A Phase II Randomized, Placebo-Controlled, Multicenter Trial to Evaluate the Protective Function of CMV-MVA Triplex Vaccine in Adult Recipients of Haploidentical Hematopoietic Stem Cell Transplant
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Participants With Cytomegalovirus (CMV) Events
研究概览
简要总结
This phase II trial studies how well Triplex vaccine works in preventing cytomegalovirus (CMV) infection in patients undergoing a hematopoietic stem cell transplantation. CMV is a virus that may be carried for life and does not cause illness in most healthy individuals. However, in people whose immune systems are lowered (such as those undergoing stem cell transplantation), CMV can reproduce and cause disease and even death. The Triplex vaccine is made up of 3 small pieces of CMV deoxyribonucleic acid (DNA) (the chemical form of genes) placed into a weakened virus called modified vaccinia Ankara (MVA) that may help produce immunity (the ability to recognize and respond to an infection) and reduce the risk of developing complications related to CMV infection.
详细描述
PRIMARY OBJECTIVE:
I. To determine if CMV-MVA multi-peptide CMV-modified vaccinia Ankara vaccine (Triplex) reduces the frequency of clinically significant CMV reactivation in CMV positive (+) haploidentical hematopoietic cell transplantation (haploHCT) adult recipients from when letermovir (Prevymis) prophylaxis is stopped at day (d)100 until d180 post HCT.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of Triplex in vaccinated, haploHCT recipients by assessing the following: non-relapse mortality (NRM) at d180 post-HCT, severe (grade 3-4) acute graft versus host disease (GVHD), and grade 3-4 adverse events (AEs) (Common Terminology Criteria for Adverse Events [CTCAE] 5.0) probably or definitely related to the vaccination within 2 weeks from each vaccination at d180 post-HCT.
II. To characterize CMV related events in recipients of Triplex compared to placebo, by assessing time-to viremia (number of days from d100 to the date of >= 625 IU/mL), duration of viremia, recurrence of viremia, incidence of late CMV viremia/disease (>= 625 IU/mL, > 200 and =< 365 days post-HCT), use of antiviral drugs (triggered by clinically significant viremia), cumulative number of CMV specific antiviral treatment days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 peripheral blood stem cell (PBSC) or bone marrow (BM) 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.)
- •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 judged appropriate by the clinical principal investigators (PIs), including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis. Patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded
- •Adult cases of multiple myeloma (MM) are excluded as HCT is not standard of care for MM, and is only performed in very advanced cases with an associated high risk of relapse and NRM. Adults with aplastic anemia are excluded because their standard management includes T cell depletion with agents such as anti-thymocyte globulin (ATG), which is not permissible on this protocol. Patients undergoing a second haploHCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
- •Patients receiving myeloablative (MA) or reduced intensity conditioning (RIC) are allowed
- •CMV seropositive (recipient)
- •Planned related HCT with molecular 3/6 (haploidentical) intermediate/high 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 and no history of disseminated cutaneous human papillomavirus (HPV) related disease
- •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 d90 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
排除标准
- •Any prior investigational CMV vaccine
- •Experimental anti-CMV chemotherapy in the last 6 months
- •Live attenuated vaccines (from the time of HCT to d70 post-HCT)
- •Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections) (from the time of HCT to d70 post-HCT)
- •Allergy treatment with antigen injections (from the time of HCT to d70 post-HCT)
- •Alemtuzumab or any equivalent in vivo T-cell depleting agent (or CD34+ selection) (from the time of HCT to d70 post-HCT)
- •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) (from the time of HCT to d70 post-HCT)
- •Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment EXCEPT Prevymis prophylaxis (prior to d100) (from the time of HCT to d70 post-HCT)
- •Conditioning regimens d30 prior to trial participation and up to d180 post-HCT
- •Disease-based radiation therapy (not total body irradiation) (from the time of HCT to d70 post-HCT)
- •Other investigational product - concurrent enrollment in other clinical trials using any investigational new drugs (IND) with unknown effects on CMV or with unknown toxicity profiles is prohibited (from the time of HCT to d70 post-HCT)
- •Other medications that might interfere with the evaluation of the investigational product (from the time of HCT to d70 post-HCT)
- •Patients with active autoimmune conditions requiring systemic immunosuppressive therapy within the previous 5 years are not eligible
- •Patients considered by PIs/protocol team to have a complicated prior therapy or HCT regimen, or who have a low survival probability (e.g., refractory leukemia and/or undergoing 2nd HCT)
- •Poor risk disease/disease status including: chronic myeloid leukemia (CML) in blast crisis, acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) beyond 2nd remission, multiple myeloma, and aplastic anemia
- •Pregnant women and women who are lactating. Triplex risks 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 with the administered vaccine, also 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)
研究组 & 干预措施
Arm I (letermovir, Triplex)
Patients receive letermovir per SOC on days 7-100 and multi-peptide CMV-modified vaccinia Ankara vaccine IM on days 100 and 128 post-HCT.
干预措施: Letermovir (Drug)
Arm I (letermovir, Triplex)
Patients receive letermovir per SOC on days 7-100 and multi-peptide CMV-modified vaccinia Ankara vaccine IM on days 100 and 128 post-HCT.
干预措施: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine (Biological)
Arm II (letermovir, placebo)
Patients receive letermovir per SOC on days 7-100 and placebo IM on days 100 and 128 post-HCT.
干预措施: Letermovir (Drug)
Arm II (letermovir, placebo)
Patients receive letermovir per SOC on days 7-100 and placebo IM on days 100 and 128 post-HCT.
干预措施: Placebo Administration (Other)
结局指标
主要结局
Number of Participants With Cytomegalovirus (CMV) Events
时间窗: From Day 100 to Day 180 post-hematopoietic stem cell transplant (HCT)
Cytomegalovirus (CMV) event was defined as CMV reactivation (DNAemia \>625 IU/ml by qPCR), viremia treated by antivirals, or detection of CMV by tissue histology (end-organ disease), from Day 100 post-HCT to Day 180 post-HCT. Trial participants were quantitatively monitored for viremia, by plasma qPCR test once every two weeks (+/- 5d) from Day 100 to Day 180. CMV monitoring used standard qPCR clinical laboratory methods to evaluate CMV viral load and possible vaccine failure.
次要结局
- Non-Relapse Mortality at Day 180 Post-Transplant(From time of transplant (Day 0) to Day 365)
- Number of Participants With Severe (Grade 3-4) Acute Graft Versus Host Disease (GVHD) at Day 100(From time of transplant (Day 0) to Day 100)
- Number of Grade 3-4 Adverse Events(From time of transplant (Day 0) to Day 365)
- Duration of Viremia(From time of transplant (Day 0) to Day 200)
- Number of Patients With Recurrence of CMV Viremia(From time of transplant (Day 0) to Day 200)
- Days From Transplant to ANC Engraftment(From time of transplant to date of ANC engraftment, up to Day 365.)
- Cumulative Incidence of Acute GVHD(From time of transplant (Day 0) to Day 100)
- Cumulative Incidence of Chronic GVHD at Day 365(From time of transplant (Day 0) to Day 365)
- Cumulative Incidence of Relapse at Day 365(From time of transplant (Day 0) to Day 365)
- Number Of Participants Died at Day 365(From time of transplant (Day 0) to Day 365)
- Overall Survival at Day 365(From time of transplant (Day 0) to Day 365)
- Non-Relapse Mortality (NRM) at Day 365(From time of transplant (Day 0) to Day 365)
- Days From Transplant to Platelet Engraftment(From time of transplant to date of platelet engraftment, up to Day 365)