CompletedNCT02396134Updated Mar 3, 2025Results posted

Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

A Phase 2 interventional study of CMVpp65-A*0201 peptide vaccine and Placebo in Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Adult Acute Lymphoblastic Leukemia in Remission and Adult Acute Myeloid Leukemia in Remission, sponsored by City of Hope Medical Center. Completed at 5 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-03-03.

Sponsored by City of Hope Medical Center · Phase 2, Interventional, and Supportive care

Phase: Phase 2
Study type: Interventional
Enrollment: 61
Allocation: Randomized
Ages: 18 Years to 75 Years
Sex: All

Study summary

This randomized phase II trial studies how well vaccine therapy works in reducing the frequency of cytomegalovirus severe infections (events) in patients with hematologic malignancies undergoing donor stem cell transplant. Vaccines made from a peptide may help the body build an effective immune response and may reduce cytomegalovirus events after donor stem cell transplant.

Read the detailed description

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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.

Conditions studied

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

Browse trials for

In context

Cytomegalovirus Infections

359 studies on the registry are indexed under Cytomegalovirus Infections; 59 are open to participants now.

This study's enrollment of 61 is close to the median of 60 across 233 interventional studies indexed under Cytomegalovirus Infections.

Browse Cytomegalovirus Infections studies →

Lead sponsor

City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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 needs to 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
HLA A*0201 High resolution, 4-digit typing is required at HLA-A2 to ensure A*0201 status.
CMV seropositive (recipient)
Planned related or unrelated HCT, with HLA donor allele matching; related donor must be an 8/8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing; unrelated donor must be an 8/8 match at HLA-A, -B, -C, and -DRB1 at high resolution using DNA-based typing; patients undergoing a second allo HCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
Planned HCT with no ex-vivo 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

Exclusion criteria

Exclusion Criteria:

Any prior investigational CMV vaccine
Experimental anti-CMV chemotherapy in the last 6 months
Planned medications from the time of HCT to day 70 post-HCT:
- Live attenuated vaccines
- Medically indicated subunit (Engerix-B for HBV; Gardasil for human papilloma virus [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; this includes anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide
- Antiviral medications with known therapeutic effects against CMV such as ganciclovir (GCV)/valine (VAL), foscarnet (FOS), cidofovir, hexadecyloxypropyl-cidofovir (CMX-001) and maribavir; acyclovir has no therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)
- Other investigational product - concurrent enrollment in other clinical trials using an investigational product 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)

Study design

Phase: Phase 2
Primary purpose: Supportive care
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 61 participants (actual)

Study arms

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: Placebo · Other: Laboratory Biomarker Analysis

Interventions

BiologicalCMVpp65-A*0201 peptide vaccine
Given SC
OtherPlacebo
Given SC
Also known as: placebo, Placebo, placebo therapy, PLCB, sham therapy
OtherLaboratory Biomarker Analysis
Correlative studies

What researchers measure

Primary outcomes

Cumulative Incidence of CMV at 100 Days
The primary endpoint was CMV event. A CMV event encompasses detection of CMV by either qPCR (termed "reactivation": DNAemia at ≥500 gc/ml = 1250iu/ml) or by tissue histology (end-organ disease). The cumulative incidence was calculated as competing risks using the method of Gooley with death viewed as a competing risk.
Time frame: Up to day 100 after HCT

Secondary outcomes

Non-Relapse Mortality (NRM) at 100 Days
NRM was defined as death without recurrent or progressive disease after transplant. Probabilities of NRM were calculated as competing risks using the method of Gooley with relapse viewed as a competing risk.
Time frame: Up to 100 days after transplant
Cumulative Incidence of Relapse at One Year
Probabilities of relapse were calculated as competing risks using the method of Gooley with death viewed as a competing risk.
Time frame: Up to 365 days after HCT

Results

Posted Jul 12, 2023

Participant flow

Participant flow — Overall Study
Milestone	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)
Started	32	29
Completed	32	29
Not completed	0	0

Outcome measures

PrimaryCumulative Incidence of CMV at 100 Days

The primary endpoint was CMV event. A CMV event encompasses detection of CMV by either qPCR (termed "reactivation": DNAemia at ≥500 gc/ml = 1250iu/ml) or by tissue histology (end-organ disease). The cumulative incidence was calculated as competing risks using the method of Gooley with death viewed as a competing risk.

Time frame:: Up to day 100 after HCT
Reported as:: Number · cases per 100 persons

Cumulative Incidence of CMV at 100 Days
cases per 100 persons	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)
Cumulative Incidence of CMV at 100 Days	25.1 (11.6 to 41.2)	13.8 (4.2 to 28.9)

SecondaryNon-Relapse Mortality (NRM) at 100 Days

NRM was defined as death without recurrent or progressive disease after transplant. Probabilities of NRM were calculated as competing risks using the method of Gooley with relapse viewed as a competing risk.

Time frame:: Up to 100 days after transplant
Reported as:: Number · cases per 100 persons

Non-Relapse Mortality (NRM) at 100 Days
cases per 100 persons	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)
Non-Relapse Mortality (NRM) at 100 Days	3.1 (0.2 to 14.0)	3.4 (0.2 to 15.3)

SecondaryCumulative Incidence of Relapse at One Year

Probabilities of relapse were calculated as competing risks using the method of Gooley with death viewed as a competing risk.

Time frame:: Up to 365 days after HCT
Reported as:: Number · cases per 100 persons

Cumulative Incidence of Relapse at One Year
cases per 100 persons	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)
Cumulative Incidence of Relapse at One Year	12.5 (3.9 to 26.5)	25.7 (11.1 to 43.3)

Adverse events

Collected over Adverse Events monitored/assessed up to 100 days post-transplant. All-Cause Mortality monitored/assessed up to 1 year post-transplant.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm I (CMVpp65-A*0201 Peptide Vaccine)	8/32 (25%)	10/32 (31.3%)	28/32 (87.5%)
Arm II (Placebo)	4/29 (13.8%)	7/29 (24.1%)	26/29 (89.7%)

Most frequent serious events

Showing 10 of 21

Most frequent serious events
Event	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)
FeverGeneral disorders	3/32	2/29
Sinus tachycardiaCardiac disorders	0/32	1/29
HematocheziaGastrointestinal disorders	0/32	1/29
Hospitalization for worsening GVHD symptomsGeneral disorders	0/32	1/29
Lung infectionInfections and infestations	1/32	1/29
DehydrationMetabolism and nutrition disorders	0/32	1/29
Electrolyte derangementsMetabolism and nutrition disorders	0/32	1/29
HyperglycemiaMetabolism and nutrition disorders	0/32	1/29
syncopeNervous system disorders	0/32	1/29
ConfusionPsychiatric disorders	0/32	1/29

Most frequent other events

Showing 10 of 157

Most frequent other events
Event	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)
AnemiaBlood and lymphatic system disorders	21/32	22/29
Lymphocyte count decreasedInvestigations	20/32	21/29
HypertensionVascular disorders	21/32	19/29
White blood cell decreasedInvestigations	18/32	18/29
Platelet count decreasedInvestigations	19/32	14/29
HyperglycemiaMetabolism and nutrition disorders	16/32	17/29
FatigueGeneral disorders	14/32	15/29
NauseaGastrointestinal disorders	16/32	11/29
HypomagnesemiaMetabolism and nutrition disorders	16/32	9/29
HyponatremiaMetabolism and nutrition disorders	15/32	14/29

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)	Total
Median	61 (25 to 72)	64 (28 to 74)	62 (25 to 74)

Sex: Female, Male
Sex: Female, Male(Participants)	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)	Total
Female	13	5	18
Male	19	24	43

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)	Total
White	21	20	41
Hispanic	9	8	17
Asian	1	0	1
Black	0	1	1
Non-disclosed	1	0	1

Region of Enrollment
Region of Enrollment(participants)	Arm I (CMVpp65-A*0201 Peptide Vaccine)	Arm II (Placebo)	Total
United States	32	29	61

Study locations

5 sites

City of Hope Medical Center
Duarte, California 91010, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota 55455, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington 98109, United States

References and documents

Publications

Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999 Mar 30;18(6):695-706. doi: 10.1002/(sici)1097-0258(19990330)18:63.0.co;2-o. PubMed 10204198 ↗

Study documents

Protocol and statistical analysis plan · Feb 19, 2020

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 3, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02396134
Lead sponsor: City of Hope Medical Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Mar 24, 2015
Start date: May 21, 2015
Primary completion: Mar 4, 2018
Completion: Sep 19, 2024
Results posted: Jul 12, 2023
Last update: Mar 3, 2025

Study contacts

Ryotaro Nakamura, MD

principal investigator · City of Hope Medical Center

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Cytomegalovirus Infections→

Other studies from this sponsor

City of Hope Medical Center

Start the discussion