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

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.

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Thrombocytopenic Purpura
• Intervention / Treatment: Drug: rituximab [MabThera/Rituxan]

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Adelaide, New South Wales, Australia, 5011
    • Gosford, New South Wales, Australia, 2250
    • Randwick, New South Wales, Australia, NSW 2031
    • Sydney, New South Wales, Australia, 2139
    • Sydney, New South Wales, Australia, 2747
    • Westmead, New South Wales, Australia, 2145
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
  • South Australia
    • Adelaide, South Australia, Australia, 5042
  • Victoria
    • Frankston, Victoria, Australia, 3199
    • Malvern, Victoria, Australia, 3144
    • Melbourne, Victoria, Australia, 3168
    • Parkville, Victoria, Australia, 3052

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: rituximab [MabThera/Rituxan]; 1000mg iv on days 1 and 15

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: May 17, 2007
• First Submitted That Met QC Criteria: May 17, 2007
• First Posted (Estimate): May 21, 2007

Study Record Updates

• Last Update Posted (Estimate): February 23, 2015
• Last Update Submitted That Met QC Criteria: February 4, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: ML20948