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CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant

ConditionsAcute Lymphoblastic LeukemiaAcute Myeloid LeukemiaChronic Lymphocytic LeukemiaChronic Myeloid Leukemia, BCR-ABL1 PositiveHematopoietic and Lymphoid System NeoplasmHodgkin LymphomaMyelodysplastic SyndromeMyelofibrosisMyeloproliferative NeoplasmNon-Hodgkin Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorCity of Hope Medical Center

About this trial

This phase II clinical trial tests how well the cytomegalovirus-modified vaccinica Ankara (CMV-MVA) Triplex vaccine given to human leukocyte antigens (HLA) matched related stem cell donors works to prevent cytomegalovirus (CMV) infection in patients undergoing hematopoietic stem cell transplant. The CMV-MVA Triplex vaccine works by causing an immune response in the donors body to the CMV virus, creating immunity to it. The donor then passes that immunity on to the patient upon receiving the stem cell transplant. Giving the CMV-MVA triplex vaccine to donors may help prevent CMV infection of patients undergoing stem cell transplantation.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

DONORS: Documented informed consent of the participant and/or legally authorized representative

Assent, when appropriate, will be obtained per institutional guidelines

DONORS: Age: 18 and above

RECIPIENTS: Documented informed consent of the participant and/or legally authorized representative

Disqualifiers

DONORS: Any prior transplant to day 1 of protocol therapy

DONORS: Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy

DONORS: Receipt of any vaccine (licensed or investigational) within 30 days prior to and after of the study vaccine

DONORS: Unfit to undergo standard stem cell mobilization and apheresis e.g. abnormal blood counts, history of stroke, uncontrolled hypertension

Trial design

Design model

Parallel

Treatments tested in this trial

  • Allogeneic Hematopoietic Stem Cell Transplantation

    Procedure/Surgery

    Undergo HCT with donor peripheral blood stem cells

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Granulocyte Colony-Stimulating Factor

    Drug

    Undergo stem cell mobilization with G-CSF

  • Hematopoietic Cell Transplantation Conditioning Regimen

    Drug

    Receive pre transplant conditioning

  • Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

    Biological/Vaccine

    Given IM

  • Pheresis

    Procedure/Surgery

    Undergo apheresis

  • Placebo Administration

    Drug

    Given IM

  • Stem Cell Mobilization Therapy

    Drug

    Undergo stem cell mobilization with G-CSF

Treatment groups

216 Participants
are divided into 2 treatment groups
Group A: Arm I (Triplex vaccination)Experimental treatment 7 interventions
Group B: Arm II (Placebo)Placebo comparator 7 interventions

Trial outcomes

Primary outcomes

1

Time from transplantation to cytomegalovirus (CMV) disease or pre-emptive treatment following CMV reactivation (efficacy)

A stratified Cox regression analysis of time to CMV disease or positron emission tomography (PET) following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

Time frame
From hematopoietic stem cell transplantation (HCT) to day 180
2

Occurrence of non-relapse mortality (safety in HCT-recipients)

A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

Time frame
Up to day 100 post HCT
3

Incidence of severe acute graft versus host disease (aGHVD) (safety in HCT-recipients)

Severe aGHVD defined as grades 3-4. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

Time frame
Up to 100 days post HCT
4

Incidence of severe adverse events (AEs) (safety in HCT-recipients)

Probably or definitely related to the vaccination per Common Terminology Criteria for Adverse Events version 5.0. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

Time frame
Within 2 weeks from transplantation and up to 1 year post HCT

Secondary outcomes

1

Time-to viremia (CMV-related events)

The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.

Time frame
From transplantation to the date of two consecutive CMV quantitative polymerase chain reaction (qPCR) > 500 gc/mL/465 IU/mL or single event of CMV qPCR >1500 CMV gc/mL/1,395 IU/mL, assessed up to 1 year post HCT
2

Duration of viremia (CMV-related events)

The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.

Time frame
Up to 1 year post HCT
3

Incidence of late CMV viremia (CMV-related events)

The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.

Time frame
Between days 100-365 post HCT
4

Use of antiviral drugs (CMV-related events)

Triggered by clinically significant viremia or CMV disease.

Time frame
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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