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Sponsors and Collaborators: |
European Group for Blood and Marrow Transplantation Genzyme |
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Information provided by: | European Group for Blood and Marrow Transplantation |
ClinicalTrials.gov Identifier: | NCT00471848 |
To assess the tolerability and effectiveness of rabbit antithymocyte globulin (ATG, Thymoglobuline) with ciclosporin in the first line treatment of patients with acquired severe aplastic anaemia, and patients with non-severe aplastic anaemia and who are transfusion dependent.
Condition | Intervention | Phase |
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Aplastic Anemia |
Drug: rabbit antithymocyte globulin |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Efficacy Study |
Official Title: | Prospective Phase II Study of Rabbit Antithymocyte Globulin (ATG, Thymoglobuline®, Genzyme) With Ciclosporin for Patients With Acquired Aplastic Anaemia and Comparison With Matched Historical Patients Treated With Horse ATG and Ciclosporin |
Estimated Enrollment: | 35 |
Study Start Date: | August 2008 |
Estimated Study Completion Date: | December 2010 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Treatment Arm: Experimental
Antithymocyte globuline with cyclosporin in first line treatment of patients with acquired severe aplastic anaemia and patients with non-severe aplastic anaemia who are transfusion dependent
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Drug: rabbit antithymocyte globulin
1.5 vials/10kg daily for 5 days
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Traditionally horse antithymocyte globulin (ATG) has been the preferred animal source of ATG as first line treatment for acquired aplastic anaemia (AA) patients who are ineligible for bone marrow transplantation (BMT). For severe AA (SAA) the combination of ATG and Ciclosporin (CSA) results in response in 60-75% of patients and the response is superior to using either agent alone. The addition of granulocyte colony stimulating factor (G-CSF) to the combination of ATG and CSA has so far shown no significant benefit in terms of response and survival, but an EBMT prospective study is currently evaluating this further in a larger number of patients. For patients with NSAA who are transfusion dependent, the combination of ATG and CSA was shown to be superior to CSA alone in an EBMT prospective randomised study, with a higher response rate, superior blood counts and improved disease free survival using the combination of ATG with CSA.
There have been no phase II studies of rabbit ATG (Thymoglobuline®) in the treatment of AA as first line therapy. Preliminary results from a small single centre study compared horse ATG (ATGAM) with rabbit ATG (Fresenius) in children and showed response rates of 93% and 47%, respectively, but it is likely that different preparations of rabbit ATG will vary in their efficacy. Rabbit ATG is more commonly used for a second course following relapse or lack of response to a first course of horse ATG. Rabbit ATG in combination with CSA and G-CSF was used in patients with SAA who had failed to respond to a course of horse ATG with CSA and G-CSF. Overall response (transfusion independence) was seen in 23/30 (77%) of patients after a median of 95 days and complete response (neutrophils > 2.0, haemoglobin > 11, and platelets > 100) in 9/30 (30%). Rabbit ATG was well tolerated; no anaphylaxis or severe side effects were reported. Another study of 43 patients treated with rabbit ATG and CSA following non-response or relapse after horse ATG and CSA, showed 30% response rate among non-responding patients and 65% response rate for relapsing patients.
Studies comparing the antibody specificities between Thymoglobuline® and Lymphoglobuline® are in broad agreement, but (a) Lymphoglobuline® has fewer studies and those reported are older, because the product is older and has been less extensively developed (b) antibodies against certain epitopes are inconsistently present (c) not all antibody specificities have been examined in some studies and (d) different methods of testing have been used. There is a view that it is the immunogen and not the animal species which is most important in creating differences between different ATGs.
Ages Eligible for Study: | 16 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Must fulfil definition of aplastic anaemia:
There must be at least two of the following:
SAA as defined by a hypocellular bone marrow of <25% cellularity and two of the following:
NSAA as defined by a hypocellular bone marrow and cytopenia in at least two cell lines and neutrophil count > 0.5 x 109/l, and red cell and/or platelet transfusion dependence
Exclusion Criteria:
Contact: Judith Marsh | 0044 208 725 3545 | judith.marsh@kch.nhs.uk |
Contact: Alain Barrois | 0031 71 526 9722 | ebmtcto@LUMC.NL |
France | |
Hopital St. Louis | Not yet recruiting |
Paris, France, 75475 | |
Contact: Gérard Socié 0033 1 42 499824 gerard.socie@paris7.jussieu.fr | |
Principal Investigator: Gérard Socié | |
Germany | |
Universitätsklinikum - Institut für klinische Transfusionsmedizin | Not yet recruiting |
Ulm, Germany, 89081 | |
Contact: Hubert Schrezenmeier 0049 731 150 550 h.schrezenmeier@blutspende.de | |
Principal Investigator: Hubert Schrezenmeier | |
Italy | |
Ospedale San Martino | Not yet recruiting |
Genova, Italy, 16132 | |
Contact: Andrea Bacigalupo 0039 010 355 469 andrea.bacigalupo@hsanmartino.liguria.it | |
Principal Investigator: Andrea Bacigalupo | |
Switzerland | |
University Hospital | Not yet recruiting |
Basel, Switzerland, 4031 | |
Contact: André Tichelli 0041 61 265 4254 tichelli@datacomm.ch | |
Principal Investigator: André Tichelli | |
United Kingdom | |
St George's Hospital/ St George's University of London | Recruiting |
London, United Kingdom, Sw17 0RE | |
Contact: Judith Marsh 0044 208 725 3545 jmarsh@sgul.ac.uk | |
Principal Investigator: Judith Marsh |
Principal Investigator: | Judith Marsh | St George's Hospital/ St George's University of London |
Responsible Party: | ( European Group for Blood and Marrow Transplantation ) |
Study ID Numbers: | EudraCT: 2007-000902-55, RATGAA07 |
Study First Received: | May 9, 2007 |
Last Updated: | October 8, 2008 |
ClinicalTrials.gov Identifier: | NCT00471848 |
Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency; France: Afssaps - French Health Products Safety Agency; Switzerland: Swissmedic; Germany: Paul-Ehrlich-Institut; Italy: Ethics Committee |
Thymoglobuline Rabbit ATG Ciclosporin Aplastic Anemia |
Antilymphocyte Serum Cyclosporine Clotrimazole Hematologic Diseases Miconazole Tioconazole |
Anemia, Aplastic Anemia Aplastic anemia Bone Marrow Diseases Cyclosporins |
Anti-Infective Agents Molecular Mechanisms of Pharmacological Action Immunologic Factors Therapeutic Uses Antifungal Agents Physiological Effects of Drugs |
Enzyme Inhibitors Antirheumatic Agents Dermatologic Agents Immunosuppressive Agents Pharmacologic Actions |