Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 2NCT02506933
Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant
A Phase 2 study testing Laboratory Biomarker Analysis and Multi-peptide CMV-Modified Vaccinia Ankara Vaccine in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Lymphoblastic Leukemia in Remission, run by City of Hope Medical Center at 3 sites in United States.
Trial summary
This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) vaccine works in reducing CMV complications in patients previously infected with CMV and are undergoing a donor hematopoietic cell transplant. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission
- What is being tested?
- Laboratory Biomarker Analysis and Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 3 sitesUnited States
- Study dates
- 21 Dec 2015to 10 May 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 17Show fewer
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
City of Hope Medical Center
Duarte, California, 91010
M D Anderson Cancer Center
Houston, Texas, 77030
About this study
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
This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) vaccine works in reducing CMV complications in patients previously infected with CMV and are undergoing a donor hematopoietic cell transplant. CMV is a virus that may reproduce and cause disease and even death in patients with lowered immune systems, such as those undergoing a hematopoietic cell transplant. By placing 3 small pieces of CMV deoxyribonucleic acid (DNA) (the chemical form of genes) into a very safe, weakened virus called MVA, the multi-peptide CMV-MVA vaccine may be able to induce immunity (the ability to recognize and respond to an infection) to CMV. This may help to reduce both CMV complications and reduce the need for antiviral drugs in patients undergoing a donor hematopoietic cell transplant.
Read the detailed description
PRIMARY OBJECTIVES:
- 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+).
SECONDARY OBJECTIVES:
- 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.
- Conditions
- 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
- Being tested
- Laboratory Biomarker Analysis, Multi-peptide CMV-Modified Vaccinia Ankara Vaccine, Placebo
- Medical subject headings
- Leukemia, Myeloid, Accelerated Phase, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myeloid, Chronic-Phase, Cytomegalovirus Infections, Hodgkin Disease, Lymphadenopathy, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Multi-peptide CMV-Modified Vaccinia Ankara VaccineBiological
Also called CMV-MVA Triplex Vaccine
Given IM
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given IM
| Study group | Role | What they receive |
|---|---|---|
| Arm I (multi-peptide CMV-MVA vaccine) | Experimental | Patients receive multi-peptide CMV-MVA vaccine IM on days 28 and 56 post-HCT. Receives: Other: Laboratory Biomarker Analysis; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine |
| Arm II (placebo) | Placebo comparator | Patients receive placebo IM on days 28 and 56 post-HCT. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytomegalovirus (CMV) Events to Day 100
Cytomegalovirus (CMV) events included CMV reactivation ≥1250 CMV DNA IU/mL, CMV viremia prompting antiviral therapy, or CMV disease before day 100 after HCT.
Measured: Prior to day 100 post-HCT
Incidence of Severe (Grade 3-4) Acute Graft-Versus-Host Disease
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].
Measured: Up to 100 days post-transplant
Secondary outcomes (1)
All-cause Mortality
Death due to any cause.
Measured: Up to 1 year post-HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2015 (estimated)
- Study start21 Dec 2015
- Primary completion25 Jan 2018
- Study completion10 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Diavax Biosciences
- Responsible party
- Sponsor
- Investigators
- Ryotaro Nakamura, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02506933
- Sponsor's protocol ID
- 14295
- Other IDs
- NCI-2015-01228, 14295, R01CA077544
- Status last verified
- Jul 2026
- First submitted
- 21 Jul 2015
- Last updated
- 28 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Aldoss I, La Rosa C, Baden LR, Longmate J, Ariza-Heredia EJ, Rida WN, Lingaraju CR, Zhou Q, Martinez J, Kaltcheva T, Dagis A, Hardwick N, Issa NC, Farol L, Nademanee A, Al Malki MM, Forman S, Nakamura R, Diamond DJ; TRIPLEX VACCINE Study Group. Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial. Ann Intern Med. 2020 Mar 3;172(5):306-316. doi: 10.7326/M19-2511. Epub 2020 Feb 11.
PubMed 32040960La Rosa C, Longmate J, Martinez J, Zhou Q, Kaltcheva TI, Tsai W, Drake J, Carroll M, Wussow F, Chiuppesi F, Hardwick N, Dadwal S, Aldoss I, Nakamura R, Zaia JA, Diamond DJ. MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults. Blood. 2017 Jan 5;129(1):114-125. doi: 10.1182/blood-2016-07-729756. Epub 2016 Oct 19.
PubMed 27760761