Clinical trial NCT00031824 (phase 3, status: completed)
Conditions: graft versus host disease
ICD codes: D89.810, D89.811, D89.813, D89.812
Drugs: cyclosporine, hydroxychloroquine, prednisone, tacrolimus
SMILES: CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C, CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1, [H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C, COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O
Eligibility 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