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

Sponsor
European Society for Blood and Marrow Transplantation (Other)
Overall Status
Terminated
CT.gov ID
NCT01163942
Collaborator
CHUGAI sanofi-aventis (Other)
205
Enrollment
71
Locations
4
Arms
116
Duration (Months)
2.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
205 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Mar 1, 2001
Actual Primary Completion Date :
Jun 1, 2008
Actual Study Completion Date :
Nov 1, 2010

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. 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

  1. Haematological response [day 240]

    The proportion of subjects who achieve a hematologic response

  2. Severe Infections [day 240]

    Incidence of severe infections

  3. 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)

  4. Complete remission [day 120]

    Time to achieving a complete remission within 120 days

  5. Relapse rate [2year]

    The relapse rate among responders

  6. Blood count [day 240]

    Median blood counts among subjects who achieve transfusion independence

  7. 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)

  8. Retreatment with ATG [day 240]

    Proportion of subjects who respond to re-treatment with ATG,

  9. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
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

Locations

Site City State Country Postal Code
1 University Hospital Pilsen Czech Republic
2 CHU Angers Angers France
3 Avicenne Hospital Bobigny France
4 University Hospital Brest France
5 CHU Clemenceau Caen France
6 CHU de Caen Caen France
7 Henri Mondor Creteil France
8 CHU Limoges Limoges France
9 Paoli-Calmettes Institute Marseille France
10 CHU Montpellier Montpellier France
11 CHU Caremeau Nimes France
12 St. Antoine Paris France
13 St. Louis Hospital Paris France
14 CHU Reims Reims France
15 CHU Toulouse Toulouse France
16 Bretonneau Hospital Tours France
17 G. Roussy Institute Villejuf France
18 Benjamin Franklin Hospital Berlin Germany
19 Charite Hospital Berlin Germany
20 Evangelisches Waldkrankenhaus Berlin Germany
21 Evangelisches Krankenhaus Diakonie Bremen Germany
22 University Hospital Cologne Germany
23 University Hospital Carl Gustav Carus Dresden Germany
24 St. Johannes-Hospital Duisburg Germany
25 University Hospital Heinrich Heine Düsseldorf Germany
26 Universitätsklinik Essen Germany
27 University Hospital Frankfurt Germany
28 University Hospital Georg August Göttingen Germany
29 Marien Hopistal Hagen Germany
30 University Hospital Halle Germany
31 Asklepios Klinik Altona Hamburg Germany
32 Hannover Medical School Hannover Germany
33 University Hospital Heidelberg Germany
34 Universitäts Klinikum Ludwigshaven Germany
35 Sana Klinikum Lübeck Germany
36 Harlachin München Germany
37 Klinkum Rechts der Isar München Germany
38 Krakenhaus München Schwabing München Germany
39 Klinikum Nord Nürnberg Germany
40 Klinikum Oldenburg Oldenburg Germany
41 Brüderkrankenhaus St. Josef Paderborn Germany
42 Klinikum Ernst von Bergmann Potsdam Germany
43 University Hospital Regensburg Germany
44 University Hospital Rostock Germany
45 Klinikum Stuttgart Stuttgart Germany
46 University Clinic Tübingen Tübingen Germany
47 University Hospital Ulm Ulm Germany
48 Deutsche Klinik für Diagnostik Wiesbaden Germany
49 University Hospital Wiesbaden Germany
50 Helios Klinikum Wuppertal Wuppertal Germany
51 Athens General Pediatric Hospital Athens Greece
52 University Hospital Patras Greece
53 Gaslini Children's Hospital Genova Italy
54 San Martino Genova Italy
55 San Raffaele Hospital Milan Italy
56 University Hospital Padova Italy
57 Groningen University Hospital Groningen Netherlands
58 Leiden University Medical Centre Leiden Netherlands
59 Erasmus MC Rotterdam Netherlands
60 Lund Unversity Lund Sweden
61 Huddinge University Hospital Stockholm Sweden
62 University Hospital Basel Switzerland
63 Hopitaux Universitaires de Geneve Geneva Switzerland
64 Monklands Hospital Airdrie United Kingdom
65 Heartlands Hospital Birmingham United Kingdom
66 Bristol Haematology & Oncology Centre Bristol United Kingdom
67 Royal Cornwall Hospitals Cornwall United Kingdom
68 The Leeds Teaching Hospitals Leeds United Kingdom
69 St George's Hospital/ St George's University of London London United Kingdom Sw17 0RE
70 St. Bartholomew's Hospital London United Kingdom
71 Wishaw General Wishaw United Kingdom

Sponsors and Collaborators

  • European Society for Blood and Marrow Transplantation
  • CHUGAI sanofi-aventis

Investigators

  • Principal Investigator: André Tichelli, Prof. MD., University Hospital, Basel, Switzerland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
European Society for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT01163942
Other Study ID Numbers:
  • Flagship AA trial
  • 41980964
First Posted:
Jul 16, 2010
Last Update Posted:
Apr 3, 2015
Last Verified:
Jul 1, 2010
Additional relevant MeSH terms:
Anemia
Anemia, Aplastic

Study Results

No Results Posted as of Apr 3, 2015