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A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant

ConditionsAccelerated Phase Chronic Myeloid Leukemia, BCR-ABL1 PositiveAcute Lymphoblastic LeukemiaAcute Myeloid LeukemiaChronic Lymphocytic LeukemiaChronic Phase Chronic Myeloid Leukemia, BCR-ABL1 PositiveHematopoietic and Lymphatic System NeoplasmHodgkin LymphomaLymphoblastic LymphomaMyelodysplastic SyndromeMyelofibrosisMyeloproliferative NeoplasmNon-Hodgkin Lymphoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorCity of Hope Medical Center

About this trial

This phase Ib trial tests the safety, side effects, and how well cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) Triplex vaccine works in enhancing CMV-specific immunity and preventing CMV viremia in patients undergoing haploidentical hematopoietic stem cell transplant. Haploidentical stem cell transplantation (haploHCT) has advanced to become the predominant procedure for patients lacking a matched donor. Compared to matched related donor transplants, the rate of significant CMV infection is higher in patients undergoing a haploHCT. Significant CMV infection is associated with an increased risk of complications and death. Vaccination is the main preventative approach to limit complications and death in immunocompromised patients at high risk of post-stem cell transplant infections. CMV-MVA Triplex vaccine, is a CMV vaccine based on the attenuated poxvirus, modified vaccinia Ankara (MVA), developed to enhance CMV-specific immunity in both healthy stem cell transplant donors and stem cell transplant patients to prevent significant CMV infection post-stem cell transplant. Giving CMV-MVA triplex vaccine may be safe, tolerable and/or effective in enhancing cytomegalovirus (CMV)-specific immunity and preventing CMV viremia in patients undergoing a haploHCT.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

DONORS: Documented informed consent of the participant. This can be done in person or informed consent can be obtained remotely.

Remote consent, when appropriate, will be obtained per institutional guidelines.

Assent, when appropriate, will be obtained per institutional guidelines.

Adult subjects who require a legally authorized representative (LAR) will not be permitted to be enrolled under this protocol.

Disqualifiers

DONORS: Any prior transplant to day 1 of protocol therapy (day 1 defined as the day after donors receive the Triplex vaccine).

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 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

Sequential

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Electronic Health Record Review

    Other intervention

    Ancillary studies

  • Haploidentical Hematopoietic Cell Transplantation

    Procedure/Surgery

    Undergo HCT

  • Letermovir

    Drug

    Given IV or PO

  • Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

    Biological/Vaccine

    Given IM

  • Myeloablative Conditioning

    Procedure/Surgery

    Receive myeloablative conditioning

  • Pheresis

    Procedure/Surgery

    Undergo apheresis

  • Recombinant Granulocyte Colony-Stimulating Factor

    Biological/Vaccine

    Given G-CSF

Treatment groups

46 Participants
are divided into 4 treatment groups
Group A: Donors (CMV-MVA Triplex vaccine, G-CSF)Experimental treatment 4 interventions
Group B: Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir)Experimental treatment 6 interventions
Group C: Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir)Experimental treatment 6 interventions
Group D: Recipients, Modality 3 (CMV-MVA Triplex vaccine)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Cytomegalovirus (CMV) reactivation prompting antiviral therapy

Will evaluate for CMV reactivation prompting antiviral therapy. Will be evaluated in patients that received a stem cell infusion from a Triplex vaccinated haploidentical donor and received the first Triplex vaccination.

Time frame
From day 0 to day 100 post-hematopoietic stem cell transplant (HCT)
2

CMV disease

Will evaluate for CMV disease based on histology. Will be evaluated in patients that received a stem cell infusion from a Triplex vaccinated haploidentical donor and received the first Triplex vaccination.

Time frame
From day 0 to day 100 post-HCT

Secondary outcomes

1

Unacceptable toxicity

Will evaluate for grade 3-4 adverse events based on Common Terminology Criteria for Adverse Events version 5.0 probably or definitely attributable to vaccination in both recipients and donors. Descriptive statistics will be used to summarize recipients and donor adverse events.

Time frame
Up to 28 days after the last Triplex vaccination
2

Serious adverse events (SAE)

Will evaluate for SAEs that are at least possibly related to Triplex vaccination in donors.

Time frame
Up to 365 days after Triplex vaccination
3

Incidence of acute graft-versus-host disease (GVHD)

Will evaluate for grade 3-4 acute GVHD. Documented/biopsy proven acute GVHD is graded according to Mount Sinai Acute GVHD International Consortium (MAGIC) grading. Cumulative incidence curves will be used to estimate acute GVHD.

Time frame
Up to day 180 post-HCT
4

Non-relapse mortality (NRM)

Will evaluate occurrence of NRM. Cumulative incidence curves will be used to estimate NRM.

Time frame
From HCT to death from other causes than disease relapse or progression, assessed up to day 180 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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