Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE

NCT02444728 | Terminated Phase 3

• 1 other identifier: CSTAR001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 15

Brief Summary

Treating severe thrombocytopenia is a challenge in the management of systemic lupus erythematosus. Although rheumatologists have followed some rules in real practice,there is very few evidence to support the current treatment algorithm. The purpose of this study is to compare the complete remission rate and partial remission rate of cyclophosphamide and hydroxychloroquine for treating severe thrombocytopenia in Chinese SLE patients.

Conditions

Thrombocytopenia

Keywords

thrombocytopenia; systemic lupus erythematosus; hydroxychloroquine; cyclophosphamide; remission

Outcome Measures

Primary Outcomes (1)

• complete remission rate

  percentage of patients whose platelet count \> 100X109/L

  at 12 month

Secondary Outcomes (1)

• partial remission rate

  at 12 month

Study Arms (2)

Group1:Hydroxychloroquine

ACTIVE COMPARATOR

Hydroxychloroquine: 100 mg tablets by mouth, 400mg everyday for 12 months Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months

Drug: Hydroxychloroquine; Drug: Methylprednisolone

Group 2:Cyclophosphamide

ACTIVE COMPARATOR

Cyclophosphamide, Azathioprine \& Methylprednisolone Cyclophosphamide: 200mg powder intravenous infusion, 1000mg every month for 6 month. Azathioprine: 100 mg tablets by mouth, everyday for 6 months. Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months

Drug: Hydroxychloroquine; Drug: Cyclophosphamide; Drug: Azathioprine; Drug: Methylprednisolone

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine 200 mg BID for 12 months

Also known as: Fenle

Group 2:Cyclophosphamide; Group1:Hydroxychloroquine

Cyclophosphamide DRUG

Cyclophosphamide 1000mg intravenous infusion every month for 6 months

Also known as: Huanlinxianan

Group 2:Cyclophosphamide

Azathioprine DRUG

After Cyclophosphamide treatment, Azathioprine 100mg once daily for 6 months

Also known as: liuzuopiaolin

Group 2:Cyclophosphamide

Methylprednisolone DRUG

Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months

Also known as: meizhuole

Group 2:Cyclophosphamide; Group1:Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients fulfilled the 1997 ACR modified or SLICC classification criteria of SLE；
• New onset thrombocytopenia: platelet count \<30X109/L(by both routine test and citric acid anti-coagulated blood count test) within 3 months

You may not qualify if:

• Thrombocytopenia caused by other reasons, including drugs；
• Positive for active HAV(hepatitis A virus)/HBV(hepatitis B virus) infection
• Active HIV(human immunodeficiency virus) or HCV(hepatitis C virus) infection;
• Active HP(Helicopter pylori) infection;
• Severe liver and kidney dysfunction；
• Severe neuropsychiatric lupus；
• No response to high dose steroid and/or cyclophosphamide 1 month prior to study enrollment；
• Uncontrolled diabetes or hypertension before entry
• Active GI bleeding 3 months before entry
• Intolerant to HCQ in the past treatment history；
• Severe bone marrow suppression or liver damage caused by cyclophosphamide in the past history；
• Active infection , including bacteria, virus, fungi, mycobacteria
• Allergy to any of the study medications
• Confirmed TTP(thrombolic thrombocytopenic purpura)or CAPS(catastrophic anti-phosphilipid syndrome)
• Platelet count less than 20X109/L with active bleeding

Sponsors & Collaborators

• Chinese SLE Treatment And Research Group: lead
• Peking Union Medical College Hospital: collaborator

Study Sites (15)

the Affiliated Hospital to Bangbu Medical University

Bengbu, Anhui, 233000, China

Location

Hebei Provincial Hospital

Shijiazhuang, Hebei, 050051, China

Location

the First Affiliated Hospital of Xiangya Medical University

Changsha, Hunan, 410000, China

Location

the Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, 010050, China

Location

Sino-Japanese Friendship Hospital of Jilin University

Changchun, Jilin, 410008, China

Location

the Affiliated Hospital of Xian Communication Hospital

Xian, Shanxi, 710000, China

Location

Xijing Hospital

Xian, Shanxi, 710032, China

Location

Xinjiang Provincial Hospital

Ürümqi, Xinjiang, 830001, China

Location

the Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650032, China

Location

Beijng Hospital

Beijing, 100006, China

Location

Beijing Chaoyang Hospital

Beijing, 100020, China

Location

China-Japan Friendship Hospital

Beijing, 100029, China

Location

Peking Union Medical College Hospital

Beijing, 100032, China

Location

Beijing Xuanwu Hospital

Beijing, 100053, China

Location

General Hospital of Tianjing Medical University

Tianjin, 300052, China

Location

Related Publications (11)

• Abu-Shakra M, Shoenfeld Y. Azathioprine therapy for patients with systemic lupus erythematosus. Lupus. 2001;10(3):152-3. doi: 10.1191/096120301676669495.

  PMID: 11315344 BACKGROUND

• Blasco LM. Hydroxychloroquine alone for severe immune thrombocytopenic purpura associated with systemic lupus erythematosus. Lupus. 2013 Jun;22(7):752-3. doi: 10.1177/0961203313490239. Epub 2013 May 22. No abstract available.

  PMID: 23698017 BACKGROUND

• Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. doi: 10.1056/NEJMoa030254.

  PMID: 12944568 BACKGROUND

• Contreras G, Tozman E, Nahar N, Metz D. Maintenance therapies for proliferative lupus nephritis: mycophenolate mofetil, azathioprine and intravenous cyclophosphamide. Lupus. 2005;14 Suppl 1:s33-8. doi: 10.1191/0961203305lu2115oa.

  PMID: 15803929 RESULT

• Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011 Apr 21;117(16):4190-207. doi: 10.1182/blood-2010-08-302984. Epub 2011 Feb 16.

  PMID: 21325604 RESULT

• Boumpas DT, Barez S, Klippel JH, Balow JE. Intermittent cyclophosphamide for the treatment of autoimmune thrombocytopenia in systemic lupus erythematosus. Ann Intern Med. 1990 May 1;112(9):674-7. doi: 10.7326/0003-4819-112-9-674.

  PMID: 2334081 RESULT

• Roach BA, Hutchinson GJ. Treatment of refractory, systemic lupus erythematosus-associated thrombocytopenia with intermittent low-dose intravenous cyclophosphamide. Arthritis Rheum. 1993 May;36(5):682-4. doi: 10.1002/art.1780360516.

  PMID: 8489547 RESULT

• Levine AB, Erkan D. Clinical assessment and management of cytopenias in lupus patients. Curr Rheumatol Rep. 2011 Aug;13(4):291-9. doi: 10.1007/s11926-011-0179-5.

  PMID: 21503695 RESULT

• Khellaf M, Chabrol A, Mahevas M, Roudot-Thoraval F, Limal N, Languille L, Bierling P, Michel M, Godeau B. Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies. Am J Hematol. 2014 Feb;89(2):194-8. doi: 10.1002/ajh.23609. Epub 2013 Nov 20.

  PMID: 24254965 RESULT

• Arnal C, Piette JC, Leone J, Taillan B, Hachulla E, Roudot-Thoraval F, Papo T, Schaeffer A, Bierling P, Godeau B. Treatment of severe immune thrombocytopenia associated with systemic lupus erythematosus: 59 cases. J Rheumatol. 2002 Jan;29(1):75-83.

  PMID: 11824975 RESULT

• Newman K, Owlia MB, El-Hemaidi I, Akhtari M. Management of immune cytopenias in patients with systemic lupus erythematosus - Old and new. Autoimmun Rev. 2013 May;12(7):784-91. doi: 10.1016/j.autrev.2013.02.001. Epub 2013 Feb 24.

  PMID: 23462431 RESULT

MeSH Terms

Conditions

Thrombocytopenia; Lupus Erythematosus, Systemic

Interventions

Hydroxychloroquine; Cyclophosphamide; Azathioprine; Methylprednisolone

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Xiaofeng Zeng, MD

  Chinese SLE Treatment And Research Group

  PRINCIPAL INVESTIGATOR

• Xiaofeng Zeng, MD

  Peking Union Medical College Hospital

  STUDY CHAIR

• Xinping Tian, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: May 14, 2015
• Study Start: July 1, 2015
• Primary Completion: December 30, 2018
• Study Completion: December 30, 2018
• Last Updated: March 14, 2022

Record last verified: 2022-02

Locations

CN (15)