Clinical trial NCT04572815: Ustekinumab for the Prevention of Acute Graft-versus-Host Disease After Unrelated Donor Hematopoietic Cell Transplant
Official title: Randomized, Placebo-Controlled, Phase II Trial Examining Ustekinumab for Prevention of Graft Vs. Host Disease After Allogeneic Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hematologic and Lymphocytic Disorder
Hematopoietic and Lymphoid System Neoplasm
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
First posted: 2020-10-01
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Grade II-IV acute graft versus host disease (GVHD) survival
timeFrame: At 6 months post-hematopoietic cell transplantation (HCT)
Secondary outcomes:
measure: Cumulative incidence of grade II-IV and grade III-IV acute GVHD
timeFrame: At 100 days post-HCT
measure: Cumulative incidence of grade II-IV and grade III-IV acute GVHD
timeFrame: At 6 months post-HCT
measure: Acute GVHD organ staging, overall grading, and classification
timeFrame: From time of HCT, assessed up to day 100 post-HCT
measure: Incidence of overall chronic GVHD
timeFrame: From time of HCT, assessed up to 2 years post-HCT
measure: Incidence of moderate-severe chronic GVHD
timeFrame: From time of HCT, assessed up to 2 years post-HCT
measure: Incidence of post-HCT relapse
timeFrame: From time of HCT, assessed up to 2 years post-HCT
measure: Incidence of non-relapse mortality
timeFrame: From time of HCT, assessed up to 2 years post-HCT
measure: Relapse-free survival
timeFrame: From time of HCT, assessed up to 2 years post-HCT
measure: Overall survival
timeFrame: From time of HCT, assessed up to 2 years post-HCT
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center,
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Stephanie J. Lee
role: PRINCIPAL_INVESTIGATOR
References: