Low-dose Rituximab and High-dose Dexamethasone as First Line Treatment for ITP

Immune Thrombocytopenic Purpura Clinical Trial

Official title:

Low-dose Rituximab and High-dose Dexamethasone as First Line Treatment for Adult Patients With Immune Thrombocytopenic Purpura.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01107951
• Other study ID #: Rituximab in PTI 001
• Status: Completed
• Phase: Phase 2
• First received: April 9, 2010
• Last updated: March 21, 2013
• Start date: April 2010
• Est. completion date: January 2013

Study information

• Verified date: March 2013
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the response rate and response duration with the combination of low-dose rituximab and high-dose dexamethasone in the treatment of adult immune thrombocytopenic purpura.

Description:

ITP is an autoimmune disorder characterized by formation of autoantibodies against platelet antigens leading platelet destruction and bleeding. Corticosteroids increase the platelet count in about 80 percent of patients.However, many patients have a relapse when the dose of corticosteroid is reduced. Debilitating side effects are common in patients who require long-term corticosteroid therapy to maintain the platelet count. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effectively raise the platelet count in some patients with ITP and there is clinical and biological evidence to suggest that, if given early, rituximab may prevent ITP relapses. Rituximab 375 mg/m2 weekly for four weeks has significant activity in patients with immune thrombocytopenia. Furthermore, using lower dose rituximab the level of B-cell depletion and the response rates appear similar to those previously observed with standard dosages in a population of ITP.

The purpose of this study is to determine the response rate and response duration with the combination of low-dose rituximab (100mg IV days 1,8, 15 and 22) and high-dose dexamethasone (40mg PO days 1,2,3,4) in untreated adult patients immune thrombocytopenic purpura.

A complete platelet response is defined as an increase in platelet counts to >150×109/L on two consecutive occasions. A partial response is defined as an increase in the platelet count to between 50 and 150×109/L on two consecutive occasions, 1 week apart. Duration of response is considered from the day of the initial infusion to the first time of relapse (platelet count <30×109/L)or to time of analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: January 2013
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Clinically confirmed immune thrombocytopenic purpura (ITP) Platelet count less than 30,000/mm3 on two occasions. Platelets >30000/mm3 with bleeding.

• Normal to increased numbers of megakaryocytes on bone marrow examination in patients = 60 years

• Subject is = 18 years

• Subject has signed and dated written informed consent.

• No sepsis or fever

• No active infection requiring therapy

• No active chronic viral infection

• HIV negative

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

Exclusion Criteria:

• Performance status above or equal to 2.

• Previous treatment with rituximab

• Immunosuppressive treatment within the last month

• Previous splenectomy

• Presence of malignant haematological disease

• Connective tissue disease

• Autoimmune hemolytic anemia

• Pregnancy and lactation

• Not willing to participate in the study.

• Expected survival of < 2 years

• Known intolerance to murine antibodies.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Immune Thrombocytopenic Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Drug:
• Rituximab and dexamethasone
Rituximab 100mg IV days 1,8,15,22. Dexamethasone 40mg PO days 1-4 (four days)

Locations

Country	Name	City	State
Mexico	Hospital Universitario Dr. Jose E Gonzalez UANL	Monterrey	Nuevo Leon

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & Publications (3)

Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med. 1994 Jun 2;330(22):1560-4. Erratum in: N Engl J Med 1994 Jul 28;331(4):283. — View Citation

Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. — View Citation

Zaja F, Battista ML, Pirrotta MT, Palmieri S, Montagna M, Vianelli N, Marin L, Cavallin M, Bocchia M, Defina M, Ippoliti M, Ferrara F, Patriarca F, Avanzini MA, Regazzi M, Baccarani M, Isola M, Soldano F, Fanin R. Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura. Haematologica. 2008 Jun;93(6):930-3. doi: 10.3324/haematol.12206. Epub 2008 Apr 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with sustained response after 6 months	Number of patients with partial and complete response after 6 months.	6 months	No
Secondary	Number of patients with complete response at month 6	Number of patients with platelet count at least 150x109/L, 6 months after therapy	month 6	No
Secondary	Bleeding	Number of patients with bleeding complication after therapy	month 6	Yes