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

Randomized, Placebo-Controlled, Phase II Trial Examining Ustekinumab for Prevention of Graft Vs. Host Disease After Allogeneic Hematopoietic Cell Transplantation

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hematopoietic and Lymphoid System Neoplasm; Hematologic and Lymphocytic Disorder
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Ustekinumab; Drug: Placebo Administration

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center,
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (ustekinumab); Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab IV. Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Biological: Ustekinumab; Given IV and SC; Other Names: CNTO1275; Stelara; CNTO 1275; Immunoglobulin G1, Anti-(Human Interleukin-12 Subunit beta (IL-12B, CLMF p40, NKSF2)) (Human Monoclonal CNTO 1275 gamma1-chain), Disulfide with Human Monoclonal CNTO 1275 kappa-chain, Dimer
Placebo Comparator: Arm II (placebo); 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 of grade III-IV acute GVHD, disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Placebo Administration; Given IV and SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 6 months post-hematopoietic cell transplantation (HCT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of grade II-IV and grade III-IV acute GVHD		At 100 days post-HCT
Cumulative incidence of grade II-IV and grade III-IV acute GVHD		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.	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.	From time of HCT, assessed up to 2 years post-HCT
Incidence of moderate-severe chronic GVHD	Will be assessed at serial study visits, and scored according to National Institutes of Health Consensus criteria.	From time of HCT, assessed up to 2 years post-HCT
Incidence of post-HCT relapse	Relapse is defined as hematologic relapse or any unplanned intervention (including withdrawal of immune suppression) to prevent progression of disease in patients with evidence (molecular, cytogenetic, flow cytometric, radiographic) of malignant disease. Will be compared using either the log-rank test (if no competing risks) or Gray's test (if competing risks are present). For time-to-event endpoints with competing risks, the log-rank test will also be used for exploratory purposes.	From time of HCT, assessed up to 2 years post-HCT
Incidence of non-relapse mortality	Non-relapse mortality indicates death with primary malignancy that served as HCT indication in remission. Will be compared using either the log-rank test (if no competing risks) or Gray's test (if competing risks are present). For time-to-event endpoints with competing risks, the log-rank test will also be used for exploratory purposes.	From time of HCT, assessed up to 2 years post-HCT
Relapse-free survival	Relapse is defined as hematologic relapse or any unplanned intervention (including withdrawal of immune suppression) to prevent progression of disease in patients with evidence (molecular, cytogenetic, flow cytometric, radiographic) of malignant disease. Will be compared using either the log-rank test (if no competing risks) or Gray's test (if competing risks are present). For time-to-event endpoints with competing risks, the log-rank test will also be used for exploratory purposes.	From time of HCT, assessed up to 2 years post-HCT
Overall survival	Will be compared using either the log-rank test (if no competing risks) or Gray's test (if competing risks are present). For time-to-event endpoints with competing risks, the log-rank test will also be used for exploratory purposes.	From time of HCT, assessed up to 2 years post-HCT

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: Stephanie J. Lee, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): October 27, 2025
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hemic and Lymphatic Diseases; Hematologic Diseases; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Intercellular Signaling Peptides and Proteins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Cytokines; Interleukins; Interleukin-12; Interleukin-23; Ustekinumab; Immunoglobulin G; Disulfides; Interleukin-12 Subunit p40
• Other Study ID Numbers: RG1005588; NCI-2020-02617 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 10421 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); R01FD006836 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No