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Graft Versus Host DiseasePhase 3NCT00031824

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

A Phase 3 study testing cyclosporine, hydroxychloroquine and prednisone in people with Graft Versus Host Disease, run by Children's Oncology Group at 104 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 29 years
Conditions the study is for
Graft Versus Host Disease
What is being tested?
cyclosporine, hydroxychloroquine and prednisone
How many people
82 participants
Where
104 sitesin 6 countries
Study dates
Apr 2002to Jan 2011
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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 daclizumab 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

Trial locations and contacts

104 sites in 6 countries.

104 sites in 6 countries

United States89 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0914

  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus

    Atlanta, Georgia, 30322

  • MBCCOP-Medical College of Georgia Cancer Center

    Augusta, Georgia, 30912-4000

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • Floating Hospital for Children

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114-2696

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7070

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60601

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University

    Cleveland, Ohio, 44106-5065

  • Presbyterian - St. Luke's Medical Center

    Colorado Springs, Colorado, 80907

  • Columbus Children's Hospital

    Columbus, Ohio, 43205-2696

  • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390-9063

  • Children's Hospital Cancer Center

    Denver, Colorado, 80218

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • Southern California Permanente Medical Group

    Downey, California, 90242

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • INOVA Fairfax Hospital

    Falls Church, Virginia, 22042-3300

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0296

  • DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • CCOP - St. Vincent Hospital Cancer Center, Green Bay

    Green Bay, Wisconsin, 54301

  • Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Children's Hospital at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Cancer Research Center of Hawaii

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine

    Houston, Texas, 77030-2399

  • M.D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • Riley Children Cancer Center at Riley Hospital for Children

    Indianapolis, Indiana, 46202-5225

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1009

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207-8482

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Markey Cancer Center at University of Kentucky Chandler Medical Center

    Lexington, Kentucky, 40536-0084

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027-0700

  • University Medical Center at Princeton

    Los Angeles, California, 90027-0700

  • Kaiser Permanente Medical Center - Los Angeles

    Los Angeles, California, 90027

  • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Jonsson Comprehensive Cancer Center at UCLA

    Los Angeles, California, 90095-1781

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • University of Wisconsin Comprehensive Cancer Center

    Madison, Wisconsin, 53792-4108

  • CCOP - Marshfield Clinic Research Foundation

    Marshfield, Wisconsin, 54449

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Miami Children's Hospital

    Miami, Florida, 33155-4069

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics - Minneapolis/St. Paul

    Minneapolis, Minnesota, 55404

  • University of Minnesota Cancer Center

    Minneapolis, Minnesota, 55455

  • Vanderbilt Children's Hospital

    Nashville, Tennessee, 37232-6310

  • Schneider Children's Hospital

    New Hyde Park, New York, 11042

  • MBCCOP - LSU Health Sciences Center

    New Orleans, Louisiana, 70112

  • Children's Hospital of New Orleans

    New Orleans, Louisiana, 70118

  • NYU Cancer Institute at New York University Medical Center

    New York, New York, 10016

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • Herbert Irving Comprehensive Cancer Center at Columbia University

    New York, New York, 10032

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609

  • Oklahoma University Medical Center

    Oklahoma City, Oklahoma, 73190

  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

    Omaha, Nebraska, 68198-3330

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Lucile Packard Children's Hospital at Stanford University Medical Center

    Palo Alto, California, 94304-1812

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • CCOP - Columbia River Oncology Program

    Portland, Oregon, 97225

  • Cancer Institute at Oregon Health and Science University

    Portland, Oregon, 97239-3098

  • Doernbecher Children's Hospital at Oregon Health & Science University

    Portland, Oregon, 97239-3098

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • Huntsman Cancer Institute at University of Utah

    Salt Lake City, Utah, 84112

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78207

  • MBCCOP - South Texas Pediatrics

    San Antonio, Texas, 78229-3900

  • Pediatric Hematology and Oncology Associates of South Texas, PLLC

    San Antonio, Texas, 78229

  • Children's Hospital and Health Center, San Diego

    San Diego, California, 92123-4282

  • UCSF Comprehensive Cancer Center

    San Francisco, California, 94143

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074-9308

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Deaconess Medical Center

    Spokane, Washington, 99210-0248

  • Cardinal Glennon Children's Hospital

    St Louis, Missouri, 63104

  • Methodist Cancer Center at Methodist Specialty and Transplant Hospital

    St Louis, Missouri, 63104

  • St. Louis Children's Hospital

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Madigan Army Medical Center

    Tacoma, Washington, 98431-0001

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • Arizona Cancer Center at University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

  • New York Medical College

    Valhalla, New York, 10595

  • Lombardi Cancer Center at Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

Other trials in United States

Canada6 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T2T 5C7

  • McGill Cancer Centre at McGill University

    Montreal, Quebec, H3H 1P3

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia5 sites

  • Royal Children's Hospital

    Brisbane, Queensland, 4029

  • Women's and Children's Hospital

    North Adelaide, South Australia, 5006

  • Royal Children's Hospital

    Parkville, Victoria, 3052

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

  • Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

Switzerland2 sites

  • Swiss Pediatric Oncology Group Bern

    Bern, CH 3010

  • Swiss Pediatric Oncology Group Lausanne

    Lausanne, CH 1011

Other trials in Switzerland

New Zealand1 site

  • Starship Children's Health

    Auckland

Other trials in New Zealand

Puerto Rico1 site

  • San Jorge Children's Hospital

    Santurce, 00912

Other trials in Puerto Rico

About this study

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

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.

Read the 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.

Keywords
graft versus host disease
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival

    Measured: Length of study

Secondary outcomes (4)

  1. Compare the efficacy of a two-drug regimen

    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.

    Measured: Length of study

  2. Compare conventional outcomes measures

    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.

    Measured: Length of study

  3. To determine if cytokine levels and T helper cell subtypes (Th1 and Th2) correlate with chronic GVHD activity and response

    Measured: Length of study

  4. Determine if whole blood hydroxychloroquine levels correlate with response and toxicity.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startApr 2002
  3. Primary completionMay 2005
  4. Study completionJan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Single group
Masking
Double blind
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00031824
Sponsor's protocol ID
ASCT0031
Other IDs
COG-ASCT0031, CCG-S9701, NCI-P02-0213
Status last verified
Feb 2014
First submitted
8 Mar 2002
Last updated
14 Feb 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Gilman AL, Schultz KR, Goldman FD, Sale GE, Krailo MD, Chen Z, Langholz B, Jacobsohn DA, Chan KW, Ryan RE, Kellick M, Neudorf SM, Godder K, Sandler ES, Sahdev I, Grupp SA, Sanders JE, Wall DA. Randomized trial of hydroxychloroquine for newly diagnosed chronic graft-versus-host disease in children: a Children's Oncology Group study. Biol Blood Marrow Transplant. 2012 Jan;18(1):84-91. doi: 10.1016/j.bbmt.2011.05.016. Epub 2011 May 30.

    PubMed 21689773

  • Rozmus J, Schultz KR, Wynne K, Kariminia A, Satyanarayana P, Krailo M, Grupp SA, Gilman AL, Goldman FD. Early and late extensive chronic graft-versus-host disease in children is characterized by different Th1/Th2 cytokine profiles: findings of the Children's Oncology Group Study ASCT0031. Biol Blood Marrow Transplant. 2011 Dec;17(12):1804-13. doi: 10.1016/j.bbmt.2011.05.011. Epub 2011 May 25.

    PubMed 21669298

  • Hall MJ, Reid JE, Wenstrup RJ. Prevalence of BRCA1 and BRCA2 mutations in women with breast carcinoma In Situ and referred for genetic testing. Cancer Prev Res (Phila). 2010 Dec;3(12):1579-85. doi: 10.1158/1940-6207.CAPR-09-0218.

    PubMed 21149333

  • Fujii H, Cuvelier G, She K, Aslanian S, Shimizu H, Kariminia A, Krailo M, Chen Z, McMaster R, Bergman A, Goldman F, Grupp SA, Wall DA, Gilman AL, Schultz KR. Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group. Blood. 2008 Mar 15;111(6):3276-85. doi: 10.1182/blood-2007-08-106286. Epub 2007 Oct 9.

    PubMed 17925486

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cyclosporine, hydroxychloroquine and prednisone in people with Graft Versus Host Disease, run by Children's Oncology Group at 104 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 104 sites in United States, Canada, Australia, Switzerland, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (time frame: Length of study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00031824, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2014.

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