Multi-antigen CMV-Modified Vaccinia Ankara Vaccine in Reducing CMV Related Complications in Patients With Blood Cancer Undergoing Donor Stem Cell Transplant
|ClinicalTrials.gov Identifier: NCT03438344|
Recruitment Status : Withdrawn (PI Withdrawal)
First Posted : February 19, 2018
Last Update Posted : November 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia in Remission Bone Marrow Transplantation Recipient Chronic Lymphocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Hematopoietic Cell Transplantation Recipient Hodgkin Lymphoma Myelodysplastic Syndrome Myelofibrosis Myeloproliferative Neoplasm Non-Hodgkin Lymphoma||Biological: Multi-antigen CMV-Modified Vaccinia Ankara Vaccine Other: Laboratory Biomarker Analysis Other: Placebo||Phase 2|
I. To determine if multi-antigen CMV-modified vaccinia Ankara vaccine (CMV-modified vaccinia Ankara [MVA] triplex) reduces the frequency of CMV events, defined as reactivation or CMV disease in CMV+, haploidentical hematopoietic cell transplantation (haploHCT) recipients.
I. To evaluate the safety and tolerability of CMV-MVA triplex in vaccinated, haploHCT recipients by assessing the following: non-relapse mortality (NRM) at 100 days post hematopoietic cell transplantation (HCT), severe (grade 3-4) acute graft versus host disease (GVHD), and grade 3-4 adverse events (AEs) probably or definitely related to the vaccination within 2 weeks from each vaccination.
II. To characterize CMV related events in recipients of CMV-MVA triplex compared to placebo, by assessing time to viremia (number of days from transplantation to the date of >= 1250 IU/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 >= 1250 IU/mL), cumulative number of CMV specific antiviral treatment days.
III. To evaluate the impact of CMV-MVA triplex on transplant related outcomes by assessing the incidence of acute graft versus host disease (aGVHD), chronic GVHD, relapse, non-relapse mortality, all-cause mortality, infections.
IV. To determine if CMV-MVA triplex increases levels, function and kinetics of CMV-specific T cell immunity in vaccinated compared to placebo treated, CMV seropositive HCT-recipients.
V. To determine whether vaccination induces adaptive natural killer (NK) cell population changes, and increase in the highly cytotoxic memory NKG2C+ NK cell.
VI. To compare GVHD biomarkers between the vaccine and placebo groups.
OUTLINE: Patients are randomized into 1 of 2 arms.
ARM I: Patients receive multi-antigen CMV-modified vaccinia Ankara 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 treatment, patients are followed up at 100, 140, 180, 270, and 365 days, and then periodically for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 a Haploidentical Hematopoietic Stem Cell Transplant|
|Estimated Study Start Date :||December 2018|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Arm I (CMV-MVA triplex vaccine)
Patients receive multi-antigen CMV-modified vaccinia Ankara vaccine via injection on days 28 and 56 post-HCT.
Biological: Multi-antigen CMV-Modified Vaccinia Ankara Vaccine
Other Name: CMV-MVA Triplex Vaccine
Other: Laboratory Biomarker Analysis
Placebo Comparator: Arm II (placebo)
Patients receive placebo via injection on days 28 and 56 post-HCT.
Other: Laboratory Biomarker Analysis
- Cytomegalovirus (CMV) events [ Time Frame: Up to 3 years ]Will include any CMV reactivation (detection of >= 1250 U/mL plasma), low-level reactivation prompting antiviral therapy, or CMV disease (defined by histology) prior to day 100 post-hematopoietic cell transplantation (HCT).
- Non-relapse mortality (NRM) [ Time Frame: At 100 days post HCT ]
- Severe (grade 3-4) acute graft versus host disease (GVHD) [ Time Frame: Up to 3 years ]
- Grade 3-4 adverse events probably/definitely related to the vaccination and modified vaccinia Ankara vector persistence [ Time Frame: Up to 3 years ]
- Duration of viremia [ Time Frame: Up to 3 years ]The primary statistical analyses will compare vaccine and placebo regarding hazards of CMV events from injection to day 100. Events prior to injection will inform Kaplan Meier estimates for both arms to obtain unbiased estimates of reactivation rates applicable to all transplanted subjects on each arm.
- Duration of anti-CMV therapy [ Time Frame: Up to 3 years ]
- Peak CMV polymerase chain reaction value [ Time Frame: Up to 3 years ]
- Recurrence of CMV viremia [ Time Frame: Up to 3 years ]
- Incidence of late CMV reactivation or disease [ Time Frame: Up to 3 years ]
- Time to engraftment [ Time Frame: Up to 3 years ]
- Incidence of acute GVHD [ Time Frame: Up to 3 years ]Will be scored using Keystone consensus criteria. Whenever possible, acute GVHD will be confirmed histologically with microscopic review.
- Incidence of chronic GVHD [ Time Frame: Up to 3 years ]
- Relapse [ Time Frame: Up to 3 years ]
- Non-relapse mortality [ Time Frame: Up to 3 years ]
- All-cause mortality [ Time Frame: Up to 3 years ]
- Infections [ Time Frame: Up to 3 years ]
- Overall survival [ Time Frame: Up to 3 years ]
- Levels of CMV-specific T cell immunity [ Time Frame: Up to 3 years ]Will also assess immunophenotyping and function.
- Natural killer cell function [ Time Frame: Up to 3 years ]Will assess cytotoxicity of NK cells against K562 target cell line compared with control (% killing) and cytokine production using flow-cytometry with intra-cellular staining of gamma-interferon and other cytokines (% of NK cells producing these cytokines).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03438344
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|United States, Georgia|
|Atlanta, Georgia, United States, 30342|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Ryotaro Nakamura, MD||City of Hope Medical Center|