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

Inclusion Criteria:

• DONORS: Documented informed consent of the participant and/or legally authorizedrepresentative

• Assent, when appropriate, will be obtained per institutional guidelines

• DONORS: Age: 18 and above

• RECIPIENTS: Documented informed consent of the participant and/or legally authorizedrepresentative

• Assent, when appropriate, will be obtained per institutional guidelines

• RECIPIENTS: Participant must be willing to comply with study and/or follow-upprocedures, 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 lymphoblasticleukemia in first or second remission, acute myeloid leukemia in first or secondremission, chronic myelogenous leukemia (in first chronic or accelerated phase, orin second chronic phase), chronic lymphocytic leukemia, myeloproliferative disordersand myelofibrosis. Patients with multiple myeloma are excluded

• RECIPIENTS: CMV seropositive

• RECIPIENTS: Planned related HCT with 8/8 (A, B, C, DRB1) high resolution humanleukocyte antigen (HLA) donor allele matching

• RECIPIENTS: Conditioning and immunosuppressive regimens according to institutionalguidelines are permitted. Patients may receive myeloablative, reduced intensity, ornonmyeloablative conditioning

• RECIPIENTS: Total bilirubin ≤ 2 X upper limit of normal (ULN) (unless has Gilbert'sdisease)

• RECIPIENTS: Aspartate aminotransferase (AST) ≤ 2.5 x ULN

• RECIPIENTS: Alanine aminotransferase (ALT) ≤ 2.5 x ULN

• RECIPIENTS: Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or theCockcroft-Gault formula

• RECIPIENTS: Left ventricular ejection fraction (LVEF) ≥ 50% Note: To be performedwithin 45 days prior to day 1 of protocol therapy

• RECIPIENTS: If able to perform pulmonary function tests: forced vital capacity (FVC)and diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) ≥ 50% ofpredicted (corrected for hemoglobin). If unable to perform pulmonary function tests:oxygen (O2) saturation > 92% on room air Note: To be performed within 45 days priorto day 1 of protocol therapy

• RECIPIENTS: Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV)*, active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR])

• If seropositive for HIV, HCV or HBV, nucleic acid quantitation must beperformed. Viral load must be undetectable

• RECIPIENTS: Meets other institutional and federal requirements for infectiousdisease titer requirements Note: Infectious disease testing to be performed within 45 days prior to day 1 of protocol therapy

• RECIPIENTS: Women of childbearing potential (WOCBP): Negative urine or serumpregnancy test. If the urine test is positive or cannot be confirmed as negative, aserum pregnancy test will be required

• RECIPIENTS: Agreement by females and males of childbearing potential* to use aneffective method of birth control (hormonal or barrier method) or abstain fromheterosexual activity prior to study entry and for up to 90 days post-HCT.

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• DONORS: Any prior transplant to day 1 of protocol therapy

• DONORS: Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21days prior to day 1 of protocol therapy

• DONORS: Receipt of any vaccine (licensed or investigational) within 30 days prior toand after of the study vaccine

• DONORS: Unfit to undergo standard stem cell mobilization and apheresis e.g. abnormalblood 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 isroutine for potential HCT donors over 60 years old and those with a history of heartdisease. Subjects in whom cardiac function is abnormal (excluding 1st degree branchblock, sinus bradycardia, sinus tachycardia or non-specific T wave changes) areineligible for Triplex vaccination

• DONORS: Positive for HIV, active hepatitis B (HBV), hepatitis C (HCV) or humanT-cell lymphotropic virus (HTLV-I/II)

• DONORS: Severe psychiatric illness. Mental deficiency sufficiently severe as to makecompliance with the donation procedure unlikely, and making informed consentimpossible

• 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 safetyconcerns with clinical study procedures

• DONORS: Prospective participants who, in the opinion of the investigator, may not beable to comply with all study procedures (including compliance issues related tofeasibility/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

• RECIPIENTS: Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) orkilled vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigeninjections)

• RECIPIENTS: Allergy treatment with antigens injections

• RECIPIENTS: Alemtuzumab or any equivalent in vivo T-cell depleting agent

• RECIPIENTS: Antiviral medications with known therapeutic effects on CMV such asvalganciclovir/ganciclovir (GCV/VAL), foscarnet (FOS), cidofovir, brincidofovir (CMX-001), maribavir. Acyclovir has no known therapeutic efficacy against CMV and isallowable as standard of care to prevent herpes simplex virus (HSV)

• RECIPIENTS: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviralCMV treatment

• RECIPIENTS: Other investigational product - concurrent enrollment in other clinicaltrials using any investigational new drug (IND) drugs with unknown effects on CMV orwith unknown toxicity profiles is prohibited

• RECIPIENTS: Other medications that might interfere with the evaluation of theinvestigational product

• RECIPIENTS: Diagnosis with autoimmune disease

• RECIPIENTS: Females only: Pregnant women and women who are lactating. The risks ofTriplex to pregnant women are unknown. Because there is an unknown but potentialrisk for adverse events in nursing infants secondary to treatment of the mother.Breastfeeding should be discontinued if the mother is enrolled on this study

• RECIPIENTS: Any other condition that would, in the investigator's judgment,contraindicate the patient's participation in the clinical study due to safetyconcerns with clinical study procedures

• RECIPIENTS: Prospective participants who, in the opinion of the investigator, maynot be able to comply with all study procedures (including compliance issues relatedto feasibility/logistics)