Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant

NCT02506933 | Active Not Recruiting Phase 2 Results DMC

• 3 other identifiers: 14295NCI-2015-01228R01CA077544
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 3

Brief Summary

This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) vaccine works in reducing CMV complications in patients previously infected with CMV and are undergoing a donor hematopoietic cell transplant. CMV is a virus that may reproduce and cause disease and even death in patients with lowered immune systems, such as those undergoing a hematopoietic cell transplant. By placing 3 small pieces of CMV deoxyribonucleic acid (DNA) (the chemical form of genes) into a very safe, weakened virus called MVA, the multi-peptide CMV-MVA vaccine may be able to induce immunity (the ability to recognize and respond to an infection) to CMV. This may help to reduce both CMV complications and reduce the need for antiviral drugs in patients undergoing a donor hematopoietic cell transplant.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Cytomegaloviral Infection; Hodgkin Lymphoma; Lymphadenopathy; Lymphoblastic Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Cytomegalovirus (CMV) Events to Day 100

  Cytomegalovirus (CMV) events included CMV reactivation ≥1250 CMV DNA IU/mL, CMV viremia prompting antiviral therapy, or CMV disease before day 100 after HCT.

  Prior to day 100 post-HCT

• Incidence of Severe (Grade 3-4) Acute Graft-Versus-Host Disease

  Severe acute graft-versus-host disease (aGVHD, grade 3-4) was monitored as every 12th subject on the vaccine arm reaches the 100 day evaluation point. aGVHD was scored using Keystone consensus criteria \[Przepiorka, D., et al., 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant, 1995. 15(6): p. 825-8\].

  Up to 100 days post-transplant

Secondary Outcomes (1)

• All-cause Mortality

  Up to 1 year post-HCT

Study Arms (2)

Arm I (multi-peptide CMV-MVA vaccine)

EXPERIMENTAL

Patients receive multi-peptide CMV-MVA vaccine IM on days 28 and 56 post-HCT.

Other: Laboratory Biomarker Analysis; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo IM on days 28 and 56 post-HCT.

Other: Laboratory Biomarker Analysis; Other: Placebo

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (multi-peptide CMV-MVA vaccine); Arm II (placebo)

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given IM

Also known as: CMV-MVA Triplex Vaccine

Arm I (multi-peptide CMV-MVA vaccine)

Placebo OTHER

Given IM

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years - 75 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 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 including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis; patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded
• Patients undergoing a second allogeneic (allo) HCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
• CMV seropositive (recipient)
• Planned related or unrelated HCT, with 8/8 (A,B,C,DRB1) high/intermediate 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
• Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within two weeks of registration

You may not qualify if:

• Any prior investigational CMV vaccine
• Experimental anti-CMV chemotherapy in the last 6 months
• Live attenuated vaccines
• Medically indicated subunit (Engerix-B for HBV; Gardasil for human papillomavirus \[HPV\]) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections)
• Allergy treatment with antigens injections
• Alemtuzumab or any equivalent in vivo T-cell depleting agent
• 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)
• Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment
• 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
• Other medications that might interfere with the evaluation of the investigational product
• Patients with active autoimmune conditions requiring systemic immunosuppressive therapy within the previous 5 years are not eligible
• Pregnant women and women who are lactating; breastfeeding should be discontinued if the mother is enrolled on this study
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., social/ psychological issues, etc
• 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)

Sponsors & Collaborators

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

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Aldoss I, La Rosa C, Baden LR, Longmate J, Ariza-Heredia EJ, Rida WN, Lingaraju CR, Zhou Q, Martinez J, Kaltcheva T, Dagis A, Hardwick N, Issa NC, Farol L, Nademanee A, Al Malki MM, Forman S, Nakamura R, Diamond DJ; TRIPLEX VACCINE Study Group. Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial. Ann Intern Med. 2020 Mar 3;172(5):306-316. doi: 10.7326/M19-2511. Epub 2020 Feb 11.

  PMID: 32040960 DERIVED

• La Rosa C, Longmate J, Martinez J, Zhou Q, Kaltcheva TI, Tsai W, Drake J, Carroll M, Wussow F, Chiuppesi F, Hardwick N, Dadwal S, Aldoss I, Nakamura R, Zaia JA, Diamond DJ. MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults. Blood. 2017 Jan 5;129(1):114-125. doi: 10.1182/blood-2016-07-729756. Epub 2016 Oct 19.

  PMID: 27760761 DERIVED

MeSH Terms

Conditions

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

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, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Lymphoma

Results Point of Contact

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

RNakamura@coh.org

6263598111

Study Officials

• Ryotaro Nakamura, MD

  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, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2015
• First Posted: July 23, 2015
• Study Start: November 5, 2015
• Primary Completion: January 25, 2018
• Study Completion (Estimated): June 9, 2026
• Last Updated: August 22, 2025
• Results First Posted: April 14, 2023

Record last verified: 2025-08

Locations

US (3)