CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia
Eligibility Criteria
Inclusion Criteria: DONORS: Documented informed consent of the participant and/or legally authorized representative Assent, when appropriate, will be obtained per institutional guidelines DONORS: Age: 18 and above RECIPIENTS: Documented informed consent of the participant and/or legally authorized representative Assent, when appropriate, will be obtained per institutional guidelines RECIPIENTS: Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT RECIPIENTS: Age: 18 and above RECIPIENTS: Karnofsky performance score ≥ 70 or ECOG ≤ 2 RECIPIENTS: 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. Patients with multiple myeloma are excluded RECIPIENTS: CMV seropositive RECIPIENTS: Planned related HCT with 8/8 (A, B, C, DRB1) high resolution human leukocyte antigen (HLA) donor allele matching RECIPIENTS: Conditioning and immunosuppressive regimens according to institutional guidelines are permitted. Patients may receive myeloablative, reduced intensity, or nonmyeloablative conditioning RECIPIENTS: Total bilirubin ≤ 2 X upper limit of normal (ULN) (unless has Gilbert's disease) RECIPIENTS: Aspartate aminotransferase (AST) ≤ 2.5 x ULN RECIPIENTS: Alanine aminotransferase (ALT) ≤ 2.5 x ULN RECIPIENTS: Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula RECIPIENTS: Left ventricular ejection fraction (LVEF) ≥ 50% Note: To be performed within 45 days prior to day 1 of protocol therapy RECIPIENTS: If able to perform pulmonary function tests: forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) ≥ 50% of predicted (corrected for hemoglobin). If unable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room air Note: To be performed within 45 days prior to day 1 of protocol therapy RECIPIENTS: Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV)*, active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable RECIPIENTS: Meets other institutional and federal requirements for infectious disease titer requirements Note: Infectious disease testing to be performed within 45 days prior to day 1 of protocol therapy RECIPIENTS: Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required RECIPIENTS: Agreement by females and males of childbearing potential* to use an effective method of birth control (hormonal or barrier method) or abstain from heterosexual activity prior to study entry and for up to 90 days post-HCT. Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) Exclusion Criteria: DONORS: Any prior transplant to day 1 of protocol therapy DONORS: Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy DONORS: Receipt of any vaccine (licensed or investigational) within 30 days prior to and after of the study vaccine DONORS: Unfit to undergo standard stem cell mobilization and apheresis e.g. abnormal blood counts, history of stroke, uncontrolled hypertension DONORS: Sickling hemoglobinopathy including hemoglobin S (HbSS), sickle cell trait (HbAS), hemoglobin sickle C disease (HbSC) DONORS: 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 bradycardia, sinus tachycardia or non-specific T wave changes) are ineligible for Triplex vaccination DONORS: Positive for HIV, active hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) DONORS: Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the donation procedure unlikely, and making informed consent impossible DONORS: Females only: Pregnant or breastfeeding DONORS: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures DONORS: 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) RECIPIENTS: Any prior investigational CMV vaccine RECIPIENTS: Experimental anti-CMV chemotherapy in the last 6 months RECIPIENTS: Prior allogeneic (allo) transplant for any condition RECIPIENTS: Live attenuated vaccines RECIPIENTS: Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections) RECIPIENTS: Allergy treatment with antigens injections RECIPIENTS: Alemtuzumab or any equivalent in vivo T-cell depleting agent RECIPIENTS: Antiviral medications with known therapeutic effects on CMV such as valganciclovir/ganciclovir (GCV/VAL), foscarnet (FOS), cidofovir, brincidofovir (CMX-001), maribavir. Acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV) RECIPIENTS: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment RECIPIENTS: 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 RECIPIENTS: Other medications that might interfere with the evaluation of the investigational product RECIPIENTS: Diagnosis with autoimmune disease RECIPIENTS: Females only: Pregnant women and women who are lactating. The risks of 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 RECIPIENTS: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures RECIPIENTS: 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)
Sites / Locations
- City of Hope Medical Center
- Northside Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Arm I (Triplex vaccination)
Arm II (Placebo)
DONORS: Donors receive Triplex vaccine IM on day 0 and then undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.
DONORS: Donors receive placebo IM on day 0 and undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.