Hematologic and Lymphocytic Disorder, Hematopoietic and Lymphoid System Neoplasm
Conditions
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. Funding Source- FDA OOPD.
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.
Interventions
DRUGPlacebo Administration
Given IV and SC
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
BIOLOGICALUstekinumab
Given IV and SC
Sponsors
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Incidence of moderate-severe chronic GVHD | 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. |
| Cumulative incidence of grade II-IV and grade III-IV acute GVHD | At 100 days post-HCT | — |
| 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. |
| 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. |
Countries
United States
Outcome results
None listed