Clinical Trial: Hydroxychloroquine in Treating Patients With Newly Diagnosed Chronic Graft-Versus-Host Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase III Trial of Hydroxychloroquine + Standard Therapy for Chronic Graft-Versus-Host Disease

Brief 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 Summary:

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. Sponsor: Children's Oncology Group

    Current Primary Outcome: Progression Free Survival [ Time Frame: Length of study ]

    Original Primary Outcome:

    Current Secondary Outcome:

    • Compare the efficacy of a two-drug regimen [ Time Frame: Length of study ]
      Compare the efficacy of a two-drug regimen including prednisone and cyclosporine versus that of a three-drug regimen including hydroxychloroquine, prednisone, and cyclosporine in patients treated for newly-diagnosed extensive chronic GVHD.
    • Compare conventional outcomes measures [ Time Frame: Length of study ]
      Compare conventional outcomes measures (event-free survival, overall survival) and health-related quality-of-life (HRQL), including longitudinal change in and magnitude of persistent disability, for the two-drug versus the three-drug regimen.
    • To determine if cytokine levels and T helper cell subtypes (Th1 and Th2) correlate with chronic GVHD activity and response [ Time Frame: Length of study ]
    • Determine if whole blood hydroxychloroquine levels correlate with response and toxicity.


    Original Secondary Outcome:

    Information By: Children's Oncology Group

    Dates:
    Date Received: March 8, 2002
    Date Started: April 2002
    Date Completion:
    Last Updated: February 12, 2014
    Last Verified: February 2014