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Status unknownNCT03304288Updated Jan 20, 2021

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

A Phase 2 interventional study of Rituximab and All-trans retinoic acid in Immune Thrombocytopenia, sponsored by Peking University People's Hospital. Status unknown at 4 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-01-20.

Sponsored by Peking University People's Hospital · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jan 2021), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 2
Study type
Interventional
Enrollment
168
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Immune Thrombocytopenia

Keywords

  • all-trans retinoid acid
  • rituximab
  • steroid-resistant
  • refractory
  • low-dose
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
168 participants (actual)

Study arms

  • Experimental
    low-dose rituximab & ATRA

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

    Drug: Rituximab · Drug: All-trans retinoic acid

  • Active comparator
    low-dose rituximab

    rituximab 100mg once weekly for 6 weeks

    Drug: Rituximab

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

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: From the start of study treatment (Day 1) up to the end of Year 1

  2. 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.

    Time frame: From the start of study treatment (Day 1) up to the end of Year 1

Secondary outcomes

  1. 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 frame: From the start of study treatment (Day 1) up to the end of Year 1

  2. 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.

    Time frame: From the start of study treatment (Day 1) up to the end of Year 1

  3. 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.

    Time frame: From the start of study treatment (Day 1) up to the end of Year 1

  4. 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.

    Time frame: From the start of study treatment (Day 1) up to the end of Year 1

  5. Initial response

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

    Time frame: From the start of study treatment (Day 1) up to the end of Week 4

06

Study locations

4 sites
  • Peking University Insititute of Hematology, Peking University People's Hospital
    Beijing, Beijing 100044, China
  • Navy General Hospital
    Beijing, Beijing 100048, China
  • Beijing Hospital
    Beijing, Beijing 100730, China
  • Beijing Tongren Hospital
    Beijing, Beijing, China
07

References and documents

Publications

  • 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. PubMed 34665865 ↗
08

Registry details

Key details

Study ID
NCT03304288
Lead sponsor
Peking University People's Hospital
Collaborators
Beijing Hospital, Navy General Hospital, Beijing, Beijing Tongren Hospital
Responsible party
Xiao-hui Zhang (Professor, Peking University People's Hospital) — Principal investigator
First posted
Oct 9, 2017
Start date
Oct 11, 2017
Primary completion
Jan 15, 2021
Completion
Feb 28, 2021 (estimated)
Last update
Jan 20, 2021

Study contacts

Xiao-hui Zhang, Professor
principal investigator · Peking University Insititute of Hematology, Peking University People's Hospital

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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