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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

ConditionsAcute Lymphoblastic LeukemiaAcute Myeloid LeukemiaChronic Myelomonocytic LeukemiaGraft Versus Host DiseaseMyelodysplastic SyndromeMyeloproliferative Neoplasm
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorCity of Hope Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Prior allogeneic HCT

Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy

Note: Conditioning regimen within 14 days prior to day 1 of protocol therapy is not considered as an exclusion criterion. Patients on maintenance chemotherapy with agents listed are not excluded

Other investigational drugs for GVHD prophylaxis

Trial design

Design model

Single group

Treatments tested in this trial

  • Allogeneic Hematopoietic Stem Cell Transplantation

    Procedure/Surgery

    Undergo allogeneic HCT

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Cyclophosphamide

    Drug

    Given IV

  • Echocardiography

    Procedure/Surgery

    Undergo ECHO

  • Fludarabine

    Drug

    Given IV

  • Melphalan

    Drug

    Given IV

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Tacrolimus

    Drug

    Given IV or PO

  • Vedolizumab

    Biological/Vaccine

    Given IV

Treatment groups

35 Participants
are divided into 1 treatment group
Group A: Prevention (vedolizumab, cyclophosphamide, tacrolimus)Experimental treatment 12 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
From starting the first dose of vedolizumab to the first observation of event, day +30, whichever comes first
2

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.

Time frame
From starting the first dose of vedolizumab to the first observation of event, day +30, whichever comes first
3

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.

Time frame
From starting the first dose of vedolizumab to the first observation of event, day +30, whichever comes first
4

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.

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

Secondary outcomes

1

Incidence of adverse events (Expansion segment)

Will be assessed using CTCAE v5.0. Will assess grade 4-5 adverse events probably or definitely attributable to study regiment by day +30 post-HCT and grade 3-5 adverse events probably or definitely attributed to study regimen by day +130 that are not UT. 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.

Time frame
From the start of first dose of vedolizumab to day +130 post-HCT
2

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

Will be assessed using CTCAE v5.0. 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.

Time frame
Up to day +180 post-HCT
3

Overall survival

Patients are considered a failure for this endpoint if they die, regardless of cause. Will be censored at last follow-up if the last known status is alive. Will be analyzed using the Kaplan-Meier curves.

Time frame
From the day of stem cell infusion until death, assessed up to 1 year post-HCT
4

Progression free survival

Patients are considered a failure for this endpoint if they die (regardless of cause) or experience disease progression or relapse. Will be censored at last follow-up if patients are alive and remain disease free. Will be analyzed using the Kaplan-Meier curves.

Time frame
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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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