CMV-MVA Triplex Vaccination of Stem Cell Donors in Preventing CMV Viremia in Participants With Blood Cancer Undergoing Donor Stem Cell Transplant

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: I. Establish the feasibility and safety of priming CMV immunity in donors by Triplex vaccination prior to peripheral blood stem cell (PBSC) harvest. SECONDARY OBJECTIVES: I. Examine if Triplex vaccination of hematopoietic stem cell transplant (HCT) donors has an impact on CMV events. OUTLINE: Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization. Participants undergo hematopoietic cell transplantation on day 0. After completion of study treatment, participants are followed up for 1 year.

Official Title
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CMV-MVA Triplex Vaccination of Stem Cell Donors to Enhance CMV Specific Immunity and Prevent CMV Viremia in Recipients After Stem Cell Transplant

Conditions
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Donor, 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, Cytomegalovirus Positive, Hematopoietic Cell Transplant Recipient, Hodgkin Lymphoma, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm, Non-Hodgkin Lymphoma, Myelofibrosis, Hematopoietic and Lymphoid Cell Neoplasm

Intervention / Treatment
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* Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 DONOR VACCINATION: Donors are eligible to be vaccinated prior to the determination of their human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV) status. The exclusion criteria for transplant is independent of eligibility for vaccination and is determined by the exclusion criteria for transplant from donors 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 Exclusion Criteria: 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 RECIPIENT: Any prior investigational CMV vaccine RECIPIENT: Experimental anti-CMV chemotherapy in the last 6 months RECIPIENT: Planned medications from the time of HCT to day 70 post-HCT RECIPIENT: Live attenuated vaccines RECIPIENT: 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) RECIPIENT: Allergy treatment with antigens injections RECIPIENT: Alemtuzumab or any equivalent in vivo T-cell depleting agent RECIPIENT: Antiviral medications with known therapeutic effects on CMV such as ganciclovir (GCV)/valganciclovir (VAL), 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) RECIPIENT: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment (Letermovir is permitted). EXCEPT for low risk patients [8/8 high resolution HLA donor allele matching HCT]) RECIPIENT: 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 RECIPIENT: Other medications that might interfere with the evaluation of the investigational product RECIPIENT: Diagnosis with autoimmune disease RECIPIENT: Pregnant women and women who are lactating. The risks of CMV-MVA-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 RECIPIENT: 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 RECIPIENT: 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention(multi-peptide CMV-modified vaccinia Ankara vaccine)<br>Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization. Participants undergo hematopoietic cell transplantation on day 0. | Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine<br>* Given via injection<br>* Other names: CMV-MVA Triplex Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility assessed by number of suitable donor/recipient pairs were approached, and the number that were successfully enrolled/vaccinated |  | Up to 1 year | 
| Incidence of adverse events (AEs) | AEs >= grade 2, probably or definitely related to vaccination will be noted in donors. | Up to 1 year | 
| Non-relapse mortality |  | At 100 days post hematopoietic stem cell transplantation (HCT) | 
| Delayed engraftment |  | Up to 1 year | 
| Severe acute graft versus host disease (aGVHD) |  | Up to 1 year | 
| Grade 3-4 AEs | Will be assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0. | Up to 1 year | 
| Therapy induced quantitative/kinetic changes in cytomegalovirus (CMV)-specific cellular immunity | T cells specific for pp65 and/or IE antigens will be measured as a possible correlate to protective function. The frequency of T cells specific for pp65 and/or IE antigens will be measured using CD137 expression assays. These CMV-specific T cells will be further characterized by CD107-associated degranulation, polyfunctional cytokines and cell-surface memory markers. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMV protection | Will assess incidence of viremia (>= 1250 IU/mL), CMV viral load and use of antivirals (recipients who reactivate CMV and are given antiviral therapy will be considered intervention failures). | Up to 1 year |