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

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

Sponsors

Lead Sponsor: Peking University People's Hospital

Collaborator: Beijing Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital

Source 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.

Overall Status Recruiting
Start Date January 1, 2017
Completion Date August 31, 2020
Primary Completion Date August 31, 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
overall response From the start of study treatment (Day 1) up to the end of Year 2
Secondary Outcome
Measure Time Frame
complete remission From the start of study treatment (Day 1) up to the end of Year 2
partial remission From the start of study treatment (Day 1) up to the end of Year 2
time to response From the start of study treatment (Day 1) up to the end of Year 2
duration of response From the start of study treatment (Day 1) up to the end of Year 2
incidence of treatment-emergent adverse events From the start of study treatment (Day 1) up to the end of Year 2
Enrollment 188
Condition
Intervention

Intervention Type: Drug

Intervention Name: Rituximab

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

Intervention Type: Drug

Intervention Name: All-trans retinoic acid

Description: ATRA was used in combination with low-dose rituximab

Arm Group Label: low-dose rituximab & ATRA

Eligibility

Criteria:

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Xiao-hui Zhang, Professor Principal Investigator Peking University Insititute of Hematology, Peking University People's Hospital
Overall Contact

Last Name: Xiao-hui Zhang, Professor

Email: [email protected]

Location
Facility: Status: Contact:
Peking University Insititute of Hematology, Peking University People's Hospital | Beijing, Beijing, 100044, China Recruiting Xiao-lu Zhu, Doctor [email protected]
Navy General Hospital | Beijing, Beijing, 100048, China Recruiting Jian-Liang Shen, Professor
Beijing Hospital | Beijing, Beijing, 100730, China Recruiting Hui Liu, Doctor
Beijing Tongren Hospital | Beijing, Beijing, China Recruiting Jing-Wen Wang, Doctor
Location Countries

China

Verification Date

May 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Peking University People's Hospital

Investigator Full Name: Xiao-hui Zhang

Investigator Title: Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: low-dose rituximab & ATRA

Type: Experimental

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

Label: low-dose rituximab

Type: Active Comparator

Description: rituximab 100mg once weekly for 6 weeks

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov