search
Back to results

The Combination of ATRA and Danazol as Second-line Treatment in Adult Immune Thrombocytopenia

Primary Purpose

Autoimmune Thrombocytopenia

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
All-trans retinoic acid
Danazol
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autoimmune Thrombocytopenia focused on measuring All-trans retinoic acid, primary immune thrombocytopenia, corticosteroid-resistant, refractory, danazol

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
  • Platelet count of less than 30×109/L at enrolment
  • 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.
  • 18 years older.

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
  • Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.

Sites / Locations

  • Beijing Hospital, Ministry of Health
  • Peking University People's Hospital, Peking University Insititute of Hematology
  • Beijing Tongren Hospital
  • PLA Navy General Hospital
  • Qilu Hospital, Shandong University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

All-trans retinoic acid ＆Danazol

Danazol

Arm Description

Danazol 400mg po and ATRA 10mg bid po

Danazol 400mg po

Outcomes

Primary Outcome Measures

the sustained platelet response at the 12-month follow-up
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 12-month follow-up.

Secondary Outcome Measures

overall response
The number of participants with platelet count >=30×10^9/L at least once and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy
primary response rate at 4 weeks
The number of participants with platelet count >=30×10^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 4 of treatment
primary response rate at 8 weeks
The number of participants with platelet count >=30×10^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 8 of treatment
time to response
Time to response was defined as the time from starting treatment to the time to achieve the response.
duration of response
Duration of response was measured from the achievement of response to the loss of response.
reduction in bleeding symptoms
Changes of bleeding after treatment. Bleeding was defined in accordance with the WHO bleeding scale (0, no bleeding; 1, petechiae; 2, mild blood loss; 3, gross blood loss; and 4, debilitating blood loss).
safety
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

Full Information

First Posted
August 15, 2012
Last Updated
September 3, 2017
Sponsor
Peking University People's Hospital
Collaborators
Beijing Municipal Science & Technology Commission, Beijing Hospital, Qilu Hospital of Shandong University, Navy General Hospital, Beijing, Beijing Tongren Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT01667263
Brief Title
The Combination of ATRA and Danazol as Second-line Treatment in Adult Immune Thrombocytopenia
Official Title
The Combination of Oral All-trans Retinoic Acid and Danazol vs Danazol as Second-line Treatment in Adult Immune Thrombocytopenia: a Multicenter, Randomized, Open-label Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
June 1, 2012 (Actual)
Primary Completion Date
July 1, 2016 (Actual)
Study Completion Date
February 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University People's Hospital
Collaborators
Beijing Municipal Science & Technology Commission, Beijing Hospital, Qilu Hospital of Shandong University, Navy General Hospital, Beijing, Beijing Tongren Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Randomized, open-label, multicentre study to compare the efficacy and safety of ATRA plus danazol with danazol monotherapy in patients with corticosteroid-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 corticosteroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. 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 ATRA+danazol and danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study, in order to compare the efficacy and safety of ATRA plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Thrombocytopenia
Keywords
All-trans retinoic acid, primary immune thrombocytopenia, corticosteroid-resistant, refractory, danazol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All-trans retinoic acid ＆Danazol
Arm Type
Experimental
Arm Description
Danazol 400mg po and ATRA 10mg bid po
Arm Title
Danazol
Arm Type
Active Comparator
Arm Description
Danazol 400mg po
Intervention Type
Drug
Intervention Name(s)
All-trans retinoic acid
Other Intervention Name(s)
Retinoid acid
Intervention Type
Drug
Intervention Name(s)
Danazol
Other Intervention Name(s)
Danocrine, Cleregil, Danol
Primary Outcome Measure Information:
Title
the sustained platelet response at the 12-month follow-up
Description
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 12-month follow-up.
Time Frame
From the start of study treatment (Day 1) up to the end of Month 12
Secondary Outcome Measure Information:
Title
overall response
Description
The number of participants with platelet count >=30×10^9/L at least once and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy
Time Frame
From the start of study treatment (Day 1) up to the end of Month 12
Title
primary response rate at 4 weeks
Description
The number of participants with platelet count >=30×10^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 4 of treatment
Time Frame
From the start of study treatment (Day 1) up to week 4 of treatment
Title
primary response rate at 8 weeks
Description
The number of participants with platelet count >=30×10^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 8 of treatment
Time Frame
From the start of study treatment (Day 1) up to week 8 of treatment
Title
time to response
Description
Time to response was defined as the time from starting treatment to the time to achieve the response.
Time Frame
From the start of study treatment (Day 1) up to the end of month 12
Title
duration of response
Description
Duration of response was measured from the achievement of response to the loss of response.
Time Frame
From the start of study treatment (Day 1) up to the end of month 12
Title
reduction in bleeding symptoms
Description
Changes of bleeding after treatment. Bleeding was defined in accordance with the WHO bleeding scale (0, no bleeding; 1, petechiae; 2, mild blood loss; 3, gross blood loss; and 4, debilitating blood loss).
Time Frame
From the start of study treatment (Day 1) up to the end of month 12
Title
safety
Description
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
Time Frame
From the start of study treatment (Day 1) up to the end of follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia; Platelet count of less than 30×109/L at enrolment 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. 18 years older. 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 Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiao-Hui Zhang, Professor
Organizational Affiliation
Peking University People's Hospital, Peking University Insititute of Hematology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Hospital, Ministry of Health
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Facility Name
Peking University People's Hospital, Peking University Insititute of Hematology
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Facility Name
Beijing Tongren Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
PLA Navy General Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Qilu Hospital, Shandong University
City
Jinan
State/Province
Shandong
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
20854919
Citation
Zhang X, Fu H, Xu L, Liu D, Wang J, Liu K, Huang X. Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes. Biol Blood Marrow Transplant. 2011 Feb;17(2):274-80. doi: 10.1016/j.bbmt.2010.09.007. Epub 2010 Sep 18.
Results Reference
background
PubMed Identifier
16292516
Citation
Nozaki Y, Tamaki C, Yamagata T, Sugiyama M, Ikoma S, Kinoshita K, Funauchi M. All-trans-retinoic acid suppresses interferon-gamma and tumor necrosis factor-alpha; a possible therapeutic agent for rheumatoid arthritis. Rheumatol Int. 2006 Jul;26(9):810-7. doi: 10.1007/s00296-005-0076-1. Epub 2005 Nov 15.
Results Reference
background
PubMed Identifier
17067661
Citation
Sakakura M, Wada H, Tawara I, Nobori T, Sugiyama T, Sagawa N, Shiku H. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thromb Res. 2007;120(2):187-93. doi: 10.1016/j.thromres.2006.09.008. Epub 2006 Oct 24.
Results Reference
background
PubMed Identifier
18299451
Citation
Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008 Mar 1;111(5):2505-15. doi: 10.1182/blood-2007-07-102798.
Results Reference
background
PubMed Identifier
16011520
Citation
Wing K, Larsson P, Sandstrom K, Lundin SB, Suri-Payer E, Rudin A. CD4+ CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses. Immunology. 2005 Aug;115(4):516-25. doi: 10.1111/j.1365-2567.2005.02186.x.
Results Reference
background
PubMed Identifier
19005182
Citation
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
Results Reference
background
Citation
LIU Wen-bin, WANG Zhao-yue, CAO Li-juan, ZHAO Xiao-juan, ZHU Ming-qing, BAI Xia, RUAN Chang-geng.Therapeutic Effect and Mechanism of All-trans-retinoic Acid Treatment in Refractory Idiopathic Thrombocytopenic Purpura.Suzhou University Journal of Medical Science.2009;3 476-479.
Results Reference
background
PubMed Identifier
28917657
Citation
Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. doi: 10.1016/S2352-3026(17)30170-9. Epub 2017 Sep 13.
Results Reference
derived

Learn more about this trial

The Combination of ATRA and Danazol as Second-line Treatment in Adult Immune Thrombocytopenia

We'll reach out to this number within 24 hrs