Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF)

Phase 3

Terminated

• Conditions: Aplastic Anaemia
• Interventions: Drug: G-CSF; Drug: Early retreatment with ATG

• Registration Number: NCT01163942
• Lead Sponsor: European Society for Blood and Marrow Transplantation

Brief Summary

The purpose of this study is to examine the effect of G-CSF on disease free survival and overall survival in aplastic anaemia patients who also receive ATG and Cyclosporin A.

Detailed Description

Open label, randomized, controlled study of G-CSF, ATG and Cyclosporin A versus ATG and Cyclosporin A. Subjects will be evaluated for hematologic response through day 240. Subjects who do not demonstrate a partial or complete remission by day 120 will be randomized to receive either a second course of ATG or continue their current regimen. Subjects who do demonstrate a partial or complete remission will continue their current regimen through day 240 or maintenance of a complete remission for 30 days. The last day of study treatment will be day 240.

Study Timeline

• Study Start: 2001-03
• Primary Completion: 2008-06
• Study First Submitted: 2010-07-14
• Study First Submitted QC: 2010-07-15
• Study First Posted: 2010-07-16
• Study Completion: 2010-11
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-19
• Last Update Posted: 2024-02-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 205

Inclusion Criteria

• Severe or very severe aplastic anemia
• Less than 6 months from diagnosis of severe aplastic anemia by bone marrow biopsy
• Ethical - Before randomization is done the subject or legally acceptable representative must give written informed consent for participation in the study

Exclusion Criteria

• Eligibility for an HLA-matched sibling donor transplant
• Prior therapy with ATG
• Cyclosporin A <4 weeks before enrollment
• Treatment with G-CSF <2 weeks before enrollment
• Other growth factors <4 weeks before enrollment
• Diagnosis of Fanconi anemia, dyskeratosis congenita or congenital bone marrow failure syndrome
• Evidence of myelodysplastic disease
• Diagnosis or previous history of carcinoma (except local cervical, basal cell, squamous cells, or melanoma)
• Subjects who have infection, hepatic, renal cardiac, metabolic or other concurrent diseases of such severity that death is imminent
• Subject is pregnant (e.g. positive HCG test) or is breast feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Yes G-CSF, No 2nd ATG	Early retreatment with ATG	Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
No G-CSF, yes 2nd ATG	Early retreatment with ATG	Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.
Yes G-CSF, No 2nd ATG	G-CSF	Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
No G-CSF, No 2nd ATG	Early retreatment with ATG	Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
Yes G-CSF, Yes 2nd ATG	G-CSF	Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.
Yes G-CSF, Yes 2nd ATG	Early retreatment with ATG	Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.
No G-CSF, No 2nd ATG	G-CSF	Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
No G-CSF, yes 2nd ATG	G-CSF	Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.

Primary Outcome Measures

Name	Time	Method
Failure free survival	day 240	To evaluate the effect of G-CSF on failure free survival and mortality in study subjects also receiving ATG and Cyclosporin A \& time to hematologic response (failure defined as death, non-response or requirement of further treatment).

Secondary Outcome Measures

Name	Time	Method
Retreatment with ATG	day 240	Proportion of subjects who respond to re-treatment with ATG,
Safety	6year	The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A
Relapse rate	2year	The relapse rate among responders
Blood count	day 240	Median blood counts among subjects who achieve transfusion independence
Severity of the disease	day 365	The proportion of subjects who have a change in severity of disease (e.g. improvement from very severe to severe aplastic anemia)
Complete remission	day 120	Time to achieving a complete remission within 120 days
Severe Infections	day 240	Incidence of severe infections
Haematological response	day 240	The proportion of subjects who achieve a hematologic response
Benefit of addition of G-CSF	day 240	The benefit due to the addition of G-CSF on death rate (i), days of hospitalization (ii), and duration of antibiotic treatment (iii)

Trial Locations

Locations (60)

University Hospital; 🇨🇭 Basel, Switzerland

CHU Angers; 🇫🇷 Angers, France

Avicenne Hospital; 🇫🇷 Bobigny, France

CHU Clemenceau; 🇫🇷 Caen, France

CHU de Caen; 🇫🇷 Caen, France

Henri Mondor; 🇫🇷 Creteil, France

CHU Limoges; 🇫🇷 Limoges, France

Paoli-Calmettes Institute; 🇫🇷 Marseille, France

CHU Montpellier; 🇫🇷 Montpellier, France

CHU Caremeau; 🇫🇷 Nimes, France

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