CMV-MVA Triplex Vaccination of Stem Cell Donors in Preventing CMV Viremia in Participants With Allogeneic Transplant
Condition: Accelerated Phase CML, BCR-ABL1 Positive; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Phase CML, BCR-ABL1 Positive; Cytomegalovirus Positive; Donor; Hematopoietic Cell Transplant Recipient; Hodgkin Lymphoma; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Myelofibrosis; Hematopoietic and Lymphoid Cell Neoplasm
MeSH terms: Viremia; Lymphoma; Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Accelerated Phase; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases
Intervention: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
Intervention description: Given via injection
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This phase II trial studies how well multi-peptide CMV-modified vaccinia Ankara (CMV-MVA
      Triplex) vaccination of stem cell donors works in preventing cytomegalovirus (CMV) viremia in
      participants with blood cancer undergoing donor stem cell transplant. Giving a vaccine to the
      donors may boost the recipient's immunity to this virus and reduce the chance of CMV disease
      after transplant.
    

Eligibility criteria:

        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

          -  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). This holds true even if donors have been
             already vaccinated according to criteria for donor vaccination

          -  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). EXCEPT for low risk patients [8/8 high resolution
             HLA donor allele matching HCT])

          -  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)