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Hydroxychloroquine in Treating Patients With Newly Diagnosed Chronic Graft-Versus-Host Disease
This study has been completed.
First Received: March 8, 2002   Last Updated: July 23, 2008   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00031824
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Drug: cyclosporine
Drug: hydroxychloroquine
Drug: prednisone
Drug: tacrolimus
Phase III

Study Type: Interventional
Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control
Official Title: Phase III Trial of Hydroxychloroquine + Standard Therapy for Chronic Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: April 2002
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.

  Eligibility

Ages Eligible for Study:   1 Year to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* newly diagnosed extensive chronic graft-versus-host disease (GVHD) of ≥ 1 organ system (e.g., lip, skin, or liver) documented by all of the following:

    • Clinicopathologic features of GVHD, including involvement of any of the following organ systems:

      • Skin changes
      • Oral changes
      • Hepatic involvement
      • Gastrointestinal involvement
      • Sicca syndrome
      • Pulmonary involvement
      • Myofascial
      • Skeletal
      • Other inflammatory conditions (e.g., myositis, arthritis, polyserositis, or unexplained pericardial, pleural, or peritoneal effusions)
      • Autoantibodies
    • Extent of disease, defined according to the following classification:

      • Limited chronic GVHD, defined by 1 of the following:

        • Localized skin involvement and/or liver dysfunction
        • Involvement of only 1 target organ
      • Extensive chronic GVHD, defined by 1 of the following:

        • Generalized skin involvement of ≥ 50% of body surface area
        • Localized skin involvement and/or liver dysfunction AND ≥ 1 of the following:

          • Liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis
          • Eye involvement (Schirmer's test with < 5 mm wetting)
          • Involvement of minor salivary glands or oral mucosa on lip biopsy
          • Involvement of any other target organs
        • Involvement of ≥ 2 target organs
    • Timing of onset, including onset of any of the following types:

      • Progressive onset defined as, evolving directly from acute GVHD, commonly with the development of typical manifestations such as oral or skin lichenoid changes or sclerodermatous skin changes
      • Quiescent onset, defined as developing after the resolution of acute GVHD
      • De novo onset, defined as developing with no prior history of acute GVHD
  • Must have ≥ 1 typical clinical manifestation of chronic GVHD that differs from that of acute GVHD (e.g., rash, anorexia, nausea, emesis, diarrhea, abdominal pain, or cholestasis)

    • Symptoms of acute GVHD allowed at the time of diagnosis of chronic GVHD
  • Prior allogeneic bone marrow, peripheral blood stem cell, or cord blood transplantation from a family member or unrelated donor for malignancy required NOTE: *Histologic confirmation may be "consistent with GVHD"

PATIENT CHARACTERISTICS:

Age:

  • 1 to 29

Performance status:

  • Lansky 50-100% OR
  • Karnofsky 50-100%

Life expectancy:

  • At least 2 months

Hematopoietic:

  • Absolute neutrophil count ≥ 1,000/mm^3, unless due to chronic GVHD (i.e., autoimmune neutropenia or bone marrow suppression)

Hepatic:

  • See Disease Characteristics

Renal:

  • Creatinine < 1.5 times upper limit of normal OR
  • Creatinine clearance ≥ 60 mL/min

Other:

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No lysosomal storage disorder
  • No uncontrolled infection (e.g., persistent bacterial, fungal, or viral infection despite appropriate antimicrobial therapy)
  • No G6PD deficiency
  • No history of psoriasis or porphyria
  • No hypersensitivity to 4-aminoquinolines
  • No prior retinal or visual field changes due to 4-aminoquinolines

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • No concurrent dacluzimab or infliximab
  • No concurrent thalidomide

Chemotherapy:

  • Not specified

Endocrine therapy:

  • Prior topical steroids for treatment of extensive chronic GVHD allowed
  • Prior adjustment to prednisone dose allowed if done as a reversal of a taper
  • Prior steroids (prednisone ≤ 1 mg/kg/day (or equivalent) for symptom management for up to 1 week before study entry allowed
  • Concurrent steroids for treatment and/or prophylaxis of acute GVHD allowed if prednisone dose is ≤ 2 mg/kg/day (or equivalent)
  • Concurrent topical steroids allowed

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • No prior treatment for extensive chronic GVHD except the following:

    • Topical treatment (e.g., tacrolimus ointment or pimecrolimus cream)
    • Adjustments of cyclosporine or tacrolimus doses for GVHD prophylaxis or treatment of acute GVHD
  • Concurrent cyclosporine or tacrolimus allowed

    • Cyclosporine must have been started before study entry
  • No other concurrent systemic or topical immunosuppressants, including any of the following:

    • Azathioprine
    • Mycophenolate mofetil
    • Psoralen-ultraviolet light therapy
    • Photopheresis
  • No administration of any of the following for 1 hour before until 2 hours after study drug administration:

    • Antacids
    • Sucralfate
    • Cholestyramine
    • Bicarbonate
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00031824

  Hide Study Locations
Locations
United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital and Health Center, San Diego
San Diego, California, United States, 92123-4282
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Children's Hospital of Orange County
Orange, California, United States, 92868
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Kaiser Permanente Medical Center - Los Angeles
Los Angeles, California, United States, 90027
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304-1812
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Southern California Permanente Medical Group
Downey, California, United States, 90242
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
University Medical Center at Princeton
Los Angeles, California, United States, 90027-0700
United States, Colorado
Children's Hospital Cancer Center
Denver, Colorado, United States, 80218
Presbyterian - St. Luke's Medical Center
Colorado Springs, Colorado, United States, 80907
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
Lombardi Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
All Children's Hospital
St. Petersburg, Florida, United States, 33701
Miami Children's Hospital
Miami, Florida, United States, 33155-4069
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207-8482
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0296
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
Atlanta, Georgia, United States, 30322
MBCCOP-Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912-4000
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60601
United States, Indiana
Riley Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202-5225
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1009
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0084
United States, Louisiana
Children's Hospital of New Orleans
New Orleans, Louisiana, United States, 70118
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maine
Maine Children's Cancer Program
Scarborough, Maine, United States, 04074-9308
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Floating Hospital for Children
Boston, Massachusetts, United States, 02111
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114-2696
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0914
United States, Minnesota
Children's Hospitals and Clinics - Minneapolis/St. Paul
Minneapolis, Minnesota, United States, 55404
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Cardinal Glennon Children's Hospital
Saint Louis, Missouri, United States, 63104
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Methodist Cancer Center at Methodist Specialty and Transplant Hospital
Saint Louis, Missouri, United States, 63104
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-3330
United States, New Jersey
Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
New York Medical College
Valhalla, New York, United States, 10595
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
Schneider Children's Hospital
New Hyde Park, New York, United States, 11042
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7070
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
Cleveland, Ohio, United States, 44106-5065
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73190
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
Doernbecher Children's Hospital at Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Children's Hospital at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232-6310
United States, Texas
Pediatric Hematology and Oncology Associates of South Texas, PLLC
San Antonio, Texas, United States, 78229
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
MBCCOP - South Texas Pediatrics
San Antonio, Texas, United States, 78229-3900
Baylor College of Medicine
Houston, Texas, United States, 77030-2399
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-9063
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78207
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Virginia
INOVA Fairfax Hospital
Falls Church, Virginia, United States, 22042-3300
United States, Washington
Madigan Army Medical Center
Tacoma, Washington, United States, 98431-0001
Deaconess Medical Center
Spokane, Washington, United States, 99210-0248
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
United States, Wisconsin
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54301
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-4108
Australia, New South Wales
Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Children's Hospital
Brisbane, Queensland, Australia, 4029
Australia, South Australia
Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Australia, Victoria
Royal Children's Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T2T 5C7
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H3H 1P3
New Zealand
Starship Children's Health
Auckland, New Zealand
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Switzerland
Swiss Pediatric Oncology Group Bern
Bern, Switzerland, CH 3010
Swiss Pediatric Oncology Group Lausanne
Lausanne, Switzerland, CH 1011
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Andrew L. Gilman, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000069231, COG-ASCT0031, CCG-S9701, NCI-P02-0213
Study First Received: March 8, 2002
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00031824     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
graft versus host disease

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Prednisone
Anti-Infective Agents
Antiprotozoal Agents
Cyclosporine
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Tacrolimus
Cyclosporins
Hormones
Antimalarials
Antiparasitic Agents
Antifungal Agents
Therapeutic Uses
Dermatologic Agents
Immune System Diseases
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Immunosuppressive Agents
Glucocorticoids
Pharmacologic Actions
Hydroxychloroquine
Graft vs Host Disease
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 27, 2009