Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of CMV-MVA Triplex (multi-peptide CMV-MVA vaccine)
in vaccinated hematopoietic cell transplant (HCT) recipients by assessing the following:
non-relapse mortality (NRM) at 100 days post HCT, severe (grade 3-4) acute graft-versus-host
disease (GVHD) (aGVHD), and grade 3-4 adverse events (AEs) (Common Terminology Criteria for
Adverse Events [CTCAE] 4.0) probably or definitely related to the vaccination within 2 weeks
from each vaccination.

II. To determine if CMV-MVA Triplex reduces the frequency of CMV events defined as
reactivation or CMV disease in allogeneic CMV positive HCT recipients (HCT-R+).

SECONDARY OBJECTIVES:

I. To characterize CMV reactivation and CMV disease in recipients of CMV-MVA Triplex compared
to placebo by assessing time-to viremia (defined as number of days from transplantation to
the date of > 500 CMV gc/mL), duration of viremia, recurrence of viremia, incidence of late
CMV viremia/disease (> 100 and =< 360 days post HCT), use of antiviral drugs (triggered by
clinically significant viremia of >= 1500 CMV gc/mL), cumulative number of CMV specific
antiviral treatment days.

II. To evaluate the impact of CMV-MVA Triplex on transplant related outcomes by assessing the
incidence of acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, non-relapse mortality,
all-cause mortality, infections.

III. To determine 1) if CMV-MVA Triplex increases levels, function and kinetics of
CMV-specific T cell immunity in vaccinated compared to placebo treated human leukocyte
antigen (HLA) A*0201, CMV seropositive HCT-recipients, 2) to determine whether vaccination
induces adaptive natural killer (NK) cell population changes, and increase in the highly
cytotoxic memory killer cell lectin-like receptor subfamily C, member 2 (NKG2C)+ NK cells,
and 3) to explore GVHD biomarkers and compare between the vaccine and placebo groups.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive multi-peptide CMV-MVA vaccine intramuscularly (IM) on days 28 and 56
post-HCT.

ARM II: Patients receive placebo IM on days 28 and 56 post-HCT.

After completion of study, patients are followed up for 1 year post-HCT.

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)