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

This study has been terminated.
(Ceased production of the study drug, Lymphoglobulin. Recruitment of patients onto the trial was too slow.)
Sponsor:
Collaborator:
CHUGAI sanofi-aventis
Information provided by:
European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT01163942
First received: July 14, 2010
Last updated: July 22, 2010
Last verified: July 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Aplastic Anaemia
 Drug: G-CSF
Drug: Early retreatment with ATG
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A RANDOMIZED CONTROLLED STUDY IN NEWLY DIAGNOSED SEVERE APLASTIC ANEMIA PATIENTS RECEIVING ANTITHYMOCYTE GLOBULIN (ATG), CYCLOSPORIN A, WITH OR WITHOUT G-CSF

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Failure free survival [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    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:
  • Haematological response [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    The proportion of subjects who achieve a hematologic response

  • Severe Infections [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    Incidence of severe infections

  • Benefit of addition of G-CSF [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    The benefit due to the addition of G-CSF on death rate (i), days of hospitalization (ii), and duration of antibiotic treatment (iii)

  • Complete remission [ Time Frame: day 120 ] [ Designated as safety issue: No ]
    Time to achieving a complete remission within 120 days

  • Relapse rate [ Time Frame: 2year ] [ Designated as safety issue: No ]
    The relapse rate among responders

  • Blood count [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    Median blood counts among subjects who achieve transfusion independence

  • Severity of the disease [ Time Frame: day 365 ] [ Designated as safety issue: No ]
    The proportion of subjects who have a change in severity of disease (e.g. improvement from very severe to severe aplastic anemia)

  • Retreatment with ATG [ Time Frame: day 240 ] [ Designated as safety issue: No ]
    Proportion of subjects who respond to re-treatment with ATG,

  • Safety [ Time Frame: 6year ] [ Designated as safety issue: Yes ]
    The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A


Enrollment: 205
Study Start Date: March 2001
Estimated Study Completion Date: November 2010
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: No G-CSF, No 2nd ATG
Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
 Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG
Active Comparator: No G-CSF, yes 2nd ATG
Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response.
 Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG
Active Comparator: Yes G-CSF, No 2nd ATG
Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response.
 Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG
Active Comparator: Yes G-CSF, Yes 2nd ATG
Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response.
 Drug: G-CSF
Yes/no addition of G-CSF
Drug: Early retreatment with ATG
Yes/no early retreatment with ATG

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01163942

  Show 71 Study Locations
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
CHUGAI sanofi-aventis
Investigators
Principal Investigator: André Tichelli, Prof. MD. University Hospital, Basel, Switzerland
  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: André Tichelli, University Hospital, Basel
ClinicalTrials.gov Identifier: NCT01163942     History of Changes
Other Study ID Numbers: Flagship AA trial, 41980964
Study First Received: July 14, 2010
Last Updated: July 22, 2010
Health Authority: Switzerland: Swissmedic
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
Italy: Ministry of Health
Netherlands: Medical Ethics Review Committee (METC)

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

ClinicalTrials.gov processed this record on May 16, 2013