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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00031824




Registration number
NCT00031824
Ethics application status
Date submitted
8/03/2002
Date registered
27/01/2003
Date last updated
14/02/2014

Titles & IDs
Public title
Hydroxychloroquine in Treating Patients With Newly Diagnosed Chronic Graft-Versus-Host Disease
Scientific title
Phase III Trial of Hydroxychloroquine + Standard Therapy for Chronic Graft-Versus-Host Disease
Secondary ID [1] 0 0
COG-ASCT0031
Secondary ID [2] 0 0
ASCT0031
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft Versus Host Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
Length of study
Secondary outcome [1] 0 0
Compare the efficacy of a two-drug regimen
Timepoint [1] 0 0
Length of study
Secondary outcome [2] 0 0
Compare conventional outcomes measures
Timepoint [2] 0 0
Length of study
Secondary outcome [3] 0 0
To determine if cytokine levels and T helper cell subtypes (Th1 and Th2) correlate with chronic GVHD activity and response
Timepoint [3] 0 0
Length of study
Secondary outcome [4] 0 0
Determine if whole blood hydroxychloroquine levels correlate with response and toxicity.
Timepoint [4] 0 0

Eligibility
Key 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 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
Minimum age
1 Year
Maximum age
29 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2002
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2011
Sample size
Target
Accrual to date
Final
82
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [3] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
5006 - North Adelaide
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
6001 - Perth
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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California
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District of Columbia
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Georgia
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Hawaii
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Utah
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Washington
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Wisconsin
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Alberta
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Quebec
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New Zealand
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Auckland
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Puerto Rico
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Santurce
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Switzerland
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Bern
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Switzerland
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Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00031824
Trial related presentations / 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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Andrew L. Gilman, MD
Address 0 0
UNC Lineberger Comprehensive Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00031824