Clinical trial NCT01163942: Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF)
Official title: A RANDOMIZED CONTROLLED STUDY IN NEWLY DIAGNOSED SEVERE APLASTIC ANEMIA PATIENTS RECEIVING ANTITHYMOCYTE GLOBULIN (ATG), CYCLOSPORIN A, WITH OR WITHOUT G-CSF
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Aplastic Anaemia
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: Sanofi
First posted: 2010-07-16
Enrollment: 205
Sex: ALL
Minimum age (years): 2
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Failure free survival
timeFrame: day 240
Secondary outcomes:
measure: Haematological response
timeFrame: day 240
measure: Severe Infections
timeFrame: day 240
measure: Benefit of addition of G-CSF
timeFrame: day 240
measure: Complete remission
timeFrame: day 120
measure: Relapse rate
timeFrame: 2year
measure: Blood count
timeFrame: day 240
measure: Severity of the disease
timeFrame: day 365
measure: Retreatment with ATG
timeFrame: day 240
measure: Safety
timeFrame: 6year
Other outcomes:
Locations:
city: Pilsen
country: Czechia
facility: University Hospital
city: Angers
country: France
facility: CHU Angers
city: Bobigny
country: France
facility: Avicenne Hospital
city: Brest
country: France
facility: University Hospital
city: Caen
country: France
facility: CHU Clemenceau
city: Caen
country: France
facility: CHU de Caen
city: Creteil
country: France
facility: Henri Mondor
city: Limoges
country: France
facility: CHU Limoges
city: Marseille
country: France
facility: Paoli-Calmettes Institute
city: Montpellier
country: France
facility: CHU Montpellier
city: Nimes
country: France
facility: CHU Caremeau
city: Paris
country: France
facility: St. Antoine
city: Paris
country: France
facility: St. Louis Hospital
city: Reims
country: France
facility: CHU Reims
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: Bretonneau Hospital
city: Villejuf
country: France
facility: G. Roussy Institute
city: Berlin
country: Germany
facility: Benjamin Franklin Hospital
city: Berlin
country: Germany
facility: Charite Hospital
city: Berlin
country: Germany
facility: Evangelisches Waldkrankenhaus
city: Bremen
country: Germany
facility: Evangelisches Krankenhaus Diakonie
city: Cologne
country: Germany
facility: University Hospital
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Duisburg
country: Germany
facility: St. Johannes-Hospital
city: Düsseldorf
country: Germany
facility: University Hospital Heinrich Heine
city: Essen
country: Germany
facility: Universitätsklinik
city: Frankfurt
country: Germany
facility: University Hospital
city: Göttingen
country: Germany
facility: University Hospital Georg August
city: Hagen
country: Germany
facility: Marien Hopistal
city: Halle
country: Germany
facility: University Hospital
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hannover
country: Germany
facility: Hannover Medical School
city: Heidelberg
country: Germany
facility: University Hospital
city: Ludwigshaven
country: Germany
facility: Universitäts Klinikum
city: Lübeck
country: Germany
facility: Sana Klinikum
city: München
country: Germany
facility: Harlachin
city: München
country: Germany
facility: Klinkum Rechts der Isar
city: München
country: Germany
facility: Krakenhaus München Schwabing
city: Nürnberg
country: Germany
facility: Klinikum Nord
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann
city: Regensburg
country: Germany
facility: University Hospital
city: Rostock
country: Germany
facility: University Hospital
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Tübingen
country: Germany
facility: University Clinic Tübingen
city: Ulm
country: Germany
facility: University Hospital Ulm
city: Wiesbaden
country: Germany
facility: Deutsche Klinik für Diagnostik
city: Wiesbaden
country: Germany
facility: University Hospital
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal
city: Athens
country: Greece
facility: Athens General Pediatric Hospital
city: Patras
country: Greece
facility: University Hospital
city: Genova
country: Italy
facility: Gaslini Children's Hospital
city: Genova
country: Italy
facility: San Martino
city: Milan
country: Italy
facility: San Raffaele Hospital
city: Padova
country: Italy
facility: University Hospital
city: Groningen
country: Netherlands
facility: Groningen University Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Lund
country: Sweden
facility: Lund Unversity
city: Stockholm
country: Sweden
facility: Huddinge University Hospital
city: Basel
country: Switzerland
facility: University Hospital
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Airdrie
country: United Kingdom
facility: Monklands Hospital
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology & Oncology Centre
city: Cornwall
country: United Kingdom
facility: Royal Cornwall Hospitals
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals
city: London
country: United Kingdom
facility: St George's Hospital/ St George's University of London
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
city: Wishaw
country: United Kingdom
facility: Wishaw General
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: André Tichelli, Prof. MD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tichelli A, de Latour RP, Passweg J, Knol-Bout C, Socie G, Marsh J, Schrezenmeier H, Hochsmann B, Bacigalupo A, Samarasinghe S, Rovo A, Kulasekararaj A, Roth A, Eikema DJ, Bosman P, Bader P, Risitano A, Dufour C; SAA Working Party of the EBMT. Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globulin and cyclosporine, with or without granulocyte colony-stimulating factor: a Severe Aplastic Anemia Working Party Trial from the European Group of Blood and Marrow Transplantation. Haematologica. 2020 May;105(5):1223-1231. doi: 10.3324/haematol.2019.222562. Epub 2019 Oct 3.
citation: Tichelli A, Schrezenmeier H, Socie G, Marsh J, Bacigalupo A, Duhrsen U, Franzke A, Hallek M, Thiel E, Wilhelm M, Hochsmann B, Barrois A, Champion K, Passweg JR. A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2011 Apr 28;117(17):4434-41. doi: 10.1182/blood-2010-08-304071. Epub 2011 Jan 13.