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NCT Number: NCT04572815

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Hematologic and Lymphocytic Disorder Hematologic Diseases Hematopoietic and Lymphoid System Neoplasm Hemic and Lymphatic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

City of Hope Comprehensive Cancer Center,, Duarte, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

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

Treatment and study plan

Placebo Administration

Drug

Given IV and SC

Quality-of-Life Assessment

Other

Ancillary studies

Other names: Quality of Life Assessment

Questionnaire Administration

Other

Ancillary studies

Ustekinumab

Biological

Given IV and SC

Other names: 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

Primary outcomes

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

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

    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.

Secondary outcomes

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

    Time frame: At 100 days post-HCT

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

    Time frame: At 6 months post-HCT

  3. Acute GVHD organ staging, overall grading, and classification

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

    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.

  4. Incidence of overall chronic GVHD

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

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

  5. Incidence of moderate-severe chronic GVHD

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

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

  6. Incidence of post-HCT relapse

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

    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.

  7. Incidence of non-relapse mortality

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

    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.

  8. Relapse-free survival

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

    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.

  9. Overall survival

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

    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.

Sponsors and collaborators

Lead sponsor

Fred Hutchinson Cancer Center

Other

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2025
Study completion
2027
First posted
Oct 1, 2020
Registry last updated
Jan 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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