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

Immune Thrombocytopenia Clinical Trial

Official title:

The Combination of Low-dose Rituximab and All-trans Retinoic Acid as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia: a Multicenter, Randomized, Open-label Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03304288
• Other study ID #: 81670116
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 11, 2017
• Est. completion date: February 28, 2021

Study information

• Verified date: January 2021
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 168
• Est. completion date: February 28, 2021
• Est. primary completion date: January 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Rituximab
Low-dose rituximab was used in combination with ATRA or as the monotherapy
• All-trans retinoic acid
ATRA was used in combination with low-dose rituximab

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	Beijing Tongren Hospital	Beijing	Beijing
China	Navy General Hospital	Beijing	Beijing
China	Peking University Insititute of Hematology, Peking University People's Hospital	Beijing	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Peking University People's Hospital	Beijing Hospital, Beijing Tongren Hospital, Navy General Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the start of study treatment (Day 1) up to the end of Year 1
Primary	sustained response	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.	From the start of study treatment (Day 1) up to the end of Year 1
Secondary	complete response	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.	From the start of study treatment (Day 1) up to the end of Year 1
Secondary	time to response	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.	From the start of study treatment (Day 1) up to the end of Year 1
Secondary	duration of response	Duration of response was measured from the achievement of response to the loss of response. Interim analysis was scheduled at 50% through recruitment.	From the start of study treatment (Day 1) up to the end of Year 1
Secondary	incidence of adverse events	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.	From the start of study treatment (Day 1) up to the end of Year 1
Secondary	Initial response	The number of patients who achieve response at 4 weeks following treatment	From the start of study treatment (Day 1) up to the end of Week 4