Triplex Vaccine in Preventing CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation

NCT04060277 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19065NCI-2019-04888
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well Triplex vaccine works in preventing cytomegalovirus (CMV) infection in patients undergoing a hematopoietic stem cell transplantation. CMV is a virus that may be carried for life and does not cause illness in most healthy individuals. However, in people whose immune systems are lowered (such as those undergoing stem cell transplantation), CMV can reproduce and cause disease and even death. The Triplex vaccine is made up of 3 small pieces of CMV deoxyribonucleic acid (DNA) (the chemical form of genes) placed into a weakened virus called modified vaccinia Ankara (MVA) that may help produce immunity (the ability to recognize and respond to an infection) and reduce the risk of developing complications related to CMV infection.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Cytomegalovirus (CMV) Events

  Cytomegalovirus (CMV) event was defined as CMV reactivation (DNAemia \>625 IU/ml by qPCR), viremia treated by antivirals, or detection of CMV by tissue histology (end-organ disease), from Day 100 post-HCT to Day 180 post-HCT. Trial participants were quantitatively monitored for viremia, by plasma qPCR test once every two weeks (+/- 5d) from Day 100 to Day 180. CMV monitoring used standard qPCR clinical laboratory methods to evaluate CMV viral load and possible vaccine failure.

  From Day 100 to Day 180 post-hematopoietic stem cell transplant (HCT)

Secondary Outcomes (13)

• Non-Relapse Mortality at Day 180 Post-Transplant

  From time of transplant (Day 0) to Day 365

• Number of Participants With Severe (Grade 3-4) Acute Graft Versus Host Disease (GVHD) at Day 100

  From time of transplant (Day 0) to Day 100

• Number of Grade 3-4 Adverse Events

  From time of transplant (Day 0) to Day 365

• Duration of Viremia

  From time of transplant (Day 0) to Day 200

• Number of Patients With Recurrence of CMV Viremia

  From time of transplant (Day 0) to Day 200

Study Arms (2)

Arm I (letermovir, Triplex)

EXPERIMENTAL

Patients receive letermovir per SOC on days 7-100 and multi-peptide CMV-modified vaccinia Ankara vaccine IM on days 100 and 128 post-HCT.

Drug: Letermovir; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Arm II (letermovir, placebo)

ACTIVE COMPARATOR

Patients receive letermovir per SOC on days 7-100 and placebo IM on days 100 and 128 post-HCT.

Drug: Letermovir; Other: Placebo Administration

Interventions

Letermovir DRUG

Given as SOC

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

Arm I (letermovir, Triplex); Arm II (letermovir, placebo)

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given IM

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

Arm I (letermovir, Triplex)

Placebo Administration OTHER

Given IM

Arm II (letermovir, placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT
• Planned peripheral blood stem cell (PBSC) or bone marrow (BM) HCT for the treatment of the following hematologic malignancies:
• Lymphoma (Hodgkin and non-Hodgkin)
• Myelodysplastic syndrome
• Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status must be in hematologic remission by bone marrow and peripheral blood. Persistent lymphadenopathy on computed tomography \[CT\] or CT/positron emission tomography \[PET\] scan without progression is allowed.)
• Acute myeloid leukemia in first or second remission
• Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase
• Other hematologic malignancies judged appropriate by the clinical principal investigators (PIs), including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis. Patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded
• Adult cases of multiple myeloma (MM) are excluded as HCT is not standard of care for MM, and is only performed in very advanced cases with an associated high risk of relapse and NRM. Adults with aplastic anemia are excluded because their standard management includes T cell depletion with agents such as anti-thymocyte globulin (ATG), which is not permissible on this protocol. Patients undergoing a second haploHCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
• Patients receiving myeloablative (MA) or reduced intensity conditioning (RIC) are allowed
• CMV seropositive (recipient)
• Planned related HCT with molecular 3/6 (haploidentical) intermediate/high resolution HLA donor allele matching
• Planned HCT with minimal to no-T cell depletion of graft
• Conditioning and immunosuppressive regimens according to institutional guidelines are permitted

You may not qualify if:

• Any prior investigational CMV vaccine
• Experimental anti-CMV chemotherapy in the last 6 months
• Live attenuated vaccines (from the time of HCT to d70 post-HCT)
• Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections) (from the time of HCT to d70 post-HCT)
• Allergy treatment with antigen injections (from the time of HCT to d70 post-HCT)
• Alemtuzumab or any equivalent in vivo T-cell depleting agent (or CD34+ selection) (from the time of HCT to d70 post-HCT)
• Antiviral medications with known therapeutic effects on CMV such as ganciclovir (GCV)/valganciclovir (VAL), foscarnet (FOS), cidofovir, CMX-001, maribavir. Acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV) (from the time of HCT to d70 post-HCT)
• Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment EXCEPT Prevymis prophylaxis (prior to d100) (from the time of HCT to d70 post-HCT)
• Conditioning regimens d30 prior to trial participation and up to d180 post-HCT
• Disease-based radiation therapy (not total body irradiation) (from the time of HCT to d70 post-HCT)
• Other investigational product - concurrent enrollment in other clinical trials using any investigational new drugs (IND) with unknown effects on CMV or with unknown toxicity profiles is prohibited (from the time of HCT to d70 post-HCT)
• Other medications that might interfere with the evaluation of the investigational product (from the time of HCT to d70 post-HCT)
• Patients with active autoimmune conditions requiring systemic immunosuppressive therapy within the previous 5 years are not eligible
• Patients considered by PIs/protocol team to have a complicated prior therapy or HCT regimen, or who have a low survival probability (e.g., refractory leukemia and/or undergoing 2nd HCT)
• Poor risk disease/disease status including: chronic myeloid leukemia (CML) in blast crisis, acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) beyond 2nd remission, multiple myeloma, and aplastic anemia

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

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

Interventions

letermovir

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; Neoplasms by Site; Lymphoma

Results Point of Contact

• Title: Dr. Ryotaro Nakamura
• Organization: City of Hope Medical Center

rnakamura@coh.org

6263598111

Study Officials

• Ryotaro Nakamura

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: August 19, 2019
• Study Start: November 27, 2019
• Primary Completion: June 6, 2023
• Study Completion (Estimated): April 7, 2030
• Last Updated: November 14, 2025
• Results First Posted: October 30, 2024

Record last verified: 2025-11

Locations

US (1)