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

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