Recruiting
Phase 2

CMV-MVA Triplex Vaccination

Sponsor:

City of Hope Medical Center

Code:

NCT06059391

Conditions

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia, BCR-ABL1 Positive

Hematopoietic and Lymphoid System Neoplasm

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation

Biospecimen Collection

Granulocyte Colony-Stimulating Factor

Hematopoietic Cell Transplantation Conditioning Regimen

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Study Details

Brief summary:

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.

Conditions

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia, BCR-ABL1 Positive

Hematopoietic and Lymphoid System Neoplasm

Study ID

NCT06059391

Start date

Jul 12, 2024

Status verified date

Mar, 2026

Completion date

Jan 1, 2029

Anticipated

Primary completion date

Jan 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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

  • Assent, when appropriate, will be obtained per institutional guidelines
  • 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 and above
  • RECIPIENTS: Karnofsky performance score ≥ 70 or ECOG ≤ 2
  • RECIPIENTS: Planned HCT for the treatment of the following hematologic malignancies: lymphoma (Hodgkin and Non-Hodgkin), myelodysplastic syndrome, acute lymphoblastic leukemia in first or second remission, acute myeloid leukemia in first or second remission, chronic myelogenous leukemia (in first chronic or accelerated phase, or in second chronic phase), chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis. Patients with multiple myeloma are excluded
  • RECIPIENTS: CMV seropositive
  • RECIPIENTS: Planned related HCT with 8/8 (A, B, C, DRB1) high resolution human leukocyte antigen (HLA) donor allele matching
  • RECIPIENTS: Conditioning and immunosuppressive regimens according to institutional guidelines are permitted. Patients may receive myeloablative, reduced intensity, or nonmyeloablative conditioning
  • RECIPIENTS: Total bilirubin ≤ 2 X upper limit of normal (ULN) (unless has Gilbert's disease)
  • RECIPIENTS: Aspartate aminotransferase (AST) ≤ 2.5 x ULN
  • RECIPIENTS: Alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • RECIPIENTS: Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  • RECIPIENTS: Left ventricular ejection fraction (LVEF) ≥ 50% Note: To be performed within 45 days prior to day 1 of protocol therapy
  • RECIPIENTS: If able to perform pulmonary function tests: forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) ≥ 50% of predicted (corrected for hemoglobin). If unable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room air Note: To be performed within 45 days prior to day 1 of protocol therapy
  • RECIPIENTS: Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV)\*, active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\])

  • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
  • RECIPIENTS: Meets other institutional and federal requirements for infectious disease titer requirements Note: Infectious disease testing to be performed within 45 days prior to day 1 of protocol therapy
  • RECIPIENTS: 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
  • RECIPIENTS: 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-HCT.

  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

  • 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
  • DONORS: Sickling hemoglobinopathy including hemoglobin S (HbSS), sickle cell trait (HbAS), hemoglobin sickle C disease (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: Positive for HIV, active hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II)
  • 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: Prior allogeneic (allo) transplant for any condition
  • RECIPIENTS: Live attenuated vaccines
  • RECIPIENTS: Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections)
  • RECIPIENTS: Allergy treatment with antigens injections
  • RECIPIENTS: Alemtuzumab or any equivalent in vivo T-cell depleting agent
  • RECIPIENTS: Antiviral medications with known therapeutic effects on CMV such as valganciclovir/ganciclovir (GCV/VAL), foscarnet (FOS), cidofovir, brincidofovir (CMX-001), maribavir. Acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)
  • RECIPIENTS: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment
  • RECIPIENTS: Other investigational product - concurrent enrollment in other clinical trials using any investigational new drug (IND) drugs with unknown effects on CMV or with unknown toxicity profiles is prohibited
  • RECIPIENTS: Other medications that might interfere with the evaluation of the investigational product
  • RECIPIENTS: Diagnosis with autoimmune disease
  • RECIPIENTS: Females only: Pregnant women and women who are lactating. The risks of Triplex to pregnant women are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother. Breastfeeding should be discontinued if the mother is enrolled on this study
  • RECIPIENTS: 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
  • RECIPIENTS: 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)

Study Design

Enrollment

216 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (Triplex vaccination)

DONORS: Donors receive Triplex vaccine IM on day 0 and then undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study.

RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.

placebo comparator: Arm II (Placebo)

DONORS: Donors receive placebo IM on day 0 and undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study.

RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo HCT with donor peripheral blood stem cells

Biospecimen Collection

Undergo blood sample collection

Granulocyte Colony-Stimulating Factor

Undergo stem cell mobilization with G-CSF

Hematopoietic Cell Transplantation Conditioning Regimen

Receive pre transplant conditioning

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Given IM

Pheresis

Undergo apheresis

Placebo Administration

Given IM

Stem Cell Mobilization Therapy

Undergo stem cell mobilization with G-CSF

Primary outcome measure

  • Time from transplantation to cytomegalovirus (CMV) disease or pre-emptive treatment following CMV reactivation (efficacy) [ Time Frame: From hematopoietic stem cell transplantation (HCT) to day 180 ]
  • Occurrence of non-relapse mortality (safety in HCT-recipients) [ Time Frame: Up to day 100 post HCT ]
  • Incidence of severe acute graft versus host disease (aGHVD) (safety in HCT-recipients) [ Time Frame: Up to 100 days post HCT ]
  • Incidence of severe adverse events (AEs) (safety in HCT-recipients) [ Time Frame: Within 2 weeks from transplantation and up to 1 year post HCT ]
  • Incidence of grade 3 and higher AEs (safety in HCT-donors) [ Time Frame: Within 14 days ]

Central Contacts and Locations

Central contacts

Vaibhav Agrawal, MD

626-359-8111vagrawal@coh.org

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Vaibhav Agrawal

626-256-4673vagrawal@coh.org

Principal Investigator:

Vaibhav Agrawal

Northside Hospital

Recruiting

Atlanta, Georgia, United States, 30342

Contacts

Scott R. Solomon, MD

404-255-1930ssolomon@bmtga.com

Principal Investigator:

Scott R. Solomon

DFCI/BWH Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Lindsey Baden, MD

617-732-6801lbaden@bwh.harvard.edu

Principal Investigator:

Lindsey Baden, MD

More Information

Sponsor

City of Hope Medical Center

Last update posted

Mar 10, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-03-10.