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

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT04572815
Collaborator
(none)
116
4
2
58.5
29
0.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Placebo Administration
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Biological: Ustekinumab
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
116 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Randomized, Placebo-Controlled, Phase II Trial Examining Ustekinumab for Prevention of Graft Vs. Host Disease After Allogeneic Hematopoietic Cell Transplantation
Actual Study Start Date :
May 14, 2021
Anticipated Primary Completion Date :
Sep 30, 2024
Anticipated Study Completion Date :
Mar 31, 2026

Arms and Interventions

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:
  • 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
  • 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.

    Drug: Placebo Administration
    Given IV and SC

    Other: Quality-of-Life Assessment
    Ancillary studies
    Other Names:
  • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

    Outcome Measures

    Primary Outcome Measures

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

    1. Cumulative incidence of grade II-IV and grade III-IV acute GVHD [At 100 days post-HCT]

    2. Cumulative incidence of grade II-IV and grade III-IV acute GVHD [At 6 months post-HCT]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Signed informed consent

    • Hematologic malignancy or disorder requiring allogeneic hematopoietic cell transplantation

    • Left ventricular ejection fraction (LVEF) >= 45%

    • 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

    • Karnofsky performance status score >= 60%

    • HCT donor is at least 8/8 (matched at human leukocyte antigen [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

    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 3 months after last dose of study drug

    • Non-myeloablative conditioning regimens

    • Prior allogeneic transplant

    • Non-malignant blood disorders (e.g. sickle cell disease, aplastic anemia)

    • Positive screening test for tuberculosis

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center, Duarte California United States 91010
    2 H. Lee Moffitt Cancer Center & Research Institute Tampa Florida United States 33612
    3 Roswell Park Cancer Institute Buffalo New York United States 14263
    4 Fred Hutch/University of Washington Cancer Consortium Seattle Washington United States 98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT04572815
    Other Study ID Numbers:
    • RG1005588
    • NCI-2020-02617
    • 10421
    • R01FD006836
    First Posted:
    Oct 1, 2020
    Last Update Posted:
    Mar 17, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 17, 2022