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

NCT01667263 | Completed Phase 2 DMC

• 2 other identifiers: U1111-1132-6877Z111107058811024
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 5

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.

Conditions

Autoimmune Thrombocytopenia

Keywords

All-trans retinoic acid; primary immune thrombocytopenia; corticosteroid-resistant; refractory; danazol

Outcome Measures

Primary Outcomes (1)

• 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.

  From the start of study treatment (Day 1) up to the end of Month 12

Secondary Outcomes (7)

• overall response

  From the start of study treatment (Day 1) up to the end of Month 12

• primary response rate at 4 weeks

  From the start of study treatment (Day 1) up to week 4 of treatment

• primary response rate at 8 weeks

  From the start of study treatment (Day 1) up to week 8 of treatment

• time to response

  From the start of study treatment (Day 1) up to the end of month 12

• duration of response

  From the start of study treatment (Day 1) up to the end of month 12

Study Arms (2)

All-trans retinoic acid ＆Danazol

EXPERIMENTAL

Danazol 400mg po and ATRA 10mg bid po

Drug: All-trans retinoic acid; Drug: Danazol

Danazol

ACTIVE COMPARATOR

Danazol 400mg po

Drug: Danazol

Interventions

All-trans retinoic acid DRUG

Also known as: Retinoid acid

All-trans retinoic acid ＆Danazol

Danazol DRUG

Also known as: Danocrine, Cleregil, Danol

All-trans retinoic acid ＆Danazol; Danazol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• years older.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Beijing Municipal Science & Technology Commission: collaborator
• Beijing Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Navy General Hospital, Beijing: collaborator
• Beijing Tongren Hospital: collaborator

Study Sites (5)

Beijing Hospital, Ministry of Health

Beijing, Beijing Municipality, 100044, China

Location

Peking University People's Hospital, Peking University Insititute of Hematology

Beijing, Beijing Municipality, 100044, China

Location

Beijing Tongren Hospital

Beijing, Beijing Municipality, China

Location

PLA Navy General Hospital

Beijing, Beijing Municipality, China

Location

Qilu Hospital, Shandong University

Jinan, Shandong, China

Location

Related Publications (8)

• 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.

  PMID: 20854919 BACKGROUND

• 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.

  PMID: 16292516 BACKGROUND

• 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.

  PMID: 17067661 BACKGROUND

• 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.

  PMID: 18299451 BACKGROUND

• 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.

  PMID: 16011520 BACKGROUND

• 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.

  PMID: 19005182 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 28917657 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Tretinoin; Danazol; deanol aceglutamate

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Xiao-Hui Zhang, Professor

  Peking University People's Hospital, Peking University Insititute of Hematology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 15, 2012
• First Posted: August 17, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: February 1, 2017
• Last Updated: September 7, 2017

Record last verified: 2017-04

Locations

CN (5)