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

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ClinicalTrials.gov Identifier: NCT03560752
Recruitment Status : Recruiting
First Posted : June 18, 2018
Last Update Posted : April 3, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE June 7, 2018
First Posted Date  ICMJE June 18, 2018
Last Update Posted Date April 3, 2020
Actual Study Start Date  ICMJE August 20, 2018
Estimated Primary Completion Date March 18, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2018)
  • Feasibility assessed by number of suitable donor/recipient pairs were approached, and the number that were successfully enrolled/vaccinated [ Time Frame: Up to 1 year ]
  • Incidence of adverse events (AEs) [ Time Frame: Up to 1 year ]
    AEs >= grade 2, probably or definitely related to vaccination will be noted in donors.
  • Non-relapse mortality [ Time Frame: At 100 days post hematopoietic stem cell transplantation (HCT) ]
  • Delayed engraftment [ Time Frame: Up to 1 year ]
  • Severe acute graft versus host disease (aGVHD) [ Time Frame: Up to 1 year ]
  • Grade 3-4 AEs [ Time Frame: Up to 1 year ]
    Will be assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.
  • Therapy induced quantitative/kinetic changes in cytomegalovirus (CMV)-specific cellular immunity [ Time Frame: Up to 1 year ]
    T cells specific for pp65 and/or IE antigens will be measured as a possible correlate to protective function. The frequency of T cells specific for pp65 and/or IE antigens will be measured using CD137 expression assays. These CMV-specific T cells will be further characterized by CD107-associated degranulation, polyfunctional cytokines and cell-surface memory markers.
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
  • Feasibility assessed by number of suitable donor/recipient pairs were approached, and the number that were successfully enrolled/vaccinated [ Time Frame: Up to 1 year ]
  • Incidence of adverse events (AEs) [ Time Frame: Up to 1 year ]
    AEs >= grade 2, probably or definitely related to vaccination will be noted in donors.
  • Non?relapse mortality [ Time Frame: At 100 days post hematopoietic stem cell transplantation (HCT) ]
  • Delayed engraftment [ Time Frame: Up to 1 year ]
  • Severe acute graft versus host disease (aGVHD) [ Time Frame: Up to 1 year ]
  • Grade 3?4 AEs [ Time Frame: Up to 1 year ]
    Will be assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.
  • Therapy induced quantitative/kinetic changes in cytomegalovirus (CMV)?specific cellular immunity [ Time Frame: Up to 1 year ]
    T cells specific for pp65 and/or IE antigens will be measured as a possible correlate to protective function. The frequency of T cells specific for pp65 and/or IE antigens will be measured using CD137 expression assays. These CMV-specific T cells will be further characterized by CD107?associated degranulation, polyfunctional cytokines and cell?surface memory markers.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
CMV protection [ Time Frame: Up to 1 year ]
Will assess incidence of viremia (>= 1250 IU/mL), CMV viral load and use of antivirals (recipients who reactivate CMV and are given antiviral therapy will be considered intervention failures).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CMV-MVA Triplex Vaccination of Stem Cell Donors in Preventing CMV Viremia in Participants With Blood Cancer Undergoing Donor Stem Cell Transplant
Official Title  ICMJE CMV-MVA Triplex Vaccination of Stem Cell Donors to Enhance CMV Specific Immunity and Prevent CMV Viremia in Recipients After Stem Cell Transplant
Brief 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.
Detailed Description

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 -10 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Acute Lymphoblastic Leukemia in Remission
  • Acute Myeloid Leukemia in Remission
  • Chronic Lymphocytic Leukemia
  • Chronic Phase Chronic Myelogenous Leukemia, 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
Intervention  ICMJE Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
Given via injection
Other Name: CMV-MVA Triplex Vaccine
Study Arms  ICMJE Experimental: Prevention(multi-peptide CMV-modified vaccinia Ankara vaccine)
Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization. Participants undergo hematopoietic cell transplantation on day 0.
Intervention: Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 7, 2018)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 18, 2021
Estimated Primary Completion Date March 18, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03560752
Other Study ID Numbers  ICMJE 18007
NCI-2018-01115 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
18007 ( Other Identifier: City of Hope Medical Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ryotaro Nakamura, MD City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP