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

Hematopoietic and Lymphoid System Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04572815
• Other study ID #: RG1005588
• Secondary ID: NCI-2020-0261710
• Status: Recruiting
• Phase: Phase 2
• Start date: May 14, 2021
• Est. completion date: September 30, 2027

Study information

• Verified date: June 2024
• Source: Fred Hutchinson Cancer Center
• Contact: Stephanie J. Lee
• Phone: 206-667-6190
• Email: sjlee[@]fredhutch.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: September 30, 2027
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematologic and Lymphocytic Disorder
• Hematologic Diseases
• Hematopoietic and Lymphoid System Neoplasm

Intervention

Drug:
• Placebo Administration
Given IV and SC

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

Biological:
• Ustekinumab
Given IV and SC

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	City of Hope Comprehensive Cancer Center,	Duarte	California
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cumulative incidence of grade II-IV and grade III-IV acute GVHD		At 100 days post-HCT
Secondary	Cumulative incidence of grade II-IV and grade III-IV acute GVHD		At 6 months post-HCT
Secondary	Acute GVHD organ staging, overall grading, and classification	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.	From time of HCT, assessed up to day 100 post-HCT
Secondary	Incidence of overall chronic GVHD	Will be assessed at serial study visits, and scored according to National Institutes of Health Consensus criteria.	From time of HCT, assessed up to 2 years post-HCT
Secondary	Incidence of moderate-severe chronic GVHD	Will be assessed at serial study visits, and scored according to National Institutes of Health Consensus criteria.	From time of HCT, assessed up to 2 years post-HCT
Secondary	Incidence of post-HCT relapse	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.	From time of HCT, assessed up to 2 years post-HCT
Secondary	Incidence of non-relapse mortality	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.	From time of HCT, assessed up to 2 years post-HCT
Secondary	Relapse-free survival	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.	From time of HCT, assessed up to 2 years post-HCT
Secondary	Overall survival	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.	From time of HCT, assessed up to 2 years post-HCT