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

• Status: Completed
• Trial end date: 2011-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclosporine; Cyclosporins; Hydroxychloroquine; Prednisone; Tacrolimus

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