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

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Primary Purpose

Status

Suspended

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Placebo Administration

Quality-of-Life Assessment

Questionnaire Administration

Ustekinumab

About this trial

This is an interventional prevention trial for Hematologic and Lymphocytic Disorder

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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/m2.

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 or conditioning regimens that use less than 75mg/m2 of melphalan
Prior allogeneic transplant
Non-malignant blood disorders (e.g. sickle cell disease, aplastic anemia)
Positive screening test for tuberculosis

Sites / Locations

City of Hope Comprehensive Cancer Center,
H. Lee Moffitt Cancer Center & Research Institute
Roswell Park Cancer Institute
Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (ustekinumab)

Arm II (placebo)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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.

Incidence of overall chronic GVHD

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

Incidence of moderate-severe chronic GVHD

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

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.

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.

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.

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.

Full Information

NCT ID

NCT04572815

First Posted

September 28, 2020

Last Updated

October 12, 2023

Sponsor

Fred Hutchinson Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT04572815

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Suspended

Why Stopped

Safety Review

Study Start Date

May 14, 2021 (Actual)

Primary Completion Date

September 30, 2024 (Anticipated)

Study Completion Date

March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fred Hutchinson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic and Lymphocytic Disorder, Hematopoietic and Lymphoid System Neoplasm

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

116 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm I (ustekinumab)

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm II (placebo)

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo Administration

Intervention Description

Given IV and SC

Intervention Type

Other

Intervention Name(s)

Quality-of-Life Assessment

Other Intervention Name(s)

Quality of Life Assessment

Intervention Description

Ancillary studies

Intervention Type

Other

Intervention Name(s)

Questionnaire Administration

Intervention Description

Ancillary studies

Intervention Type

Biological

Intervention Name(s)

Ustekinumab

Other Intervention Name(s)

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

Intervention Description

Given IV and SC

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

At 6 months post-hematopoietic cell transplantation (HCT)

Secondary Outcome Measure Information:

Title

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

Time Frame

At 100 days post-HCT

Title

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

Time Frame

At 6 months post-HCT

Title

Acute GVHD organ staging, overall grading, and classification

Description

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.

Time Frame

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

Title

Incidence of overall chronic GVHD

Description

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

Time Frame