Immune Thrombocytopenia
Conditions
Keywords
all-trans retinoid acid, rituximab, steroid-resistant, refractory, low-dose
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.
Interventions
DRUGRituximab
Low-dose rituximab was used in combination with ATRA or as the monotherapy
DRUGAll-trans retinoic acid
ATRA was used in combination with low-dose rituximab
Sponsors
Beijing Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
Countries
China
Outcome results
None listed