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

NCT00031824 | Completed Phase 3 DMC

• 4 other identifiers: ASCT0031COG-ASCT0031CCG-S9701NCI-P02-0213
• Study Type: interventional
• Target: 82
• Locations: 6 countries
• Sites: 104

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.

Conditions

Graft Versus Host Disease

Keywords

graft versus host disease

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Length of study

Secondary Outcomes (4)

• Compare the efficacy of a two-drug regimen

  Length of study

• Compare conventional outcomes measures

  Length of study

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

  Length of study

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

Interventions

cyclosporine DRUG

hydroxychloroquine DRUG

prednisone DRUG

tacrolimus DRUG

Eligibility Criteria

• Age: 1 Year - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (104)

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

University Medical Center at Princeton

Los Angeles, California, 90027-0700, United States

Location

Kaiser Permanente Medical Center - Los Angeles

Los Angeles, California, 90027, United States

Location

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304-1812, United States

Location

Children's Hospital and Health Center, San Diego

San Diego, California, 92123-4282, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Presbyterian - St. Luke's Medical Center

Colorado Springs, Colorado, 80907, United States

Location

Children's Hospital Cancer Center

Denver, Colorado, 80218, United States

Location

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Children's National Medical Center

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

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0296, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207-8482, United States

Location

Miami Children's Hospital

Miami, Florida, 33155-4069, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

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

Atlanta, Georgia, 30322, United States

Location

MBCCOP-Medical College of Georgia Cancer Center

Augusta, Georgia, 30912-4000, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 96813, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60601, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Riley Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, 46202-5225, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1009, United States

Location

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536-0084, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

Location

Maine Children's Cancer Program

Scarborough, Maine, 04074-9308, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Floating Hospital for Children

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114-2696, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0914, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

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

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Methodist Cancer Center at Methodist Specialty and Transplant Hospital

St Louis, Missouri, 63104, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, 68198-3330, United States

Location

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Schneider Children's Hospital

New Hyde Park, New York, 11042, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, 10032, United States

Location

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

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

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

Chapel Hill, North Carolina, 27599-7070, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

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

Cleveland, Ohio, 44106-5065, United States

Location

Columbus Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Oklahoma University Medical Center

Oklahoma City, Oklahoma, 73190, United States

Location

CCOP - Columbia River Oncology Program

Portland, Oregon, 97225, United States

Location

Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Doernbecher Children's Hospital at Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Children's Hospital at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232-6310, United States

Location

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

Dallas, Texas, 75390-9063, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-2399, United States

Location

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78207, United States

Location

MBCCOP - South Texas Pediatrics

San Antonio, Texas, 78229-3900, United States

Location

Pediatric Hematology and Oncology Associates of South Texas, PLLC

San Antonio, Texas, 78229, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

INOVA Fairfax Hospital

Falls Church, Virginia, 22042-3300, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Deaconess Medical Center

Spokane, Washington, 99210-0248, United States

Location

Madigan Army Medical Center

Tacoma, Washington, 98431-0001, United States

Location

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, 54301, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792-4108, United States

Location

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, 54449, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Royal Children's Hospital

Brisbane, Queensland, 4029, Australia

Location

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Alberta Children's Hospital

Calgary, Alberta, T2T 5C7, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Starship Children's Health

Auckland, New Zealand

Location

San Jorge Children's Hospital

Santurce, 00912, Puerto Rico

Location

Swiss Pediatric Oncology Group Bern

Bern, CH 3010, Switzerland

Location

Swiss Pediatric Oncology Group Lausanne

Lausanne, CH 1011, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 21689773 RESULT

• 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.

  PMID: 21669298 RESULT

• 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.

  PMID: 21149333 RESULT

• 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.

  PMID: 17925486 RESULT

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclosporine; Hydroxychloroquine; Prednisone; Tacrolimus

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Macrolides; Lactones; Organic Chemicals

Study Officials

• Andrew L. Gilman, MD

  UNC Lineberger Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2002
• First Posted: January 27, 2003
• Study Start: April 1, 2002
• Primary Completion: May 1, 2005
• Study Completion: January 1, 2011
• Last Updated: February 14, 2014

Record last verified: 2014-02

Locations

CH (2); AU (5); PR (1); NZ (1); CA (6); US (89)