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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 : Recruiting
First Posted : October 9, 2017
Last Update Posted : June 1, 2020
Sponsor:
Collaborators:
Beijing Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital
Information provided by (Responsible Party):
Xiao-hui Zhang, 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.

Condition or disease Intervention/treatment Phase
Immune Thrombocytopenia Drug: Rituximab Drug: All-trans retinoic acid Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 1, 2017
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2020


Arm Intervention/treatment
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
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

Active Comparator: low-dose rituximab
rituximab 100mg once weekly for 6 weeks
Drug: Rituximab
Low-dose rituximab was used in combination with ATRA or as the monotherapy




Primary Outcome Measures :
  1. 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. Interim analysis was scheduled at 50% through recruitment.


Secondary Outcome Measures :
  1. 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. Interim analysis was scheduled at 50% through recruitment.

  2. 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. Interim analysis was scheduled at 50% through recruitment.

  3. 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. Interim analysis was scheduled at 50% through recruitment.

  4. 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. Interim analysis was scheduled at 50% through recruitment.

  5. incidence of treatment-emergent adverse events [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
    All patients were assessed for treatment-emergent adverse events 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. Interim analysis was scheduled at 50% through recruitment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03304288


Contacts
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Contact: Xiao-hui Zhang, Professor zhangxh100@sina.com

Locations
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China, Beijing
Peking University Insititute of Hematology, Peking University People's Hospital Recruiting
Beijing, Beijing, China, 100044
Contact: Xiao-lu Zhu, Doctor       zhuxl0614@163.com   
Navy General Hospital Recruiting
Beijing, Beijing, China, 100048
Contact: Jian-Liang Shen, Professor         
Beijing Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Hui Liu, Doctor         
Beijing Tongren Hospital Recruiting
Beijing, Beijing, China
Contact: Jing-Wen Wang, Doctor         
Sponsors and Collaborators
Peking University People's Hospital
Beijing Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital
Investigators
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Principal Investigator: Xiao-hui Zhang, Professor Peking University Insititute of Hematology, Peking University People's Hospital
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Responsible Party: Xiao-hui Zhang, Professor, Peking University People's Hospital
ClinicalTrials.gov Identifier: NCT03304288    
Other Study ID Numbers: 81670116
First Posted: October 9, 2017    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020

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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
Keywords provided by Xiao-hui Zhang, Peking University People's Hospital:
all-trans retinoid acid
rituximab
steroid-resistant
refractory
low-dose
Additional relevant MeSH terms:
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Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Pathologic Processes
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Skin Manifestations
Signs and Symptoms
Rituximab
Tretinoin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Keratolytic Agents
Dermatologic Agents