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Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF) (SAA-G-CSF)

This study has been terminated.
(Ceased production of the study drug, Lymphoglobulin. Recruitment of patients onto the trial was too slow.)
CHUGAI sanofi-aventis
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation Identifier:
First received: July 14, 2010
Last updated: April 2, 2015
Last verified: July 2010
The purpose of this study is to examine the effect of G-CSF on disease free survival and overall survival in aplastic anaemia patients who also receive ATG and Cyclosporin A.

Condition Intervention Phase
Aplastic Anaemia
Drug: G-CSF
Drug: Early retreatment with ATG
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by European Group for Blood and Marrow Transplantation:

Primary Outcome Measures:
  • Failure free survival [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    To evaluate the effect of G-CSF on failure free survival and mortality in study subjects also receiving ATG and Cyclosporin A & time to hematologic response (failure defined as death, non-response or requirement of further treatment).

Secondary Outcome Measures:
  • Haematological response [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    The proportion of subjects who achieve a hematologic response

  • Severe Infections [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    Incidence of severe infections

  • Benefit of addition of G-CSF [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    The benefit due to the addition of G-CSF on death rate (i), days of hospitalization (ii), and duration of antibiotic treatment (iii)

  • Complete remission [ Time Frame: day 120 ] [ Designated as safety issue: No ]
    Time to achieving a complete remission within 120 days

  • Relapse rate [ Time Frame: 2year ] [ Designated as safety issue: No ]
    The relapse rate among responders

  • Blood count [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    Median blood counts among subjects who achieve transfusion independence

  • Severity of the disease [ Time Frame: day 365 ] [ Designated as safety issue: No ]
    The proportion of subjects who have a change in severity of disease (e.g. improvement from very severe to severe aplastic anemia)

  • Retreatment with ATG [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    Proportion of subjects who respond to re-treatment with ATG,

  • Safety [ Time Frame: 6year ] [ Designated as safety issue: Yes ]
    The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A

Enrollment: 205
Study Start Date: March 2001
Study Completion Date: November 2010
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: No G-CSF, No 2nd ATG
Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG
Active Comparator: No G-CSF, yes 2nd ATG
Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.
Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG
Active Comparator: Yes G-CSF, No 2nd ATG
Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG
Active Comparator: Yes G-CSF, Yes 2nd ATG
Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.
Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG

Detailed Description:
Open label, randomized, controlled study of G-CSF, ATG and Cyclosporin A versus ATG and Cyclosporin A. Subjects will be evaluated for hematologic response through day 240. Subjects who do not demonstrate a partial or complete remission by day 120 will be randomized to receive either a second course of ATG or continue their current regimen. Subjects who do demonstrate a partial or complete remission will continue their current regimen through day 240 or maintenance of a complete remission for 30 days. The last day of study treatment will be day 240.

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Severe or very severe aplastic anemia
  • Less than 6 months from diagnosis of severe aplastic anemia by bone marrow biopsy
  • Ethical - Before randomization is done the subject or legally acceptable representative must give written informed consent for participation in the study

Exclusion Criteria:

  • Eligibility for an HLA-matched sibling donor transplant
  • Prior therapy with ATG
  • Cyclosporin A <4 weeks before enrollment
  • Treatment with G-CSF <2 weeks before enrollment
  • Other growth factors <4 weeks before enrollment
  • Diagnosis of Fanconi anemia, dyskeratosis congenita or congenital bone marrow failure syndrome
  • Evidence of myelodysplastic disease
  • Diagnosis or previous history of carcinoma (except local cervical, basal cell, squamous cells, or melanoma)
  • Subjects who have infection, hepatic, renal cardiac, metabolic or other concurrent diseases of such severity that death is imminent
  • Subject is pregnant (e.g. positive HCG test) or is breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01163942

  Hide Study Locations
Czech Republic
University Hospital
Pilsen, Czech Republic
CHU Angers
Angers, France
Avicenne Hospital
Bobigny, France
University Hospital
Brest, France
CHU Clemenceau
Caen, France
CHU de Caen
Caen, France
Henri Mondor
Creteil, France
CHU Limoges
Limoges, France
Paoli-Calmettes Institute
Marseille, France
CHU Montpellier
Montpellier, France
CHU Caremeau
Nimes, France
St. Antoine
Paris, France
St. Louis Hospital
Paris, France
CHU Reims
Reims, France
CHU Toulouse
Toulouse, France
Bretonneau Hospital
Tours, France
G. Roussy Institute
Villejuf, France
Benjamin Franklin Hospital
Berlin, Germany
Charite Hospital
Berlin, Germany
Evangelisches Waldkrankenhaus
Berlin, Germany
Evangelisches Krankenhaus Diakonie
Bremen, Germany
University Hospital
Cologne, Germany
University Hospital Carl Gustav Carus
Dresden, Germany
St. Johannes-Hospital
Duisburg, Germany
University Hospital Heinrich Heine
Düsseldorf, Germany
Essen, Germany
University Hospital
Frankfurt, Germany
University Hospital Georg August
Göttingen, Germany
Marien Hopistal
Hagen, Germany
University Hospital
Halle, Germany
Asklepios Klinik Altona
Hamburg, Germany
Hannover Medical School
Hannover, Germany
University Hospital
Heidelberg, Germany
Universitäts Klinikum
Ludwigshaven, Germany
Sana Klinikum
Lübeck, Germany
München, Germany
Klinkum Rechts der Isar
München, Germany
Krakenhaus München Schwabing
München, Germany
Klinikum Nord
Nürnberg, Germany
Klinikum Oldenburg
Oldenburg, Germany
Brüderkrankenhaus St. Josef
Paderborn, Germany
Klinikum Ernst von Bergmann
Potsdam, Germany
University Hospital
Regensburg, Germany
University Hospital
Rostock, Germany
Klinikum Stuttgart
Stuttgart, Germany
University Clinic Tübingen
Tübingen, Germany
University Hospital Ulm
Ulm, Germany
Deutsche Klinik für Diagnostik
Wiesbaden, Germany
University Hospital
Wiesbaden, Germany
Helios Klinikum Wuppertal
Wuppertal, Germany
Athens General Pediatric Hospital
Athens, Greece
University Hospital
Patras, Greece
Gaslini Children's Hospital
Genova, Italy
San Martino
Genova, Italy
San Raffaele Hospital
Milan, Italy
University Hospital
Padova, Italy
Groningen University Hospital
Groningen, Netherlands
Leiden University Medical Centre
Leiden, Netherlands
Erasmus MC
Rotterdam, Netherlands
Lund Unversity
Lund, Sweden
Huddinge University Hospital
Stockholm, Sweden
University Hospital
Basel, Switzerland
Hopitaux Universitaires de Geneve
Geneva, Switzerland
United Kingdom
Monklands Hospital
Airdrie, United Kingdom
Heartlands Hospital
Birmingham, United Kingdom
Bristol Haematology & Oncology Centre
Bristol, United Kingdom
Royal Cornwall Hospitals
Cornwall, United Kingdom
The Leeds Teaching Hospitals
Leeds, United Kingdom
St George's Hospital/ St George's University of London
London, United Kingdom, Sw17 0RE
St. Bartholomew's Hospital
London, United Kingdom
Wishaw General
Wishaw, United Kingdom
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
CHUGAI sanofi-aventis
Principal Investigator: André Tichelli, Prof. MD. University Hospital, Basel, Switzerland
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: European Group for Blood and Marrow Transplantation Identifier: NCT01163942     History of Changes
Other Study ID Numbers: Flagship AA trial  41980964 
Study First Received: July 14, 2010
Last Updated: April 2, 2015
Health Authority: Switzerland: Swissmedic
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
Italy: Ministry of Health
Netherlands: Medical Ethics Review Committee (METC)

Additional relevant MeSH terms:
Anemia, Aplastic
Hematologic Diseases
Bone Marrow 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
Adjuvants, Immunologic processed this record on December 02, 2016