ustekinumab for the prevention of acute graft-versus-host disease after unrelated donor hematopoietic cell transplant

Conditions: Hematologic and Lymphocytic Disorder; Hematopoietic and Lymphoid System Neoplasm

Summary: this phase ii trial studies how well ustekinumab works in preventing acute graft-versus-host disease after unrelated donor hematopoietic cell transplant. sometimes the transplanted cells from a donor can attack the body's normal tissues (called graft-versus-host disease). giving ustekinumab after the transplant may help prevent acute graft-versus-host disease by controlling the body's immune response. funding source- fda oopd.

outline: patients are randomized to 1 of 2 arms. arm i: between 4 and 72 hours prior to start of hct conditioning therapy, patients receive ustekinumab intravenously (iv). beginning 8 weeks after receiving iv ustekinumab, patients receive ustekinumab subcutaneously (sc) on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-hct in the absence of grade iii-iv acute gvhd, disease relapse or unacceptable toxicity. note: hct infusion takes place on day 0. arm ii: between 4 and 72 hours prior to start of hct conditioning therapy, patients receive a placebo iv. beginning 8 weeks after iv placebo, patients receive a placebo sc on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-hct in the absence grade iii-iv acute gvhd, of disease relapse, or unacceptable toxicity. note: hct infusion takes place on day 0. after completion of study, patients are followed up at 6, 9, 12, 18, and 24 months post-hct.

Eligibility criteria:
inclusion criteria: * age 18 - 70 * signed informed consent. * hematologic malignancy or disorder requiring allogeneic hematopoietic cell transplantation * adequate vital organ function: 1. left ventricular ejection fraction (lvef) ≥ 50% 2. forced expiratory volume in 1 second (fev1), forced vital capacity (fvc), and diffusion capacity of the lung for carbon monoxide (dlco) ≥ 50% of predicted values on pulmonary function tests 3. transaminases (aspartate aminotransferase \[ast\], aspartate aminotransferase \[alt\]) \< 3 times upper limit of normal values 4. creatinine clearance ≥ 50 cc/min. * performance status: karnofsky performance status score ≥ 70%. * hct donor is at least 8/8 (matched at hla-a, -b, -c, -drb1) matched with the recipient * pbsc (peripheral blood mobilized stem cells) as graft source * fully myeloablative, reduced-toxicity ablative, or reduced-intensity conditioning regimens. if melphalan is part of the conditioning regimen, dose must be at least 75mg/m\^2 exclusion criteria: * active infection not controlled with appropriate antimicrobial therapy * human immunodeficiency virus (hiv), hepatitis b, or hepatitis c infection * anti-thymocyte globulin (atg) as part of the conditioning regimen or gvhd prophylaxis * pregnant or nursing women * subjects of childbearing age unwilling to use an effective birth control method or refrain from sexual intercourse until 15 weeks after last dose of study drug * non-myeloablative conditioning regimens or conditioning regimens that use less than 75mg/m\^2 of melphalan * prior allogeneic transplant * non-malignant blood disorders (e.g. sickle cell disease, aplastic anemia) * positive screening test for tuberculosis