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Trials / Recruiting

RecruitingNCT06815003

Vedolizumab Plus Post-transplant Cyclophosphamide and Short Course Tacrolimus for the Prevention of Graft Versus Host Disease in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation After Reduced Intensity Conditioning

Phase-2 Study of Vedolizumab Plus Post-Transplant Cyclophosphamide and Short Course Tacrolimus for Graft-versus-Host Disease Prevention After Reduced Intensity Conditioning Peripheral Blood Stem Cell Allogeneic Hematopoietic Cell Transplantation

Status
Recruiting
Phase
Phase 2
Study type
Interventional
Enrollment
35 (estimated)
Sponsor
City of Hope Medical Center · Academic / Other
Sex
All
Age
18 Years – 80 Years
Healthy volunteers
Not accepted

Summary

This phase II trial studies how well vedolizumab plus post-transplant cyclophosphamide (PTCy) and short course tacrolimus work for the prevention of graft versus host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT) after reduced intensity conditioning. Allogeneic HCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a donor. Giving reduced conditioning chemotherapy before an allogeneic HCT helps kill cancer cells in the body and helps make room in the patient's bone marrow for new stem cells to grow using less than standard doses of chemotherapy. Sometimes, the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Vedolizumab is a monoclonal antibody, which is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). It may reduce inflammation. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill cancer cells. It may also lower the body's immune response. Tacrolimus suppresses the immune system by preventing the activation of certain types of immune cells. Giving vedolizumab plus PTCy and short course tacrolimus may be effective at preventing GVHD after allogeneic HCT.

Detailed description

PRIMARY OBJECTIVES: I. Assess the safety and describe the toxicity profile of adding vedolizumab at a fixed dose level to post-transplant cyclophosphamide (PTCy) -based graft-versus-host disease (GVHD) prophylaxis with tacrolimus after mobilized peripheral blood stem cell (PBSC) allogeneic hematopoietic cell transplantation (HCT) from a matched related/unrelated donor. (Safety lead-in segment) II. Assess the efficacy of vedolizumab in combination with PTCy by grade 2-4 acute GVHD-free survival by day+180 after allogeneic hematopoietic cell transplantation (HCT). (Expansion segment) SECONDARY OBJECTIVES: I. Continue safety assessment of vedolizumab + PTCy combination as GVHD prophylaxis in the expansion cohort. II. Estimate overall survival (OS), progression-free survival (PFS), cumulative incidences of relapse/disease progression, and non-relapse mortality (NRM) at 100 days, and 1-year post-transplant. III. Estimate rates of acute GVHD (day 100 and 180 post-HCT), lower gastrointestinal (GI) GVHD (day 100 and day 180 post-HCT), chronic GvHD (1-year post-HCT), infections (100 and 180 days and 1 year post HCT). IV. Estimate rates of complete remission, and neutrophil recovery. V. Evaluate and describe the cytokine release syndrome (CRS) post-HCT by assessing the incidence, frequency, and severity of CRS. EXPLORATORY OBJECTIVES: I. Donor cell engraftment will be assessed by count monitoring and short tandem repeat (STR) chimerism analysis on days +30 and day +100. II. Describe the kinetics of immune cell recovery. III. Evaluate patient's quality of life on day +100, 6 months and one-year post-HCT. IV. Describe the kinetics of GVHD biomarkers, and inflammatory cytokines for up to 100 days post-HCT. V. Obtain a preliminary estimate of gut microbiome diversity at baseline (preferably before fludarabine administration), and then on days +14, +30, +60, +100, and +180 after HCT. OUTLINE: Patients receive reduced intensity conditioning with fludarabine intravenously (IV) on days -7 to -3 and melphalan IV on day -2. Patients then undergo allogeneic HCT on day 0. Patients also receive vedolizumab IV over 30 minutes on days -1, +13, +41, +69, +97, +125, and +153, cyclophosphamide IV on days +3 and +4, and tacrolimus IV or orally (PO) on day +5 to day +95 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening, blood sample collection on study, and bone marrow biopsy throughout the study. After completion of study treatment, patients are followed up at 30 days after the last dose of vedolizumab, day +180 and at 1 year.

Conditions

Interventions

TypeNameDescription
PROCEDUREAllogeneic Hematopoietic Stem Cell TransplantationUndergo allogeneic HCT
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy
PROCEDUREComputed TomographyUndergo CT
DRUGCyclophosphamideGiven IV
PROCEDUREEchocardiographyUndergo ECHO
DRUGFludarabineGiven IV
DRUGMelphalanGiven IV
PROCEDUREMultigated Acquisition ScanUndergo MUGA
OTHERQuestionnaire AdministrationAncillary studies
DRUGTacrolimusGiven IV or PO
BIOLOGICALVedolizumabGiven IV

Timeline

Start date
2025-04-18
Primary completion
2028-10-15
Completion
2028-10-15
First posted
2025-02-07
Last updated
2025-06-27

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT06815003. Inclusion in this directory is not an endorsement.