Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02396134|
Recruitment Status : Active, not recruiting
First Posted : March 24, 2015
Last Update Posted : February 21, 2022
|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) increases levels, function and kinetics of CMV-specific T cell immunity in vaccinated compared to placebo treated human leukocyte antigen (HLA) A*0201 allogeneic CMV positive hematopoietic stem cell transplant (HCT) recipients (HCT-R+). (Entire cohort) II. To provide a preliminary evaluation of the incidence of CMV reactivation between day 56 and day 180 in patients who receive standard letermovir (Prevymis) prophylaxis (from day 14 through day 100), comparable to the evaluation of an expansion cohort in a pilot study, or the futility stage of a phase II trial. (Letermovir combination cohort) III. To determine if CMVPepVax increases levels, function and kinetics of CMV-specific T cell immunity in vaccinated HCT patients who receive standard Prevymis prophylaxis. (Letermovir combination cohort)
I. To determine, within the constraints of a pilot cohort, if CMVPepVax reduces the frequency of CMV events alone or in combination with Prevymis defined as reactivation or CMV disease in HLA A*0201 allogeneic HCT-R+.
II. 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.
III. 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 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.
IV. To determine whether vaccination induces adaptive natural killer (NK) cell population changes, and increase in the highly cytotoxic memory NKG2C+ NK cells.
V. To determine the impact of CMVPepVax on CMV immune reconstitution in patients who undergo treatment with antiviral agent Prevymis.
VI. To explore GVHD biomarkers and compare between the vaccine and placebo groups.
VII. To characterize CMV reactivation after day 180
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 :||133 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 :||December 21, 2022|
|Estimated Study Completion Date :||December 21, 2022|
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: placebo, Placebo, placebo therapy, PLCB, sham therapy
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.
- Levels of CD8+ T cells binding to A2-cytomegalovirus (CMV)-dextramers [ Time Frame: Up to day 365 after hematopoietic cell transplant ]The longitudinal cytomegalovirus-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.
- CMV reactivation [>= 1,250 IU/mL] or CMV disease in patients who receive standard Prevymis prophylaxis [ Time Frame: Up to 180 days after hematopoietic cell transplant ]
- non-relapse mortality (NRM) [ Time Frame: At 100 days after HCT ]Time of death as day post HCT
- Severe (grade 3-4) aGVHD [ Time Frame: Within 100 days after HCT ]Highest overall grade
- Grade 3-4 AEs (CTCAE version 4.0) probably or definitely related to the vaccination [ Time Frame: Within 2 weeks of vaccination ]MEDDRA code
- Time to viremia [ Time Frame: Between day 56 and 180 days after HCT ]Number of days from transplantation to the first date of >= 500 CMV gc/mL (or antiviral therapy)
- Duration of viremia [ Time Frame: Up to 365 days after HCT ]Duration (days) between the date of first viremia episode (outcome #7) and date of undetectable of viremia
- Incidence of late CMV viremia [ Time Frame: From 180 through 360 days after HCT ]Number of days from transplantation to the first date of >= 500 CMV gc/mL (or antiviral therapy) after day 180, either as a first event or a recurrence after earlier viremia became non-detectable
- Use of antiviral drugs [ Time Frame: Up to 365 days after HCT ]Day post-HCT of first CMV-directed antiviral dose
- Cumulative number of CMV specific antiviral treatment days [ Time Frame: Up to 365 days after HCT ]Total number of days of treatment during time frame
- Time to engraftment [ Time Frame: Up to 365 days after HCT ]Day post HCT of first adequate cell count
- Incidence of aGVHD [ Time Frame: Within 100 days after HCT ]Day of first aGVHD of any grade
- Incidence of cGVHD [ Time Frame: Up to 365 days after HCT ]Day of first cGVHD
- Incidence of relapse [ Time Frame: Up to 365 days after HCT ]Day of relapse
- All-cause mortality [ Time Frame: Up to 365 days after HCT ]Day of death
- Incidence of non-CMV infections [ Time Frame: Up to 365 days after HCT ]Day of infection
- CMV reactivation (>= 1,250 IU/mL) or CMV disease post-HCT [ Time Frame: Up to 180 days after hematopoietic cell transplant ]Day of event
- Immune reconstitution measured as levels, function and kinetics of CMV-specific T cells through day 365 post-HCT in patients who receive standard Prevymis prophylaxis (day 14 through day 100). [ Time Frame: at days 28, 42, 56, 70, 84, 100, 140, 180, 270 and 365 after hematopoietic cell transplant ]The measurement of function is determined by "dextramer-binding CD8 T cells/microliter, and "kinetics" will be determined as "% change" from the baseline (day 28) value at each time point below
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|