CMV-MVA Triplex Vaccination of Stem Cell Donors in Preventing CMV Viremia in Participants With Blood Cancer Undergoing Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. Establish the feasibility and safety of priming CMV immunity in donors by Triplex
vaccination prior to peripheral blood stem cell (PBSC) harvest.

SECONDARY OBJECTIVES:

I. Examine if Triplex vaccination of hematopoietic stem cell transplant (HCT) donors has an
impact on CMV events.

OUTLINE:

Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60
and -14 prior to granulocyte colony stimulating factor mobilization. Participants undergo
hematopoietic cell transplantation on day 0.

After completion of study treatment, participants are followed up for 1 year.

Inclusion Criteria:

- DONOR: Ability to comprehend the investigational nature of the study and provide
informed consent

- DONOR: Willing to receive Triplex vaccination, a minimum of 14 days prior to the PBSC
collection

- DAY 28 DONOR VACCINATION: Donors are eligible to be vaccinated prior to the
determination of their human immunodeficiency virus (HIV), hepatitis B virus (HBV),
hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV) status. The
exclusion criteria for transplant is independent of eligibility for vaccination and is
determined by the exclusion criteria for transplant from donors

- RECIPIENT: All subjects must have the ability to understand and the willingness to
sign a written informed consent

- RECIPIENT: Participant must be willing to comply with study and/or follow-up
procedures, including willingness to be followed for one year post-HCT

- RECIPIENT: Age 18 to 75 years

- RECIPIENT: 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, acute myeloid leukemia in first or second
remission, chronic myelogenous leukemia (in first chronic or accelerated phase, or in
second chronic phase), chronic lymphocytic leukemia, myeloproliferative disorders and
myelofibrosis (City of Hope [COH] only). Patients with multiple myeloma are excluded

- RECIPIENT: CMV seropositive

- RECIPIENT: Planned related HCT with 8/8 (A, B, C, DRB1) high resolution HLA donor
allele matching

- RECIPIENT: Conditioning and immunosuppressive regimens according to institutional
guidelines are permitted

- RECIPIENT: Negative serum or urine beta-human chorionic gonadotropin (HCG) test
(female patient of childbearing potential only) within two weeks of registration

- RECIPIENT: Seronegative for HIV, HCV and active HBV (surface antigen negative) within
2 months of registration

- RECIPIENT: Agreement by females of childbearing potential and males with partners of
childbearing potential to use effective contraception (hormonal or barrier method 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:

- TRANSPLANT FROM DONOR: Unfit to undergo standard stem cell mobilization and apheresis
e.g. abnormal blood counts, history of stroke, uncontrolled hypertension

- TRANSPLANT FROM DONOR: Sickling hemoglobinopathy including HbSS, HbAS, HbSC

- TRANSPLANT FROM DONOR: Positive for human immunodeficiency virus (HIV), active
hepatitis B (hepatitis B virus [HBV]), hepatitis C (hepatitis C virus [HCV]) or human
T‐cell lymphotropic virus (HTLV‐I/II)

- TRANSPLANT FROM DONOR: Donors with impaired cardiac function are excluded.
Electrocardiography is routine for potential HCT donors over 60 years old and those
with a history of heart disease. Subjects in whom cardiac function is abnormal
(excluding 1st degree branch block, sinus brachycardia, sinus tachycardia or
non‐specific T wave changes) are ineligible for Triplex vaccination

- TRANSPLANT FROM DONOR: Severe psychiatric illness. Mental deficiency sufficiently
severe as to make compliance with the donation procedure unlikely, and making informed
consent impossible

- RECIPIENT: Any prior investigational CMV vaccine

- RECIPIENT: Experimental anti-CMV chemotherapy in the last 6 months

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

- RECIPIENT: Live attenuated vaccines

- RECIPIENT: 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)

- RECIPIENT: Allergy treatment with antigens injections

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

- RECIPIENT: Antiviral medications with known therapeutic effects on CMV such as
ganciclovir (GCV)/valganciclovir (VAL), 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)

- RECIPIENT: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV
treatment (Letermovir is permitted)

- RECIPIENT: 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

- RECIPIENT: Other medications that might interfere with the evaluation of the
investigational product

- RECIPIENT: Diagnosis with autoimmune disease

- RECIPIENT: Pregnant women and women who are lactating. The risks of CMV-MVA-Triplex to
pregnant women are unknown. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother. Breastfeeding should
be discontinued if the mother is enrolled on this study

- RECIPIENT: 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

- RECIPIENT: 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)