Aplastic AnemiaPhase 2RATGAA07NCT00471848
Rabbit Antithymocyte Globulin (Thymoglobuline) With Ciclosporin for Patients With Acquired Aplastic Anaemia
A Phase 2 study testing rabbit antithymocyte globulin in people with Aplastic Anemia, run by European Society for Blood and Marrow Transplantation at 14 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- rabbit antithymocyte globulin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 14 sitesin 6 countries
- Study dates
- Aug 2008to Feb 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
Show all 14Show fewer
- 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
- Have acquired aplastic anaemia
- Time from diagnosis to study registration maximum 6 months
- No prior treatment except for haemopoietic growth factors given for no more than four weeks, and androgens
- Age minimum 16 years with no upper age limit
Who cannot join
- Eligibility for an human leukocyte antigens (HLA)-matched sibling donor transplant for SAA patients
- Prior therapy with ATG or CSA
- Haematopoeitic growth factors more than 4 weeks before study enrolment
- Diagnosis of Fanconi anaemia, dyskeratosis congenita or congenital bone marrow failure syndrome
- Evidence of myelodysplastic disease
- Paroxysmal nocturnal haemoglobinuria with evidence of significant haemolysis, history of Paroxysmal Nocturnal Hemoglobinuria (PNH) associated thrombosis or a PNH clone >50% by flow cytometry
Show all 10Show fewer
- Diagnosis or previous history of carcinoma (except local cervical, basal cell, squamous cells, or melanoma)
- Subject is pregnant (e.g. positive Human Chorionic Gonadotropin (HCG) test) or is breast feeding
- Severe uncontrolled infection or unexplained fever >38 degrees Celsius
- Subjects who have hepatic, renal cardiac, metabolic or other concurrent diseases of such severity that life expectancy is less than 3 months
Trial locations and contacts
14 sites in 6 countries.
14 sites in 6 countries
United Kingdom5 sites
Royal Bournemouth
Bournemouth
Addenbrooke's Hospital
Cambridge
St George's Hospital/ St George's University of London
London, Sw17 0RE
King's College Hospital
London
Nottingham Universitry Hospital Trust
Nottingham
Germany4 sites
University Hospital Essen
Essen
University Hospital Eppendorf
Hamburg
Medical University Hannover
Hanover
Universitätsklinikum - Institut für klinische Transfusionsmedizin
Ulm, 89081
Saudi Arabia1 site
King Faisal Specialist Hospital & Research Cnetre
Riyadh
About this 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
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.
Read the 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 European Group for Blood and Marrow Transplantation (EBMT) prospective study is currently evaluating this further in a larger number of patients. For patients with non-severe aplastic anaemia (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.
- Conditions
- Aplastic Anemia
- Being tested
- rabbit antithymocyte globulin
- Keywords
- Thymoglobuline, Rabbit ATG, Ciclosporin, Aplastic Anemia
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rabbit antithymocyte globulinDrug
Also called Thymoglobuline
1.5 vials/10kg daily for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Antithymocyte globulin with cyclosporin in first line treatment of patients with acquired severe aplastic anaemia and patients with non-severe aplastic anaemia who are transfusion dependent Receives: Drug: rabbit antithymocyte globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Response to Rabbit Antithymocyte Globulin (Thymoglobuline)
Complete Response (CR) defined as:
Haemoglobin normal for age and gender, neutrophils > 1.5 x 10E9/l, platelets > 150 x 10E9/l.
Partial Response (PR) defined as:
- transfusion independence (if previously dependent) or
- doubling or normalisation of at least one cell line or
- increase of baseline haemoglobin of > 3 g/dl (if initially <6) + neutrophils of > 0.5 x 10E9/l + platelets of > 20 x 10E9/l (if initially < 20)
No Response (MR) is defined as: worse or not meeting criteria above
Measured: at 6months
Secondary outcomes (1)
Failure Free and Overall Survival of Participants to Rabbit Antithymocyte Globulin (Thymoglobuline)
Failure free survival is defined as a failure of the protocol: no achievement of response, relapse, disease progression requiring a second course of immune suppressive therapy (IST) or a stem cell transplant, death, or later clonal disorders such as Paroxysmal Nocturnal Hemoglobinuria (PNH), Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML).
Measured: at 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2007 (estimated)
- Study startAug 2008
- Primary completionOct 2011
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Society for Blood and Marrow Transplantation
- Sponsor type
- Research network
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Judith Marsh, Prof. MD., Principal investigator, King's College Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00471848
- Sponsor's protocol ID
- EudraCT: 2007-000902-55
- Other IDs
- RATGAA07
- Acronym
- RATGAA07
- Status last verified
- Apr 2026
- First submitted
- 9 May 2007
- Last updated
- 12 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Marsh JC, Bacigalupo A, Schrezenmeier H, Tichelli A, Risitano AM, Passweg JR, Killick SB, Warren AJ, Foukaneli T, Aljurf M, Al-Zahrani HA, Hochsmann B, Schafhausen P, Roth A, Franzke A, Brummendorf TH, Dufour C, Oneto R, Sedgwick P, Barrois A, Kordasti S, Elebute MO, Mufti GJ, Socie G; European Blood and Marrow Transplant Group Severe Aplastic Anaemia Working Party. Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party. Blood. 2012 Jun 7;119(23):5391-6. doi: 10.1182/blood-2012-02-407684. Epub 2012 Apr 27.
PubMed 22544699
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00471848
- Acronym / sponsor ID
- RATGAA07 / EudraCT: 2007-000902-55
- Conditions
- Aplastic Anemia
- Keywords
- Thymoglobuline, Rabbit ATG, Ciclosporin, Aplastic Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- European Society for Blood and Marrow TransplantationResearch network
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Aug 2008
- Primary completion
- Oct 2011 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 10 May 2007 (estimated)
- Results
- Posted 18 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 European Group for Blood and Marrow Transplantation (EBMT) prospective study is currently evaluating this further in a larger number of patients. For patients with non-severe aplastic anaemia (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: rabbit antithymocyte globulinAntithymocyte globulin with cyclosporin in first line treatment of patients with acquired severe aplastic anaemia and patients with non-severe aplastic anaemia who are transfusion dependent |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Must fulfil definition of aplastic anaemia:
- 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
- Have acquired aplastic anaemia
- Time from diagnosis to study registration maximum 6 months
Key exclusion criteria (10 listed)
- Eligibility for an human leukocyte antigens (HLA)-matched sibling donor transplant for SAA patients
- Prior therapy with ATG or CSA
- Haematopoeitic growth factors more than 4 weeks before study enrolment
- Diagnosis of Fanconi anaemia, dyskeratosis congenita or congenital bone marrow failure syndrome
- Evidence of myelodysplastic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rabbit antithymocyte globulinAlso: Thymoglobuline1.5 vials/10kg daily for 5 days | Drug | Treatment Arm |
Primary outcome
Number of Participants With Response to Rabbit Antithymocyte Globulin (Thymoglobuline)
Time frame: at 6months
Complete Response (CR) defined as: Haemoglobin normal for age and gender, neutrophils > 1.5 x 10E9/l, platelets > 150 x 10E9/l. Partial Response (PR) defined as: * transfusion independence (if previously dependent) or * doubling or normalisation of at least one cell line or * increase of baseline haemoglobin of > 3 g/dl (if initially <6) + neutrophils of > 0.5 x 10E9/l + platelets of > 20 x 10E9/l (if initially < 20) No Response (MR) is defined as: worse or not meeting criteria above
1 secondary outcome
Failure Free and Overall Survival of Participants to Rabbit Antithymocyte Globulin (Thymoglobuline)
Time frame: at 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22544699Marsh JC, Bacigalupo A, Schrezenmeier H, Tichelli A, Risitano AM, Passweg JR, Killick SB, Warren AJ, Foukaneli T, Aljurf M, Al-Zahrani HA, Hochsmann B, Schafhausen P, Roth A, Franzke A, Brummendorf TH, Dufour C, Oneto R, Sedgwick P, Barrois A, Kordasti S, Elebute MO, Mufti GJ, Socie G; European Blood and Marrow Transplant Group Severe Aplastic Anaemia Working Party. Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party. Blood. 2012 Jun 7;119(23):5391-6. doi: 10.1182/blood-2012-02-407684. Epub 2012 Apr 27.
- Sponsor's websiteLink provided by the sponsor.
- PublicationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith Marsh, Prof. MD. principal investigator
King's College Hospital NHS Trust
14 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rabbit antithymocyte globulin in people with Aplastic Anemia, run by European Society for Blood and Marrow Transplantation at 14 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United Kingdom, Germany, France, Italy, Saudi Arabia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Response to Rabbit Antithymocyte Globulin (Thymoglobuline) (time frame: at 6months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00471848, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.