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

Phase 2
Completed
Conditions
Idiopathic Thrombocytopenic Purpura
Interventions
Registration Number
NCT00475423
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
122
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1rituximab [MabThera/Rituxan]-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving a Complete Hematological Response (CR) or Confirmed Partial Hematological Response (PR)Week 8

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.

Secondary Outcome Measures
NameTimeMethod
Cluster of Differentiation 19 (CD19) B Cell CountBaseline, Weeks 1, 3, and 8, Follow-up Months 4, 6, 8, 10, and 12, and Last Day

Value of mean CD19+ B cell count at baseline. The standard reference range for CD19 is 0.05 to 0.35 x10\^9/L.

Percentage of Participants Who Achieved CRWeek 52

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.

Percentage of Participants Who Achieved PRWeek 52

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.

Percentage of Participants With Continued CR From Week 8 to Week 52Week 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.

Duration of CR in Participants With Continued CR From Week 8 Until Week 52Week 8 to 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.

Time to Inititiation of New ITP Therapy - Percentage of Participants With an EventWeek 52

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.

Time to CRBaseline to Week 52

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.

Time to PRBaseline to Week 52

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.

Percentage of Participants Who Achieved MRWeek 52

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.

Percentage of Participants With a Therapeutic ResponseWeek 26 and Week 52

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.

Change From Baseline in CD19 B Cell CountWeeks 3, 8 and Months 4, 6, 8, 10 and 12, and last day

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.

Duration of MR in Participants With Continued MR From Week 8 Until Week 52Week 8 to 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.

Percentage of Therapeutic RespondersWeek 26 and Week 52

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.

Percentage of Participants With Hematological CR, PR, or Minor Response (MR)Week 8

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.

Duration of PR in Participants With Continued PR From Week 8 Until Week 52Week 8 to 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.

Time to Initiation of New ITP TherapyBaseline to Week 52

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.

Time to MRBaseline to Week 52

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.

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