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

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ClinicalTrials.gov Identifier: NCT03304288
Recruitment Status : Active, not recruiting
First Posted : October 9, 2017
Last Update Posted : January 20, 2021
Sponsor:
Collaborators:
Beijing Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital
Information provided by (Responsible Party):
Xiao-hui Zhang, Peking University People's Hospital

Tracking Information
First Submitted Date  ICMJE October 3, 2017
First Posted Date  ICMJE October 9, 2017
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE October 11, 2017
Actual Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2021)
  • overall response [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 1 ]
    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 [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 1 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 3, 2017)
overall response [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
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 2-year follow-up.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2021)
  • complete response [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 1 ]
    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 Frame: From the start of study treatment (Day 1) up to the end of Year 1 ]
    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 [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 1 ]
    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 [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 1 ]
    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 [ Time Frame: From the start of study treatment (Day 1) up to the end of Week 4 ]
    The number of patients who achieve response at 4 weeks following treatment
Original Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2017)
  • complete remission [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
    The number of participants (responders) with platelet count>=100x10^9/L (CR) and the absence of bleeding, without rescue medication at 2-year follow-up.
  • partial remission [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
    The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) without the administration of any other platelet increasing therapy
  • time to response [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
    Time to response was defined as the time from starting treatment to the time to achieve the response
  • duration of response [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
    Duration of response was measured from the achievement of response to the loss of response.
  • safety [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
    All patients were assessed for safety every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Combination of Low-dose Rituximab and ATRA as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Immune Thrombocytopenia
Intervention  ICMJE
  • Drug: Rituximab
    Low-dose rituximab was used in combination with ATRA or as the monotherapy
  • Drug: All-trans retinoic acid
    ATRA was used in combination with low-dose rituximab
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Rituximab
    • Drug: All-trans retinoic acid
  • Active Comparator: low-dose rituximab
    rituximab 100mg once weekly for 6 weeks
    Intervention: Drug: Rituximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 16, 2021)
168
Original Estimated Enrollment  ICMJE
 (submitted: October 3, 2017)
188
Estimated Study Completion Date  ICMJE February 28, 2021
Actual Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03304288
Other Study ID Numbers  ICMJE 81670116
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Xiao-hui Zhang, Peking University People's Hospital
Study Sponsor  ICMJE Peking University People's Hospital
Collaborators  ICMJE
  • Beijing Hospital
  • Navy General Hospital, Beijing
  • Beijing Tongren Hospital
Investigators  ICMJE
Principal Investigator: Xiao-hui Zhang, Professor Peking University Insititute of Hematology, Peking University People's Hospital
PRS Account Peking University People's Hospital
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP