of developpement Identifier: NCT00948727     History of Changes
Other Study ID Numbers: P021004
First Posted: July 29, 2009    Key Record Dates
Last Update Posted: October 1, 2009
Last Verified: July 2009

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors