A Phase 2, Single Arm, Multicohort, Open Label, Multicenter Trial of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Patients With High-risk Myeloid Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Sanofi
- 主要终点
- Frequency of life-threatening (grade 4) immune cell-associated neurotoxicity syndrome (ICANS) that does not resolve to grade 1 within 72 hours despite therapy
研究概览
简要总结
This is a multicenter, parallel multicohort, phase 2, single-arm study for adjunctive treatment in participants with high-risk myeloid malignancies undergoing allogeneic HSCT. The purpose of this study is to assess the safety and preliminary efficacy of off-the-shelf (OTS) ex vivo expanded NK cells (SAR445419) in improving relapse free survival (RFS).
详细描述
The expected duration of the study for a participant is about 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Age 18-65 (Cohort A - MAC) or 18-75 (Cohort B - RIC)
- •Participants with high-risk AML/MDS who are scheduled to undergo stem cell transplantation with matched sibling donor (MSD), matched unrelated donor (MUD) or haploidentical donor sourced HSCT
- •Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) ≤ 3 (cohort A / MAC participants only)
- •Adequate major non-hematopoietic organ system function
- •Karnofsky performance score ≥70%
- •Body weight ≥45 kg
排除标准
- •AML beyond CR1
- •Presence of FLT3 mutations
- •Uncontrolled bacterial, viral, or fungal infections at time of enrollment
- •Positive test for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS)
- •Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection
- •Diagnosis of prior immunodeficiency or organ transplantation requiring immunosuppressive therapy
- •Active or chronic autoimmune condition requiring systemic immunosuppressive or immunomodulatory therapy
- •Prior allogeneic transplantation
- •HSCT graft DSA ≥3000 MFI
- •Current use of systemic corticosteroids at physiologic doses ≤ 0.2 mg/kg/day of prednisone or equivalent
- •Use of checkpoint inhibitor therapy within 4 weeks prior to the start of HSCT conditioning regimen The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
High risk AML and MDS
Participants with high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic HSCT will receive 3 doses of SAR445419. A myeloablative conditioning (MAC) and a reduced intensity conditioning (RIC) cohort will be included.
干预措施: SAR445419 (Drug)
结局指标
主要结局
Frequency of life-threatening (grade 4) immune cell-associated neurotoxicity syndrome (ICANS) that does not resolve to grade 1 within 72 hours despite therapy
时间窗: From baseline up to 2 years
Frequency of life-threatening (grade 4) infusion related reactions (IRR) or cytokine release syndrome (CRS) that does not resolve to grade 1 within 72 hours despite therapy
时间窗: From baseline up to 2 years
Frequency of graft failure
时间窗: 100 days post HSCT
Frequency of primary or secondary graft failure
Rate of relapse free survival (RFS) post allogeneic hematopoietic stem cell transplantation (HSCT)
时间窗: 12 months post HSCT
Percentage of patients who are relapse free and alive at 12 months from the date of HSCT and who received at least the first 2 planned doses of SAR445419
Frequency of cytomegalovirus (CMV) reactivation/infection in CMV seronegative participants who receive a CMV seronegative HSCT graft
时间窗: From baseline up to 2 years
Frequency of grade 3-4 acute graft versus host disease (aGVHD)
时间窗: From baseline up to 2 years
Frequency of non-relapse mortality (NRM)
时间窗: 100 days post HSCT
Frequency of life threatening (grade 4) tumor lysis syndrome (TLS)
时间窗: From baseline up to 2 years
Frequency of overall mortality
时间窗: 100 days post HSCT
次要结局
- Number of participants with acute Graft-Versus-Host-Disease (aGVHD)(6, 12, 18 and 24 months post-HSCT)
- Frequency of secondary graft failure(100 days and 12, 18 and 24 months post-HSCT)
- Proportion of participants who are alive and do not need ongoing immune suppression to control GVHD(6, 12, 18 and 24 months post-HSCT)
- Rate of relapse free survival (RFS)(6, 12, 18 and 24 months post-HSCT)
- Frequency of primary graft failure(28 days post-HSCT)
- Change from baseline in Quality of life in Acute Myeloid Leukemia (AML-QoL) score(28 and 100 days and 6, 9 and 12 months post HSCT)
- Change from baseline in Patient Global Impression of Severity (PGIS) score(28 and 100 days and 6, 9 and 12 months post HSCT)
- Frequency of adverse events (AEs)(From baseline up to 2 years)
- Rate of overall survival (OS)(6, 12, 18 and 24 months post-HSCT)
- Rate of GVHD-free relapse-free survival (GRFS)(6, 12, 18 and 24 months post-HSCT)
- Time to hematologic recovery (platelet and neutrophil count recovery) post-HSCT(From baseline up to approximately 180 days)
- Number of participants with chronic Graft-Versus-Host-Disease (cGVHD)(6, 12, 18 and 24 months post-HSCT)
- Rate of non-relapse mortality (NRM)(6, 12, 18 and 24 months post-HSCT)
- Frequency of donor cell engraftment(28 and 100 days, and 6 and 12 months post-HSCT)
- Cumulative incidence of CMV reactivation or infection and symptomatic BK-virus (BKV) hemorrhagic cystitis(100 days and 6 and 12 months post-HSCT)
- Change from baseline in Functional Assessment of Chronic Illness Therapy GP5 question (FACIT-GP5) score(7, 14 and 35 days post-HSCT)
- Cumulative incidence of relapse(6, 12, 18 and 24 months post-HSCT)
- Cumulative incidence of grade 2-4 and grade 3-4 infections during the on-treatment period(Until 30 days after the last administration of SAR445419)
- Change from baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) score(28 and 100 days and 6, 9 and 12 months post HSCT)
- Change from baseline in Patient Global Impression of Change (PGIC) score(28 and 100 days and 6, 9 and 12 months post HSCT)