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

NCT04572815 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: RG1005588NCI-2020-0261710421R01FD006836
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 4

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.

Conditions

Hematologic and Lymphocytic Disorder; Hematopoietic and Lymphoid System Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

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

• Incidence of overall chronic GVHD

  From time of HCT, assessed up to 2 years post-HCT

• Incidence of moderate-severe chronic GVHD

  From time of HCT, assessed up to 2 years post-HCT

Study Arms (2)

Arm I (ustekinumab)

EXPERIMENTAL

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; Other: Questionnaire Administration; Biological: Ustekinumab

Arm II (placebo)

PLACEBO COMPARATOR

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.

Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Placebo Administration DRUG

Given IV and SC

Arm II (placebo)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (ustekinumab); Arm II (placebo)

Questionnaire Administration OTHER

Ancillary studies

Arm I (ustekinumab); Arm II (placebo)

Ustekinumab BIOLOGICAL

Given IV and SC

Also known as: CNTO 1275, CNTO1275, 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, Stelara

Arm I (ustekinumab)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 - 70
• Signed informed consent.
• Hematologic malignancy or disorder requiring allogeneic hematopoietic cell transplantation
• Adequate vital organ function:
• Left ventricular ejection fraction (LVEF) ≥ 50%
• 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
• Transaminases (aspartate aminotransferase \[AST\], aspartate aminotransferase \[ALT\]) \< 3 times upper limit of normal values
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (4)

City of Hope Comprehensive Cancer Center,

Duarte, California, 91010, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Hematologic Diseases

Interventions

Ustekinumab; Immunoglobulin G; Interleukin-12 Subunit p40; Disulfides

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Interleukin-12; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Interleukin-23; Biological Factors; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Stephanie J. Lee

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 1, 2020
• Study Start: May 14, 2021
• Primary Completion: October 27, 2025
• Study Completion (Estimated): June 30, 2027
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)