Prospective Phase II Study of Rabbit Antithymocyte Globulin (ATG, Thymoglobuline®, Genzyme) With Ciclosporin for Patients With Acquired Aplastic Anaemia

King Faisal Specialist Hospital & Research Center

Status and phase: Completed; Phase 2

Conditions: Acquired Aplastic Anaemia

Treatments: Drug: Rabbit ATG, Thymoglobuline (Genzyme)

Study type: Interventional

Funder types: Other

Identifiers

NCT01530555

2081-005

Details and patient eligibility

About

To assess the tolerability and efficacy of rabbit antithymocyte globulin (ATG, Thymoglobuline®) with ciclosporin (CSA) in the first line treatment of patients with acquired severe aplastic anaemia (SAA), and patients with non-severe aplastic anaemia (NSAA) and who are transfusion dependent. To compare the response rate of the combination of rabbit ATG (Thymoglobuline® and CSA from this pilot study with the response rate observed in a series of matched AA patients; treated after 1994 with the combination of horse ATG (Lymphoglobuline®) and CSA; obtained from the EBMT database (comparative study).

Enrollment: 35 patients

Sex: All

Ages: 16 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. To define aplastic anaemia there must be at least two of the following: (1) haemoglobin < 10g/dl; (2) platelet count < 50 x 109/l; (3) neutrophil count < 1.5 x 109/l, and a hypocellular bone marrow on bone marrow biopsy
2. Time from diagnosis to study registration ≤ 6mths
3. No prior treatment except for haemopoietic growth factors given for no more than 4 weeks, and androgens.
4. Age ≥ 16yrs (≥ 18yrs in Germany in accordance with German law), 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 enrollment
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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Treatment arm

Experimental group

Description:

1. Rabbit ATG, Thymoglobuline (Genzyme) 1.5 vials/10kg (3.75mg/kg) daily for 5 days given as an intravenous infusion over 12-18 hours. 2. Ciclosporin (CSA) 5mg/kg/day orally from day +1 for a minimum of 6 months, with later tailing according to individual patient response. Aim to maintain trough whole blood CSA levels between 150 and 250 ng/ml.

Treatment:

Drug: Rabbit ATG, Thymoglobuline (Genzyme)