CMV-MVA Triplex Vaccination of Stem Cell Donors in Preventing CMV Viremia in Participants With Allogeneic Transplant

Launched by CITY OF HOPE MEDICAL CENTER · Jun 7, 2018

Keywords

ClinConnect Summary

This clinical trial is studying a new vaccine called CMV-MVA Triplex, aimed at helping stem cell donors prevent a virus called cytomegalovirus (CMV) from affecting patients receiving transplants. The idea is that by vaccinating the donors before they give their stem cells, it might boost the immune system of the patients and lower the risk of developing CMV-related health issues after the transplant. This trial is focused on patients with various types of blood cancers, such as leukemia and lymphoma, who are planned to receive a stem cell transplant from a related donor.

To participate, donors need to understand the study and agree to receive the vaccine at least two weeks before donating their stem cells. Recipients must be between 18 and 75 years old, have specific types of blood cancers, and be willing to follow up for a year after the transplant. They also need to be CMV positive and matched with their donor in terms of certain genetic markers. Participants in this trial can expect to receive close monitoring throughout the study to ensure their safety and to see how well the vaccine works. It’s important to know that there are specific health requirements for both donors and recipients to be eligible, and those with certain health conditions or who are pregnant cannot participate.

Gender

ALL

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)