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

Phase 3
Completed
Conditions
Graft Versus Host Disease
Registration Number
NCT00031824
Lead Sponsor
Children's Oncology Group
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 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
82
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Progression Free SurvivalLength of study
Secondary Outcome Measures
NameTimeMethod
Compare the efficacy of a two-drug regimenLength 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 measuresLength 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 responseLength of study
Determine if whole blood hydroxychloroquine levels correlate with response and toxicity.

Trial Locations

Locations (103)

Arizona Cancer Center at University of Arizona Health Sciences Center

🇺🇸

Tucson, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Southern California Permanente Medical Group

🇺🇸

Downey, California, United States

City of Hope Comprehensive Cancer Center

🇺🇸

Duarte, California, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

University Medical Center at Princeton

🇺🇸

Los Angeles, California, United States

Kaiser Permanente Medical Center - Los Angeles

🇺🇸

Los Angeles, California, United States

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Jonsson Comprehensive Cancer Center at UCLA

🇺🇸

Los Angeles, California, United States

Children's Hospital and Research Center at Oakland

🇺🇸

Oakland, California, United States

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Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States

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