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

NCT06815003 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24473NCI-2025-00341P30CA033572
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Graft Versus Host Disease; Myelodysplastic Syndrome; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (5)

• Incidence of primary engraftment failure (Safety lead-in segment)

  Will be assessed as an unacceptable toxicity (UT). Will include type, severity, duration, and attribution/association with the study regimen and dose limiting toxicity (DLT) occurrence. Tables will be constructed to summarize the observed incidence, severity, and type of toxicity, including, but not limiting infections, other adverse events of special interest, and severe adverse events. Point estimates and corresponding exact 90% confidence intervals (CIs) will be provided for each measure of toxicity/adverse events.

  From starting the first dose of vedolizumab to the first observation of event, day +30, whichever comes first

• Incidence of severe infusion reaction (Safety lead-in segment)

  Will be assessed as a UT. Will assess severe infusion reactions, grade 4 per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0, after receiving the 1st or 2nd dose of vedolizumab. Will include type, severity, duration, and attribution/association with the study regimen and DLT occurrence. Tables will be constructed to summarize the observed incidence, severity, and type of toxicity, including, but not limiting infections, other adverse events of special interest, and severe adverse events. Point estimates and corresponding exact 90% CIs will be provided for each measure of toxicity/adverse events.

  From starting the first dose of vedolizumab to the first observation of event, day +30, whichever comes first

• Incidence of grade 4-5 adverse events (Safety lead-in segment)

  Will be assessed as a UT. Will assess grade 4-5 adverse events based on CTCAE v 5.0 probably or definitely attributable to vedolizumab. Will include type, severity, duration, and attribution/association with the study regimen and DLT occurrence. Tables will be constructed to summarize the observed incidence, severity, and type of toxicity, including, but not limiting infections, other adverse events of special interest, and severe adverse events. Point estimates and corresponding exact 90% CIs will be provided for each measure of toxicity/adverse events.

  From starting the first dose of vedolizumab to the first observation of event, day +30, whichever comes first

• Non-relapse mortality (NRM) (Safety lead-in segment)

  Will be assessed as a UT. Defined as death occurring in a patient from causes other than relapse or progression. Deaths from relapse/progression will be considered a competing risk. NRM will be censored at last follow-up if patients are alive and remain disease free. Will be analyzed using the Kaplan-Meier curves.

  From date of stem cell infusion until non-disease related death, assessed up to 1 year post-hematopoietic cell transplant (HCT)

• Incidence of grade 2-4 acute graft versus host disease (GVHD)-free survival

  Will be assessed among patients in the safety lead-in and dose expansion segments. Will be estimated using Kaplan-Meier curve.

  From start of HCT to first occurrence of grade 2-4 acute GVHD followed until day +180 or death from any cause, whichever occurs first, assessed up to 1 year post-HCT

Secondary Outcomes (13)

• Incidence of adverse events (Expansion segment)

  From the start of first dose of vedolizumab to day +130 post-HCT

• Incidence of grade 3-5 adverse events at least probably attributable to vedolizumab, but not UT

  Up to day +180 post-HCT

• Overall survival

  From the day of stem cell infusion until death, assessed up to 1 year post-HCT

• Progression free survival

  From the date of stem cell infusion to the date of death, disease relapse/progression, whichever occurs first, assessed up to 1 year post-HCT

• Relapse/progression rate

  From day of stem cell infusion (day 0) to 1 year post-HCT

Study Arms (1)

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

EXPERIMENTAL

Patients receive reduced intensity conditioning with fludarabine 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 PO on day +5 to day +95 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT and ECHO or MUGA during screening, blood sample collection on study, and bone marrow biopsy throughout the study.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Drug: Melphalan; Procedure: Multigated Acquisition Scan; Other: Questionnaire Administration; Drug: Tacrolimus; Biological: Vedolizumab

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic HCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalan for Injection-Hepatic Delivery System, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Questionnaire Administration OTHER

Ancillary studies

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, FK-506, FK506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Vedolizumab BIOLOGICAL

Given IV

Also known as: Entyvio, Immunoglobulin G1, anti-(human integrin LPAM-1 (lymphocyte Peyer's patch adhesion molecule 1)) (human-Mus musculus heavy chain), disulfide with human-Mus musculus kappa-chain, dimer, LDP 02, LDP-02, LDP02, MLN0002, MLN02

Prevention (vedolizumab, cyclophosphamide, tacrolimus)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 and ≤ 80 years old
• Note: Patients \> 70 years of age must have Karnofsky performance status ≥ 80 and hematopoietic cell transplantation-comorbidity index (HCT-CI) ≤ 2
• Karnofsky performance status ≥ 70%
• Patients with the following diagnosis, eligible to undergo allogeneic HCT from an 8/8 match related/unrelated donor (A, B, C, DR by high resolution typing)
• Acute Leukemias (acute myeloid leukemia \[AML\] or acute lymphoblastic leukemia \[ALL\]) in complete remission with bone marrow (BM) blast of \< 5%
• Myelodysplastic syndrome (blast \< 10%)
• Myeloproliferative neoplasm (MPN) other than myelofibrosis (MF) needing HCT
• Chronic myelomonocytic leukemia (CMML)
• Hemoglobin ≥ 9g/dL (within 30 days prior to day 1 of protocol therapy)
• NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
• Total bilirubin ≤ 2.0 mg/dL (unless has Gilbert's disease) AND serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) \< 5 times the upper limit of normal (ULN) (within 30 days prior to day 1 of protocol therapy)

You may not qualify if:

• Prior allogeneic HCT
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy
• Other investigational drugs for GVHD prophylaxis
• Herbal medications
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Clinically significant uncontrolled illness
• Active infection not responding to antibiotics
• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Females only: Pregnant or breastfeeding
• Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Graft vs Host Disease; Myelodysplastic Syndromes; Myeloproliferative Disorders

Interventions

Stem Cell Transplantation; Specimen Handling; Biopsy; Cyclophosphamide; fludarabine; Melphalan; Tacrolimus; vedolizumab; Immunoglobulin G; Disulfides; LDP-02

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds

Study Officials

• Monzr M. Al Malki

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2025
• First Posted: February 7, 2025
• Study Start: April 18, 2025
• Primary Completion (Estimated): October 15, 2028
• Study Completion (Estimated): October 15, 2028
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

US (1)