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

Peking University

Status and phase: Unknown; Phase 2

Conditions: Immune Thrombocytopenia

Treatments: Drug: All-trans retinoic acid; Drug: Rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT03304288

81670116

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 168 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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168 participants in 2 patient groups

low-dose rituximab & ATRA

Experimental group

Description:

rituximab 100mg once weekly for 6 weeks and oral all-trance retinoid acid 20mg/m\^2 qd for 12 weeks.

Treatment:

Drug: All-trans retinoic acid

Drug: Rituximab

low-dose rituximab

Active Comparator group

Description:

rituximab 100mg once weekly for 6 weeks

Treatment:

Drug: Rituximab