Rituximab as Second Line Treatment for ITP

NCT00344149 | Completed Phase 3 DMC

• 2 other identifiers: 3114ITP001
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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.

Conditions

Immune Thrombocytopenia (ITP)

Keywords

Idiopathic Thrombocytopenic Purpura; Rituximab; Splenectomy; Response; Treatment; treatment of Idiopathic Thrombocytopenic Purpura

Outcome Measures

Primary Outcomes (1)

• 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.

  1.5 years

Secondary Outcomes (4)

• Response rates

  1.5 years

• Relapse rate

  1.5 years

• Mortality rate

  1.5 years

• Complications rate

  1.5 years

Study Arms (2)

Rituximab

EXPERIMENTAL

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

Drug: Rituximab (Mabthera)

Placebo

PLACEBO COMPARATOR

I.V infusion of NaCl 0.9%

Drug: Rituximab (Mabthera)

Interventions

Rituximab (Mabthera) DRUG

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

Placebo; Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subject is \>18 years
• Subject has signed and dated written informed consent.
• Subject is able to understand and comply with protocol requirements and instructions, and intends to complete the study as planned.
• Females in fertile age should express willingness for use of contraceptive means for 6 months following the administration of the study drugs.

You may not qualify if:

• Previous splenectomy, chemotherapy, treatment with anti-D Ig, rituximab, or immune-suppressive treatments other than corticosteroids, Dapsone or Danazol
• Underlying malignancy or previous history of malignancy in the past 5 years (except skin carcinoma)
• Pregnancy and lactation
• Not willing to participate in the study
• Expected survival of \< 2 years
• Known intolerance to murine antibodies
• Females in child-bearing age not willing to use contraception for 6 months
• HIV-positive/AIDS-, Hepatitis -B virus positive- or Hepatitis -C virus positive
• Patients with a definite Systemic Lupus Erythematosus (SLE) (\> 4 of the American College of Rheumatology Criteria)
• Patients currently involved in another clinical trial with evaluation of drug treatment
• 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
• Medical history of relapsing or chronic severe infectious diseases or any other underlying pathology predisposing to serious infections
• Known Primary or secondary immune deficiency syndromes
• 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.

Sponsors & Collaborators

• Ostfold Hospital Trust: lead
• Oslo University Hospital: collaborator
• South-Eastern Regional Health Authority: collaborator

Study Sites (1)

Østfold Hospital Trust in Fredrikstad and National hospital in Oslo

Fredrikstad and Oslo, 1603, Norway

Location

Related Publications (2)

• 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.

  PMID: 15059147 BACKGROUND

• 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.

  PMID: 25662413 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Waleed Ghanima, MD. PhD

Study Record Dates

• First Submitted: June 22, 2006
• First Posted: June 26, 2006
• Study Start: June 1, 2006
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: March 26, 2014

Record last verified: 2014-03

Locations

NO (1)