Clinical trial NCT03304288: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Keywords: all-trans retinoid acid
rituximab
steroid-resistant
refractory
low-dose
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Hospital
name: Navy General Hospital, Beijing
name: Beijing Tongren Hospital
First posted: 2017-10-09
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: overall response
timeFrame: From the start of study treatment (Day 1) up to the end of Year 1
measure: sustained response
timeFrame: From the start of study treatment (Day 1) up to the end of Year 1
Secondary outcomes:
measure: complete response
timeFrame: From the start of study treatment (Day 1) up to the end of Year 1
measure: time to response
timeFrame: From the start of study treatment (Day 1) up to the end of Year 1
measure: duration of response
timeFrame: From the start of study treatment (Day 1) up to the end of Year 1
measure: incidence of adverse events
timeFrame: From the start of study treatment (Day 1) up to the end of Year 1
measure: Initial response
timeFrame: From the start of study treatment (Day 1) up to the end of Week 4
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Insititute of Hematology, Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Navy General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tongren Hospital
state: Beijing
Study officials:
affiliation: Peking University Insititute of Hematology, Peking University People's Hospital
name: Xiao-hui Zhang, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu YJ, Liu H, Zeng QZ, Liu Y, Wang JW, Wang WS, Jia-Feng, Zhou HB, Huang QS, He Y, Fu HX, Zhu XL, Jiang Q, Jiang H, Chang YJ, Xu LP, Huang XJ, Zhang XH. All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP. Blood. 2022 Jan 20;139(3):333-342. doi: 10.1182/blood.2021013393.