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Rituximab in Adult Acquired Idiopathic Thrombotic Thrombocytopenic Purpura (PTTritux)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00907751
First received: May 22, 2009
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

Multicentric non-randomized phase II opened prospective study (10 centres involved).

Primary endpoint:

  • To evaluate the kinetics of B-cell depletion by rituximab and its pharmacokinetics in patients treated with rituximab in association with plasma exchanges.

Secondary endpoints:

  • To evaluate the tolerance of rituximab, the volume of plasma and the number of plasma exchange sessions required to achieve a durable complete remission, and to determinate the duration of B-cell depletion.
  • To evaluate the incidence of persistent severe acquired ADAMTS13 deficiency following treatment with rituximab, as well as the incidence of relapses.

Condition Intervention Phase
Thrombotic Thrombocytopenic Purpura
Drug: rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Association of Rituximab to Plasma Exchange in Adult Acquired Idiopathic Thrombotic Thrombocytopenic Purpura

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • To evaluate the kinetics of B-cell depletion by rituximab and its pharmacokinetics in patients treated with rituximab in association with plasma exchanges [ Time Frame: at 1, 3, 6, 9, 12, 18 and 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the tolerance of rituximab, the volume of plasma and the number of plasma exchange sessions required to achieve a durable complete remission, and to determinate the duration of B-cell depletion [ Time Frame: at 1, 3, 6, 9, 12, 18 and 24 months ] [ Designated as safety issue: No ]
  • To evaluate the incidence of persistent severe acquired ADAMTS13 deficiency following treatment with rituximab, as well as the incidence of relapses. [ Time Frame: at 1, 3, 6, 9, 12, 18 and 24 months ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: May 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Microangiopathic hemolytic anemia (< 12 g/dL) with thrombocytopenia (<50 G/L)
Drug: rituximab
Patients will be treated according to the recommendations of the Reference Centre for the management of thrombotic microangiopathies. Infusions of rituximab (375 mg/m2) will be added to this treatment at day 1, 4 and 15, immediately after plasma exchange sessions.
Other Name: rituximab

Detailed Description:

Duration of the study:

3 years and 2 months, including 1 year of inclusion and 2 years of participation for the patient.

Experimental plan:

Patients fulfilling the inclusion criteria of the study will be treated according to the recommendations of the Reference Centre for the management of thrombotic microangiopathies. If patients present refractory TTP, infusions of rituximab (375 mg/m2) will be added to this treatment at day 1, 4 and 15, immediately after plasma exchange sessions.On diagnosis, during treatment and after remission achievement, the following values will be explored: ADAMTS13 activity, ADAMTS13 inhibitors and anti-ADAMTS13 antibodies, B-cell lymphocytes quantification by immunophenotyping, and serum gammaglobulin level by serum protein electrophoresis. Rituximab will also be quantified.

Number of patients:

Each participating centre may recruit and include 1 patient/year.Amongst 10 participating centres, a total number of 10 patients should be included.

Specific activities during the study:

Three infusions of rituximab (375 mg/m2 /infusion), immediately after plasma exchange sessions on day 1, 4 and 15. Blood samplings at day 1, 4 and 15, at 1 month and then every 3 month until month 24.

Expected results and perspectives:

This study should provide evidence as to whether the association of rituximab to plasma exchanges allo an efficient B-cell depletion. If yes, a randomized study should be performed to evaluate the role of rituximab at the acute phase of acquired idiopathic TTP, immediately after the diagnosis was established.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Microangiopathic hemolytic anemia (< 12 g/dL) with thrombocytopenia <50 G/L, and mild or no renal failure (Serum creatinine < 150 µmol/L),
  • negative Beta HCG and ongoing contraception during treatment and during the 24 months following the last infusion of rituximab,
  • refractory TTP (after 4 days of standard treatment)
  • > 18 year old
  • and signed written informed consent.

Exclusion Criteria:

  • Hemolytic uremic syndrome (platelet count ³ 50 G/L and serum creatinine ³ 150 micromol/L),
  • TTP associated with another condition (HIV infection, cancer and/or chemotherapy, transplantation),
  • previous treatment with vincristine or cyclophosphamide or other immunomodulatory drugs (except steroids), within 2 months before inclusion ;
  • ongoing or planned pregnancy, lactation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00907751

Locations
France
Saint-Antoine Hospital, Hematology
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Paul COPPO, Md Ph D Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00907751     History of Changes
Other Study ID Numbers: P060801
Study First Received: May 22, 2009
Last Updated: February 26, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Diseases
Hemorrhage
Immune System Diseases
Pathologic Processes
Signs and Symptoms
Skin Manifestations
Thrombocytopenia
Thrombophilia
Thrombotic Microangiopathies
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014