Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine if cytomegalovirus (CMV)peptide(Pep)vaccine(Vax) (CMVpp65-A*0201 peptide
vaccine) reduces the frequency of CMV events defined as reactivation or CMV disease in human
leukocyte antigen (HLA) A*0201 allogeneic CMV positive hematopoietic stem cell transplant
(HCT) recipients (HCT-R+).

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of CMVPepVax 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 characterize CMV reactivation and CMV disease in recipients of CMVPepVax compared to
placebo by assessing time-to viremia (defined as number of days from transplantation to the
date of >= 500 CMV genome copies [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), cumulative number of CMV specific
antiviral treatment days.

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

IV. To determine if CMVPepVax increases levels, function and kinetics of CMV-specific T cell
immunity in vaccinated compared to placebo treated HLA A*0201, CMV seropositive
HCT-recipients.

V. To determine whether vaccination induces adaptive natural killer (NK) cell population
changes, and increase in the highly cytotoxic memory NKG2C+ NK cells.

VI. 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 CMVpp65-A*0201 peptide vaccine subcutaneously (SC) on days 28 and 56
after HCT.

ARM II: Patients receive placebo SC on days 28 and 56 after HCT.

After completion of study treatment, patients are followed up to day 365 after 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 needs to 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

- HLA A*0201 High resolution, 4-digit typing is required at HLA-A2 to ensure A*0201
status.

- CMV seropositive (recipient)

- Planned related or unrelated HCT, with HLA donor allele matching; related donor must
be an 8/8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and
-DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing; unrelated
donor must be an 8/8 match at HLA-A, -B, -C, and -DRB1 at high resolution using
DNA-based typing; patients undergoing a second allo HCT are not eligible (patients who
have undergone a previous autologous HCT are eligible)

- Planned HCT with no ex-vivo 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

- Planned medications from the time of HCT to day 70 post-HCT:

- Live attenuated vaccines

- Medically indicated subunit (Engerix-B for HBV; Gardasil for human papilloma
virus [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; this includes
anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide

- Antiviral medications with known therapeutic effects against CMV such as
ganciclovir (GCV)/valine (VAL), foscarnet (FOS), cidofovir,
hexadecyloxypropyl-cidofovir (CMX-001) and maribavir; acyclovir has no
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 an investigational product 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)