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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 102
- 试验地点
- 4
- 主要终点
- Cytomegalovirus (CMV) Events to Day 100
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES:
I. 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:
I. 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.
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, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（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 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 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
排除标准
- •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
- •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)
研究组 & 干预措施
Arm I (multi-peptide CMV-MVA vaccine)
Patients receive multi-peptide CMV-MVA vaccine IM on days 28 and 56 post-HCT.
干预措施: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine (Biological)
Arm II (placebo)
Patients receive placebo IM on days 28 and 56 post-HCT.
干预措施: Placebo (Other)
Arm II (placebo)
Patients receive placebo IM on days 28 and 56 post-HCT.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (multi-peptide CMV-MVA vaccine)
Patients receive multi-peptide CMV-MVA vaccine IM on days 28 and 56 post-HCT.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Cytomegalovirus (CMV) Events to Day 100
时间窗: Prior to day 100 post-HCT
Cytomegalovirus (CMV) events included CMV reactivation ≥1250 CMV DNA IU/mL, CMV viremia prompting antiviral therapy, or CMV disease before day 100 after HCT.
Incidence of Severe (Grade 3-4) Acute Graft-Versus-Host Disease
时间窗: Up to 100 days post-transplant
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 \[Przepiorka, D., et al., 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant, 1995. 15(6): p. 825-8\].
次要结局
- All-cause Mortality(Up to 1 year post-HCT)