Ustekinumab for the Prevention of Acute Graft Versus Host Disease After Unrelated Donor Hematopoietic Cell Transplant
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 |
---|---|---|
|
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
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:
Other: Questionnaire Administration
Ancillary studies
Biological: Ustekinumab
Given IV and SC
Other Names:
|
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:
Other: Questionnaire Administration
Ancillary studies
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
Inclusion Criteria:
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Signed informed consent
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Hematologic malignancy or disorder requiring allogeneic hematopoietic cell transplantation
-
Left ventricular ejection fraction (LVEF) >= 45%
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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
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Transaminases (aspartate aminotransferase [AST], aspartate aminotransferase [ALT]) < 3 times upper limit of normal values
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Creatinine clearance >= 50 cc/min
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Karnofsky performance status score >= 60%
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HCT donor is at least 8/8 (matched at human leukocyte antigen [HLA]-A, -B, -C, -DRB1) matched with the recipient
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PBSC (peripheral blood mobilized stem cells) as graft source
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Fully myeloablative, reduced-toxicity ablative, or reduced-intensity conditioning regimens
Exclusion Criteria:
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Active infection not controlled with appropriate antimicrobial therapy
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Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
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Anti-thymocyte globulin (ATG) as part of the conditioning regimen or GVHD prophylaxis
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Pregnant or nursing women
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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
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Non-myeloablative conditioning regimens
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Prior allogeneic transplant
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Non-malignant blood disorders (e.g. sickle cell disease, aplastic anemia)
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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.- RG1005588
- NCI-2020-02617
- 10421
- R01FD006836