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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)

Primary Purpose

Aplastic Anaemia

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
G-CSF
Early retreatment with ATG
Sponsored by
European Society for Blood and Marrow Transplantation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anaemia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital
  • CHU Angers
  • Avicenne Hospital
  • University Hospital
  • CHU Clemenceau
  • CHU de Caen
  • Henri Mondor
  • CHU Limoges
  • Paoli-Calmettes Institute
  • CHU Montpellier
  • CHU Caremeau
  • St. Antoine
  • St. Louis Hospital
  • CHU Reims
  • CHU Toulouse
  • Bretonneau Hospital
  • G. Roussy Institute
  • Benjamin Franklin Hospital
  • Charite Hospital
  • Evangelisches Waldkrankenhaus
  • Evangelisches Krankenhaus Diakonie
  • University Hospital
  • University Hospital Carl Gustav Carus
  • St. Johannes-Hospital
  • University Hospital Heinrich Heine
  • Universitätsklinik
  • University Hospital
  • University Hospital Georg August
  • Marien Hopistal
  • University Hospital
  • Asklepios Klinik Altona
  • Hannover Medical School
  • University Hospital
  • Universitäts Klinikum
  • Sana Klinikum
  • Harlachin
  • Klinkum Rechts der Isar
  • Krakenhaus München Schwabing
  • Klinikum Nord
  • Klinikum Oldenburg
  • Brüderkrankenhaus St. Josef
  • Klinikum Ernst von Bergmann
  • University Hospital
  • University Hospital
  • Klinikum Stuttgart
  • University Clinic Tübingen
  • University Hospital Ulm
  • Deutsche Klinik für Diagnostik
  • University Hospital
  • Helios Klinikum Wuppertal
  • Athens General Pediatric Hospital
  • University Hospital
  • Gaslini Children's Hospital
  • San Martino
  • San Raffaele Hospital
  • University Hospital
  • Groningen University Hospital
  • Leiden University Medical Centre
  • Erasmus MC
  • Lund Unversity
  • Huddinge University Hospital
  • University Hospital
  • Hopitaux Universitaires de Geneve
  • Monklands Hospital
  • Heartlands Hospital
  • Bristol Haematology & Oncology Centre
  • Royal Cornwall Hospitals
  • The Leeds Teaching Hospitals
  • St George's Hospital/ St George's University of London
  • St. Bartholomew's Hospital
  • Wishaw General

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

No G-CSF, No 2nd ATG

No G-CSF, yes 2nd ATG

Yes G-CSF, No 2nd ATG

Yes G-CSF, Yes 2nd ATG

Arm Description

Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.

Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.

Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.

Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.

Outcomes

Primary Outcome Measures

Failure free survival
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
The proportion of subjects who achieve a hematologic response
Severe Infections
Incidence of severe infections
Benefit of addition of G-CSF
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 to achieving a complete remission within 120 days
Relapse rate
The relapse rate among responders
Blood count
Median blood counts among subjects who achieve transfusion independence
Severity of the disease
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
Proportion of subjects who respond to re-treatment with ATG,
Safety
The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A

Full Information

First Posted
July 14, 2010
Last Updated
April 2, 2015
Sponsor
European Society for Blood and Marrow Transplantation
Collaborators
CHUGAI sanofi-aventis
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1. Study Identification

Unique Protocol Identification Number
NCT01163942
Brief Title
Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF)
Acronym
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

2. Study Status

Record Verification Date
July 2010
Overall Recruitment Status
Terminated
Why Stopped
Ceased production of the study drug, Lymphoglobulin. Recruitment of patients onto the trial was too slow.
Study Start Date
March 2001 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Society for Blood and Marrow Transplantation
Collaborators
CHUGAI sanofi-aventis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anaemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
205 (Actual)

8. Arms, Groups, and Interventions

Arm Title
No G-CSF, No 2nd ATG
Arm Type
Active Comparator
Arm Description
Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
Arm Title
No G-CSF, yes 2nd ATG
Arm Type
Active Comparator
Arm Description
Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.
Arm Title
Yes G-CSF, No 2nd ATG
Arm Type
Active Comparator
Arm Description
Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
Arm Title
Yes G-CSF, Yes 2nd ATG
Arm Type
Active Comparator
Arm Description
Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
Yes/no addition of G-CSF
Intervention Type
Drug
Intervention Name(s)
Early retreatment with ATG
Intervention Description
Yes/no early retreatment with ATG
Primary Outcome Measure Information:
Title
Failure free survival
Description
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).
Time Frame
day 240
Secondary Outcome Measure Information:
Title
Haematological response
Description
The proportion of subjects who achieve a hematologic response
Time Frame
day 240
Title
Severe Infections
Description
Incidence of severe infections
Time Frame
day 240
Title
Benefit of addition of G-CSF
Description
The benefit due to the addition of G-CSF on death rate (i), days of hospitalization (ii), and duration of antibiotic treatment (iii)
Time Frame
day 240
Title
Complete remission
Description
Time to achieving a complete remission within 120 days
Time Frame
day 120
Title
Relapse rate
Description
The relapse rate among responders
Time Frame
2year
Title
Blood count
Description
Median blood counts among subjects who achieve transfusion independence
Time Frame
day 240
Title
Severity of the disease
Description
The proportion of subjects who have a change in severity of disease (e.g. improvement from very severe to severe aplastic anemia)
Time Frame
day 365
Title
Retreatment with ATG
Description
Proportion of subjects who respond to re-treatment with ATG,
Time Frame
day 240
Title
Safety
Description
The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A
Time Frame
6year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
André Tichelli, Prof. MD.
Organizational Affiliation
University Hospital, Basel, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital
City
Pilsen
Country
Czech Republic
Facility Name
CHU Angers
City
Angers
Country
France
Facility Name
Avicenne Hospital
City
Bobigny
Country
France
Facility Name
University Hospital
City
Brest
Country
France
Facility Name
CHU Clemenceau
City
Caen
Country
France
Facility Name
CHU de Caen
City
Caen
Country
France
Facility Name
Henri Mondor
City
Creteil
Country
France
Facility Name
CHU Limoges
City
Limoges
Country
France
Facility Name
Paoli-Calmettes Institute
City
Marseille
Country
France
Facility Name
CHU Montpellier
City
Montpellier
Country
France
Facility Name
CHU Caremeau
City
Nimes
Country
France
Facility Name
St. Antoine
City
Paris
Country
France
Facility Name
St. Louis Hospital
City
Paris
Country
France
Facility Name
CHU Reims
City
Reims
Country
France
Facility Name
CHU Toulouse
City
Toulouse
Country
France
Facility Name
Bretonneau Hospital
City
Tours
Country
France
Facility Name
G. Roussy Institute
City
Villejuf
Country
France
Facility Name
Benjamin Franklin Hospital
City
Berlin
Country
Germany
Facility Name
Charite Hospital
City
Berlin
Country
Germany
Facility Name
Evangelisches Waldkrankenhaus
City
Berlin
Country
Germany
Facility Name
Evangelisches Krankenhaus Diakonie
City
Bremen
Country
Germany
Facility Name
University Hospital
City
Cologne
Country
Germany
Facility Name
University Hospital Carl Gustav Carus
City
Dresden
Country
Germany
Facility Name
St. Johannes-Hospital
City
Duisburg
Country
Germany
Facility Name
University Hospital Heinrich Heine
City
Düsseldorf
Country
Germany
Facility Name
Universitätsklinik
City
Essen
Country
Germany
Facility Name
University Hospital
City
Frankfurt
Country
Germany
Facility Name
University Hospital Georg August
City
Göttingen
Country
Germany
Facility Name
Marien Hopistal
City
Hagen
Country
Germany
Facility Name
University Hospital
City
Halle
Country
Germany
Facility Name
Asklepios Klinik Altona
City
Hamburg
Country
Germany
Facility Name
Hannover Medical School
City
Hannover
Country
Germany
Facility Name
University Hospital
City
Heidelberg
Country
Germany
Facility Name
Universitäts Klinikum
City
Ludwigshaven
Country
Germany
Facility Name
Sana Klinikum
City
Lübeck
Country
Germany
Facility Name
Harlachin
City
München
Country
Germany
Facility Name
Klinkum Rechts der Isar
City
München
Country
Germany
Facility Name
Krakenhaus München Schwabing
City
München
Country
Germany
Facility Name
Klinikum Nord
City
Nürnberg
Country
Germany
Facility Name
Klinikum Oldenburg
City
Oldenburg
Country
Germany
Facility Name
Brüderkrankenhaus St. Josef
City
Paderborn
Country
Germany
Facility Name
Klinikum Ernst von Bergmann
City
Potsdam
Country
Germany
Facility Name
University Hospital
City
Regensburg
Country
Germany
Facility Name
University Hospital
City
Rostock
Country
Germany
Facility Name
Klinikum Stuttgart
City
Stuttgart
Country
Germany
Facility Name
University Clinic Tübingen
City
Tübingen
Country
Germany
Facility Name
University Hospital Ulm
City
Ulm
Country
Germany
Facility Name
Deutsche Klinik für Diagnostik
City
Wiesbaden
Country
Germany
Facility Name
University Hospital
City
Wiesbaden
Country
Germany
Facility Name
Helios Klinikum Wuppertal
City
Wuppertal
Country
Germany
Facility Name
Athens General Pediatric Hospital
City
Athens
Country
Greece
Facility Name
University Hospital
City
Patras
Country
Greece
Facility Name
Gaslini Children's Hospital
City
Genova
Country
Italy
Facility Name
San Martino
City
Genova
Country
Italy
Facility Name
San Raffaele Hospital
City
Milan
Country
Italy
Facility Name
University Hospital
City
Padova
Country
Italy
Facility Name
Groningen University Hospital
City
Groningen
Country
Netherlands
Facility Name
Leiden University Medical Centre
City
Leiden
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
Facility Name
Lund Unversity
City
Lund
Country
Sweden
Facility Name
Huddinge University Hospital
City
Stockholm
Country
Sweden
Facility Name
University Hospital
City
Basel
Country
Switzerland
Facility Name
Hopitaux Universitaires de Geneve
City
Geneva
Country
Switzerland
Facility Name
Monklands Hospital
City
Airdrie
Country
United Kingdom
Facility Name
Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Bristol Haematology & Oncology Centre
City
Bristol
Country
United Kingdom
Facility Name
Royal Cornwall Hospitals
City
Cornwall
Country
United Kingdom
Facility Name
The Leeds Teaching Hospitals
City
Leeds
Country
United Kingdom
Facility Name
St George's Hospital/ St George's University of London
City
London
ZIP/Postal Code
Sw17 0RE
Country
United Kingdom
Facility Name
St. Bartholomew's Hospital
City
London
Country
United Kingdom
Facility Name
Wishaw General
City
Wishaw
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31582549
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.
Results Reference
derived
PubMed Identifier
21233311
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.
Results Reference
derived

Learn more about this trial

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

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