Rituximab as Second Line Treatment for ITP

NCT ID: NCT00344149

Last Updated: 2014-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2014-03-31

Brief Summary

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.

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

Conditions

Immune Thrombocytopenia (ITP)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rituximab

I.V infusion of Rituximab 375 mg/m2 per week for 4 weeks

Group Type: EXPERIMENTAL

Rituximab (Mabthera)

Intervention Type: DRUG

I.V infusion of Rituximab 375 mg/m2 per week for 4 weeks

Placebo

I.V infusion of NaCl 0.9%

Group Type: PLACEBO_COMPARATOR

Rituximab (Mabthera)

Intervention Type: DRUG

I.V infusion of Rituximab 375 mg/m2 per week for 4 weeks

Interventions

Rituximab (Mabthera)

I.V infusion of Rituximab 375 mg/m2 per week for 4 weeks

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: collaborator

South-Eastern Regional Health Authority

UNKNOWN

Sponsor Role: collaborator

Ostfold Hospital Trust

OTHER

Sponsor Role: lead

Responsible Party

Waleed Ghanima

Dr Waleed Ghanima, MD. PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Waleed Ghanima, MD

Role: PRINCIPAL_INVESTIGATOR

Østfold Hospital trust in Fredrikstad

Pål Andre Holme

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Finn Wisløff, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ullevaal University Hospital

Anders Waage, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Olavs Hospital, Trondheim, Norway

Geir Tjønnfjord, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rikshospitalet- Oslo-Norway

Peter Meyer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rogaland sentralt sykehus - Stavanger-Norway

Marc Michel, MD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Internal medicine Henri Mondor University Hospital Créteil- France

Locations

Østfold Hospital Trust in Fredrikstad and National hospital in Oslo

Fredrikstad and Oslo, , Norway

Countries

Norway

References

Cooper N, Stasi R, Cunningham-Rundles S, Feuerstein MA, Leonard JP, Amadori S, Bussel JB. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004 Apr;125(2):232-9. doi: 10.1111/j.1365-2141.2004.04889.x.

Reference Type: BACKGROUND

PMID: 15059147 (View on PubMed)

Ghanima W, Khelif A, Waage A, Michel M, Tjonnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. doi: 10.1016/S0140-6736(14)61495-1. Epub 2015 Feb 5.

Reference Type: DERIVED

PMID: 25662413 (View on PubMed)

Other Identifiers

ITP001

Identifier Type: -

Identifier Source: secondary_id

3114

Identifier Type: -

Identifier Source: org_study_id