CMV-MVA Triplex Vaccination of Stem Cell Donors in Preventing CMV Viremia in Participants With Allogeneic Transplant

NCT03560752 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18007NCI-2018-01115
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well multi-peptide CMV-modified vaccinia Ankara (CMV-MVA Triplex) vaccination of stem cell donors works in preventing cytomegalovirus (CMV) viremia in participants with blood cancer undergoing donor stem cell transplant. Giving a vaccine to the donors may boost the recipient's immunity to this virus and reduce the chance of CMV disease after transplant.

Conditions

Accelerated Phase CML, BCR-ABL1 Positive; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Phase CML, BCR-ABL1 Positive; Cytomegalovirus Positive; Donor; Hematopoietic Cell Transplant Recipient; Hodgkin Lymphoma; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Myelofibrosis; Hematopoietic and Lymphoid Cell Neoplasm

Outcome Measures

Primary Outcomes (5)

• Delayed Engraftment

  Time to neutrophil engraftment was defined as days from stem cell infusion to the first of three consecutive days of absolute neutrophil count ≥0.5 x 109/L. Delayed engraftment was defined as ≥20 days to neutrophil recovery.

  Up to 1 year from stem cell infusion.

• Severe (Grade III-IV) Acute Graft Versus Host Disease

  Acute graft versus host disease (aGvHD) happens within days or as late as 6 months after allogeneic transplants. The three main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract.

  Up to 6 months from stem cell infusion

• Number of Recipients With Grade 3-4 Adverse Events

  Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.

  Up to 1 year from stem cell infusion.

• Number of Donors With Grade 2-3 Adverse Events

  Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.

  Up to 6 months after G-CSF mobilization

• 100-Day Non-Relapse Mortality (NRM)

  NRM was defined as death without recurrent or progressive disease after allogeneic transplant. Probabilities of NRM were estimated with the use of cumulative incidence curves, with relapse viewed as a competing risk.

  From stem cell infusion up to 100 days post-HSCT (hematopoietic stem cell transplantation).

Study Arms (2)

Donor (multi-peptide CMV-modified vaccinia Ankara vaccine)

EXPERIMENTAL

Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization.

Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Receipient (multi-peptide CMV-modified vaccinia Ankara vaccine)

EXPERIMENTAL

Participants undergo hematopoietic cell transplantation on day 0 and receive multi-peptide CMV-modified Vaccinia Ankara vaccine injection on days 28 and 56.

Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Interventions

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given via injection

Also known as: CMV-MVA Triplex Vaccine

Donor (multi-peptide CMV-modified vaccinia Ankara vaccine); Receipient (multi-peptide CMV-modified vaccinia Ankara vaccine)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• DONOR: Ability to comprehend the investigational nature of the study and provide informed consent
• DONOR: Willing to receive Triplex vaccination, a minimum of 14 days prior to the PBSC collection

You may not qualify if:

• RECIPIENT: All subjects must have the ability to understand and the willingness to sign a written informed consent
• RECIPIENT: Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT
• RECIPIENT: Age 18 to 75 years
• RECIPIENT: 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 (City of Hope \[COH\] only). Patients with multiple myeloma are excluded
• RECIPIENT: CMV seropositive
• RECIPIENT: Planned related HCT with 8/8 (A, B, C, DRB1) high resolution HLA donor allele matching
• RECIPIENT: Conditioning and immunosuppressive regimens according to institutional guidelines are permitted
• RECIPIENT: Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within two weeks of registration
• RECIPIENT: Seronegative for HIV, HCV and active HBV (surface antigen negative) within 2 months of registration
• RECIPIENT: Agreement by females of childbearing potential and males with partners of childbearing potential to use effective contraception (hormonal or barrier method or abstinence) prior to study entry and for up to 90 days post-HCT. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• TRANSPLANT FROM DONOR: Unfit to undergo standard stem cell mobilization and apheresis e.g. abnormal blood counts, history of stroke, uncontrolled hypertension
• TRANSPLANT FROM DONOR: Sickling hemoglobinopathy including HbSS, HbAS, HbSC
• TRANSPLANT FROM DONOR: Positive for human immunodeficiency virus (HIV), active hepatitis B (hepatitis B virus \[HBV\]), hepatitis C (hepatitis C virus \[HCV\]) or human T-cell lymphotropic virus (HTLV-I/II). This holds true even if donors have been already vaccinated according to criteria for donor vaccination
• TRANSPLANT FROM DONOR: 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 brachycardia, sinus tachycardia or non-specific T wave changes) are ineligible for Triplex vaccination
• TRANSPLANT FROM DONOR: Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the donation procedure unlikely, and making informed consent impossible

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

Related Publications (1)

• La Rosa C, Aldoss I, Park Y, Yang D, Zhou Q, Gendzekhadze K, Kaltcheva T, Rida W, Dempsey S, Arslan S, Artz A, Ball B, Nikolaenko L, Pullarkat VA, Nakamura R, Diamond DJ. Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus-specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis. Am J Hematol. 2023 Apr;98(4):588-597. doi: 10.1002/ajh.26824. Epub 2023 Jan 11.

  PMID: 36594185 DERIVED

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; 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; Lymphoma; Neoplasms by Site

Results Point of Contact

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

rnakamura@coh.org

626-359-8111

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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: June 18, 2018
• Study Start: August 20, 2018
• Primary Completion: January 22, 2022
• Study Completion (Estimated): July 29, 2026
• Last Updated: December 10, 2025
• Results First Posted: January 31, 2024

Record last verified: 2025-11

Locations

US (1)