Ustekinumab for the Prevention of Acute Graft-versus-Host Disease After Unrelated Donor Hematopoietic Cell Transplant

Phase 2Active Not RecruitingNCT04572815

Fred Hutchinson Cancer Center116 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

116

Conditions

Hematologic and Lymphocytic Disorder

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Grade II-IV acute graft versus host disease (GVHD) survival

Will be treated as a binary outcome, and the Cochran-Mantel-Haenszel test will be used to compare the two groups based on the stratification factors.

Time frame: At 6 months post-hematopoietic cell transplantation (HCT)

Secondary Outcomes

Cumulative incidence of grade II-IV and grade III-IV acute GVHD

Time frame: At 100 days post-HCT

Cumulative incidence of grade II-IV and grade III-IV acute GVHD

Time frame: At 6 months post-HCT

Acute GVHD organ staging, overall grading, and classification

Minnesota risk criteria will be used to assess organ involvement, individual organ staging, and overall acute GVHD grade. Risk classification will be performed per MacMillan et al.

Time frame: From time of HCT, assessed up to day 100 post-HCT

Incidence of overall chronic GVHD

Will be assessed at serial study visits, and scored according to National Institutes of Health Consensus criteria.