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 recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by European Group for Blood and Marrow Transplantation.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT00471848
First received: May 9, 2007
Last updated: August 23, 2012
Last verified: August 2012
  Purpose

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
Aplastic Anemia
Drug: rabbit antithymocyte globulin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by European Group for Blood and Marrow Transplantation:

Primary Outcome Measures:
  • Response [ Time Frame: at 6months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Failure free and overall survival [ Time Frame: at 2 years ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: August 2008
Estimated Study Completion Date: December 2012
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471848

Locations
France
Henri Mondor Hospital
Creteil, France
Hopital St. Louis
Paris, France, 75475
Germany
University Hospital Essen
Essen, Germany
University Hospital Eppendorf
Hamburg, Germany
Medical University Hannover
Hannover, Germany
Universitätsklinikum - Institut für klinische Transfusionsmedizin
Ulm, Germany, 89081
Italy
Ospedale San Martino
Genova, Italy, 16132
Saudi Arabia
King Faisal Specialist Hospital & Research Cnetre
Riyadh, Saudi Arabia
Switzerland
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
Investigators
Principal Investigator: Judith Marsh, Prof. MD. King's College Hospital London
  More Information

No publications provided by European Group for Blood and Marrow Transplantation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT00471848     History of Changes
Other Study ID Numbers: EudraCT: 2007-000902-55, RATGAA07
Study First Received: May 9, 2007
Last Updated: August 23, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Switzerland: Swissmedic
Germany: Paul-Ehrlich-Institut
Suadi Arabia: Office of Reaearch Affairs
Italy: Ethics Committee

Keywords provided by European Group for Blood and Marrow Transplantation:
Thymoglobuline
Rabbit ATG
Ciclosporin
Aplastic Anemia

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Bone Marrow Diseases
Hematologic Diseases
Antilymphocyte Serum
Cyclosporine
Cyclosporins
Anti-Infective Agents
Antifungal Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014