Clinical trial NCT01107951: Low-dose Rituximab and High-dose Dexamethasone as First Line Treatment for ITP
Official title: Low-dose Rituximab and High-dose Dexamethasone as First Line Treatment for Adult Patients With Immune Thrombocytopenic Purpura.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immune Thrombocytopenic Purpura
Keywords: Rituximab
Dexamethasone
Low-dose
ITP
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2010-04-21
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with sustained response after 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Number of patients with complete response at month 6
timeFrame: month 6
measure: Bleeding
timeFrame: month 6
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose E Gonzalez UANL
state: Nuevo Leon
Study officials:
affiliation: Hospital Universitario
name: David Gomez-Almaguer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1056/NEJM199406023302203.
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. doi: 10.1056/NEJMoa030254.
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.