Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant
Condition: 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; Cytomegaloviral Infection; Hodgkin Lymphoma; Lymphadenopathy; Lymphoblastic Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma
MeSH terms: Cytomegalovirus Infections; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphadenopathy
Intervention: Laboratory Biomarker Analysis; Multi-peptide CMV-Modified Vaccinia Ankara Vaccine; Placebo
Intervention description: Correlative studies; Given IM; Given IM
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus
      (CMV)-modified vaccinia Ankara (MVA) vaccine works in reducing CMV complications in patients
      previously infected with CMV and are undergoing a donor hematopoietic cell transplant. CMV is
      a virus that may reproduce and cause disease and even death in patients with lowered immune
      systems, such as those undergoing a hematopoietic cell transplant. By placing 3 small pieces
      of CMV deoxyribonucleic acid (DNA) (the chemical form of genes) into a very safe, weakened
      virus called MVA, the multi-peptide CMV-MVA vaccine may be able to induce immunity (the
      ability to recognize and respond to an infection) to CMV. This may help to reduce both CMV
      complications and reduce the need for antiviral drugs in patients undergoing a donor
      hematopoietic cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All subjects must have the ability to understand and the willingness to sign a written
             informed consent

          -  Participant must be willing to comply with study and/or follow-up procedures,
             including willingness to be followed for one year post-HCT

          -  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 (for acute
                  lymphoblastic leukemia/lymphoblastic lymphoma, the disease status must be in
                  hematologic remission by bone marrow and peripheral blood; persistent
                  lymphadenopathy on computed tomography [CT] or CT/positron emission tomography
                  (PET) scan without progression is allowed)

               -  Acute myeloid leukemia in first or second remission

               -  Chronic myelogenous leukemia in first chronic or accelerated phase, or in second
                  chronic phase

               -  Other hematologic malignancies including chronic lymphocytic leukemia,
                  myeloproliferative disorders and myelofibrosis; patients with multiple myeloma
                  and those with non-malignant disease such as aplastic anemia are excluded

               -  Patients undergoing a second allogeneic (allo) HCT are not eligible (patients who
                  have undergone a previous autologous HCT are eligible)

          -  CMV seropositive (recipient)

          -  Planned related or unrelated HCT, with 8/8 (A,B,C,DRB1) high/intermediate resolution
             HLA donor allele matching

          -  Planned HCT with minimal to no-T cell depletion of graft

          -  Conditioning and immunosuppressive regimens according to institutional guidelines are
             permitted

          -  Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient
             of childbearing potential only) within two weeks of registration

          -  Seronegative for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and
             active hepatitis B virus (HBV) (surface antigen negative) within 2 months of
             registration

          -  Agreement by females of childbearing potential and sexually active males to use an
             effective method of contraception (hormonal or barrier method of birth control 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:

          -  Any prior investigational CMV vaccine

          -  Experimental anti-CMV chemotherapy in the last 6 months

          -  Live attenuated vaccines

          -  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)

          -  Allergy treatment with antigens injections

          -  Alemtuzumab or any equivalent in vivo T-cell depleting agent

          -  Antiviral medications with known therapeutic effects on CMV such as ganciclovir
             (GCV)/valganciclovir (VAL), foscarnet (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)

          -  Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment

          -  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

          -  Other medications that might interfere with the evaluation of the investigational
             product

          -  Patients with active autoimmune conditions requiring systemic immunosuppressive
             therapy within the previous 5 years are not eligible

          -  Pregnant women and women who are lactating; breastfeeding should be discontinued if
             the mother is enrolled on this study

          -  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

          -  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)