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Trial record 1 of 1 for:    RATGAA07
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Rabbit Antithymocyte Globulin (Thymoglobuline) With Ciclosporin for Patients With Acquired Aplastic Anaemia (RATGAA07)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00471848
Recruitment Status : Unknown
Verified August 2012 by European Group for Blood and Marrow Transplantation.
Recruitment status was:  Active, not recruiting
First Posted : May 10, 2007
Last Update Posted : August 24, 2012
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation

Brief Summary:
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 or disease Intervention/treatment Phase
Aplastic Anemia Drug: rabbit antithymocyte globulin Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : August 2008
Actual Primary Completion Date : September 2010
Estimated Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment Arm
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
Drug: rabbit antithymocyte globulin
1.5 vials/10kg daily for 5 days
Other Name: Thymoglobuline

Primary Outcome Measures :
  1. Response [ Time Frame: at 6months ]

Secondary Outcome Measures :
  1. Failure free and overall survival [ Time Frame: at 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Must fulfil definition of aplastic anaemia:

    There must be at least two of the following:

    • haemoglobin < 10g/dl
    • platelet count < 50 x 109/l
    • neutrophil count < 1.5 x 109/l, and a hypocellular bone marrow on bone marrow biopsy

    SAA as defined by a hypocellular bone marrow of <25% cellularity and two of the following:

    • neutrophil count < 0.5 x 109/l
    • platelets < 20 x 109/l
    • reticulocytes < 20 x 109/l

    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

  2. Have acquired aplastic anaemia
  3. Time from diagnosis to study registration maximum 6 months
  4. No prior treatment except for haemopoietic growth factors given for no more than four weeks, and androgens
  5. Age minimum 16 years with no upper age limit

Exclusion Criteria:

  1. Eligibility for an HLA-matched sibling donor transplant for SAA patients
  2. Prior therapy with ATG or CSA
  3. Haematopoeitic growth factors more than 4 weeks before study enrolment
  4. Diagnosis of Fanconi anaemia, dyskeratosis congenita or congenital bone marrow failure syndrome
  5. Evidence of myelodysplastic disease
  6. Paroxysmal nocturnal haemoglobinuria with evidence of significant haemolysis, history of PNH associated thrombosis or a PNH clone >50% by flow cytometry
  7. Diagnosis or previous history of carcinoma (except local cervical, basal cell, squamous cells, or melanoma)
  8. Subject is pregnant (e.g. positive HCG test) or is breast feeding
  9. Severe uncontrolled infection or unexplained fever >38oC
  10. Subjects who have hepatic, renal cardiac, metabolic or other concurrent diseases of such severity that life expectancy is less than 3 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00471848

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Henri Mondor Hospital
Creteil, France
Hopital St. Louis
Paris, France, 75475
University Hospital Essen
Essen, Germany
University Hospital Eppendorf
Hamburg, Germany
Medical University Hannover
Hannover, Germany
Universitätsklinikum - Institut für klinische Transfusionsmedizin
Ulm, Germany, 89081
Ospedale San Martino
Genova, Italy, 16132
Saudi Arabia
King Faisal Specialist Hospital & Research Cnetre
Riyadh, Saudi Arabia
University Hospital
Basel, Switzerland, 4031
United Kingdom
Royal Bournemouth
Bournemouth, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
St George's Hospital/ St George's University of London
London, United Kingdom, Sw17 0RE
King's College Hospital
London, United Kingdom
Nottingham Universitry Hospital Trust
Nottingham, United Kingdom
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
Genzyme, a Sanofi Company
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Principal Investigator: Judith Marsh, Prof. MD. King's College Hospital, London
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: European Group for Blood and Marrow Transplantation Identifier: NCT00471848    
Other Study ID Numbers: EudraCT: 2007-000902-55
First Posted: May 10, 2007    Key Record Dates
Last Update Posted: August 24, 2012
Last Verified: August 2012
Keywords provided by European Group for Blood and Marrow Transplantation:
Rabbit ATG
Aplastic Anemia
Additional relevant MeSH terms:
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Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents