Overview

This trial is active, not recruiting.

Condition aplastic anemia
Treatment rabbit antithymocyte globulin
Phase phase 2
Sponsor European Group for Blood and Marrow Transplantation
Collaborator Genzyme, a Sanofi Company
Start date August 2008
End date September 2010
Trial size 35 participants
Trial identifier NCT00471848, EudraCT: 2007-000902-55, RATGAA07

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose 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
rabbit antithymocyte globulin Thymoglobuline
1.5 vials/10kg daily for 5 days

Primary Outcomes

Measure
Response
time frame: at 6months

Secondary Outcomes

Measure
Failure free and overall survival
time frame: at 2 years

Eligibility Criteria

Male or female participants at least 16 years old.

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

Additional Information

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
Principal investigator Judith Marsh, Prof. MD.
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2012.
Information provided to ClinicalTrials.gov by European Group for Blood and Marrow Transplantation.