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

NCT07020533 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 24168NCI-2025-03633P30CA033572
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia; Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphatic System Neoplasm; Hodgkin Lymphoma; Lymphoblastic Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Acute Lymphoblastic Leukemia; Accelerated Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

  From day 0 to day 100 post-HCT

Secondary Outcomes (15)

• Unacceptable toxicity

  Up to 28 days after the last Triplex vaccination

• Serious adverse events (SAE)

  Up to 365 days after Triplex vaccination

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

  Up to day 180 post-HCT

• Non-relapse mortality (NRM)

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

• CMV events

  Up to day 180 post-HCT

Study Arms (4)

Donors (CMV-MVA Triplex vaccine, G-CSF)

EXPERIMENTAL

Participants receive CMV-MVA Triplex vaccine IM once and then receive G-CSF on study. Additionally, participants undergo apheresis on study as well as blood sample collection on study and may optionally undergo blood sample collection during follow up.

Procedure: Biospecimen Collection; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine; Procedure: Pheresis; Biological: Recombinant Granulocyte Colony-Stimulating Factor

Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir)

EXPERIMENTAL

Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100 and receive letermovir IV over 1 hour or PO QD on days 7 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Procedure: Haploidentical Hematopoietic Cell Transplantation; Drug: Letermovir; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine; Procedure: Myeloablative Conditioning

Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir)

EXPERIMENTAL

Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100 and receive letermovir IV over 1 hour or PO QD on days 7 to 28. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Procedure: Haploidentical Hematopoietic Cell Transplantation; Drug: Letermovir; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine; Procedure: Myeloablative Conditioning

Recipients, Modality 3 (CMV-MVA Triplex vaccine)

EXPERIMENTAL

Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Procedure: Haploidentical Hematopoietic Cell Transplantation; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine; Procedure: Myeloablative Conditioning

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Donors (CMV-MVA Triplex vaccine, G-CSF); Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 3 (CMV-MVA Triplex vaccine)

Electronic Health Record Review OTHER

Ancillary studies

Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 3 (CMV-MVA Triplex vaccine)

Letermovir DRUG

Given IV or PO

Also known as: 2-((4S)-8-Fluoro-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)-4H-quinazolin-4-yl)acetic Acid, AIC246, MK-8228, Prevymis

Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir)

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given IM

Also known as: CMV-MVA Triplex Vaccine, Multi-antigen CMV-Modified Vaccinia Ankara Vaccine

Donors (CMV-MVA Triplex vaccine, G-CSF); Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 3 (CMV-MVA Triplex vaccine)

Myeloablative Conditioning PROCEDURE

Receive myeloablative conditioning

Also known as: Myeloablation, Myeloablative, Myeloablative Cytoreduction

Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 3 (CMV-MVA Triplex vaccine)

Pheresis PROCEDURE

Undergo apheresis

Also known as: Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis, Hemapheresis

Donors (CMV-MVA Triplex vaccine, G-CSF)

Recombinant Granulocyte Colony-Stimulating Factor BIOLOGICAL

Given G-CSF

Also known as: Recombinant Colony-Stimulating Factor 3, rhG-CSF

Donors (CMV-MVA Triplex vaccine, G-CSF)

Haploidentical Hematopoietic Cell Transplantation PROCEDURE

Undergo HCT

Also known as: Haploidentical Stem Cell Transplantation, HLA-Haploidentical Hematopoietic Cell Transplantation, Stem Cell Transplantation, Haploidentical

Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir); Recipients, Modality 3 (CMV-MVA Triplex vaccine)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• DONORS: Age: 18 - 75.
• DONORS: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• DONORS: Agreement by females and males of childbearing potential\* to use an effective method of birth control (hormonal or barrier method) or abstain from heterosexual activity prior to study entry and for up to 90 days post-vaccination.
• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only).
• RECIPIENTS: Documented informed consent of the participant and/or legally authorized representative. 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.
• RECIPIENTS: Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT.
• RECIPIENTS: Age: 18 - 75.
• RECIPIENTS: Planned peripheral blood stem cell (PBSC) or bone marrow (BM) HCT for the treatment of the following hematologic malignancies:

You may not qualify if:

• 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.
• DONORS: Sickling hemoglobinopathy including hemoglobin (Hb)SS, HbAS, HbSC.
• DONORS: Donors with impaired cardiac function are excluded. Electrocardiography is routine for potential HCT donors over 60 years old and those with a history of heart disease. Subjects in whom cardiac function is abnormal (excluding 1st degree branch block, sinus bradycardia, sinus tachycardia or non-specific T wave changes) are ineligible for Triplex vaccination.
• DONORS: Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the donation procedure unlikely and making informed consent impossible.
• DONORS: Females only: Pregnant or breastfeeding.
• DONORS: 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.
• DONORS: 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).
• RECIPIENTS: Any prior investigational CMV vaccine.
• RECIPIENTS: Experimental anti-CMV chemotherapy in the last 6 months.
• RECIPIENTS: Live attenuated vaccines (planned medications from the time of HCT to day 70 post-HCT).
• RECIPIENTS: Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections) (planned medications from the time of HCT to day 70 post-HCT).
• RECIPIENTS: Allergy treatment with antigen injections (planned medications from the time of HCT to day 70 post-HCT).

Sponsors & Collaborators

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

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Northside Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Chronic-Phase; Hodgkin Disease; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin

Interventions

Specimen Handling; Stem Cell Transplantation; letermovir; Bone Marrow Purging; Blood Component Removal; pegylated granulocyte colony-stimulating factor

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Lymphoma

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Ryotaro Nakamura

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 13, 2025
• Study Start (Estimated): May 8, 2026
• Primary Completion (Estimated): February 14, 2030
• Study Completion (Estimated): February 14, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (3)