Abatacept in Treating Patients with Steroid Refractory Chronic Graft-Versus-Host Disease

Inclusion Criteria

• Participants must be recipients of an allogeneic bone marrow or stem cell transplantation with myeloablative or reduced intensity conditioning regimens
• Participants must be at least 100 days after the transplantation or a donor lymphocyte infusion
• Participants must have cGVHD (as defined by the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease)
• Participants may have either extensive or limited cGVHD requiring systemic treatment
• Participants must have steroid refractory cGVHD, defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at >= 0.5 mg/kg/day (or equivalent) for at least 4 weeks; patients may remain on steroids while enrolled in the study
• FOR THE PHASE II PORTION OF THE STUDY: Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms; patients with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible
• No addition or subtraction of other immunosuppressive medications for at least 4 weeks prior to starting treatment
• On stable immunosuppressive regimen for 2 weeks prior to enrollment; adjustment of immunosuppressive medications to maintain a therapeutic level is permitted
• Women of child-bearing potential (WOCBP) comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below) * Post-menopause is defined as: ** Women who have had amenorrhea for >= 12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH) level > 35 mIU/mL ** Women who have irregular menstrual periods and a documented serum FSH level > 35 mIU/mL ** Women who are taking hormone replacement therapy (HRT)
• The following women are WOCBP: * Women using the following methods to prevent pregnancy: Oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides) * Women who are practicing abstinence * Women who have a partner who is sterile (e.g., due to vasectomy)
• WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 10 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized
• WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 0 to 48 hours before the first dose of study drug
• Women must not be breast-feeding
• Sexually active fertile men must use effective birth control if their partners are WOCBP
• Life expectancy of greater than > 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1500/mm^3
• Serum creatinine =< 2.0 mg/dL OR
• Renal function assessed by calculated creatinine clearance >= 60 ml/min by Cockcroft-Gault formula
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless hepatic dysfunction is caused by cGVHD)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (unless hepatic dysfunction is caused by cGVHD)
• Patients much have a negative purified protein derivative (PPD) skin test and a negative Quantiferon assay or a tuberculosis (TB) T-spot test; indeterminate results, due to lack of response to the mitogen control reflecting their immunocompromised state, will be permitted
• Must possess the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Any serious medical condition (including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), laboratory abnormality, or psychiatric illness/social situation that would prevent the subject from signing the informed consent form or limit compliance with study requirements
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Use of any other experimental drug or therapy within 28 days of starting treatment with abatacept
• Use of biologic antibody therapy for cGVHD with rituximab, alemtuzumab, or antithymocyte globulin (ATG) within 3 months of starting treatment with abatacept
• Use of tumor necrosis factor (TNF) alpha inhibitors within four weeks prior to study entry
• Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
• New immunosuppressive medication or extracorporeal photochemotherapy (ECP) within 28 days of starting treatment with abatacept
• Donor lymphocyte infusion within 100 days prior to enrollment
• Active malignant disease relapse or other active malignancy with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast
• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Known seropositive for or positive viral load for human immunodeficiency virus (HIV) or positive viral loads for infectious hepatitis, type B (HBV) or C (HCV)
• Uncontrolled intercurrent active infection; controlled infection on long term suppressive or maintenance therapy is permissible
• Use of live vaccines within four weeks of starting abatacept