Back to results

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

Primary Purpose

Immune Thrombocytopenia

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Rituximab

All-trans retinoic acid

About this trial

This is an interventional treatment trial for Immune Thrombocytopenia focused on measuring all-trans retinoid acid, rituximab, steroid-resistant, refractory, low-dose

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Peking University Insititute of Hematology, Peking University People's Hospital
Navy General Hospital
Beijing Hospital
Beijing Tongren Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

low-dose rituximab & ATRA

low-dose rituximab

Arm Description

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

rituximab 100mg once weekly for 6 weeks

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

Initial response

The number of patients who achieve response at 4 weeks following treatment

Full Information

NCT ID

NCT03304288

First Posted

October 3, 2017

Last Updated

January 16, 2021

Sponsor

Peking University People's Hospital

Collaborators

Beijing Hospital, Navy General Hospital, Beijing, Beijing Tongren Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03304288

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Unknown status

Study Start Date

October 11, 2017 (Actual)

Primary Completion Date

January 15, 2021 (Actual)

Study Completion Date

February 28, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University People's Hospital

Collaborators

Beijing Hospital, Navy General Hospital, Beijing, Beijing Tongren Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Immune Thrombocytopenia

Keywords

all-trans retinoid acid, rituximab, steroid-resistant, refractory, low-dose

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

168 (Actual)

8. Arms, Groups, and Interventions

Arm Title

low-dose rituximab & ATRA

Arm Type

Experimental

Arm Description

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

Arm Title

low-dose rituximab

Arm Type

Active Comparator

Arm Description

rituximab 100mg once weekly for 6 weeks

Intervention Type

Drug

Intervention Name(s)

Rituximab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

All-trans retinoic acid

Intervention Description

ATRA was used in combination with low-dose rituximab

Primary Outcome Measure Information:

Title

overall response

Description

Time Frame