Rituximab as Second Line Treatment for ITP

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

Norway

Study Type

Interventional

Intervention

Rituximab (Mabthera)

About this trial

This is an interventional treatment trial for Immune Thrombocytopenia (ITP) focused on measuring Idiopathic Thrombocytopenic Purpura, Rituximab, Splenectomy, Response, Treatment, treatment of Idiopathic Thrombocytopenic Purpura

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion criteria: 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 History of soft tissue, bone or joint infections (fascitis, abscess, osteomyelitis, septic arthritis) during the last year prior to inclusion in the study 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 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.

Sites / Locations

Østfold Hospital Trust in Fredrikstad and National hospital in Oslo

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rituximab

Placebo

Arm Description

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

I.V infusion of NaCl 0.9%

Outcomes

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.

Secondary Outcome Measures

Response rates

Relapse rate

Mortality rate

Complications rate

Including bleeding, infections and thromboembolic events

Full Information

NCT ID

NCT00344149

First Posted

June 22, 2006

Last Updated

March 25, 2014

Sponsor

Ostfold Hospital Trust

Collaborators

Oslo University Hospital, South-Eastern Regional Health Authority

1. Study Identification

Unique Protocol Identification Number

NCT00344149

Brief Title

Rituximab as Second Line Treatment for ITP

Official Title

Rituximab as Second Line Treatment for ITP; A Multicenter, Randomized, Double Blind, Placebo-controlled, Phase III Study. "The RITP Study"

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Completed

Study Start Date

June 2006 (undefined)

Primary Completion Date

March 2014 (Actual)

Study Completion Date

March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ostfold Hospital Trust

Collaborators

Oslo University Hospital, South-Eastern Regional Health Authority

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Immune Thrombocytopenia (ITP)

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

112 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rituximab

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

I.V infusion of NaCl 0.9%

Intervention Type

Drug

Intervention Name(s)

Rituximab (Mabthera)

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Response rates

Time Frame

1.5 years

Title

Relapse rate

Time Frame

1.5 years

Title

Mortality rate

Time Frame

1.5 years

Title

Complications rate

Description

Including bleeding, infections and thromboembolic events

Time Frame

1.5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 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. Exclusion criteria: 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 History of soft tissue, bone or joint infections (fascitis, abscess, osteomyelitis, septic arthritis) during the last year prior to inclusion in the study 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 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.

Overall Study Officials: