Phase I Trial of Brentuximab Vedotin for Refractory Chronic Graft-vs.-Host Disease (GVHD)

Inclusion Criteria: * Recipients of allogeneic hematopoietic cell transplantation (HCT) after either myeloablative or reduced intensity conditioning regimens. Any donor source of stem cells is eligible. * Participants must be at least 100 days after HCT. * Patients must have steroid refractory cGVHD, defined as having persistent signs and symptoms of chronic GVHD (section 13.1) despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms. * Stable dose of corticosteroids for 4 weeks prior to enrollment * No addition or subtraction of other immunosuppressive medications (e.g., calcineurin inhibitors, sirolimus, mycophenolate mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug * Serum Cr ≤ 3 gm / dL * Adequate hepatic function (total bilirubin \< 2.0 mg/dl, AST \< 5x ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD. For patients with abnormal LFTs as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment. Abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situation. * Patients must have adequate bone marrow function as defined by ANC ≥ 1000 / µl and platelets ≥ 20,000 / µl without growth factor or transfusional support * Negative pregnancy test for females of child bearing age * Age ≥ 18 - The safety and effectiveness of brentuximab vedotin has not been established in the pediatric population. Clinical trials of brentuximab vedotin included only 9 pediatric patients and this number is not sufficient to determine whether they respond differently than adult patients. * The effects of brentuximab vedotin on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Ongoing prednisone requirement \> 1 mg/kg/day (or equivalent) * Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment. * ECP therapy within 4 weeks prior to enrollment * Active malignant disease relapse * Active, uncontrolled infection * Uncontrolled cardiac angina or symptomatic congestive heart failure (NYHA Class III or IV). * Karnofsky performance status \< 30 * Prior use of brentuximab vedotin for GVHD is not allowed. Prior use of brentuximab vedotn for the treatment of malignancy is allowed. * Pregnant women are excluded from this study because brentuximab vedotin is a chemotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with brentuximab vedotin, breastfeeding should be discontinued if the mother is treated with brentuximab vedotin.