Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant
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|ClinicalTrials.gov Identifier: NCT02506933|
Recruitment Status : Active, not recruiting
First Posted : July 23, 2015
Results First Posted : April 14, 2023
Last Update Posted : April 14, 2023
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|Condition or disease||Intervention/treatment||Phase|
|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 Cytomegaloviral Infection Hodgkin Lymphoma Lymphadenopathy Lymphoblastic Lymphoma Myelodysplastic Syndrome Myelofibrosis Myeloproliferative Neoplasm Non-Hodgkin Lymphoma||Other: Laboratory Biomarker Analysis Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine Other: Placebo||Phase 2|
I. To evaluate the safety and tolerability of CMV-MVA Triplex (multi-peptide CMV-MVA vaccine) in vaccinated hematopoietic cell transplant (HCT) recipients by assessing the following: non-relapse mortality (NRM) at 100 days post HCT, severe (grade 3-4) acute graft-versus-host disease (GVHD) (aGVHD), and grade 3-4 adverse events (AEs) (Common Terminology Criteria for Adverse Events [CTCAE] 4.0) probably or definitely related to the vaccination within 2 weeks from each vaccination.
II. To determine if CMV-MVA Triplex reduces the frequency of CMV events defined as reactivation or CMV disease in allogeneic CMV positive HCT recipients (HCT-R+).
I. To characterize CMV reactivation and CMV disease in recipients of CMV-MVA Triplex compared to placebo by assessing time-to viremia (defined as number of days from transplantation to the date of > 500 CMV gc/mL), duration of viremia, recurrence of viremia, incidence of late CMV viremia/disease (> 100 and =< 360 days post HCT), use of antiviral drugs (triggered by clinically significant viremia of >= 1500 CMV gc/mL), cumulative number of CMV specific antiviral treatment days.
II. To evaluate the impact of CMV-MVA Triplex on transplant related outcomes by assessing the incidence of acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, non-relapse mortality, all-cause mortality, infections.
III. To determine 1) if CMV-MVA Triplex increases levels, function and kinetics of CMV-specific T cell immunity in vaccinated compared to placebo treated human leukocyte antigen (HLA) A*0201, CMV seropositive HCT-recipients, 2) to determine whether vaccination induces adaptive natural killer (NK) cell population changes, and increase in the highly cytotoxic memory killer cell lectin-like receptor subfamily C, member 2 (NKG2C)+ NK cells, and 3) to explore GVHD biomarkers and compare between the vaccine and placebo groups.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive multi-peptide CMV-MVA vaccine intramuscularly (IM) on days 28 and 56 post-HCT.
ARM II: Patients receive placebo IM on days 28 and 56 post-HCT.
After completion of study, patients are followed up for 1 year post-HCT.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||102 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Supportive Care|
|Official Title:||A Phase II Randomized, Placebo-Controlled, Multicenter Trial to Evaluate the Protective Function of a CMV-MVA Triplex Vaccine in Recipients of an Allogeneic Hematopoietic Stem Cell Transplant|
|Actual Study Start Date :||November 5, 2015|
|Actual Primary Completion Date :||January 25, 2018|
|Estimated Study Completion Date :||December 30, 2023|
Experimental: Arm I (multi-peptide CMV-MVA vaccine)
Patients receive multi-peptide CMV-MVA vaccine IM on days 28 and 56 post-HCT.
Other: Laboratory Biomarker Analysis
Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
Other Name: CMV-MVA Triplex Vaccine
Placebo Comparator: Arm II (placebo)
Patients receive placebo IM on days 28 and 56 post-HCT.
Other: Laboratory Biomarker Analysis
- Cytomegalovirus (CMV) Events to Day 100 [ Time Frame: Prior to day 100 post-HCT ]Cytomegalovirus (CMV) events included CMV reactivation ≥1250 CMV DNA IU/mL, CMV viremia prompting antiviral therapy, or CMV disease before day 100 after HCT.
- Incidence of Severe (Grade 3-4) Acute Graft-Versus-Host Disease [ Time Frame: Up to 100 days post-transplant ]Severe acute graft-versus-host disease (aGVHD, grade 3-4) was monitored as every 12th subject on the vaccine arm reaches the 100 day evaluation point. aGVHD was scored using Keystone consensus criteria [Przepiorka, D., et al., 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant, 1995. 15(6): p. 825-8].
- All-cause Mortality [ Time Frame: Up to 1 year post-HCT ]Death due to any cause.
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|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- All subjects must have the ability to understand and the willingness to sign a written informed consent
- Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT
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 (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status must be in hematologic remission by bone marrow and peripheral blood; persistent lymphadenopathy on computed tomography [CT] or CT/positron emission tomography (PET) scan without progression is allowed)
- Acute myeloid leukemia in first or second remission
- Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase
- Other hematologic malignancies including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis; patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded
- Patients undergoing a second allogeneic (allo) HCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
- CMV seropositive (recipient)
- Planned related or unrelated HCT, with 8/8 (A,B,C,DRB1) high/intermediate resolution HLA donor allele matching
- Planned HCT with minimal to no-T cell depletion of graft
- Conditioning and immunosuppressive regimens according to institutional guidelines are permitted
- Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within two weeks of registration
- Seronegative for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and active hepatitis B virus (HBV) (surface antigen negative) within 2 months of registration
- Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control 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
- Any prior investigational CMV vaccine
- Experimental anti-CMV chemotherapy in the last 6 months
- Live attenuated vaccines
- 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)
- Allergy treatment with antigens injections
- Alemtuzumab or any equivalent in vivo T-cell depleting agent
- Antiviral medications with known therapeutic effects on CMV such as ganciclovir (GCV)/valganciclovir (VAL), foscarnet (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)
- Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment
- 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
- Other medications that might interfere with the evaluation of the investigational product
- Patients with active autoimmune conditions requiring systemic immunosuppressive therapy within the previous 5 years are not eligible
- Pregnant women and women who are lactating; breastfeeding should be discontinued if the mother is enrolled on this study
- 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
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02506933
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Ryotaro Nakamura, MD||City of Hope Medical Center|
Documents provided by City of Hope Medical Center:
|Responsible Party:||City of Hope Medical Center|
|Other Study ID Numbers:||
NCI-2015-01228 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
14295 ( Other Identifier: City of Hope Medical Center )
R01CA077544 ( U.S. NIH Grant/Contract )
|First Posted:||July 23, 2015 Key Record Dates|
|Results First Posted:||April 14, 2023|
|Last Update Posted:||April 14, 2023|
|Last Verified:||March 2023|
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Accelerated Phase
Neoplasms by Histologic Type
Immune System Diseases
Bone Marrow Diseases
DNA Virus Infections