The Combination of Low-dose Rituximab and ATRA as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia
- Registration Number
- NCT03304288
- Lead Sponsor
- Peking University People's Hospital
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 168
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description low-dose rituximab & ATRA All-trans retinoic acid rituximab 100mg once weekly for 6 weeks and oral all-trance retinoid acid 20mg/m\^2 qd for 12 weeks. low-dose rituximab Rituximab rituximab 100mg once weekly for 6 weeks low-dose rituximab & ATRA Rituximab rituximab 100mg once weekly for 6 weeks and oral all-trance retinoid acid 20mg/m\^2 qd for 12 weeks.
- Primary Outcome Measures
Name Time Method overall response From the start of study treatment (Day 1) up to the end of Year 1 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.
sustained response From the start of study treatment (Day 1) up to the end of Year 1 The number of participants that can maintain the platelet count \> 30 x 109/L, an absence of bleeding events, and without requirement for any other ITP-specific treatment for 6 consecutive months after achievement of response. Interim analysis was scheduled at 50% through recruitment.
- Secondary Outcome Measures
Name Time Method time to response From the start of study treatment (Day 1) up to the end of Year 1 Time to response was defined as the time from starting treatment to the time to achieve the response. Interim analysis was scheduled at 50% through recruitment.
incidence of adverse events From the start of study treatment (Day 1) up to the end of Year 1 All patients were assessed for adverse events every week during the first 4 weeks of treatment, and at 2-weeks interval for the following 5 months, and monthly thereafter. Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Interim analysis was scheduled at 50% through recruitment.
Initial response From the start of study treatment (Day 1) up to the end of Week 4 The number of patients who achieve response at 4 weeks following treatment
complete response From the start of study treatment (Day 1) up to the end of Year 1 The number of participants (responders) with 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.
duration of response From the start of study treatment (Day 1) up to the end of Year 1 Duration of response was measured from the achievement of response to the loss of response. Interim analysis was scheduled at 50% through recruitment.
Trial Locations
- Locations (4)
Beijing Tongren Hospital
🇨🇳Beijing, Beijing, China
Navy General Hospital
🇨🇳Beijing, Beijing, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Peking University Insititute of Hematology, Peking University People's Hospital
🇨🇳Beijing, Beijing, China