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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04572815.
PRIMARY OBJECTIVE:
I. To determine the grade II-IV acute graft versus host disease (GVHD)-free survival at 6 months post-hematopoietic cell transplantation (HCT) when ustekinumab is combined with standard of care pharmacologic GVHD prophylaxis.
SECONDARY OBJECTIVES:
I. Estimate the cumulative incidence of grade II-IV and grade III-IV acute GVHD for both ustekinumab- and placebo-treated subjects.
II. Compare acute GVHD organ involvement and severity between ustekinumab- and placebo-treated subjects.
III. Examine the cumulative incidence of National Institutes of Health (NIH)-defined overall chronic GVHD, and NIH moderate-severe chronic GVHD for ustekinumab- and placebo-treated subjects.
IV. Estimate post-HCT relapse, non-relapse mortality, relapse-free survival, and overall survival for ustekinumab- and placebo-treated subjects.
EXPLORATORY OBJECTIVES:
I. Compare the composite endpoints GVHD relapse-free survival (GRFS) (grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppressive therapy, relapse, death) and chronic GVHD relapse-free survival (CRFS) (moderate-severe chronic GVHD, relapse, death) between ustekinumab- and placebo-treated subjects.
II. Compare exposure to therapeutic glucocorticoid agents (separately considering systemic steroid use and topical agents) between ustekinumab- and placebo-treated subjects.
III. Compare change in patient-reported outcomes between ustekinumab- and placebo-treated subjects.
IV. Examine the biologic effect of ustekinumab therapy.
V. Examine incidence of infectious complications after HCT.
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.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorStephanie Joi Lee
