Hydroxychloroquine in Treating Patients With Newly Diagnosed Chronic Graft-Versus-Host Disease
Condition: Graft Versus Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Hydroxychloroquine may decrease the immune response and be effective in treating
      chronic graft-versus-host disease. It is not yet known if standard therapy for
      graft-versus-host disease is more effective with or without hydroxychloroquine.

      PURPOSE: Randomized phase III trial to compare the effectiveness of standard therapy alone
      with that of standard therapy plus hydroxychloroquine in treating patients who have newly
      diagnosed chronic graft-versus-host disease.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the efficacy of prednisone and cyclosporine with vs without hydroxychloroquine
           in patients with newly diagnosed extensive chronic graft-versus-host disease (GVHD).

      Secondary

        -  Compare the event-free and overall survival in patients treated with these regimens.

        -  Compare the health-related quality of life, including longitudinal change in and
           magnitude of persistent disability, in patients treated with these regimens.

        -  Correlate cytokine levels and T-helper cell subtypes with chronic GVHD activity and
           response in patients treated with these regimens.

        -  Correlate whole blood hydroxychloroquine levels with response and toxicity in patients
           treated with these regimens.

      OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients
      are randomized to one of two treatment arms.

      Patients may receive standard therapy comprising prednisone orally or IV 2-3 times daily or
      every other day and cyclosporine orally or IV twice daily or tacrolimus orally twice daily or
      IV by continuous infusion before randomization. Patients not receiving cyclosporine or
      tacrolimus prior to randomization may receive cyclosporine or tacrolimus after randomization
      according to institutional preference.

        -  Arm I: Within 10-14 days of beginning therapy with prednisone and cyclosporine or
           tacrolimus, patients receive oral hydroxychloroquine twice daily.

        -  Arm II: Patients receive standard therapy with prednisone and cyclosporine or tacrolimus
           as in arm I and oral placebo twice daily.

      In both arms, treatment continues for 9 months in the absence of disease progression or
      unacceptable toxicity. Patients with no response after 2 months of therapy are taken off
      study.

      Quality of life is assessed at baseline, 1 month, 9 months, and 1 year.

      Patients are followed every month for 3 months and at 9 months.

      PROJECTED ACCRUAL: A total of 232 patients (116 per treatment arm) will be accrued for this
      study within 3.6 years.
    

Intervention name(s): cyclosporine; hydroxychloroquine; prednisone; tacrolimus
Intervention type(s): Drug; Drug; Drug; Drug
Intervention MeSH terms: Cyclosporine; Hydroxychloroquine; Prednisone; Tacrolimus; Cyclosporins
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Primary purpose: Supportive Care
Keywords: graft versus host disease