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


Phase 3
1 Year
29 Years
Not Enrolling
Both
Graft Versus Host Disease

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care

Principal Investigator

Andrew L. Gilman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000069231

NCT ID:

NCT00031824

Start Date:

April 2002

Completion Date:

Related Keywords:

  • Graft Versus Host Disease
  • graft versus host disease
  • Graft vs Host Disease

Name

Location

Baylor College of MedicineHouston, Texas  77030
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Chicago Cancer Research CenterChicago, Illinois  60637
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Children's Hospital of MichiganDetroit, Michigan  48201
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Kaiser Permanente Medical Center - Los AngelesLos Angeles, California  90027
New York Medical CollegeValhalla, New York  10595
Deaconess Medical CenterSpokane, Washington  99210-0248
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
CCOP - St. Vincent Hospital Cancer Center, Green BayGreen Bay, Wisconsin  54301
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
MBCCOP - LSU Health Sciences CenterNew Orleans, Louisiana  70112
Madigan Army Medical CenterTacoma, Washington  98431-5048
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Maine Children's Cancer ProgramScarborough, Maine  04074-9308
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Floating Hospital for ChildrenBoston, Massachusetts  02111
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Schneider Children's HospitalNew Hyde Park, New York  11042
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
City of Hope Comprehensive Cancer CenterDuarte, California  91010
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Southern California Permanente Medical GroupDowney, California  90242
Kosair Children's HospitalLouisville, Kentucky  40202-3830
St. Louis Children's HospitalSaint Louis, Missouri  63110
Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Markey Cancer Center at University of Kentucky Chandler Medical CenterLexington, Kentucky  40536-0084
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97201-3098
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve UniversityCleveland, Ohio  44106
Oklahoma University Medical CenterOklahoma City, Oklahoma  73104
M.D. Anderson Cancer Center at University of TexasHouston, Texas  77030
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
CCOP - Marshfield Clinic Research FoundationMarshfield, Wisconsin  54449
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Lombardi Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos Angeles, California  90048-1865
Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781
Lucile Packard Children's Hospital at Stanford University Medical CenterPalo Alto, California  95798
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite CampusAtlanta, Georgia  30342
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Children's Hospital and Health Center, San DiegoSan Diego, California  92123-4282
MBCCOP-Medical College of Georgia Cancer CenterAugusta, Georgia  30912-4000
Riley Children Cancer Center at Riley Hospital for ChildrenIndianapolis, Indiana  46202-5225
Cancer Center at Hackensack University Medical CenterHackensack, New Jersey  07601
Doernbecher Children's Hospital at Oregon Health & Science UniversityPortland, Oregon  97239-3098
Vanderbilt Children's HospitalNashville, Tennessee  37232-6310
Simmons Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390-9063
MBCCOP - South Texas PediatricsSan Antonio, Texas  78229-3900
Children's Hospital Cancer CenterDenver, Colorado  80218
DeVos Children's HospitalGrand Rapids, Michigan  49503
Children's Hospitals and Clinics - Minneapolis/St. PaulMinneapolis, Minnesota  55404
Columbus Children's HospitalColumbus, Ohio  43205-2696
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Children's Hospital at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033
University Medical Center at PrincetonLos Angeles, California  90027-0700
Methodist Cancer Center at Methodist Specialty and Transplant HospitalSaint Louis, Missouri  63104
Pediatric Hematology and Oncology Associates of South Texas, PLLCSan Antonio, Texas  78229