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

Phase 3

Terminated

• Conditions: Aplastic Anaemia
• Interventions: Drug: G-CSF; Drug: Early retreatment with ATG

• Registration Number: NCT01163942
• Lead Sponsor: European Society for Blood and Marrow Transplantation

Brief Summary

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.

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.

Study Timeline

• Study Start: 2001-03
• Primary Completion: 2008-06
• Study First Submitted: 2010-07-14
• Study First Submitted QC: 2010-07-15
• Study First Posted: 2010-07-16
• Study Completion: 2010-11
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-19
• Last Update Posted: 2024-02-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 205

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Yes G-CSF, No 2nd ATG	Early retreatment with ATG	Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
No G-CSF, yes 2nd ATG	Early retreatment with ATG	Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.
Yes G-CSF, No 2nd ATG	G-CSF	Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
No G-CSF, No 2nd ATG	Early retreatment with ATG	Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
Yes G-CSF, Yes 2nd ATG	G-CSF	Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.
Yes G-CSF, Yes 2nd ATG	Early retreatment with ATG	Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.
No G-CSF, No 2nd ATG	G-CSF	Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
No G-CSF, yes 2nd ATG	G-CSF	Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.

Primary Outcome Measures

Name	Time	Method
Failure free survival	day 240	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

Name	Time	Method
Safety	6year	The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A
Retreatment with ATG	day 240	Proportion of subjects who respond to re-treatment with ATG,
Relapse rate	2year	The relapse rate among responders
Blood count	day 240	Median blood counts among subjects who achieve transfusion independence
Severity of the disease	day 365	The proportion of subjects who have a change in severity of disease (e.g. improvement from very severe to severe aplastic anemia)
Complete remission	day 120	Time to achieving a complete remission within 120 days
Severe Infections	day 240	Incidence of severe infections
Haematological response	day 240	The proportion of subjects who achieve a hematologic response
Benefit of addition of G-CSF	day 240	The benefit due to the addition of G-CSF on death rate (i), days of hospitalization (ii), and duration of antibiotic treatment (iii)

Trial Locations

Locations (60)

Groningen University Hospital; 🇳🇱 Groningen, Netherlands

St. Antoine; 🇫🇷 Paris, France

Benjamin Franklin Hospital; 🇩🇪 Berlin, Germany

Evangelisches Waldkrankenhaus; 🇩🇪 Berlin, Germany

Charite Hospital; 🇩🇪 Berlin, Germany

St. Louis Hospital; 🇫🇷 Paris, France

Henri Mondor; 🇫🇷 Creteil, France

CHU Limoges; 🇫🇷 Limoges, France

CHU Reims; 🇫🇷 Reims, France

Paoli-Calmettes Institute; 🇫🇷 Marseille, France

CHU Caremeau; 🇫🇷 Nimes, France

Bretonneau Hospital; 🇫🇷 Tours, France

G. Roussy Institute; 🇫🇷 Villejuf, France

University Hospital Georg August; 🇩🇪 Göttingen, Germany

Klinikum Nord; 🇩🇪 Nürnberg, Germany

Hannover Medical School; 🇩🇪 Hannover, Germany

Sana Klinikum; 🇩🇪 Lübeck, Germany

Brüderkrankenhaus St. Josef; 🇩🇪 Paderborn, Germany

Klinkum Rechts der Isar; 🇩🇪 München, Germany

University Hospital Ulm; 🇩🇪 Ulm, Germany

Krakenhaus München Schwabing; 🇩🇪 München, Germany

Harlachin; 🇩🇪 München, Germany

Klinikum Oldenburg; 🇩🇪 Oldenburg, Germany

Klinikum Ernst von Bergmann; 🇩🇪 Potsdam, Germany

University Clinic Tübingen; 🇩🇪 Tübingen, Germany

Deutsche Klinik für Diagnostik; 🇩🇪 Wiesbaden, Germany

Helios Klinikum Wuppertal; 🇩🇪 Wuppertal, Germany

Athens General Pediatric Hospital; 🇬🇷 Athens, Greece

Gaslini Children's Hospital; 🇮🇹 Genova, Italy

San Raffaele Hospital; 🇮🇹 Milan, Italy

Huddinge University Hospital; 🇸🇪 Stockholm, Sweden

Monklands Hospital; 🇬🇧 Airdrie, United Kingdom

St George's Hospital/ St George's University of London; 🇬🇧 London, United Kingdom

CHU Montpellier; 🇫🇷 Montpellier, France

Universitäts Klinikum; 🇩🇪 Ludwigshaven, Germany

CHU Angers; 🇫🇷 Angers, France

CHU Clemenceau; 🇫🇷 Caen, France

CHU de Caen; 🇫🇷 Caen, France

Avicenne Hospital; 🇫🇷 Bobigny, France

CHU Toulouse; 🇫🇷 Toulouse, France

Universitätsklinik; 🇩🇪 Essen, Germany

University Hospital Carl Gustav Carus; 🇩🇪 Dresden, Germany

Evangelisches Krankenhaus Diakonie; 🇩🇪 Bremen, Germany

University Hospital Heinrich Heine; 🇩🇪 Düsseldorf, Germany

St. Johannes-Hospital; 🇩🇪 Duisburg, Germany

Asklepios Klinik Altona; 🇩🇪 Hamburg, Germany

Marien Hopistal; 🇩🇪 Hagen, Germany

Klinikum Stuttgart; 🇩🇪 Stuttgart, Germany

Leiden University Medical Centre; 🇳🇱 Leiden, Netherlands

San Martino; 🇮🇹 Genova, Italy

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Lund Unversity; 🇸🇪 Lund, Sweden

Heartlands Hospital; 🇬🇧 Birmingham, United Kingdom

Hopitaux Universitaires de Geneve; 🇨🇭 Geneva, Switzerland

Bristol Haematology & Oncology Centre; 🇬🇧 Bristol, United Kingdom

Royal Cornwall Hospitals; 🇬🇧 Cornwall, United Kingdom

The Leeds Teaching Hospitals; 🇬🇧 Leeds, United Kingdom

Wishaw General; 🇬🇧 Wishaw, United Kingdom

St. Bartholomew's Hospital; 🇬🇧 London, United Kingdom

University Hospital; 🇨🇭 Basel, Switzerland