The Combination of Low-dose Rituximab and ATRA as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia

Peking University People's Hospital168 enrolled

Overview

Randomized, open-label, multicentre study to assess the efficacy and safety of the combination of low-dose rituximab and ATRA in patients with steroid-resistant/relapsed ITP.

Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients achieve remission from first-line therapies. However, the underlying mechanism of steroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. Rituximab has been shown to partly improve the complete remission rate of ITP. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haematopoiesis, making it a possible treatment option. A multicentre prospective study was performed in non-splenectomized ITP patients who were either resistant to a standard dose of corticosteroids or had relapsed. Patients were randomized to the low-dose rituximab+ATRA and the low-dose rituximab monotherapy groups. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Interim analysis was scheduled at 50% through recruitment. Adverse events are also recorded throughout the study, in order to assess the efficacy and safety of the combination of low-dose rituximab and ATRA in patients with steroid-resistant/relapsed ITP.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

168

Conditions

Immune Thrombocytopenia

Interventions

RituximabDRUG

Low-dose rituximab was used in combination with ATRA or as the monotherapy

All-trans retinoic acidDRUG

ATRA was used in combination with low-dose rituximab

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * ITP confirmed by excluding other supervened causes of thrombocytopenia; * Platelet count of less than 30×10\^9/L at enrollment; * Patients who did not achieve a sustained response to treatment with full dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation; * ECOG\<2. Exclusion Criteria: * Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus) * Congestive heart failure * Severe arrhythmia * Nursing or pregnant women * Aspartate aminotransferase and alanine transaminase levels ≥ 3×the upper limit of the normal threshold criteria * Creatinine or serum bilirubin levels each 1•5 times or more than the normal range * Active or previous malignancy * Patients with other diseases were undergoing treatment with immunosuppressants * Patients with ITP had received rituximab

Locations (4)

Peking University Insititute of Hematology, Peking University People's Hospital

Beijing, Beijing Municipality, China

Navy General Hospital

Beijing, Beijing Municipality, China

Beijing Hospital

Beijing, Beijing Municipality, China

Beijing Tongren Hospital

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

overall response

The number of participants (responders) with platelet count \>=30x10\^9/L and at least a 2-fold increase in the baseline count (PR) or a platelet count \>=100x10\^9/L (CR) and the absence of bleeding, without rescue medication at 1-year follow-up. Interim analysis was scheduled at 50% through recruitment.