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

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

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.

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Rituximab and dexamethasone

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario Dr. Jose E Gonzalez UANL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Rituximab -dexamethasone; only one arm receive four doses weekly rituximab and four dosis daily dexamethasona	Drug: Rituximab and dexamethasone; Rituximab 100mg IV days 1,8,15,22. Dexamethasone 40mg PO days 1-4 (four days); Other Names: Mabthera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with sustained response after 6 months	Number of patients with partial and complete response after 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Bleeding	Number of patients with bleeding complication after therapy	month 6

Collaborators and Investigators

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez
• Investigators: Principal Investigator: David Gomez-Almaguer, MD, Hospital Universitario

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: N Engl J Med 1994 Jul 28;331(4):283.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): January 1, 2013

Study Registration Dates

• First Submitted: April 9, 2010
• First Submitted That Met QC Criteria: April 20, 2010
• First Posted (ESTIMATE): April 21, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): March 22, 2013
• Last Update Submitted That Met QC Criteria: March 21, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Rituximab; Dexamethasone; ITP; Low-dose
• 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; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Dexamethasone; Rituximab
• Other Study ID Numbers: Rituximab in PTI 001