Rituximab as Second Line Treatment for ITP

This study has been completed.
Sponsor:
Collaborators:
Oslo University Hospital
South-Eastern Regional Health Authority
Information provided by (Responsible Party):
Waleed Ghanima, Ostfold Hospital Trust
ClinicalTrials.gov Identifier:
NCT00344149
First received: June 22, 2006
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized thrombocytopenia.

Splenectomy is the standard treatment for patients who fails the first-line treatment: corticosteroid. Rituximab, has recently emerged as a promising treatment for ITP. The aim of the study is to determine whether early treatment with Rituximab can result in durable remissions, and consequently, lead to the avoidance of splenectomy in a significant number of patients.


Condition Intervention Phase
Immune Thrombocytopenia (ITP)
Drug: Rituximab (Mabthera)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Rituximab as Second Line Treatment for ITP; A Multicenter, Randomized, Double Blind, Placebo-controlled, Phase III Study. "The RITP Study"

Resource links provided by NLM:


Further study details as provided by Ostfold Hospital Trust:

Primary Outcome Measures:
  • The primary endpoint is treatment failure as defined by a composite end point of Splenectomy performed at any time after randomization or Meeting the predefined Criteria for Splenectomy at or after week 12 that is if splenectomy is not performed. [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rates [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  • Relapse rate [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  • Mortality rate [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  • Complications rate [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
    Including bleeding, infections and thromboembolic events


Enrollment: 112
Study Start Date: June 2006
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
I.V infusion of Rituximab 375 mg/m2 per week for 4 weeks
Drug: Rituximab (Mabthera)
I.V infusion of Rituximab 375 mg/m2 per week for 4 weeks
Placebo Comparator: Placebo
I.V infusion of NaCl 0.9%
Drug: Rituximab (Mabthera)
I.V infusion of Rituximab 375 mg/m2 per week for 4 weeks

Detailed Description:

ITP is an autoimmune disorder characterized by formation of autoantibodies against platelet antigens leading to premature platelet destruction and persistent thrombocytopenia often resulting in bleeding.

The goal of treatment is to raise the platelet count to a hemostatically safe level.

Treatment with corticosteroids rarely results in durable responses, and most of the patients will ultimately require a second-line treatment. Splenectomy results in a high rate of sustained remissions. However, the procedure is invasive and is associated with considerable short and long term morbidity and mortality. Rituximab, a chimeric anti-CD20 antibody with a B-cell depleting effect, has recently emerged as a promising treatment for ITP.

The study aims to determine whether early treatment with Rituximab can result in durable remissions, and consequently, avoidance of splenectomy in a clinical significant number of patients.

The main objective of this study is to assess the rate of treatment failure (splenectomy or meeting criteria for splenectomy after week 12) at 1.5-year in a prospective, randomized, placebo-controlled, double-blind, multi-centre

  Eligibility

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

Inclusion Criteria:

  1. ITP with platelet count <30 x 109 /l after 2 weeks of treatment with prednisolon or during prednisolon tapering period i.e. from week three of prednisolon initiation. Patients with platelet count between 30 -50 are eligible if a higher platelet count is considered necessary, because of : concomitant medical illness predisposing to bleeding (hypertension, GI bleeding, bleeding diathesis, previous history of bleeding) concomitant medical condition requiring platelet blocking agents/ anticoagulation, persistent bleeding despite platelets > 30 x 109 /l, prior to surgery, or because of other patient related factors necessitating higher platelet count as occupation, hobby, psychological intolerability.
  2. Subject is >18 years
  3. Subject has signed and dated written informed consent.
  4. Subject is able to understand and comply with protocol requirements and instructions, and intends to complete the study as planned.
  5. Females in fertile age should express willingness for use of contraceptive means for 6 months following the administration of the study drugs.

Exclusion criteria:

  1. Previous splenectomy, chemotherapy, treatment with anti-D Ig, rituximab, or immune-suppressive treatments other than corticosteroids, Dapsone or Danazol
  2. Underlying malignancy or previous history of malignancy in the past 5 years (except skin carcinoma)
  3. Pregnancy and lactation
  4. Not willing to participate in the study
  5. Expected survival of < 2 years
  6. Known intolerance to murine antibodies
  7. Females in child-bearing age not willing to use contraception for 6 months
  8. HIV-positive/AIDS-, Hepatitis -B virus positive- or Hepatitis -C virus positive
  9. Patients with a definite Systemic Lupus Erythematosus (SLE) (> 4 of the American College of Rheumatology Criteria)
  10. Patients currently involved in another clinical trial with evaluation of drug treatment
  11. Bacterial infections, viral infections, fungal infections, myco-bacterial infections (excluding fungal infections) or other evolutive infections or any other infections episode requiring hospitalisation or treatment with an antibiotics 4 weeks before selection for IV route or within 2 weeks before selection for oral route
  12. History of soft tissue, bone or joint infections (fascitis, abscess, osteomyelitis, septic arthritis) during the last year prior to inclusion in the study
  13. Medical history of relapsing or chronic severe infectious diseases or any other underlying pathology predisposing to serious infections
  14. Known Primary or secondary immune deficiency syndromes
  15. Administration of a living vaccine within 4 weeks preceding the inclusion in the study -16- Previous treatment with any lymphocytes depleting medication (e.g.: MabCampath®)

17- Previous treatment with inhibitors of leucocytes transmigration (e.g.: Tysabri®) 18- Known intolerance to human monoclonal antibodies 19- Known severe chronic pulmonary obstructive Disease (FEV < 50% or functional dyspnoea grade 3) 20- Known congestive heart failure NYHA (New York Heart Association classification of heart failure) class III and IV 21- Recent episode (<6 months) of acute coronary syndrome.

  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: NCT00344149

Locations
Norway
Østfold Hospital Trust in Fredrikstad and National hospital in Oslo
Fredrikstad and Oslo, Norway, 1603
Sponsors and Collaborators
Ostfold Hospital Trust
Oslo University Hospital
South-Eastern Regional Health Authority
Investigators
Principal Investigator: Waleed Ghanima, MD Østfold Hospital trust in Fredrikstad
Principal Investigator: Pål Andre Holme Oslo University Hospital
Principal Investigator: Finn Wisløff, MD, PhD Ullevaal University Hospital
Principal Investigator: Anders Waage, MD, PhD St. Olavs hospital- Trondheim-Norway
Principal Investigator: Geir Tjønnfjord, MD, PhD Rikshospitalet- Oslo-Norway
Principal Investigator: Peter Meyer, MD, PhD Rogaland sentralt sykehus - Stavanger-Norway
Principal Investigator: Marc Michel, MD Dept. of Internal medicine Henri Mondor University Hospital Créteil- France
  More Information

Additional Information:
Publications:
Responsible Party: Waleed Ghanima, Dr Waleed Ghanima, MD. PhD, Ostfold Hospital Trust
ClinicalTrials.gov Identifier: NCT00344149     History of Changes
Other Study ID Numbers: 3114, ITP001
Study First Received: June 22, 2006
Last Updated: March 25, 2014
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by Ostfold Hospital Trust:
Idiopathic Thrombocytopenic Purpura
Rituximab
Splenectomy
Response
Treatment
treatment of Idiopathic Thrombocytopenic Purpura

Additional relevant MeSH terms:
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 22, 2014