Accelerated Phase CML, BCR-ABL1 PositivePhase 1NCT03560752
CMV-MVA Triplex Vaccination of Stem Cell Donors in Preventing CMV Viremia in Participants With Allogeneic Transplant
A Phase 1 study testing Multi-peptide CMV-Modified Vaccinia Ankara Vaccine in people with Accelerated Phase CML, BCR-ABL1 Positive and Acute Lymphoblastic Leukemia in Remission, run by City of Hope Medical Center at 1 site in United States.
Trial summary
This phase II trial studies how well multi-peptide CMV-modified vaccinia Ankara (CMV-MVA Triplex) vaccination of stem cell donors works in preventing cytomegalovirus (CMV) viremia in participants with blood cancer undergoing donor stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Accelerated Phase CML, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission
- What is being tested?
- Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2018to 28 Jun 2027
- Phase
- Phase 1
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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- DONOR: Ability to comprehend the investigational nature of the study and provide informed consent
- DONOR: Willing to receive Triplex vaccination, a minimum of 14 days prior to the PBSC collection
- DONOR VACCINATION: Donors are eligible to be vaccinated prior to the determination of their human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV) status. The exclusion criteria for transplant is independent of eligibility for vaccination and is determined by the exclusion criteria for transplant from donors
- RECIPIENT: All subjects must have the ability to understand and the willingness to sign a written informed consent
- RECIPIENT: Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT
- RECIPIENT: Age 18 to 75 years
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- RECIPIENT: 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, acute myeloid leukemia in first or second remission, chronic myelogenous leukemia (in first chronic or accelerated phase, or in second chronic phase), chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis (City of Hope [COH] only). Patients with multiple myeloma are excluded
- RECIPIENT: CMV seropositive
- RECIPIENT: Planned related HCT with 8/8 (A, B, C, DRB1) high resolution HLA donor allele matching
- RECIPIENT: Conditioning and immunosuppressive regimens according to institutional guidelines are permitted
- RECIPIENT: Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within two weeks of registration
- RECIPIENT: Seronegative for HIV, HCV and active HBV (surface antigen negative) within 2 months of registration
- RECIPIENT: Agreement by females of childbearing potential and males with partners of childbearing potential to use effective contraception (hormonal or barrier method 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
- TRANSPLANT FROM DONOR: Unfit to undergo standard stem cell mobilization and apheresis e.g. abnormal blood counts, history of stroke, uncontrolled hypertension
- TRANSPLANT FROM DONOR: Sickling hemoglobinopathy including HbSS, HbAS, HbSC
- TRANSPLANT FROM DONOR: Positive for human immunodeficiency virus (HIV), active hepatitis B (hepatitis B virus [HBV]), hepatitis C (hepatitis C virus [HCV]) or human T-cell lymphotropic virus (HTLV-I/II). This holds true even if donors have been already vaccinated according to criteria for donor vaccination
- TRANSPLANT FROM DONOR: Donors with impaired cardiac function are excluded. Electrocardiography is routine for potential HCT donors over 60 years old and those with a history of heart disease. Subjects in whom cardiac function is abnormal (excluding 1st degree branch block, sinus brachycardia, sinus tachycardia or non-specific T wave changes) are ineligible for Triplex vaccination
- TRANSPLANT FROM DONOR: Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the donation procedure unlikely, and making informed consent impossible
- RECIPIENT: Any prior investigational CMV vaccine
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- RECIPIENT: Experimental anti-CMV chemotherapy in the last 6 months
- RECIPIENT: Planned medications from the time of HCT to day 70 post-HCT
- RECIPIENT: Live attenuated vaccines
- RECIPIENT: 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)
- RECIPIENT: Allergy treatment with antigens injections
- RECIPIENT: Alemtuzumab or any equivalent in vivo T-cell depleting agent
- RECIPIENT: Antiviral medications with known therapeutic effects on CMV such as ganciclovir (GCV)/valganciclovir (VAL), 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)
- RECIPIENT: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment (Letermovir is permitted). EXCEPT for low risk patients [8/8 high resolution HLA donor allele matching HCT])
- RECIPIENT: 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
- RECIPIENT: Other medications that might interfere with the evaluation of the investigational product
- RECIPIENT: Diagnosis with autoimmune disease
- RECIPIENT: Pregnant women and women who are lactating. The risks of CMV-MVA-Triplex to pregnant women are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother. Breastfeeding should be discontinued if the mother is enrolled on this study
- RECIPIENT: 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
- RECIPIENT: 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
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: CMV-MVA Triplex Vaccination of Stem Cell Donors to Enhance CMV Specific Immunity and Prevent CMV Viremia in Recipients After Stem Cell Transplant
This phase II trial studies how well multi-peptide CMV-modified vaccinia Ankara (CMV-MVA Triplex) vaccination of stem cell donors works in preventing cytomegalovirus (CMV) viremia in participants with blood cancer undergoing donor stem cell transplant. Giving a vaccine to the donors may boost the recipient's immunity to this virus and reduce the chance of CMV disease after transplant.
Read the detailed description
PRIMARY OBJECTIVES:
- Establish the feasibility and safety of priming CMV immunity in donors by Triplex vaccination prior to peripheral blood stem cell (PBSC) harvest.
SECONDARY OBJECTIVES:
- Examine if Triplex vaccination of hematopoietic stem cell transplant (HCT) donors has an impact on CMV events.
OUTLINE:
Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization. Participants undergo hematopoietic cell transplantation on day 0.
After completion of study treatment, participants are followed up for 1 year.
- Conditions
- Accelerated Phase CML, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission, Chronic Lymphocytic Leukemia, Chronic Phase CML, BCR-ABL1 Positive, Cytomegalovirus Positive
- Being tested
- Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
- Medical subject headings
- Leukemia, Myeloid, Accelerated Phase, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myeloid, Chronic-Phase, Hodgkin Disease, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Lymphoma, Non-Hodgkin, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi-peptide CMV-Modified Vaccinia Ankara VaccineBiological
Also called CMV-MVA Triplex Vaccine
Given via injection
| Study group | Role | What they receive |
|---|---|---|
| Donor (multi-peptide CMV-modified vaccinia Ankara vaccine) | Experimental | Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization. Receives: Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine |
| Receipient (multi-peptide CMV-modified vaccinia Ankara vaccine) | Experimental | Participants undergo hematopoietic cell transplantation on day 0 and receive multi-peptide CMV-modified Vaccinia Ankara vaccine injection on days 28 and 56. Receives: Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delayed Engraftment
Time to neutrophil engraftment was defined as days from stem cell infusion to the first of three consecutive days of absolute neutrophil count ≥0.5 x 109/L. Delayed engraftment was defined as ≥20 days to neutrophil recovery.
Measured: Up to 1 year from stem cell infusion.
Severe (Grade III-IV) Acute Graft Versus Host Disease
Acute graft versus host disease (aGvHD) happens within days or as late as 6 months after allogeneic transplants. The three main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract.
Measured: Up to 6 months from stem cell infusion
Number of Recipients With Grade 3-4 Adverse Events
Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.
Measured: Up to 1 year from stem cell infusion.
Number of Donors With Grade 2-3 Adverse Events
Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.
Measured: Up to 6 months after G-CSF mobilization
100-Day Non-Relapse Mortality (NRM)
NRM was defined as death without recurrent or progressive disease after allogeneic transplant. Probabilities of NRM were estimated with the use of cumulative incidence curves, with relapse viewed as a competing risk.
Measured: From stem cell infusion up to 100 days post-HSCT (hematopoietic stem cell transplantation).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2018
- Study start20 Aug 2018
- Primary completion22 Jan 2022
- Study completion28 Jun 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 (1)Papers the sponsor has linked to this study.
- Other trials for Accelerated Phase CML, 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 1
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ryotaro Nakamura, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03560752
- Sponsor's protocol ID
- 18007
- Other IDs
- NCI-2018-01115, 18007
- Status last verified
- Sep 2026
- First submitted
- 7 Jun 2018
- Last updated
- 28 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
La Rosa C, Aldoss I, Park Y, Yang D, Zhou Q, Gendzekhadze K, Kaltcheva T, Rida W, Dempsey S, Arslan S, Artz A, Ball B, Nikolaenko L, Pullarkat VA, Nakamura R, Diamond DJ. Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus-specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis. Am J Hematol. 2023 Apr;98(4):588-597. doi: 10.1002/ajh.26824. Epub 2023 Jan 11.
PubMed 36594185