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CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant

Primary Purpose

Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Biospecimen Collection
Granulocyte Colony-Stimulating Factor
Hematopoietic Cell Transplantation Conditioning Regimen
Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
Pheresis
Placebo Administration
Stem Cell Mobilization Therapy
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (Triplex vaccination)

Arm II (Placebo)

Arm Description

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.

Outcomes

Primary Outcome Measures

Time from transplantation to cytomegalovirus (CMV) disease or pre-emptive treatment following CMV reactivation (efficacy)
A stratified Cox regression analysis of time to CMV disease or positron emission tomography (PET) following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Occurrence of non-relapse mortality (safety in HCT-recipients)
A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Incidence of severe acute graft versus host disease (aGHVD) (safety in HCT-recipients)
Severe aGHVD defined as grades 3-4. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Incidence of severe adverse events (AEs) (safety in HCT-recipients)
Probably or definitely related to the vaccination per Common Terminology Criteria for Adverse Events version 5.0. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Incidence of grade 3 and higher AEs (safety in HCT-donors)
A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.

Secondary Outcome Measures

Time-to viremia (CMV-related events)
The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.
Duration of viremia (CMV-related events)
The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.
Incidence of late CMV viremia (CMV-related events)
The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.
Use of antiviral drugs (CMV-related events)
Triggered by clinically significant viremia or CMV disease.
Cumulative number of CMV specific antiviral treatment days (CMV-related events)
Incidence of CMV disease (CMV-related events)
Time to engraftment (transplant-related events)
Incidence of aGVHD and chronic GVHD (transplant-related events)
Estimated using the Kaplan-Meier or Fine-Gray estimators, as appropriate, and compared using the log-rank test or the corresponding sub-distribution test of Gray.
Incidence of relapse (transplant-related events)
Estimated using the Kaplan-Meier or Fine-Gray estimators, as appropriate, and compared using the log-rank test or the corresponding sub-distribution test of Gray.
Non-relapse mortality (transplant-related events)
All-cause mortality (transplant-related events)
Incidence of infections (transplant-related events)
Estimated using the Kaplan-Meier or Fine-Gray estimators, as appropriate, and compared using the log-rank test or the corresponding sub-distribution test of Gray.
Levels and kinetics of CMV-specific T cell immunity, combined with immunophenotyping, and functional studies (immunological function)
Generalized estimating equations will be used to estimate the effect of Triplex on log10-transformed concentration of CMV-specific T cells measured post-HCT. Initial regression model will include an indicator variable for Triplex vaccine status of the donor, study day as a categorical variable, and vaccine status by study day interaction term (saturated model). For each post-HCT day, difference in average log-10 concentration between study arms and its 95% confidence interval will be calculated. Primary analysis will include all post-HCT measurements. Additional analyses will be conducted in which measurements after CMV reactivation are excluded.

Full Information

First Posted
September 22, 2023
Last Updated
September 22, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT06059391
Brief Title
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Official Title
Placebo-Controlled and Randomized Phase 2 Trial of CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors to Enhance CMV-Specific Immunity and Prevent CMV Viremia in Recipients After Hematopoietic Stem Cell Transplant
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 25, 2023 (Anticipated)
Primary Completion Date
August 14, 2025 (Anticipated)
Study Completion Date
August 14, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II clinical trial tests how well the cytomegalovirus-modified vaccinica Ankara (CMV-MVA) Triplex vaccine given to human leukocyte antigens (HLA) matched related stem cell donors works to prevent cytomegalovirus (CMV) infection in patients undergoing hematopoietic stem cell transplant. The CMV-MVA Triplex vaccine works by causing an immune response in the donors body to the CMV virus, creating immunity to it. The donor then passes that immunity on to the patient upon receiving the stem cell transplant. Giving the CMV-MVA triplex vaccine to donors may help prevent CMV infection of patients undergoing stem cell transplantation.
Detailed Description
PRIMARY OBJECTIVE: I. To determine whether multi-peptide CMV-modified vaccinia Ankara vaccine (Triplex) is safe and effective in protecting against CMV events defined as viremia requiring antiviral preemptive therapy (PET) or CMV end organ disease. SECONDARY OBJECTIVE: I. To examine if Triplex vaccination of hematopoietic stem cell transplant (HCT) donors has an impact on CMV events. OUTLINE: Donors are randomized to 1 of 2 arms. ARM I: DONORS: Donors receive Triplex vaccine intramuscularly (IM) on day 0 and then undergo stem cell mobilization with granulocyte colony-stimulating factor (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. ARM II: 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. After completion of study treatment, donors follow up on days 90, 180 and 365 after vaccination and recipients follow up on days 14, 28, 42, 56, 70, 100, 140, 180, 270, and 365 after transplantation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, BCR-ABL1 Positive, Hematopoietic and Lymphoid System Neoplasm, Hodgkin Lymphoma, Myelodysplastic Syndrome, Myelofibrosis, Myeloproliferative Neoplasm, Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This trial is observer-blinded because of the handling of the vaccine and the placebo may vary. The investigators, treating clinicians, participants, and other study staff, including the nurses involved in soliciting or recording of adverse events, will be blinded through the day 180 visit.
Allocation
Randomized
Enrollment
216 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (Triplex vaccination)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (Placebo)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic
Intervention Description
Undergo HCT with donor peripheral blood stem cells
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo blood sample collection
Intervention Type
Drug
Intervention Name(s)
Granulocyte Colony-Stimulating Factor
Other Intervention Name(s)
Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, GCSF, Granulocyte Colony Stimulating Factor, Pluripoietin
Intervention Description
Undergo stem cell mobilization with G-CSF
Intervention Type
Drug
Intervention Name(s)
Hematopoietic Cell Transplantation Conditioning Regimen
Other Intervention Name(s)
HCT Conditioning Regimen, HSCT Conditioning Regimen, Stem Cell Transplant Conditioning
Intervention Description
Receive pre transplant conditioning
Intervention Type
Biological
Intervention Name(s)
Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
Other Intervention Name(s)
CMV-MVA Triplex Vaccine, Multi-antigen CMV-Modified Vaccinia Ankara Vaccine
Intervention Description
Given IM
Intervention Type
Procedure
Intervention Name(s)
Pheresis
Other Intervention Name(s)
Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis, Hemapheresis
Intervention Description
Undergo apheresis
Intervention Type
Drug
Intervention Name(s)
Placebo Administration
Intervention Description
Given IM
Intervention Type
Drug
Intervention Name(s)
Stem Cell Mobilization Therapy
Other Intervention Name(s)
Chemomobilization, Hematopoietic Stem Cell Mobilization, Mobilization Therapy, Stem-cell mobilization
Intervention Description
Undergo stem cell mobilization with G-CSF
Primary Outcome Measure Information:
Title
Time from transplantation to cytomegalovirus (CMV) disease or pre-emptive treatment following CMV reactivation (efficacy)
Description
A stratified Cox regression analysis of time to CMV disease or positron emission tomography (PET) following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Time Frame
From hematopoietic stem cell transplantation (HCT) to day 180
Title
Occurrence of non-relapse mortality (safety in HCT-recipients)
Description
A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Time Frame
Up to day 100 post HCT
Title
Incidence of severe acute graft versus host disease (aGHVD) (safety in HCT-recipients)
Description
Severe aGHVD defined as grades 3-4. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Time Frame
Up to 100 days post HCT
Title
Incidence of severe adverse events (AEs) (safety in HCT-recipients)
Description
Probably or definitely related to the vaccination per Common Terminology Criteria for Adverse Events version 5.0. A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Time Frame
Within 2 weeks from transplantation and up to 1 year post HCT
Title
Incidence of grade 3 and higher AEs (safety in HCT-donors)
Description
A stratified Cox regression analysis of time to CMV disease or PET following CMV reactivation prior to Day 180 post-HCT will be performed. The estimated hazard ratio and its 95% confidence interval will be calculated. Secondary analyses will include the Fine-Gray model for competing risk.
Time Frame
Within 14 days
Secondary Outcome Measure Information:
Title
Time-to viremia (CMV-related events)
Description
The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.
Time Frame
From transplantation to the date of two consecutive CMV quantitative polymerase chain reaction (qPCR) > 500 gc/mL/465 IU/mL or single event of CMV qPCR >1500 CMV gc/mL/1,395 IU/mL, assessed up to 1 year post HCT
Title
Duration of viremia (CMV-related events)
Description
The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.
Time Frame
Up to 1 year post HCT
Title
Incidence of late CMV viremia (CMV-related events)
Description
The number and percentage of recipients who receive treatment prior to the study recommended level of CMV viremia for PET will be tabulated by treatment group. Total days on antivirals for CMV reactivation (induction, maintenance, and total) will be assessed for each HCT recipient with treatment groups compared using Wilcoxson's rank sum test. Other characterizations of viremia and response to therapy will be descriptive in nature.
Time Frame
Between days 100-365 post HCT
Title
Use of antiviral drugs (CMV-related events)
Description
Triggered by clinically significant viremia or CMV disease.
Time Frame
Up to 1 year post HCT
Title
Cumulative number of CMV specific antiviral treatment days (CMV-related events)
Time Frame
Up to 1 year post HCT
Title
Incidence of CMV disease (CMV-related events)
Time Frame
Up to 1 year post HCT
Title
Time to engraftment (transplant-related events)
Time Frame
Up to 1 year post HCT
Title
Incidence of aGVHD and chronic GVHD (transplant-related events)
Description
Estimated using the Kaplan-Meier or Fine-Gray estimators, as appropriate, and compared using the log-rank test or the corresponding sub-distribution test of Gray.
Time Frame
Up to 1 year post HCT
Title
Incidence of relapse (transplant-related events)
Description
Estimated using the Kaplan-Meier or Fine-Gray estimators, as appropriate, and compared using the log-rank test or the corresponding sub-distribution test of Gray.
Time Frame
Up to 1 year post HCT
Title
Non-relapse mortality (transplant-related events)
Time Frame
Up to 1 year post HCT
Title
All-cause mortality (transplant-related events)
Time Frame
Up to 1 year post HCT
Title
Incidence of infections (transplant-related events)
Description
Estimated using the Kaplan-Meier or Fine-Gray estimators, as appropriate, and compared using the log-rank test or the corresponding sub-distribution test of Gray.
Time Frame
Up to 1 year post HCT
Title
Levels and kinetics of CMV-specific T cell immunity, combined with immunophenotyping, and functional studies (immunological function)
Description
Generalized estimating equations will be used to estimate the effect of Triplex on log10-transformed concentration of CMV-specific T cells measured post-HCT. Initial regression model will include an indicator variable for Triplex vaccine status of the donor, study day as a categorical variable, and vaccine status by study day interaction term (saturated model). For each post-HCT day, difference in average log-10 concentration between study arms and its 95% confidence interval will be calculated. Primary analysis will include all post-HCT measurements. Additional analyses will be conducted in which measurements after CMV reactivation are excluded.
Time Frame
Up to 1 year post HCT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vaibhav Agrawal
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vaibhav Agrawal
Phone
626-256-4673
Ext
62705
Email
vagrawal@coh.org
First Name & Middle Initial & Last Name & Degree
Vaibhav Agrawal
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Scott R. Solomon
Phone
404-255-1930
Email
ssolomon@bmtga.com
First Name & Middle Initial & Last Name & Degree
Scott R. Solomon

12. IPD Sharing Statement

Learn more about this trial

CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant

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