Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant
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|ClinicalTrials.gov Identifier: NCT02396134|
Recruitment Status : Active, not recruiting
First Posted : March 24, 2015
Last Update Posted : December 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Hodgkin Lymphoma Adult Non-Hodgkin Lymphoma Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Cytomegaloviral Infection Hematopoietic and Lymphoid Cell Neoplasm HLA-A*0201 Positive Cells Present Myelodysplastic Syndrome Adult Lymphoblastic Lymphoma Chronic Lymphocytic Leukemia Myelofibrosis Myeloproliferative Neoplasm||Biological: CMVpp65-A*0201 peptide vaccine Other: Placebo Other: Laboratory Biomarker Analysis||Phase 2|
I. To determine if cytomegalovirus (CMV)peptide(Pep)vaccine(Vax) (CMVpp65-A*0201 peptide vaccine) reduces the frequency of CMV events defined as reactivation or CMV disease in human leukocyte antigen (HLA) A*0201 allogeneic CMV positive hematopoietic stem cell transplant (HCT) recipients (HCT-R+).
I. To evaluate the safety and tolerability of CMVPepVax 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 characterize CMV reactivation and CMV disease in recipients of CMVPepVax compared to placebo by assessing time-to viremia (defined as number of days from transplantation to the date of >= 500 CMV genome copies [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), cumulative number of CMV specific antiviral treatment days.
III. To evaluate the impact of CMVPepVax on transplant related outcomes by assessing the incidence of acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, non-relapse mortality, all-cause mortality, infections.
IV. To determine if CMVPepVax increases levels, function and kinetics of CMV-specific T cell immunity in vaccinated compared to placebo treated HLA A*0201, 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 cells.
VI. 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 CMVpp65-A*0201 peptide vaccine subcutaneously (SC) on days 28 and 56 after HCT.
ARM II: Patients receive placebo SC on days 28 and 56 after HCT.
After completion of study treatment, patients are followed up to day 365 after HCT.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||96 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Supportive Care|
|Official Title:||A Phase II Randomized, Placebo-Controlled, Multicenter Trial to Evaluate Protective Function of an Optimized Dose of CMVPepVax in Recipients of an Allogeneic Hematopoietic Stem Cell Transplant|
|Actual Study Start Date :||May 21, 2015|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||June 2019|
Experimental: Arm I (CMVpp65-A*0201 peptide vaccine)
Patients receive CMVpp65-A*0201 peptide vaccine SC on days 28 and 56 after HCT.
Biological: CMVpp65-A*0201 peptide vaccine
Other: Laboratory Biomarker Analysis
Placebo Comparator: Arm II (placebo)
Patients receive placebo SC on days 28 and 56 after HCT.
Other Name: PLCB
Other: Laboratory Biomarker Analysis
- CMV events encompassing any CMV reactivation defined as >= 500 CMV gc/mL or CMV disease [ Time Frame: Up to day 100 after HCT ]Each randomized study subject will be followed according to the study calendar for the occurrence of CMV reactivation events, which are defined in terms of either viremia, low-level viremia treated with antivirals, or CMV disease. Both initial and recurrent events will be recorded, with patients considered at risk for recurrent events after completion of a full planned course of a full course of anti-viral therapy. Vaccine and placebo groups will be compared with regard to the hazard of CMV events, using the Anderson-Gill approach to repeated events.
- non-relapse mortality (NRM) [ Time Frame: At 100 days after HCT ]
- Severe (grade 3-4) aGVHD probably or definitely related to the vaccination [ Time Frame: Within 100 days after HCT ]
- Grade 3-4 AEs graded by CTCAE version 4.0 probably or definitely related to the vaccination [ Time Frame: Within 2 weeks of vaccination ]
- Time to viremia [ Time Frame: Up to 365 days after HCT ]Defined as the number of days from transplantation to the date of >= 500 CMV gc/mL
- Duration of viremia [ Time Frame: Up to 365 days after HCT ]
- Incidence of late CMV viremia [ Time Frame: Up to 360 days after HCT ]
- Use of antiviral drugs triggered by clinically significant viremia >= 1,500 CMV gc/mL [ Time Frame: Up to 365 days after HCT ]
- Cumulative number of CMV specific antiviral treatment days [ Time Frame: Up to 365 days after HCT ]
- Time to engraftment [ Time Frame: Up to 365 days after HCT ]
- Incidence of aGVHD [ Time Frame: Within 100 days after HCT ]
- Incidence of cGVHD [ Time Frame: Up to 365 days after HCT ]
- Incidence of relapse [ Time Frame: Up to 365 days after HCT ]
- All-cause mortality [ Time Frame: Up to 365 days after HCT ]
- Incidence of infections [ Time Frame: Up to 365 days after HCT ]
- PD-1 expression [ Time Frame: Up to day 365 after HCT ]
- NK phenotype assessed by change in cytotoxicity [ Time Frame: From day 28 to day 365 after HCT ]
- NK function assessed by change in cytokine production [ Time Frame: From day 28 to day 365 after HCT ]
- Levels of CD8+ T cells binding to A2-CMV-dextramers [ Time Frame: Up to day 365 after HCT ]The longitudinal CMV-specific cellular assay data will be modeled on a logarithmic scale, using a generalized estimating equation approach to accommodate the stochastic dependence through time. This produces an estimated multiplicative effect of vaccination, qualified by a valid estimate of variability.
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): NCT02396134
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Minnesota|
|University of Minnesota/Masonic Cancer Center|
|Minneapolis, Minnesota, United States, 55455|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Ryotaro Nakamura, MD||City of Hope Medical Center|