Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant

Inclusion Criteria: * HLA A\*0201 subtype * CMV seropositive * Able and willing to sign the informed consent form (ICF) * Willingness to be followed for the planned duration of the trial (6 months post-HCT) * Seronegative for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and active hepatitis B virus (HBV) (surface antigen negative) * Planned related or unrelated HCT, with 8/8 or 7/8 (A, B, C, DRB1) high resolution HLA donor allele matching * HCT for the treatment of hematologic cancers including, but not limited to: * Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status needs to be in hematologic remission by bone marrow/peripheral blood; persistent lymphadenopathy on computed tomography \[CT\] or CT/positron emission tomography \[PET\] scan without progression is allowed) * Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase * Hodgkin and non-Hodgkin lymphoma * Myelodysplastic syndrome * Planned HCT with minimal to no-T cell depletion of graft * Use of contraception up to 90 days post-HCT * Negative pregnancy test for female recipient * DISEASE STATUS: Recipients to be enrolled are patients eligible for allogeneic HCT, who were diagnosed with hematologic cancers including: * Acute lymphoblastic leukemia (ALL); B-precursor ALL; T cell ALL * Acute myeloid leukemia (AML), acute promyelocytic leukemia; treatment related AML * Chronic lymphoid leukemia; adult T cell leukemia/lymphoma, chronic lymphocytic leukemia not otherwise specified (NOS), hairy cell leukemia; prolymphocytic leukemia (B or T); T cell large granular (gran.) lymphocytic (lymph.) leukemia (leuk) * Chronic myeloproliferative disease (CML); chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome; chronic idiopathic myelofibrosis; CML - Philadelphia chromosome; essential thrombocythemia; polycythemia vera * Leukemia, not otherwise specified (NOS) * Myelodysplastic syndrome, NOS; chronic myelomonocytic leukemia * Hodgkin lymphoma, NOS; Hodgkin lymphoma nodular lymphocyte predominant (LP), NOS; Hodgkin lymphoma - like post-transplant lymphoproliferative disorder (PTLD) * Lymphoma, NOS * Non-Hodgkin lymphoma (NHL); anaplastic large-cell lymphoma (ALCL), cutaneous, ALCL, systemic; Burkitt lymphoma/leukemia; cutaneous T-cell lymphoma (CTCL)/mycosis fungoides; CTCL/Sezary syndrome; diffuse large B-cell lymphoma; mucosa associated lymphoid tissue (MALT)-lymphoma; extranodal natural killer (NK)/T cell lymphoma, extranodal NK/T lymphoma nasal; follicular lymphoma; lymphoplasmacytic lymphoma mantle cell lymphoma; mediastinal large B-cell lymphoma; nodal marginal zone B-cell lymphoma (lymph.); NHL aggressive, NOS; NHL indolent, NOS; NHL, NOS; peripheral T cell lymphoma, NOS; PTLD (monoclonal); PTLD (polyclonal); precursor (precur.) B-lymphoblastic lymphoma; precur T-lymphoblastic lymphoma; primary central nervous system (CNS) lymphoma; primary effusion lymphoma; small lymphocytic lymphoma, NOS * Myeloma, NOS; monoclonal gammopathy of undetermined significance (MGUS); solitary plasmacytoma * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately * All medications, supportive care, blood products or radiation therapy taken or administered during the trial will be documented in the subject's clinical/hospital and case report form (CRF), using City of Hope (COH) guidelines; the subject's clinical information will be recorded on the appropriate CRF * Concurrent enrollment in other clinical trials using an investigational product is prohibited * The use of alemtuzumab for immunosuppression is not permitted in this study * Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment is not allowed * Medications that might interfere with the evaluation of the investigational product should not be administered, from 30 days prior to participation on the trial and up to 14 days after the second vaccination (day 70 post-HCT); medications in this category include, but are not limited to: * Live attenuated vaccines * Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections) * Antiviral treatment for herpes simplex virus (HSV), human herpes virus 6 (HHV6), Epstein-Barr virus (EBV) and adenovirus including the use of GVC/VAL, FOS, Cidofovir, CMX-001 may also suppress reactivation of CMV, thus it will not be allowed in this study; patients requiring such treatment before randomization (day 28) will be removed from the study and replaced; reasons for removal will be reported in the patient's CRF * All enrolled recipients who will require anti-CMV therapy before day 28 will be replaced, treated and monitored as required by COH standard of care; GVC/VAL, FOS, Cidofovir, CMX-001 may be used according to COH standard of care (SOC) for preemptive management of CMV viremia; should antiviral treatment be required after day 28, the planned 2nd vaccine injection at day 56 will not be administered (vaccine arm only) * All subjects must have the ability to understand and the willingness to sign a written informed consent Exclusion Criteria: * A poor-risk patient, as defined by any of the following: * Chronic myelogenous leukemia in blast crisis * Acute myeloid leukemia beyond second remission * Multiple myeloma * Aplastic anemia * Planned immunosuppression with alemtuzumab or any equivalent in vivo T-cell depleting agent * In vitro T cell depleted graft * Planned prophylactic therapy with CMV immunoglobulin * Planned CMV prophylactic therapy * Experimental anti-CMV chemotherapy in the last 6 months * Diagnosed with autoimmune disease * Receipt of the following substances: * Any prior investigational CMV vaccine * Live attenuated vaccines, medically indicated subunit or killed vaccines from 30 days prior to participation in the trial and up to 14 days after the second vaccination (day 70 post-HCT) * Investigational research products or allergy treatment with antigens injections from 30 days prior to participation in the trial and up to 14 days after the second vaccination (day 70 post-HCT) * Pregnant and/or breast feeding if a female recipient * Refusing to use contraception up to 90 days post-HCT * POST-HCT STUDY-SPECIFIC EXCLUSIONS: * On days 28 and 56 post-HCT (immunization day for the vaccine arm) all study recipients (vaccine and observation arms) will be reviewed for eligibility and ruled ineligible to initiate or continue in the study and receive vaccination (for the vaccine arm) if: * Diagnosed with \> grade 2 graft-versus-host disease (GVHD) before day 28 post-HCT, and diagnosed with \> grade 2 GVHD between day 28 post-HCT and administration of the 2nd vaccine at day 56 * Received steroid therapy with prednisone \> 1 mg/kg/day, less than 7 days prior to injection * Had relapse * Experience graft failure (absolute neutrophil count \< 500/mm\^3) * Received antiviral treatment with GVC/VAL, FOS, Cidofovir, CMX-001 at any point during the 28 day period * There are ongoing non-hematological post-HCT toxicities \>= grade 3 non-hematological (hem) adverse events (AE's), with exception of grade 3 glucose intolerance and grade 3 non-hem labs; cholesterol, triglyceride, and hyperglycemia