Prednisolone +/- Addition of Anti-CD20 Antibody, Rituximab, in Patients With Immune Hemolytic Anemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier:
NCT01134432
First received: May 28, 2010
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

The conventional treatment in warm-antibody dependent autoimmune haemolytic anaemia (AIHA) is high-dose glucocorticoid, but in more than half of the patients, haemolytic activity will recur after end of treatment or during the gradual reduction in dose of the drug. As a result, many patients will finally be splenectomized or be treated with long-term glucocorticoids or other immunosuppressive drugs as azathioprine or cyclophosphamide. Recent studies have shown however, that some patients will respond to treatment with the chimeric anti-CD 20 antibody Rituximab and is some cases, the response is permanent. In most of the studies, Rituximab has been used in refractory disease or at least as second line treatment. In this study, patients with AIHA are randomized to receive either high-dose prednisolone with gradual reduction in dose over 2-3 months alone or in combination with Rituximab 375 mg/m2 once a week for 4 weeks. The efficacy of Rituximab will be evaluated by a comparison of the patients in the two treatment arms. The primary treatment goal is a reduction in the number of patients who obtain long-term complete or partial remission. The secondary treatment goal is a reduction in patients who will be splenectomised or receive other immunosuppressive drugs. Finally a comparison of side effects of the treatments will take place.


Condition Intervention Phase
Anemia, Hemolytic, Autoimmune
Drug: prednisolone + mabthera
Drug: Prednisolone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anti-CD20 Antibody Rituximab in Addition to Prednisolone in Treatment of Warm Antibody Related Autoimmune Hemolytic Anemia. A Randomised Danish Multicenter Trial.

Resource links provided by NLM:


Further study details as provided by Copenhagen University Hospital at Herlev:

Primary Outcome Measures:
  • Number of patients in each group in complete or partial remission [ Time Frame: End of treatment and follow-up for 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Side effects [ Time Frame: End of treatment plus follow-up for 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 65
Study Start Date: March 2005
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prednisolone + Rituximab Drug: prednisolone + mabthera

Prednisolone: 1,5 mg/kg for two weeks with gradually reduced dosis over two months.

Mabthera: 375 mg/m2 once a week for four weeks

Other Name: mabthera equals Rituximab
Active Comparator: Prednisolone Drug: Prednisolone
Prednisolone: 1,5 mg/kg for two weeks and then gradually reduced dosis over two months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or over
  • Clinical and biochemical signs of haemolytic anaemia
  • Positive Coombs test with anti-IgG on its own or with anti-CD3d
  • Adequate contraceptive measures (intrauterine device, contraceptive pill or gestagen deposit) for women of childbearing potential

Exclusion Criteria:

  • Performance status > 2
  • Previous treatment with Rituximab
  • Other immune suppressive or anti neoplastic treatment including prednisolone within 3 months
  • Auto immune haemolytic anaemia within 6 months
  • Other serious disease
  • Pregnant women and nursing mothers. Adequate contraceptive measures must be taken for the duration of the study.
  • Contraindication for treatment with Rituximab, i.e. patients that develop hypersensitivity/allergy to the contents of the drug or have antibodies against murine proteins.
  • Active infection which requires antibiotic treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01134432

Locations
Denmark
Aalborg Hospital
Aalborg, Denmark, DK-9000
Rigshospitalet - Copenhagen University Hospital
Copenhagen, Denmark, DK-2100
Esbjerg Sygehus
Esbjerg, Denmark, DK-6700
Haderslev Sygehus
Haderslev, Denmark, DK-6100
Department of Haematology, Herlev Hospital
Herlev, Denmark, DK-2730
Holstebro Sygehus
Holstebro, Denmark, DK-7500
Naestved Sygehus
Naestved, Denmark, DK-4700
Odense University Hospital
Odense, Denmark, DK-5000
Roskilde Hospital
Roskilde, Denmark, DK-4000
Vejle Hospital
Vejle, Denmark, DK-7100
Viborg Sygehus
Viborg, Denmark, DK-8800
Sponsors and Collaborators
Copenhagen University Hospital at Herlev
Investigators
Principal Investigator: Henrik S Birgens, MD Department of Haematology (L121), Copenhagen University Hospital Herlev
  More Information

No publications provided

Responsible Party: Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier: NCT01134432     History of Changes
Other Study ID Numbers: AIHA-KA04062-gms
Study First Received: May 28, 2010
Last Updated: September 9, 2013
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Copenhagen University Hospital at Herlev:
autoimmune hemolytic anemia
hemolytic anemia
Rituximab
Treatment of autoimmune hemolytic anemia
warm antibody dependant autoimmune hemolytic anemia

Additional relevant MeSH terms:
Anemia
Hemolysis
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hematologic Diseases
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Rituximab
Prednisolone
Methylprednisolone Hemisuccinate
Antibodies
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on September 22, 2014