A Study of MabThera (Rituximab) in Patients With Idiopathic Thrombocytopenic Purpura.

Study Overview
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Brief Summary
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This single arm study will evaluate the efficacy and safety of MabThera monotherapy in patients with refractory, relapsing or chronic idiopathic thrombocytopenic purpura (ITP). Patients will receive infusions of MabThera 1000mg i.v. on days 1 and 15. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Official Title
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An Open Label Study of a Fixed Dose Regimen of MabThera on Overall Response Rate in Patients With Refractory, Relapsing or Chronic Idiopathic Thrombocytopenic Purpura.

Conditions
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Idiopathic Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: rituximab [MabThera/Rituxan]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; refractory, relapsing or chronic idiopathic thrombocytopenic purpura; stable therapy during 3 weeks prior to study entry. Exclusion Criteria: newly diagnosed ITP (<6 weeks); prior treatment with MabThera; active bleeding requiring platelet transfusion within 7 days prior to entry into study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: rituximab [MabThera/Rituxan]<br>* 1000mg iv on days 1 and 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Complete Hematological Response (CR) or Confirmed Partial Hematological Response (PR) | Percentage of participants with an overall response at Week 8 achieving a CR or PR as evaluated by platelets, new or increased Idiopathic Thrombocytopenic Purpura (ITP)-related treatments and corticosteroids given for Adverse Events (AEs). CR was defined as a platelet count of greater than (>) 150x10^9/ liters (L) over at least 2 consecutive measurements at least 2 weeks apart, but no more than 60 days apart, with no increase in concomitant ITP therapy or initiation of new ITP therapy. PR was defined as platelet count of >50x10^9/L over at least 2 consecutive measurements at least <2 weeks apart, but no more than 60 days apart, with no increase in concomitant ITP therapy or initiation of new ITP therapy. Overall response rate (participants who achieved CR or confirmed PR) was evaluated using platelets, new or increased ITP related treatments, and corticosteroids given for AEs. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hematological CR, PR, or Minor Response (MR) | Percentage of participants with CR, PR, and MR at Week 8 as evaluated by platelet count where CR is greater than or equal to (≥)150x10^9/L, PR ≥ 50x10^9/L, MR equals (=) 30x10^9/L over 2 consecutive measurements at least 2 weeks apart but no more than 60 days apart with no increase in concomitant therapy or initiation of new ITP therapy. | Week 8 | 
| Percentage of Participants Who Achieved CR | CR was defined as platelet counts >150x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, and with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Week 52 | 
| Time to CR | Time to CR was defined as the time from the first infusion to the first date on which CR was achieved. CR was defined as platelet counts >150x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, and with no increase in concomitant ITP therapy or initiation of new ITP therapy. Participants without an event were censored at the date of last assessment. | Baseline to Week 52 | 
| Percentage of Participants Who Achieved PR | PR was defined as platelet counts >50x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Week 52 | 
| Time to PR | Time to response was defined as the time from the first infusion to the first date on which PR was achieved. PR was defined as platelet counts > 50x10^9/L over ≥ 2 consecutive measurements ≥ 2 weeks apart, but no more than 60 days apart, with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Baseline to Week 52 | 
| Percentage of Participants Who Achieved MR | MR was defined as participants registered with chronic ITP with a platelet count of >30x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, with a 50 to 100% reduction in the dose intensity of concomitant ITP therapy compared with that at screening, and with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Week 52 | 
| Time to MR | Time to response was defined as the time from the first infusion to the first date on which MR was achieved. MR was defined as participants registered with chronic ITP with a platelet count of >30x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, with a 50 percent (%) to 100% reduction in the dose intensity of concomitant ITP therapy compared with that at screening, and with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Baseline to Week 52 | 
| Percentage of Participants With Continued CR From Week 8 to Week 52 | The number of participants with a durable CR assessed in CR responders whose responses were sustained from Week 8 through to the end of the study or withdrawal, irrespective of change of treatment. CR was defined as platelet counts >150x10^9/L over ≥2 consecutive measurements ≥ 2 weeks apart, but no more than 60 days apart, and with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Week 8 to Week 52 | 
| Duration of CR in Participants With Continued CR From Week 8 Until Week 52 | Duration of response was assessed in all responders who reached Week 8 and was defined as the time from Week 8 to the end of CR, irrespective of change of treatment. CR was defined as platelet counts >150x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, and with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Week 8 to Week 52 | 
| Duration of PR in Participants With Continued PR From Week 8 Until Week 52 | Duration of PR was assessed in all responders who reached Week 8 and was defined as the time from Week 8 to the end of PR, irrespective of change of treatment. PR was defined as platelet counts >50x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Week 8 to Week 52 | 
| Duration of MR in Participants With Continued MR From Week 8 Until Week 52 | Duration of response was assessed in all responders who reached Week 8 and was defined as the time from Week 8 to the end of MR, irrespective of change of treatment. MR was defined as participants registered with ITP in relapse with a platelet count of > 30x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, with no increase in concomitant ITP therapy or initiation of new ITP therapy. Participants registered with chronic ITP with a platelet count of >30x10^9/L over ≥2 consecutive measurements ≥2 weeks apart, but no more than 60 days apart, with a 50% to 100% reduction in the dose intensity of concomitant ITP therapy compared with that at screening, and with no increase in concomitant ITP therapy or initiation of new ITP therapy. | Week 8 to Week 52 | 
| Time to Inititiation of New ITP Therapy - Percentage of Participants With an Event | Percentage of participants with an event of initiation of new ITP therapy and/or increase in dose of existing ITP therapy, including date on which decision made in relation to splenectomy, from time of first treatment to Week 52. | Week 52 | 
| Time to Initiation of New ITP Therapy | Median time in days to initiation of new ITP therapy and/or increase in dose of existing ITP therapy, including date on which decision made in relation to splenectomy, from time of first treatment to Week 52. | Baseline to Week 52 | 
| Percentage of Therapeutic Responders | Percentage of participants with a therapeutic response, defined as achieving CR, PR, or MR assessed at Week 26 and Week 52 or hematological response, defined as achieving CR, PR, or MR at Week 8. CR was defined as no platelet response or no reduction in the dose intensity of concomitant ITP therapy compared with that at screening. PR response was defined as at least a minor platelet response that enabled a 50% to 99% reduction in the dose intensity of concomitant ITP therapy compared with that at screening. MR was defined as at least a minor platelet response that enabled a 1% to 49% reduction in the dose intensity of concomitant ITP therapy compared with that at screening. | Week 26 and Week 52 | 
| Percentage of Participants With a Therapeutic Response | Number of therapeutic responder participants by CR, PR, MR, or no response (NR) measured at Week 26 and Week 52. CR was defined as no platelet response or no reduction in the dose intensity of concomitant ITP therapy compared with that at screening. PR was defined as at least minor platelet response that enabled a 50% to 99% reduction in the dose intensity of concomitant ITP therapy compared with that at screening. MR was defined as at least minor platelet response that enabled a 1% to 49% reduction in the dose intensity of concomitant ITP therapy compared with that at screening. | Week 26 and Week 52 | 
| Cluster of Differentiation 19 (CD19) B Cell Count | Value of mean CD19+ B cell count at baseline. The standard reference range for CD19 is 0.05 to 0.35 x10^9/L. | Baseline, Weeks 1, 3, and 8, Follow-up Months 4, 6, 8, 10, and 12, and Last Day | 
| Change From Baseline in CD19 B Cell Count | Actual values of CD19+ mean B cell count assessed at Weeks 3 and 8, and Months 4, 6, 8, 10 and 12, and last day. The standard reference range for CD19 is 0.05 to 0.35 x10^9/L. | Weeks 3, 8 and Months 4, 6, 8, 10 and 12, and last day |