CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant

NCT06059391 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 23008NCI-2023-06837P30CA033572R01CA266783
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (5)

• Time from transplantation to cytomegalovirus (CMV) disease or pre-emptive treatment following CMV reactivation (efficacy)

  A stratified Cox regression analysis of time to CMV disease or positron emission tomography (PET) following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

  From hematopoietic stem cell transplantation (HCT) to day 180

• Occurrence of non-relapse mortality (safety in HCT-recipients)

  A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

  Up to day 100 post HCT

• Incidence of severe acute graft versus host disease (aGHVD) (safety in HCT-recipients)

  Severe aGHVD defined as grades 3-4. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

  Up to 100 days post HCT

• Incidence of severe adverse events (AEs) (safety in HCT-recipients)

  Probably or definitely related to the vaccination per Common Terminology Criteria for Adverse Events version 5.0. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

  Within 2 weeks from transplantation and up to 1 year post HCT

• Incidence of grade 3 and higher AEs (safety in HCT-donors)

  A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

  Within 14 days

Secondary Outcomes (13)

• Time-to viremia (CMV-related events)

  From transplantation to the date of two consecutive CMV quantitative polymerase chain reaction (qPCR) > 500 gc/mL/465 IU/mL or single event of CMV qPCR >1500 CMV gc/mL/1,395 IU/mL, assessed up to 1 year post HCT

• Duration of viremia (CMV-related events)

  Up to 1 year post HCT

• Incidence of late CMV viremia (CMV-related events)

  Between days 100-365 post HCT

• Use of antiviral drugs (CMV-related events)

  Up to 1 year post HCT

• Cumulative number of CMV specific antiviral treatment days (CMV-related events)

  Up to 1 year post HCT

Study Arms (2)

Arm I (Triplex vaccination)

EXPERIMENTAL

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Drug: Granulocyte Colony-Stimulating Factor; Drug: Hematopoietic Cell Transplantation Conditioning Regimen; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine; Procedure: Pheresis; Drug: Stem Cell Mobilization Therapy

Arm II (Placebo)

PLACEBO COMPARATOR

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Drug: Granulocyte Colony-Stimulating Factor; Drug: Hematopoietic Cell Transplantation Conditioning Regimen; Procedure: Pheresis; Drug: Placebo Administration; Drug: Stem Cell Mobilization Therapy

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Arm I (Triplex vaccination); Arm II (Placebo)

Granulocyte Colony-Stimulating Factor DRUG

Undergo stem cell mobilization with G-CSF

Also known as: Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, GCSF, Granulocyte Colony Stimulating Factor, Pluripoietin

Arm I (Triplex vaccination); Arm II (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 (Triplex vaccination)

Pheresis PROCEDURE

Undergo apheresis

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

Arm I (Triplex vaccination); Arm II (Placebo)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HCT with donor peripheral blood stem cells

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Arm I (Triplex vaccination); Arm II (Placebo)

Hematopoietic Cell Transplantation Conditioning Regimen DRUG

Receive pre transplant conditioning

Also known as: HCT Conditioning Regimen, HSCT Conditioning Regimen, Stem Cell Transplant Conditioning

Arm I (Triplex vaccination); Arm II (Placebo)

Placebo Administration DRUG

Given IM

Arm II (Placebo)

Stem Cell Mobilization Therapy DRUG

Undergo stem cell mobilization with G-CSF

Also known as: Chemomobilization, Hematopoietic Stem Cell Mobilization, Mobilization Therapy, Stem-cell mobilization

Arm I (Triplex vaccination); Arm II (Placebo)

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 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

You may not qualify if:

• 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

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

DFCI/BWH Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin

Interventions

Stem Cell Transplantation; Specimen Handling; Granulocyte Colony-Stimulating Factor; Blood Component Removal; Hematopoietic Stem Cell Mobilization

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Vaibhav Agrawal, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vaibhav Agrawal, MD

CONTACT

626-359-8111; vagrawal@coh.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This trial is observer-blinded because of the handling of the vaccine and the placebo may vary. The investigators, treating clinicians, participants, and other study staff, including the nurses involved in soliciting or recording of adverse events, will be blinded through the day 180 visit.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 28, 2023
• Study Start: July 12, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

US (3)