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

NCT ID: NCT04572815

Last Updated: 2026-01-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-14
• Study Completion Date: 2027-06-30

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.

Conditions

Hematologic and Lymphocytic Disorder; Hematopoietic and Lymphoid System Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Ustekinumab

Intervention Type: BIOLOGICAL

Given IV and SC

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.

Group Type: PLACEBO_COMPARATOR

Placebo Administration

Intervention Type: DRUG

Given IV and SC

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Placebo Administration

Given IV and SC

Intervention Type: DRUG

Quality-of-Life Assessment

Ancillary studies

Intervention Type: OTHER

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Ustekinumab

Given IV and SC

Intervention Type: BIOLOGICAL

Other Intervention Names

Quality of Life Assessment; 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie J. Lee

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

City of Hope Comprehensive Cancer Center,

Duarte, California, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2020-02617

Identifier Type: REGISTRY

Identifier Source: secondary_id

10421

Identifier Type: OTHER

Identifier Source: secondary_id

R01FD006836

Identifier Type: FDA

Identifier Source: secondary_id

View Link

RG1005588

Identifier Type: -

Identifier Source: org_study_id