Phase II Clinical Trial to Optimize the Dose of an Anti-NKG2A Monoclonal Antibody (humZ270 MAb, IPH2201) for Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Haploidentical Transplantation with Post- Transplantation Cyclophosphamide
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Graft-versus-host disease-free and progression-free survival (GPFS)
研究概览
简要总结
The goal of this clinical trial is to evaluate the effectiveness and safety of the anti-NKG2A monoclonal antibody (Monalizumab) in patients undergoing haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy). The main questions this trial aims to answer are:
- Does Monalizumab improve graft-versus-host disease-free and progression-free survival (GPFS) in patients after Haplo-SCT?
- What are the safety and side effects of Monalizumab in this patient group?
- How does Monalizumab affect the reconstitution and function of NK cells in patients undergoing Haplo-SCT?
- Researchers will administer Monalizumab to participants on day +30 and +44 after transplantation to see if it enhances immune responses and prevents disease relapse or GVHD.
Participants will:
- Receive Monalizumab intravenously at 1 mg/kg on day +30 and day +44 after Haplo-SCT
- Be monitored for clinical outcomes such as GVHD, survival rates, and immune function for up to one year after the transplant
- Undergo regular checkups and tests to assess the effectiveness and safety of the treatment
详细描述
This Phase II non-randomized, open-label, single-arm, monocentric clinical trial aims to evaluate the safety, efficacy, and biological impact of Monalizumab (humZ270 mAb, IPH2201), an anti-NKG2A monoclonal antibody, in patients undergoing haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy). The study is designed to investigate how the optimization of the dose of this novel antibody can improve the graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) in patients with hematological malignancies, specifically Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS).
Background and Rationale:
Haploidentical stem cell transplantation with PT-Cy as GVHD prophylaxis is a widely used option for patients requiring allogeneic transplantation. However, relapse and GVHD remain significant issues, leading to a GPFS of approximately 30-40%. Alloreactive natural killer (NK) cells play a critical role in graft-versus-tumor (GVT) effects, anti-GVHD, and anti-infectious responses. CD94/NKG2A+ NK cells are prominent early post-transplant, but their effectiveness can be limited. By using anti-NKG2A antibody, NK cell alloreactivity can be enhanced, circumventing the need for an NK alloreactive donor. Preclinical studies have demonstrated that anti-NKG2A antibody treatment restores NK cell-mediated lysis of AML cells, both in vitro and in vivo. This trial aims to assess the clinical benefits of optimizing the dose of anti-NKG2A monoclonal antibody in the Haplo-SCT setting.
Monalizumab is a first-in-class humanized IgG4 antibody targeting the NKG2A receptor on NK cells. It has previously been tested in Phase I trials in solid tumors with promising results at a dosage of 10 mg/kg. In this study, the aim is to optimize the dosage for patients undergoing Haplo-SCT.
Study Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients capable of providing informed consent according to ICH/ GCP, and national/local regulations and be willing to comply with all study-related procedures.
- •Adult patients aged ≥18 years old, without any restriction of gender and race.
- •Patients with a hematologic malignancy represented either by Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) or Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN).
- •Patients lacking a HLA identical donor and receiving haploidentical stem cell transplant with GVHD/HVG prophylaxis consisting of Cyclophosphamide: 40 or 50 mg/kg/day, day +3 and +4, Cyclosporine A: 3 mg/kg/day from day +5, Mycophenolate mofetil: 45 mg/kg/day, from day +5 to day +
- •Patient who has received haplo-SCT with a myeloablative or reduced intensity or nonmyeloblative conditioning followed, either by a bone marrow or a peripheral blood stem cell (PBSC) graft.
- •Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 8 days prior to start of study drug for women of childbearing potential.
- •Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 52 weeks after the last dose of study therapy. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 52 weeks after the patient receives his last dose of study therapy contraception.
排除标准
- •Patients aged < 18 years old.
- •Active uncontrolled infections.
- •CNS involvement of AML disease.
- •Karnofsky performance status (KPS) <60% or severe organ dysfunction, including a left ventricular ejection fraction <40%, DLCO <50% or creatinine clearance <50 ml/min (as per transplant eligibility).
- •Pregnant or breast-feeding or intending to become pregnant during the study.
- •Patients who rapidly relapse after allogenic-SCT before day 30 after allogenic-SCT.
- •Patients who experience acute GVHD before day +30 after allogenic-SCT.
- •Patients treated with a second allogeneic Allo-SCT.
研究组 & 干预措施
monalizumab treatment arm
This study includes a single arm, where all patients will receive Monalizumab (humZ270 mAb, IPH2201), an anti-NKG2A monoclonal antibody, as the intervention. Monalizumab is administered intravenously at a dose of 1 mg/kg on day +30 and day +44 after undergoing haploidentical stem cell transplantation (Haplo-SCT). The use of post-transplantation cyclophosphamide (PT-Cy) is part of the conditioning regimen and inclusion criteria but is not part of the protocol-specified intervention.
Monalizumab aims to enhance the immune function of NK cells by blocking the NKG2A receptor, potentially improving graft-versus-host disease (GVHD)-free and progression-free survival (GPFS).
干预措施: Monalizumab (anti-NKG2A monoclonal antibody) (Drug)
结局指标
主要结局
Graft-versus-host disease-free and progression-free survival (GPFS)
时间窗: GPFS will be evaluated 1 year after Haplo-SCT with PT-Cy and Monalizumab administration on day +30 and +44.
GPFS is defined as the time from Haplo-SCT with post-transplant cyclophosphamide (PT-Cy) until the occurrence of either graft-versus-host disease (GVHD) or disease progression/relapse. This measure evaluates the combined effect of Monalizumab (NKG2A blockade) in preventing both GVHD and disease progression. It is a comprehensive indicator of treatment efficacy, assessing whether the addition of Monalizumab improves patient outcomes by prolonging the period free of both GVHD and disease progression.
次要结局
- Overall Survival (OS)(Overall Survival (OS) will be evaluated at 1 year after Haplo-SCT)
- Progression-Free Survival (PFS)(PFS will be evaluated at 1 year after Haplo-SCT)
- Non-Relapse Mortality (NRM)(NRM will be evaluated at 1 year after Haplo-SCT)
- Incidence of Acute and Chronic GVHD(GVHD incidence will be assessed at 6 months and 1 year after Haplo-SCT)
- Post-transplant Viral Infections(Post-transplant viral infections will be assessed until 100 days after Haplo-SCT)